Alzheimer's Prevention

Latest Research News

Data from 876 patients (average age 78) in the 30-year Cardiovascular Health Study show that virtually any type of aerobic physical activity can improve brain volume and reduce Alzheimer's risk.

A higher level of physical activity was associated with larger brain volumes in the frontal, temporal, and parietal lobes including the hippocampus, thalamus and basal ganglia. Among those with MCI or Alzheimer's (25% of the participants), higher levels of physical activity were also associated with less brain atrophy. An increase in physical activity was also associated with larger grey matter volumes in the left inferior orbitofrontal cortex and the left precuneus.

Further analysis of 326 of the participants found that those with the highest energy expenditure were half as likely to have developed Alzheimer's disease five years later.

Physical activity was assessed using the Minnesota Leisure-Time Activities questionnaire, which calculates kilocalories/week using frequency and duration of time spent in 15 different leisure-time activities: swimming, hiking, aerobics, jogging, tennis, racquetball, walking, gardening, mowing, raking, golfing, bicycling, dancing, calisthenics, and riding an exercise cycle.

The study does not look at whether some types of physical activity are better than others, unfortunately, but its message that overall physical activity, regardless of type, helps in the fight against cognitive impairment is encouraging.

http://www.eurekalert.org/pub_releases/2016-03/ip-dko030916.php

http://www.eurekalert.org/pub_releases/2016-03/uops-bmc031016.php

I've spoken before about how the presence or absence of the “Alzheimer's gene” may affect which lifestyle changes are beneficial for you. A new study has added to that idea with a finding that seafood consumption was associated with fewer signs of Alzheimer's-related pathology, but only among those with the APOEe4 gene.

Seafood consumption was also associated with increased mercury levels in the brain, with levels rising the more seafood was consumed. However, higher levels of mercury were not correlated with any neuropathologies.

Fish oil supplementation was not associated with any differences in neuropathology. However, higher levels of alpha-linolenic acid (an omega-3 fatty acid found in flaxseed, chia seeds, walnuts, etc) were associated with a reduced chance of cerebral infarctions.

The study involved 554 deceased participants (average age 89.9 years) from the long-running Memory and Aging Project (MAP) conducted by Rush University Medical Center. The participants had completed annual dietary questionnaires over a number of years. The brains of 286 participants were autopsied, to assess neuropathologies and mercury levels.

The average educational attainment of the participants was 14.6 years; 67% were women.

The finding tempers the evidence from many studies that eating fish reduces Alzheimer's risk. However, it is consistent with what I believe is becoming apparent: that there are different paths to Alzheimer's, and thus different factors involved in preventing it, depending on your own particular gene-environment attributes.

http://www.eurekalert.org/pub_releases/2016-02/nioe-scm020116.php

A two-year study which involved metabolic testing of 50 people, suggests that Alzheimer's disease consists of three distinct subtypes, each one of which may need to be treated differently. The finding may help explain why it has been so hard to find effective treatments for the disease.

The subtypes are:

  • Inflammatory, in which markers such as C-reactive protein and serum albumin to globulin ratios are increased.
  • Non-inflammatory, in which these markers are not increased but other metabolic abnormalities (such as insulin resistance, hypovitaminosis D, and hyper-homocysteinemia) are present. This tends to affect slightly older individuals than the first subtype: 80s rather than 70s.
  • Cortical, which affects relatively young individuals (typically 50s- early 70s) and appears more widely distributed across the brain than the other subtypes, showing widespread cortical atrophy rather than marked hippocampal atrophy. It typically presents with language and number difficulties first, rather than memory loss. Typically, there is an impaired ability to hold onto a train of thought. It is often misdiagnosed, typically affects people without a family history of Alzheimer's, who do not have an Alzheimer's-related gene, and is associated with a significant zinc deficiency (Zinc is implicated in multiple Alzheimer's-related metabolic processes, such as insulin resistance, chronic inflammation, ADAM10 proteolytic activity, and hormonal signaling. Zinc deficiency is relatively common, and associated with increasing age.).

The cortical subtype appears to be fundamentally a different condition than the other two.

I note a study I reported on last year, that found different molecular structures of amyloid-beta fibrils in the brains of Alzheimer's patients with different clinical histories and degrees of brain damage. That was a very small study, indicative only. However, I do wonder if there's any connection between these two findings. At the least, I think this approach a promising one.

The idea that there are different types of Alzheimer's disease is of course consistent with the research showing a variety of genetic risk factors, and an earlier study indicating at least two pathways to Alzheimer's.

It's also worth noting that the present study built on an earlier study, which showed that a program of lifestyle, exercise and diet changes designed to improve the body's metabolism reversed cognitive decline within 3-6 months in nine out of 10 patients with early Alzheimer's disease or its precursors. Note that this was a very small pilot program, and needs a proper clinical trial. Nevertheless, it is certainly very interesting.

http://www.eurekalert.org/pub_releases/2015-09/uoc--adc091615.php

Bredesen, D.E. 2015. Metabolic profiling distinguishes three subtypes of Alzheimer's disease. AGING, 7 (8), 595-600. Full text at http://www.impactaging.com/papers/v7/n8/full/100801.html

Bredesen, D.E. 2014. Reversal of cognitive decline: A novel therapeutic program. AGING, Vol 6, No 9 , pp 707-717. Full text at http://www.impactaging.com/papers/v6/n9/full/100690.html

A large, two-year study challenges the evidence that regular exercise helps prevent age-related cognitive decline.

The study involved 1,635 older adults (70-89) who were enrolled in the Lifestyle Interventions and Independence for Elders (LIFE) study. They were sedentary adults who were at risk for mobility disability but able to walk about a quarter mile. Participants had no significant cognitive impairment (as measured by the MMSE) at the beginning of the study. Around 90% (1476) made it to the end of the study, and were included in the analysis.

Half the participants were randomly assigned to a structured, moderate-intensity physical activity program that included walking, resistance training, and flexibility exercises, and the other half to a health education program of educational workshops and upper-extremity stretching.

In the physical activity condition, participants were expected to attend 2 center-based visits per week and perform home-based activity 3 to 4 times per week. The sessions progressed toward a goal of 30 minutes of walking at moderate intensity, 10 minutes of primarily lower-extremity strength training with ankle weights, and 10 minutes of balance training and large muscle group flexibility exercises.

The health education group attended weekly health education workshops during the first 26 weeks of the intervention and at least monthly sessions thereafter. Sessions lasted 60 to 90 minutes and consisted of interactive and didactic presentations, facilitator demonstrations, guest speakers, or field trips. Sessions included approximately 10 minutes of group discussion and interaction and 5 to 10 minutes of upper-extremity stretching and flexibility exercises.

Cognitive assessments were made at the beginning of the study and at 24 months, as well as a computerized assessment at either 18 or 30 months.

At the end of the study, there was no significant difference in cognitive score, or incidence of MCI or dementia, between the two groups. However, those in the exercise group who were 80 years or older ( 307) and those with poorer baseline physical performance ( 328) did show significantly better performance in executive function.

Executive function is not only a critical function in retaining the ability to live independently, research has also shown that it is the most sensitive cognitive domain to physical exercise.

Note also that there was no absolute control group — that is, people who received no intervention. Both groups showed remarkably stable cognitive scores over the two years, suggesting that both interventions were in fact effective in “holding the line”.

While this finding is disappointing and a little surprising, it is not entirely inconsistent with the research. Studies into the benefits of physical exercise for fighting age-related cognitive decline and dementia have produced mixed results. It does seem clear that the relationship is not a simple one, and what's needed is a better understanding of the complexities of the relationship. For example, elements of exercise that are critical, and the types of people (genes; health; previous social, physical, and cognitive attributes) that may benefit.

http://www.eurekalert.org/pub_releases/2015-08/tjnj-eop082115.php

There are five healthy behaviors that appear to significantly reduce the risk of dementia,

A 35-year study that monitored the healthy behaviors of 2,235 Welsh men aged 45 to 59 at the beginning of the study has found that those who consistently followed at least four of these five healthy behaviors — regular exercise, no smoking, acceptable BMI, high fruit and vegetable intake, and low/moderate alcohol intake — experienced a 60% reduction in dementia and cognitive decline compared with people who followed none. They also had 70% fewer instances of diabetes, heart disease, and stroke,.

Exercise was the most important of these factors.

Only 5% of the men were living a healthy lifestyle (i.e., following at least 4 of these healthy behaviors). Just under half of the 2235 men were non-smokers (46%), and around a third (35%) had an acceptable BMI. Only 15 men ate their “5+” daily (!!), so the requirement was reduced to only three or more portions of fruit and vegetables, enabling 18% to reach it. 39% exercised regularly and 59% reported alcohol intake within the guidelines. Only two men managed five healthy behaviors, and 109 managed four; 19% managed three; 36% two; 31% one; 8% couldn’t manage any.

http://www.futurity.org/five-healthy-behaviors-can-reduce-dementia-risk/

http://www.eurekalert.org/pub_releases/2013-12/cu-3ys120913.php

Elwood, P., Galante, J., Pickering, J., Palmer, S., Bayer, A., Ben-Shlomo, Y., … Gallacher, J. (2013). Healthy Lifestyles Reduce the Incidence of Chronic Diseases and Dementia: Evidence from the Caerphilly Cohort Study. PLoS ONE, 8(12), e81877. doi:10.1371/journal.pone.0081877

A pilot study involving 17 older adults with mild cognitive impairment and 18 controls (aged 60-88; average age 78) has found that a 12-week exercise program significantly improved performance on a semantic memory task, and also significantly improved brain efficiency, for both groups.

The program involved treadmill walking at a moderate intensity. The semantic memory tasks involved correctly recognizing names of celebrities well known to adults born in the 1930s and 40s (difficulty in remembering familiar names is one of the first tasks affected in Alzheimer’s), and recalling words presented in a list. Brain efficiency was demonstrated by a decrease in the activation intensity in the 11 brain regions involved in the memory task. The brain regions with improved efficiency corresponded to those involved in Alzheimer's disease, including the precuneus region, the temporal lobe, and the parahippocampal gyrus.

Participants also improved their cardiovascular fitness, by about 10%.

http://www.eurekalert.org/pub_releases/2013-07/uom-emb073013.php

Smith, J.C. et al. 2013. Semantic Memory Functional MRI and Cognitive Function After Exercise Intervention in Mild Cognitive Impairment. Journal of Alzheimer’s Disease, 37 (1), 197-215.

Data from the population-based Finnish Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) study has revealed that healthy dietary choices in midlife may prevent dementia in later years. Out of 2,000 participants, 1,449 took part in the follow-up. The participants were 39 to 64 years old at baseline and 65 to 75 years old at follow-up.

Those who ate the healthiest diet at around age 50 had an almost 90% lower risk of dementia in a 14-year follow-up study than those whose diet was the least healthy.

Healthy foods included vegetables, berries and fruits, fish and unsaturated fats from milk products and spreads; unhealthy foods included sausages, eggs, sweets, sugary drinks, salty fish and saturated fats from milk products and spreads.

Consistent with other research, a high intake of saturated fats was also linked to poorer cognition and an increased risk of mild cognitive impairment 21 years later. A higher saturated fat intake was also associated with an increased risk of dementia among those carrying the “Alzheimer's gene”, ApoE4.

Those consuming 3 to 5 cups of coffee daily had a smaller risk of dementia than those consuming less or more.

http://www.eurekalert.org/pub_releases/2014-03/uoef-hmd031014.php

Eskelinen, Marjo: The effects of midlife diet on late-life cognition: an epidemiological approach. Publications of the University of Eastern Finland. Dissertations in Health Sciences., no 220. http://epublications.uef.fi/pub/urn_isbn_978-952-61-1394-4/

Eskelinen MH, Ngandu T, Helkala E-L, Tuomilehto J, Nissinen A, Soininen H, Kivipelto M. Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study. Int J Geriatr Psychiatry 23(7): 741, 2008.

Laitinen MH, Ngandu T, Rovio S, Helkala E-L, Uusitalo U, Viitanen M, Nissinen A, Tuomilehto J, Soininen H, Kivipelto M. Fat Intake at Midlife and Risk of Dementia and Alzheimer's Disease: A Population-Based Study. Dement Geriatr Cogn Disord 22(1): 99, 2006.

Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M. Midlife Coffee and Tea Drinking and the Risk of Late-Life Dementia: A Population-based CAIDE Study. J Alzheimers Dis 16(1): 85-91, 2009.

Eskelinen MH, Ngandu T, Tuomilehto J, Soininen H, Kivipelto M. Midlife Healthy Diet Index and Late-Life Dementia and Alzheimer's Disease. Dement Geriatr Cogn Disord Extra 1(1): 103-112, 2011.

Analysis of 5715 cases from the National Alzheimer's Coordinating Center (NACC) database has found that nearly 80% of more than 4600 Alzheimer's disease patients showed some degree of vascular pathology, compared with 67% of the controls, and 66% in the Parkinson's group. The link was especially strong for younger patients with Alzheimer’s.

The findings support the view that early management of vascular risk factors, such as high blood pressure and cholesterol, and adopting a 'heart healthy' diet as well as exercise and other lifestyles in midlife, may delay or prevent the onset of dementia due to Alzheimer's.

http://www.eurekalert.org/pub_releases/2013-07/uops-pss070913.php

[3612] Toledo JB, Arnold SE, Raible K, Brettschneider J, Xie SX, Grossman M, Monsell SE, Kukull WA, Trojanowski JQ. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain [Internet]. 2013 ;136(9):2697 - 2706. Available from: http://brain.oxfordjournals.org/content/136/9/2697

I’ve been happily generous with cinnamon on my breakfast ever since the first hints came out that cinnamon might help protect against Alzheimer’s (it’s not like it’s an ordeal to add cinnamon!). Now a new study has revealed why. Two compounds found in cinnamon —cinnamaldehyde and epicatechin —appear to help prevent tau tangles (one of the characteristics of Alzheimer’s).

Cinnamaldehyde protects tau from oxidative stress, by binding to two residues of an amino acid called cysteine on the tau protein. This protects the cysteine residues from changing in ways that contribute to the development of Alzheimer’s.

Epicatechin is a powerful antioxidant that I have mentioned before. Found in a number of foods, including blueberries, chocolate, and red wine, it similarly responds to oxidation by sequestering reactive byproducts such as the cysteine residues.

The findings also help explain previous research showing cinnamon’s beneficial effects in managing blood glucose and other problems associated with diabetes. Higher glucose levels lead to oxidative stress.

Given the early stage of the research, the researchers do caution against eating more than typical amounts of cinnamon – but there’s surely no harm in including it in your daily diet, and it may well do some good!

http://www.futurity.org/top-stories/can-cinnamon-prevent-alzheimer%e2%80%99s-tangles/

[3432] George RC, Lew J, Graves DJ. Interaction of Cinnamaldehyde and Epicatechin with Tau: Implications of Beneficial Effects in Modulating Alzheimer's Disease Pathogenesis. Journal of Alzheimer's disease: JAD. 2013 .

Previous research has pointed to an association between not having teeth and a higher risk of cognitive decline and dementia. One reason might have to do with inflammation — inflammation is a well-established risk factor, and at least one study has linked gum disease to a higher dementia risk. Or it might have to do with the simple mechanical act of chewing, reducing blood flow to the brain. A new study has directly investigated chewing ability in older adults.

The Swedish study, involving 557 older adults (77+), found that those with multiple tooth loss, and those who had difficulty chewing hard food such as apples, had a significantly higher risk of developing cognitive impairments (cognitive status was measured using the MMSE). However, when adjusted for sex, age, and education, tooth loss was no longer significant, but chewing difficulties remained significant.

In other words, what had caused the tooth loss didn’t matter. The important thing was to maintain chewing ability, whether with your own natural teeth or dentures.

This idea that the physical act of chewing might affect your cognitive function (on a regular basis; I don’t think anyone is suggesting that you’re brighter when you chew!) is an intriguing and unexpected one. It does, however, give even more emphasis to the importance of physical exercise, which is a much better way of increasing blood flow to the brain.

The finding also reminds us that there are many things going on in the brain that may deteriorate with age and thus lead to cognitive decline and even dementia.

Sad to say, another large study has given the thumbs down to ginkgo biloba preventing Alzheimer’s disease.

The randomized, double-blind trial took place over five years, involving 2854 older adults (70+) who had presented to their primary care physician with memory complaints. Half were given a twice-daily dose of 120 mg standardised ginkgo biloba extract and half a placebo.

After five years, 4% of those receiving ginkgo biloba had been diagnosed with probable Alzheimer's disease, compared with 5% in the placebo group — an insignificant difference. There was no significant difference between the groups in mortality, stroke, or cardiovascular events, either.

The French study confirms the findings of an earlier American trial, and is also consistent with another large, long-running study that found no benefits of ginkgo biloba for age-related cognitive decline.

Green tea is thought to have wide-ranging health benefits, especially in the prevention of cardiovascular disease, inflammatory diseases, and diabetes. These are all implicated in the development of age-related cognitive impairment, so it’s no surprise that regular drinking of green tea has been suggested as one way to help protect against age-related cognitive decline and dementia. A new mouse study adds to that evidence by showing how a particular compound in green tea promotes neurogenesis.

The chemical EGCG, (epigallocatechin-3 gallate) is a known anti-oxidant, but this study shows that it also has a specific benefit in increasing the production of neural progenitor cells. Like stem cells, these progenitor cells can become different types of cell.

Mice treated with EGCG displayed better object recognition and spatial memory than control mice, and this improved performance was associated with the number of progenitor cells in the dentate gyrus and increased activity in the sonic hedgehog signaling pathway (confirming the importance of this pathway in adult neurogenesis in the hippocampus).

The findings add to evidence that green tea may help protect against cognitive impairment and dementia.

A review of three high quality trials comparing the putative benefits of omega-3 fatty acids for preventing age-related cognitive decline, has concluded that there is no evidence that taking fish oil supplements helps fight cognitive decline. The trials involved a total of 3,536 healthy older adults (60+). In two studies, participants were randomly assigned to receive gel capsules containing omega-3 PUFA or olive or sunflower oil for six or 24 months. In the third study, participants were randomly assigned to receive tubs of margarine spread for 40 months (regular margarine versus margarine fortified with omega-3 PUFA).

The researchers found no benefit from taking the omega-3 capsules or margarine spread compared to placebo capsules or margarines (sunflower oil, olive oil or regular margarine). Participants given omega-3 did not score better on the MMSE or on other tests of cognitive function such as verbal learning, digit span and verbal fluency.

The researchers nevertheless stress that longer term studies are needed, given that there was very little deterioration in cognitive function in any of the groups.

[3015] Sydenham E, Dangour AD, Lim W-S. Omega 3 fatty acid for the prevention of cognitive decline and dementia. In: Collaboration TC, Sydenham E Cochrane Database of Systematic Reviews. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2012. Available from: http://summaries.cochrane.org/CD005379/fish-oils-for-the-prevention-of-dementia-in-older-people

A study designed to compare the relative benefits of exercise and diet control on Alzheimer’s pathology and cognitive performance has revealed that while both are beneficial, exercise is of greater benefit in reducing Alzheimer’s pathology and cognitive impairment.

The study involved mice genetically engineered with a mutation in the APP gene (a familial risk factor for Alzheimer’s), who were given either a standard diet or a high-fat diet (60% fat, 20% carbohydrate, 20% protein vs 10% fat, 70% carbohydrate, 20% protein) for 20 weeks (from 2-3 to 7-8 months of age). Some of the mice on the high-fat diet spent the second half of that 20 weeks in an environmentally enriched cage (more than twice as large as the standard cage, and supplied with a running wheel and other objects). Others on the high-fat diet were put back on a standard diet in the second 10 weeks. Yet another group were put on a standard diet and given an enriched cage in the second 10 weeks.

Unsurprisingly, those on the high-fat diet gained significantly more weight than those on the standard diet, and exercise reduced that gain — but not as much as diet control (i.e., returning to a standard diet) did. Interestingly, this was not the result of changes in food intake, which either stayed the same or slightly increased.

More importantly, exercise and diet control were roughly equal in reversing glucose intolerance, but exercise was more effective than diet control in ameliorating cognitive impairment. Similarly, while amyloid-beta pathology was significantly reduced in both exercise and diet-control conditions, exercise produced the greater reduction in amyloid-beta deposits and level of amyloid-beta oligomers.

It seems that diet control improves metabolic disorders induced by a high-fat diet — conditions such as obesity, hyperinsulinemia and hypercholesterolemia — which affects the production of amyloid-beta. However exercise is more effective in tackling brain pathology directly implicated in dementia and cognitive decline, because it strengthens the activity of an enzyme that decreases the level of amyloid-beta.

Interestingly, and somewhat surprisingly, the combination of exercise and diet control did not have a significantly better effect than exercise alone.

The finding adds to the growing pile of evidence for the value of exercise in maintaining a healthy brain in later life, and helps explain why. Of course, as I’ve discussed on several occasions, we already know other mechanisms by which exercise improves cognition, such as boosting neurogenesis.

I have reported previously on research suggesting that rapamycin, a bacterial product first isolated from soil on Easter Island and used to help transplant patients prevent organ rejection, might improve learning and memory. Following on from this research, a new mouse study has extended these findings by adding rapamycin to the diet of healthy mice throughout their life span. Excitingly, it found that cognition was improved in young mice, and abolished normal cognitive decline in older mice.

Anxiety and depressive-like behavior was also reduced, and the mice’s behavior demonstrated that rapamycin was acting like an antidepressant. This effect was found across all ages.

Three "feel-good" neurotransmitters — serotonin, dopamine and norepinephrine — all showed significantly higher levels in the midbrain (but not in the hippocampus). As these neurotransmitters are involved in learning and memory as well as mood, it is suggested that this might be a factor in the improved cognition.

Other recent studies have suggested that rapamycin inhibits a pathway in the brain that interferes with memory formation and facilitates aging.

Following on from mouse studies, a human study has investigated whether caffeine can help prevent older adults with mild cognitive impairment from progressing to dementia.

The study involved 124 older adults (65-88) who were thoroughly cognitively assessed, given brain scans, and had a fasting blood sample taken. They were then followed for 2 to 4 years, during which their cognitive status was re-assessed annually. Of the 124 participants, 69 (56%) were initially assessed as cognitively normal (average age 73), 32 (26%) with MCI (average age 76.5), and 23 (19%) with dementia (average age 77). The age differences were significant.

Those with MCI on initial assessment showed significantly lower levels of caffeine in their blood than those cognitively healthy; levels in those with dementia were also lower but not significantly. Those initially healthy who developed MCI over the study period similarly showed lower caffeine levels than those who didn’t develop MCI, but again, due to the wide individual variability (and the relatively small sample size), this wasn’t significant. However, among those with MCI who progressed to dementia (11, i.e. a third of those with MCI), caffeine levels were so much lower that the results were significant.

This finding revealed an apparently critical level of caffeine dividing those who progressed to dementia and those who did not — more specifically, all of those who progressed to dementia were below this level, while around half of those who remained stable were at the level or above. In other words, low caffeine would seem to be necessary but not sufficient.

On the other hand (just to show that this association is not as simple as it appears), those already with dementia had higher caffeine levels than those with MCI who progressed to dementia.

The critical factor may have to do with three specific cytokines — GCSF, IL-10, and IL-6 — which all showed markedly lower levels in those converting from MCI to dementia. Comparison of the three stable-MCI individuals with the highest caffeine levels and the three with the lowest levels, and the three from the MCI-to-dementia group with comparable low levels, revealed that high levels of those cytokines were matched with high caffeine levels, while, in both groups, low caffeine levels were matched to low levels of those cytokines.

These cytokines are associated with inflammation — an established factor in cognitive decline and dementia.

The level of coffee needed to achieve the ‘magic’ caffeine level is estimated at around 3 cups a day. While caffeine can be found in other sources, it is thought that in this study, as in the mouse studies, coffee is the main source. Moreover, mouse research suggests that caffeine is interacting with an as yet unidentified component of coffee to boost levels of these cytokines.

This research has indicated that caffeine has several beneficial effects on the brain, including suppressing levels of enzymes that produce amyloid-beta, as well as these anti-inflammatory effects.

It’s suggested that the reason high levels of caffeine don’t appear to benefit those with dementia is because higher levels of these cytokines have become re-established, but this immune response would appear to come too late to protect the brain. This is consistent with other evidence of the importance of timing.

Do note that in mouse studies, the same benefits were not associated with decaffeinated coffee.

While this study has some limitations, the findings are consistent with previous epidemiologic studies indicating coffee/caffeine helps protect against cognitive impairment and dementia. Additionally, in keeping with the apparent anti-inflammatory action, a long-term study tracking the health and coffee consumption of more than 400,000 older adults recently found that coffee drinkers had reduced risk of dying from heart disease, lung disease, pneumonia, stroke, diabetes, infections, injuries and accidents.

Cao, C., Loewenstein, D. a, Lin, X., Zhang, C., Wang, L., Duara, R., Wu, Y., et al. (2012). High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia. Journal of Alzheimer’s disease : JAD, 30(3), 559–72. doi:10.3233/JAD-2012-111781

Freedman, N.D. et al. 2012. Association of Coffee Drinking with Total and Cause-Specific Mortality. N Engl J Med, 366, 1891-1904.

A new study, involving 1,219 dementia-free older adults (65+), has found that the more omega-3 fatty acids the person consumed, the lower the level of beta-amyloid in the blood (a proxy for brain levels). Consuming a gram of omega-3 more than the average per day was associated with 20-30% lower beta-amyloid levels. A gram of omega-3 equates to around half a fillet of salmon per week.

Participants provided information about their diet for an average of 1.2 years before their blood was tested for beta-amyloid. Other nutrients investigated —saturated fatty acids, omega-6 polyunsaturated fatty acids, mono-unsaturated fatty acid, vitamin E, vitamin C, beta-carotene, vitamin B12, folate and vitamin D — were not associated with beta-amyloid levels.

The results remained after adjusting for age, education, gender, ethnicity, amount of calories consumed and APOE gene status.

The findings are consistent with previous research associating higher levels of omega-3 and/or fish intake with lower risk of Alzheimer’s. Additionally, another recent study provides evidence that the brains of those with Alzheimer’s disease, MCI, and the cognitively normal, all have significantly different levels of omega-3 and omega-6 fatty acids. That study concluded that the differences were due to both consumption and metabolic differences.

[2959] Gu Y, Schupf N, Cosentino SA, Luchsinger J a, Scarmeas N. Nutrient Intake and Plasma Β-Amyloid. Neurology [Internet]. 2012 ;78(23):1832 - 1840. Available from: http://www.neurology.org/content/78/23/1832

Cunnane, S.C. et al. 2012. Plasma and Brain Fatty Acid Profiles in Mild Cognitive Impairment and Alzheimer’s Disease. Journal of Alzheimer’s Disease, 29 (3), 691-697.

Data from the Women's Health Study, involving 6,183 older women (65+), has found that it isn’t the amount of fat but the type of fat that is associated with cognitive decline. The women were given three cognitive function tests at two-yearly intervals, and filled out very detailed food frequency surveys at the beginning of the study.

Women who consumed the highest amounts of saturated fat (such as that from animals) had significantly poorer cognitive function compared to those who consumed the lowest amounts. Women who instead had a high intake of monounsaturated fats (such as olive oil) had better cognitive scores over time. Total fat, polyunsaturated fat, and trans fat, were not associated with cognitive performance.

The findings are consistent with research associating the Mediterranean diet (high in olive oil) with lower Alzheimer’s risk, and studies linking diets high in saturated fats with greater cognitive decline.

A study involving 86 older women (aged 70-80) with probable MCI has compared the effectiveness of resistance and aerobic training in improving executive function. The women were randomly allocated either to resistance training, aerobic training, or balance and tone training (control group). The programs all ran twice weekly for six months.

The 60-minute classes involved lifting weights (resistance training), outdoor walking (aerobic training), or stretching, balancing, and relaxation exercises (control).

Executive function was primarily assessed by the Stroop Test (measuring selective attention/conflict resolution), and also by Trail Making Tests (set-shifting) and Verbal Digits Tests (working memory). Associative memory (face-scene pairs) and problem-solving ability (Everyday Problems Test) were also assessed.

The study found that resistance training significantly improved performance on the Stroop Test and also the associative memory task. These improvements were associated with changes in some brain regions. In contrast to previous studies in healthy older adults, aerobic training didn’t produce any significant cognitive improvement, although it did produce significantly better balance and mobility, and cardiovascular capacity, compared to the control.

Interestingly, a previous study from these researchers demonstrated that it took a year of resistance training to achieve such results in cognitively healthy women aged 65-75. This suggests that the benefits may be greater for those at greater risk.

It may be that the greater benefits of resistance training over aerobic training are not be solely due to physical differences in the exercise. The researchers point out that resistance training required more cognitive engagement (“If you’re lifting weights you have to monitor your sets, your reps, you use weight machines and you have to adjust the seat, etc.”) compared to walking.

Note that impaired associative memory is one of the earliest cognitive functions affected in Alzheimer’s.

It’s also worth noting that exercise compliance was low (55-60%), suggesting that benefits might have been greater if the participants had been more motivated — or found the programs more enjoyable! The failure of aerobic exercise to improve cognition is somewhat surprising, and perhaps it, too, may be attributed to insufficient engagement — in terms of intensity as well as amount.

The researchers have put up a YouTube video of the resistance training exercises used in the study.

A four-year study involving 716 elderly (average age 82) has revealed that those who were most physically active were significantly less likely to develop Alzheimer’s than those least active. The study is unique in that, in addition to self-reports of physical and social activity, activity was objectively measured (for up to 10 days) through a device worn on the wrist. This device (an actigraph) enabled everyday activity, such as cooking, washing the dishes, playing cards and even moving a wheelchair with a person's arms, to be included in the analysis.

Cognitive performance was assessed annually. Over the study period, 71 participants (10%) developed Alzheimer’s.

The study found that those in the bottom 10% of daily physical activity were more than twice as likely (2.3 times) to develop Alzheimer's disease as those in the top 10%. Those in the bottom 10% of intensity of physical activity were almost three times (2.8 times) as likely to develop Alzheimer's disease as people in the top 10%.

Moreover, the level of activity was associated with the rate of cognitive decline.

The association remained after motor function, depression, chronic health conditions, and APOE gene status were taken into account.

The findings should encourage anyone who feels that physical exercise is beyond them to nevertheless engage in milder forms of daily activity.

 

Addendum:

Another recent study, involving 331 cognitively healthy elderly, has also found that higher levels of physical activity were associated with better cognitive performance (specifically, a shorter time to complete the Trail-making test, and higher levels of verbal fluency) and less brain atrophy. Activity levels were based on the number of self-reported light and hard activities for at least 30 minutes per week. Participants were assessed in terms of MMSE score, verbal fluency, and visuospatial ability.

A study involving 1,575 older adults (aged 58-76) has found that those with DHA levels in the bottom 25% had smaller brain volume (equivalent to about 2 years of aging) and greater amounts of white matter lesions. Those with levels of all omega-3 fatty acids in the bottom quarter also scored lower on tests of visual memory, executive function, and abstract thinking.

The finding adds to the evidence that higher levels of omega-3 fatty acids reduce dementia risk.

For more about omega-3 oils and cognition

Following on from research showing an association between lower walking speed and increased risk of dementia, and weaker hand grip strength and increased dementia risk, a large study has explored whether this association extends to middle-aged and younger-old adults.

Part of the long-running Framingham study, the study involved 2,410 men and women with an average age of 62, who underwent brain scans and tests for walking speed, hand grip strength and cognitive function. During the follow-up period of up to 11 years, 34 people (1.4%) developed dementia (28 Alzheimer’s) and 79 people (3.3%) had a stroke.

Those who had a slower walking speed at the start of the study were one-and-a-half times more likely to develop dementia compared to people with faster walking speed, while stronger hand grip strength was associated with a 42% lower risk of stroke or transient ischemic attack in people over age 65.

Slower walking speed and weaker hand grip strength were also associated with lower brain volume and poorer cognitive performance. Specifically, those with slower walking speed scored significantly worse on tests of visual reproduction, paired associate learning, executive function, visual organization, and language (Boston Naming test). Higher hand grip strength was associated with higher scores on tests of visual reproduction, executive function, visual organization, language and abstraction (similarities test).

While the nature of the association is not yet understood, the findings do seem to support the benefits of physical fitness. At the least, these physical attributes can serve as pointers to the need for more investigation of an older person’s brain health. But they might also serve as a warning to improve physical fitness.

Camargo, E.C., Beiser, A., Tan, Z.S., Au, R., DeCarli, C., Pikula, A., Kelly-Hayes, M., Kase, C., Wolf, P. & Seshadri, S. 2012. Walking Speed, Handgrip Strength and Risk of Dementia and Stroke: The Framingham Offspring Study. To be presented April 25 at the American Academy of Neurology's 64th Annual Meeting in New Orleans.

We know that physical exercise greatly helps you prevent cognitive decline with aging. We know that mental stimulation also helps you prevent age-related cognitive decline. So it was only a matter of time before someone came up with a way of combining the two. A new study found that older adults improved executive function more by participating in virtual reality-enhanced exercise ("exergames") that combine physical exercise with computer-simulated environments and interactive videogame features, compared to the same exercise without the enhancements.

The Cybercycle Study involved 79 older adults (aged 58-99) from independent living facilities with indoor access to a stationary exercise bike. Of the 79, 63 participants completed the three-month study, meaning that they achieved at least 25 rides during the three months.

Unfortunately, randomization was not as good as it should have been — although the researchers planned to randomize on an individual basis, various technical problems led them to randomize on a site basis (there were eight sites), with the result that the cybercycle group and the control bike group were significantly different in age and education. Although the researchers took this into account in the analysis, that is not the same as having groups that match in these all-important variables. However, at least the variables went in opposite directions: while the cybercycle group was significantly younger (average 75.7 vs 81.6 years), it was significantly less educated (average 12.6 vs 14.8 years).

Perhaps also partly off-setting the age advantage, the cybercycle group was in poorer shape than the control group (higher BMI, glucose levels, lower physical activity level, etc), although these differences weren’t statistically significant. IQ was also lower for the cybercycle group, if not significantly so (but note the high averages for both groups: 117.6 vs 120.6). One of the three tests of executive function, Color Trails, also showed a marked group difference, but the large variability in scores meant that this difference was not statistically significant.

Although participants were screened for disorders such as Alzheimer’s and Parkinson’s, and functional disability, many of both groups were assessed as having MCI — 16 of the 38 in the cybercycle group and 14 of the 41 in the control bike group.

Participants were given cognitive tests at enrolment, one month later (before the intervention began), and after the intervention ended. The stationary bikes were identical for both groups, except the experimental bike was equipped with a virtual reality display. Cybercycle participants experienced 3D tours and raced against a "ghost rider," an avatar based on their last best ride.

The hypothesis was that cybercycling would particularly benefit executive function, and this was borne out. Executive function (measured by the Color Trails, Stroop test, and Digits Backward) improved significantly more in the cybercycle condition, and indeed was the only cognitive task to do so (other cognitive tests included verbal fluency, verbal memory, visuospatial skill, motor function). Indeed, the control group, despite getting the same amount of exercise, got worse at the Digits Backward test, and failed to show any improvement on the Stroop test.

Moreover, significantly fewer cybercyclists progressed to MCI compared to the control group (three vs nine).

There were no differences in exercise quantity or quality between the two groups — which does argue against the idea that cyber-enhanced physical activity would be more motivating. However, the cybercycling group did tend to comment on their enjoyment of the exercise. While the enjoyment may not have translated into increased activity in this situation, it may well do so in a longer, less directed intervention — i.e. real life.

It should also be remembered that the intervention was relatively short, and that other cognitive tasks might take longer to show improvement than the more sensitive executive function. This is supported by the fact that levels of the brain growth factor BDNF, assessed in 30 participants, showed a significantly greater increase of BDNF in cybercyclists.

I should also emphasize that the level of physical exercise really wasn't that great, but nevertheless the size of the cybercycle's effect on executive function was greater than usually produced by aerobic exercise (a medium effect rather than a small one).

The idea that activities that combine physical and mental exercise are of greater cognitive benefit than the sum of benefits from each type of exercise on its own is not inconsistent with previous research, and in keeping with evidence from animal studies that physical exercise and mental stimulation help the brain via different mechanisms. Moreover, I have an idea that enjoyment (in itself, not as a proxy for motivation) may be a factor in the cognitive benefits derived from activities, whether physical or mental. Mere speculation, derived from two quite separate areas of research: the idea of “flow” / “being in the zone”, and the idea that humor has physiological benefits.

Of course, as discussed, this study has a number of methodological issues that limit its findings, but hopefully it will be the beginning of an interesting line of research.  

The study involved 104 healthy older adults (average age 87) participating in the Oregon Brain Aging Study. Analysis of the nutrient biomarkers in their blood revealed that those with diets high in omega 3 fatty acids and in vitamins C, D, E and the B vitamins had higher scores on cognitive tests than people with diets low in those nutrients, while those with diets high in trans fats were more likely to score more poorly on cognitive tests.

These were dose-dependent, with each standard deviation increase in the vitamin BCDE score ssociated with a 0.28 SD increase in global cognitive score, and each SD increase in the trans fat score associated with a 0.30 SD decrease in global cognitive score.

Trans fats are primarily found in packaged, fast, fried and frozen food, baked goods and margarine spreads.

Brain scans of 42 of the participants found that those with diets high in vitamins BCDE and omega 3 fatty acids were also less likely to have the brain shrinkage associated with Alzheimer's, while those with high trans fats were more likely to show such brain atrophy.

Those with higher omega-3 scores also had fewer white matter hyperintensities. However, this association became weaker once depression and hypertension were taken into account.

Overall, the participants had good nutritional status, but 7% were deficient in vitamin B12 (I’m surprised it’s so low, but bear in mind that these are already a select group, being healthy at such an advanced age) and 25% were deficient in vitamin D.

The nutrient biomarkers accounted for 17% of the variation in cognitive performance, while age, education, APOE genotype (presence or absence of the ‘Alzheimer’s gene’), depression and high blood pressure together accounted for 46%. Diet was more important for brain atrophy: here, the nutrient biomarkers accounted for 37% of the variation, while the other factors accounted for 40% (meaning that diet was nearly as important as all these other factors combined!).

The findings add to the growing evidence that diet has a significant role in determining whether or not, and when, you develop Alzheimer’s disease.

Dietary changes affect levels of biomarkers associated with Alzheimer's

In a study involving 20 healthy older adults (mean age 69.3) and 29 older adults who had amnestic mild cognitive impairment (mean age 67.6), half the participants were randomly assigned to a high–saturated fat/high–simple carbohydrate diet (HIGH) and half to a low–saturated fat/low–simple carbohydrate diet (LOW) for four weeks, in order to investigate the effects on biomarkers associated with Alzheimer’s.

For the healthy participants, the LOW diet decreased the level of amyloid-beta 42 in the cerebrospinal fluid, while the HIGH diet increased its level. The HIGH diet also lowered the CSF insulin concentration. For those with aMCI, the LOW diet increased the levels of amyloid-beta 42 and increased the CSF insulin concentration. For both groups, the level of apolipoprotein E in the CSF increased in the LOW diet and decreased in the HIGH diet.

For both groups, the LOW diet improved performance on delayed visual recall tests, but didn’t affect scores on other cognitive measures (bear in mind that the diet was only followed for a month).

The researchers suggest that the different results of the unhealthy diet in participants with aMCI may be due to the diet’s short duration. The fact that diet was bringing about measurable changes in CSF biomarkers so quickly, and that the HIGH diet moved healthy brains in the direction of Alzheimer’s, speaks to the potential of dietary intervention.

Why coffee helps protect against Alzheimer's disease

Support for the value of coffee in decreasing the risk of Alzheimer’s comes from a mouse study, which found that an as yet unidentified ingredient in coffee interacts with caffeine in such a way that blood levels of a growth factor called GCSF (granulocyte colony stimulating factor) increases. GCSF is a substance greatly decreased in patients with Alzheimer's disease and demonstrated to improve memory in Alzheimer's mice.

The finding points to the value of caffeinated coffee, as opposed to decaffeinated coffee or to other sources of caffeine. Moreover, only "drip" coffee was used; the researchers caution that they don’t know whether instant caffeinated coffee would provide the same GCSF response.

There are three ways that GCSF seems to improve memory performance in the Alzheimer's mice: by recruiting stem cells from bone marrow to enter the brain and remove beta-amyloid protein; by increasing the growth of new synapses; by increasing neurogenesis.

The amount of coffee needed to provide this protection, however, is estimated to be about 4 to 5 cups a day. The researchers also believe that this daily coffee intake is best begun at least by middle age (30s – 50s), although starting even in older age does seem to have some protective effect.

Weirdly (I thought), the researchers remarked that "The average American gets most of their daily antioxidants intake through coffee". Perhaps this points more to the defects in their diet than to the wonders of coffee! But the finding is consistent with other research showing an association between moderate consumption of coffee and decreased risk of Parkinson's disease, Type II diabetes and stroke.

A just-completed clinical trial has investigated GCSF treatment to prevent Alzheimer's in patients with mild cognitive impairment, and the results should be known soon.

[2442] Bayer-Carter JL, Green PS, Montine TJ, VanFossen B, Baker LD, Watson SG, Bonner LM, Callaghan M, Leverenz JB, Walter BK, et al. Diet Intervention and Cerebrospinal Fluid Biomarkers in Amnestic Mild Cognitive Impairment. Arch Neurol [Internet]. 2011 ;68(6):743 - 752. Available from: http://archneur.ama-assn.org/cgi/content/abstract/68/6/743

Cao, C., Wang, L., Lin, X., Mamcarz, M., Zhang, C., Bai, G., Nong, J., Sussman, S. & Arendash, G.  2011.Caffeine Synergizes with Another Coffee Component to Increase Plasma GCSF: Linkage to Cognitive Benefits in Alzheimer's Mice. Journal of Alzheimer's Disease, 25(2), 323-335.

Another study showing the value of exercise for preserving your mental faculties in old age. This time it has to do with the development of small brain lesions or infarcts called "silent strokes." Don’t let the words “small” and “silent” fool you — these lesions have been linked to memory problems and even dementia, as well as stroke, an increased risk of falls and impaired mobility.

The study involved 1,238 people taken from the Northern Manhattan Study, a long-running study looking at stroke and vascular problems in a diverse community. Their brains were scanned some six years after completing an exercise questionnaire, when they were an average of 70 years old. The scans found that 16% of the participants had these small brain lesions.

Those who had reported engaging in moderate to intense exercise were 40% less likely to have these infarcts compared to people who did no regular exercise. Depressingly, there was no significant difference between those who engaged in light exercise and those who didn’t exercise (which is not to say that light exercise doesn’t help in other regards! a number of studies have pointed to the value of regular brisk walking for fighting cognitive decline). This is consistent with earlier findings that only the higher levels of activity consistently protect against stroke.

The results remained the same after other vascular risk factors such as high blood pressure, high cholesterol and smoking, were accounted for. Of the participants, 43% reported no regular exercise; 36% engaged in regular light exercise (e.g., golf, walking, bowling or dancing); 21% engaged in regular moderate to intense exercise (e.g., hiking, tennis, swimming, biking, jogging or racquetball).

However, there was no association with white matter lesions, which have also been associated with an increased risk of stroke and dementia.

Moreover, this effect was not seen among those with Medicaid or no health insurance, suggesting that lower socioeconomic status (or perhaps poorer access to health care) is associated with negative factors that counteract the benefits of exercise. Previous research has found that lower SES is associated with higher cardiovascular disease regardless of access to care.

Of the participants, 65% were Hispanic, 17% non-Hispanic black, and 15% non-Hispanic white. Over half (53%) had less than high school education, and 47% were on Medicaid or had no health insurance.

A long-term study of older adults with similar levels of education has found that those with the thinnest cerebral cortex in specific brain regions were the most likely to develop dementia. Among those in whom these signature brain areas were the thinnest at the beginning of the study, 55% developed dementia over the next decade, compared with 20% of those with average cortical thickness and none of those in whom cortical thickness was above average. Those with the thinnest cortical areas also developed Alzheimer's significantly faster.

The study involved two independent samples. In the first group, 33 people were followed for an average of 11 years, during which time eight developed Alzheimer's. In the second group, 32 people were followed for an average of seven years, and seven of them developed the disease. (So 23% developed Alzheimer’s in total.) Participants were divided into three groups based on cortical thickness in the key areas: 11 had the lowest levels, 9 had the highest, and 45 were average.

A new study finds out why curcumin might help protect against dementia, and links two factors associated with Alzheimer’s and Parkinson’s diseases: DNA damage by reactive oxygen species (ROS), and excessive levels of copper and iron in parts of the brain. It turns out that high levels of copper or iron help generate large numbers of ROS and interfere with DNA repair.

While small amounts of iron and copper are vital, these are normally bound by proteins. However, when there’s too much, it can overwhelm the proteins and the result is "free" iron or copper ions circulating in the blood, able to initiate chemical reactions that produce reactive oxygen species. Moreover, the free copper and iron also interferes with the activity of two enzymes that repair DNA, NEIL1 and NEIL2.

However, the curry spice curcumin binds to iron and copper and was extremely effective in protecting the NEIL enzymes from the metals.

Hegde, M.L., Hegde, P.M. , Rao, K.S.J. & Mitra, S. 2011. Oxidative Genome Damage and Its Repair in Neurodegenerative Diseases: Function of Transition Metals as a Double-Edged Sword. Journal of Alzheimer's Disease , 25 (1), 183-198.

A review of 23 longitudinal studies of older adults (65+) has found that small amounts of alcohol were associated with lower incidence rates of overall dementia and Alzheimer dementia, but not of vascular dementia or age-related cognitive decline. A three-year German study involving 3,327 adults aged 75+ extends the evidence to the older-old.

The study found alcohol consumption was significantly associated with 3 other factors that helped protect against dementia: better education, not living alone, and absence of depression. Nevertheless, the lower risk remained after accounting for these factors.

The ‘magic’ amount of alcohol was between 20-29g, roughly 2-3 drinks a day. As in other studies, a U-shaped effect was found, with higher risk found among both those who consumed less than this amount of alcohol, and those who consumed more.

Another study has come out proclaiming the cognitive benefits of walking for older adults. Previously sedentary adults aged 55-80 who walked around a track for 40 minutes on three days a week for a year increased the size of their hippocampus, as well as their level of BDNF. Those assigned to a stretching routine showed no such growth. There were 120 participants in the study.

The growth of around 2% contrasts with the average loss of 1.4% hippocampal tissue in the stretching group — an amount of atrophy considered “normal” with age. Although both groups improved their performance on a computerized spatial memory test, the walkers improved more.

The findings are consistent with a number of animal studies showing aerobic exercise increases neurogenesis and BDNF in the hippocampus, and human studies pointing to a lower risk of cognitive decline and dementia in those who walk regularly.

A study involving 68 healthy older adults (65-85) has compared brain activity among four groups, determined whether or not they carry the Alzheimer’s gene ApoE4 and whether their physical activity is reported to be high or low. The participants performed a task involving the discrimination of famous people, which engages 15 different functional regions of the brain. Among those carrying the gene, those with higher physical activity showed greater activation in many regions than those who were sedentary. Moreover, physically active people with the gene had greater brain activity than physically active people without the gene.

And adding to the evidence supporting the potential for exercise to lower the risk of dementia, another recent study has found that after ten years exercise (in terms of the number of different types of exercises performed and number of exercise sessions lasting at least 20 minutes) was inversely associated with the onset of cognitive impairment. The study used data from the National Long Term Care Survey.

Following on from previous studies showing that drinking beet juice can lower blood pressure, a study involving 14 older adults (average age 75) has found that after two days of eating a high-nitrate breakfast, which included 16 ounces of beet juice, blood flow to the white matter of the frontal lobes (especially between the dorsolateral prefrontal cortex and anterior cingulate cortex) had increased. This area is critical for executive functioning.

Poor blood flow in the brain is thought to be a factor in age-related cognitive decline and dementia.

High concentrations of nitrates are found in beets, as well as in celery, cabbage and other leafy green vegetables like spinach and some lettuce. When you eat high-nitrate foods, good bacteria in the mouth turn nitrate into nitrite. Research has found that nitrites can help open up the blood vessels in the body, increasing blood flow and oxygen specifically to places that are lacking oxygen.

There have been mixed findings about the benefits of DHA (an omega-3 fatty acid), but in a study involving 485 older adults (55+) with age-related cognitive impairment, those randomly assigned to take DHA for six months improved the score on a visuospatial learning and episodic memory test. Higher levels of DHA in the blood correlated with better scores on the paired associate learning task. DHA supplementation was also associated with better verbal recognition, but not better working memory or executive function.

Other research has found no benefit from DHA to those already with Alzheimer’s, although those with Alzheimer’s tend to have lower levels of DHA in the blood. These findings reinforce the idea that the benefit of many proactive lifestyle strategies, such as diet and exercise, may depend mainly on their use before systems deteriorate.

The daily dose of algal DHA was 900 mg. The study took place at 19 clinical sites in the U.S., and those involved had an MMSE score greater than 26.

A seven-year study involving 271 Finns aged 65-79 has revealed that increases in the level of homocysteine in the blood were associated with increasing risk of developing Alzheimer’s (each micromolar increase in the concentration of homocysteine increased the risk of Alzheimer's by 16%), while increases in the level of vitamin B12 decreased the risk (each picomolar increase in concentration of B12 reduced risk by 2%). A larger study is needed to confirm this. 17 people (6%) developed Alzheimer’s over the course of the study.

Still, these results are consistent with a number of other studies showing greater risk with higher homocysteine and lower B12. High levels of vitamin B12 are known to lower homocysteine. However, studies directly assessing the effects of B12 supplements have had mixed results. Low levels of B12 are common in the elderly.

A long-running study involving 299 older adults (average age 78) has found that those who walked at least 72 blocks during a week of recorded activity (around six to nine miles) had greater gray matter volume nine years later. Gray matter does shrink as we get older, so this is not about growth so much as counteracting decline. Walking more than 72 blocks didn’t appear to confer any additional benefit (in terms of gray matter volume). Moreover, when assessed four years after that, those who had shown this increased brain size were only half as likely to have developed dementia (40% of the participants had developed dementia by this point).

Low levels of DHA, an omega-3 fatty acid, have been found in the brains of those with Alzheimer's disease, but the reason has not been known. A new study has found that lower levels of DHA in the liver (where most brain DHA is manufactured) were correlated with greater cognitive problems in the Alzheimer’s patients. Moreover, comparison of postmortem livers from Alzheimer’s patients and controls found reduced expression of a protein that converts a precursor acid into DHA, meaning the liver was less able to make DHA from food.

The findings may explain why clinical trials in which Alzheimer's patients are given omega-3 fatty acids have had mixed results. They also suggest that it might be possible to identify at-risk persons using specific blood tests, and perhaps delay the development of Alzheimer’s with a chemically enhanced form of DHA.

A two-year study involving 271 older adults (70+) with mild cognitive impairment has found that the rate of brain atrophy in those taking folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), was significantly slower than in those taking a placebo, with those taking the supplements experiencing on average 30% less brain atrophy. Higher rates of atrophy were associated with lower cognitive performance. Moreover those who with the highest levels of homocysteine at the beginning of the trial benefited the most, with 50% less brain shrinkage. High levels of homocysteine are a risk factor for Alzheimer’s, and folate, B12 and B6 help regulate it.

The finding that atrophy can be slowed in those with MCI offers hope that the treatment could delay the development of Alzheimer’s, since MCI is a major risk factor for Alzheimer’s, and faster brain atrophy is typical of those who go on to develop Alzheimer’s.

Following on from previous research with mice that demonstrated that a diet rich in methionine could increase the risk of developing Alzheimer's Disease through its effect on homocysteine levels, a new study has found that these effects were reversible if the mice then switched to a healthier diet. The mice, after five months on a methionine-rich diet, were divided into two groups, with one group continuing the diet and the second switching to the healthy diet for an additional two months. The cognitive impairment, and the build-up in amyloid plaques, was completely reversed after two months.

Methionine is an amino acid typically found in red meats, fish, beans, eggs, garlic, lentils, onions, yogurt and seeds. I note, however, that most of the items in this list are usually considered healthy! Fish, in particular, has been shown in a number of studies to reduce the risk of Alzheimer’s. The point is that methionine in itself is an essential amino acid and necessary for a healthy brain, but this indicates that, as with many foods, moderation is important. Clearly a balance is required; equally clearly, we still haven’t quite worked out the ‘perfect’ Alzheimer’s-prevention diet. Nevertheless, this study is welcome in demonstrating that diet can have such an effect on the brain, and adds to our knowledge of what makes a good diet for staving off dementia.

A German study involving nearly 4000 older adults (55+) has found that physical activity significantly reduced the risk of developing mild cognitive impairment over a two-year period. Nearly 14% of those with no physical activity at the start of the study developed cognitive impairment, compared to 6.7% of those with moderate activity, and 5.1% of those with high activity. Moderate activity was defined as less than 3 times a week.

In another report, a study involving 1,324 individuals without dementia found those who reported performing moderate exercise during midlife or late life were significantly less likely to have MCI. Midlife moderate exercise was associated with 39% reduction in the odds of developing MCI, and moderate exercise in late life was associated with a 32% reduction. Light exercise (such as bowling, slow dancing or golfing with a cart) or vigorous exercise (including jogging, skiing and racquetball) were not significantly associated with reduced risk for MCI.

And in a clinical trial involving 33 older adults (55-85) with MCI has found that women who exercised at high intensity levels with an aerobics trainer for 45 to 60 minutes per day, four days per week, significantly improved performance on multiple tests of executive function, compared to those who engaged in low-intensity stretching exercises. The results for men were less significant: high-intensity aerobics was associated only with improved performance on one cognitive task, Trail-making test B, a test of visual attention and task-switching.

Following on from studies showing that a Mediterranean-like diet may be associated with a lower risk of Alzheimer's disease and may lengthen survival in people with Alzheimer's, a six-year study of 712 New Yorkers has revealed that those who were most closely following a Mediterranean-like diet were 36% less likely to have brain infarcts (small areas of dead tissue linked to thinking problems), compared to those who were least following the diet. Those moderately following the diet were 21% less likely to have brain damage. The association was comparable to the effects of high blood pressure — that is, not eating a Mediterranean-like diet was like having high blood pressure. The Mediterranean diet includes high intake of vegetables, legumes, fruits, cereals, fish and monounsaturated fatty acids such as olive oil; low intake of saturated fatty acids, dairy products, meat and poultry; and mild to moderate amounts of alcohol.

The study will be presented at the American Academy of Neurology's 62nd Annual Meeting in Toronto April 10 to April 17, 2010.

A study has found that gerbils given a ‘cocktail’ of DHA, uridine and choline performed significantly better on learning and memory tests than untreated gerbils, and their brains had up to 70% more phosphatides (a type of molecule that forms cell membranes) than controls, suggesting that new synapses are forming. Some of the gerbils received all three compounds and some received only two; the improvements were greatest in those given all three. An earlier study had found that the treatment improved function in rats with cognitive impairment. Omega-3 fatty acids are found in fish, eggs, flaxseed and meat from grass-fed animals. Choline is found in meats, nuts and eggs. Uridine cannot be obtained from food sources, but is a component of human breast milk and can be produced in the body.

Older news items (pre-2010) brought over from the old website

Diet

Olive oil compound may help against Alzheimer's

Oleocanthal, a naturally-occurring compound found in extra-virgin olive oil, has been found to change the size of ADDLs, impeding their ability to bind to synapses — thought to be a crucial first step in Alzheimer’s development. The compound also protected synapses from structural damage caused by ADDLs.

Pitt, J. et al. 2009. Alzheimer's-associated Aβ oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal. Toxicology and Applied Pharmacology, 240 (2), 189-197.

http://www.eurekalert.org/pub_releases/2009-09/mcsc-omh092909.php

Alzheimer's-fighting compounds need regular consumption

A rat study has found that the amount of polyphenols from grapeseed extract that can reach the brain is as much as 200% higher on the 10th consecutive day of feeding as compared to the first. The finding points to the value of regular consumption. Polyphenols are thought to prevent the formation of beta-amyloid protein.

Ferruzzi, M.G. et al. 2009. Bioavailability of Gallic Acid and Catechins from Grape Seed Polyphenol Extract is Improved by Repeated Dosing in Rats: Implications for Treatment in Alzheimer’s Disease. Journal of Alzheimer's Disease, 18 (1), 113-124.

http://www.eurekalert.org/pub_releases/2009-08/pu-ssh081709.php

Exercise and Mediterranean-type diet associated with lower risk for Alzheimer's

A New York study involving 1880 elderly (average age 77) is the first to investigate both exercise and diet in connection with the later development of Alzheimer’s (within a five and a half year period). Participants were asked about their activity in the two weeks prior to the interview, about the regularity and duration, as well as the quality (vigorous, moderate, light). They were also asked about their food consumption over the previous year, and their responses grouped into nine food categories, the sum of which represented a Mediterranean-type diet score. Those who were very physically active had a 33% risk reduction of Alzheimer's; those who adhered more strongly to a Mediterranean-type diet had a 40% risk reduction. Those who did both had a 60% reduction. A Mediterranean-type diet is typically characterized by high intake of fish, vegetables, legumes, fruits, cereals and monounsaturated fatty acids; relatively low intake of dairy products, meats and saturated fats; and moderate alcohol consumption.

Scarmeas, N. et al. 2009. Physical Activity, Diet, and Risk of Alzheimer Disease. Journal of the American Medical Association, 302(6), 627-637.
Full text available at http://jama.ama-assn.org/cgi/content/full/302/6/627?home

http://www.eurekalert.org/pub_releases/2009-08/cumc-eam080609.php

Mediterranean diet associated with lower risk of cognitive impairment

A study of 1,393 individuals with no cognitive problems and 482 patients with mild cognitive impairment has found that eating a Mediterranean diet was associated with less risk of developing mild cognitive impairment or of transitioning from MCI to Alzheimer's disease. Over an average of 4.5 years of follow-up, 275 of the 1,393 developed MCI. The third with the highest scores for Mediterranean diet adherence had a 28% lower risk of developing MCI compared to the third with the lowest scores, while the middle third had 17% less risk. Among the 482 with MCI, 106 developed Alzheimer's disease over an average 4.3 years of follow-up. The third with the highest scores for Mediterranean diet adherence had 48% less chance of developing Alzheimer’s and those in the middle third had 45% less chance. A number of the components of the Mediterranean diet have been associated with reduced risk of developing MCI or Alzheimer’s.

Scarmeas, N. et al. 2009. Mediterranean Diet and Mild Cognitive Impairment. Archives of Neurology, 66(2), 216-225.

http://www.eurekalert.org/pub_releases/2009-02/jaaj-mda020509.php

Moderate drinking can reduce risks of Alzheimer's dementia and cognitive decline

A review of 44 studies has concluded that moderate drinkers often have lower risks of Alzheimer's disease and other cognitive loss. Moderate alcohol consumption generally is defined as 1 drink or less per day for women and 1-2 drinks or less per day for men.

Collins, M.A. et al. 2008. Alcohol in Moderation, Cardioprotection, and Neuroprotection: Epidemiological Considerations and Mechanistic Studies. Alcoholism: Clinical and Experimental Research, Published Online 20 November

http://www.eurekalert.org/pub_releases/2008-12/luhs-mdc122908.php

Midlife coffee drinking reduces risk of dementia

A large, long-running Finnish study has found that those who were coffee drinkers at midlife had lower risk for dementia and Alzheimer’s later in life compared to those drinking no or only little coffee midlife. The lowest risk was found among moderate coffee drinkers (drinking 3-5 cups of coffee/day). Tea drinking was relatively uncommon and was not associated with dementia.

Eskelinen, M.H. et al. 2009. Midlife Coffee and Tea Drinking and the Risk of Late-Life Dementia: A Population-based CAIDE Study. Journal of Alzheimer's Disease, 16(1).

http://www.physorg.com/news151225794.html

Gingko biloba does not prevent dementia

A six-year study involving over 3000 older adults has found no reduction in the rate of dementia for those taking twice-daily 120 mg doses of Ginkgo biloba.

DeKosky, S.T. et al. Ginkgo biloba for prevention of dementia: A randomized controlled trial. JAMA, 300, 2253.

http://www.eurekalert.org/pub_releases/2008-11/jaaj-gbd111308.php
http://www.eurekalert.org/pub_releases/2008-11/wfub-gpi111808.php

Red grape seeds may help prevent Alzheimer's disease

Research into the nearly 5000 compounds contained in red wine to reveal the source of the health benefits seen from red wine has revealed that polyphenols derived from red grape seeds may be useful agents to prevent or treat Alzheimer's disease. Red grape seeds currently being developed with the name of Meganatural AZ were found to significantly reduce cognitive deterioration in genetically engineered mice, by preventing the formation of amyloid beta. The mice were given the extract before the age at which they normally develop signs of disease, suggesting the extract may help prevent or postpone the development of Alzheimer’s. The major polyphenol components in the grape seed extract product are catechin and epicatechin, which are also abundant in tea and cocoa. Unlike the polyphenol resveratrol, which has been shown to have similar effects, but requires extremely high doses, the catechins appear to be effective at much lower doses. Further research will of course be needed before human recommendations can be made.

Wang, J. et al. 2008. Grape-Derived Polyphenolics Prevent Aβ Oligomerization and Attenuate Cognitive Deterioration in a Mouse Model of Alzheimer's Disease. Journal of Neuroscience, 28, 6388-6392.

http://www.eurekalert.org/pub_releases/2008-06/tmsh-pnr061708.php
http://www.eurekalert.org/pub_releases/2008-06/sfn-sig061708.php

Vitamin E or C does not reduce risk of dementia or Alzheimer's

A five-year study involving nearly 3000 people has found that use of Vitamin C or E or both was not associated with a reduced risk of developing dementia or Alzheimer’s.

Gray, S.L. et al. 2008. Antioxidant Vitamin Supplement Use and Risk of Dementia or Alzheimer's Disease in Older Adults. Journal of the American Geriatrics Society, 56 (2), 291–295.

http://www.eurekalert.org/pub_releases/2008-02/bpl-veo020408.php

Why fish oil is good for you

Confirming previous research indicating that fish oil helps delay or prevent Alzheimer’s, a new study shows why. The study reveals that the omega-3 fatty acid DHA found in fish oil increases the production of LR11, a protein that is found at reduced levels in Alzheimer's patients and which is known to destroy the protein that forms the "plaques" associated with the disease. The study looked at both rodent brains and human brain cells. Still to be determined is what the optimal dose should be.

Ma, Q-L. et al. 2007. Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein with Reduced Expression in Sporadic Alzheimer's Disease (AD): Relevance to AD Prevention. Journal of Neuroscience, 27 (52), 14299 - 14307.

http://www.eurekalert.org/pub_releases/2007-12/uoc--wfo122107.php

Healthy diet lowers risk of dementia

A very large study of older adults has found that those who regularly consumed omega-3 rich oils, such as canola oil, flaxseed oil and walnut oil, reduced their risk of dementia by 60% compared to people who did not regularly consume such oils. People who ate fruits and vegetables daily also reduced their risk of dementia by 30% compared to those who didn’t regularly eat fruits and vegetables. Additionally, those who ate fish at least once a week had a 35% lower risk of Alzheimer’s and a 40% lower risk of dementia, but only if they did not carry ApoE4 gene. And finally, the study found those who didn’t have the gene but consumed an unbalanced diet characterized by regular use of omega-6 rich oils, but not omega-3 rich oils or fish, were twice as likely to develop dementia compared to those who didn’t eat omega-6 rich oils, which include sunflower or grape seed oil. The study did not find any association between consuming corn oil, peanut oil, lard, meat or wine and lowering risk of dementia.

Barberger-Gateau, P. et al. 2007. Dietary patterns and risk of dementia: The Three-City cohort study. Neurology, 69, 1921-1930.

http://www.eurekalert.org/pub_releases/2007-11/aaon-efo110607.php

Higher level of certain fatty acid associated with lower dementia risk

A nine year study of 899 participants in the Framingham Heart Study (average age 76 years) has found that those with the highest levels of an omega-3 polyunsaturated fatty acid known as docosahexaenoic acid (DHA) had a 47% lower risk of developing dementia and 39% lower risk of developing Alzheimer's. Among the participants who completed the dietary questionnaire, those in this top quartile of blood DHA levels reported that they ate an average of .18 grams of DHA a day and an average of three fish servings a week. Those in the other quartiles ate substantially less fish.

Schaefer, E.J. et al. 2006. Plasma Phosphatidylcholine Docosahexaenoic Acid Content and Risk of Dementia and Alzheimer Disease. Archives of Neurology, 63, 1545-1550.

http://www.eurekalert.org/pub_releases/2006-11/jaaj-hlo110906.php

Omega-3 fatty acids may slow cognitive decline in some patients with very mild Alzheimer's disease

Several studies have shown that eating fish, which is high in omega-3 fatty acids, may protect against Alzheimer's disease. A Swedish study has now tested whether supplements could have similar effects. Patients with mild-to-moderate Alzheimer’s who took 1.7 grams of DHA and .6g of EPA showed the same rate of cognitive decline as those taking a placebo, however, among a subgroup of 32 patients with very mild cognitive impairment, those who took the fatty acids experienced less decline in six months compared with those who took placebo. It may be that anti-inflammatory effects are an important reason for the benefit, potentially explaining why effects were seen only in those with very early-stage disease, when levels of inflammation seem to be higher.

Freund-Levi;, Y. et al. 2006. w-3 Fatty Acid Treatment in 174 Patients With Mild to Moderate Alzheimer Disease: OmegAD Study: A Randomized Double-blind Trial. Archives of Neurology, 63, 1402-1408.

http://www.eurekalert.org/pub_releases/2006-10/jaaj-ofa100506.php

Cabernet sauvignon red wine reduces the risk of Alzheimer's disease

A mouse study has found moderate consumption of the red wine Cabernet Sauvignon significantly reduced Alzheimer’s-type deterioration of spatial memory function. The Cabernet Sauvignon used contained a very low content of resveratrol, 10-fold lower than the minimal effective concentration shown to promote Aß clearance in vitro. It is suggested that, instead, the benefit occurred through promoting non-amyloidogenic processing of amyloid precursor protein. The finding supports epidemiological evidence indicating that moderate wine consumption (one drink per day for women and two for men) may help reduce the relative risk for Alzheimer’s.

Wang, J. et al. 2006. Moderate consumption of Cabernet Sauvignon attenuates Aß neuropathology in a mouse model of Alzheimer’s disease. FASEB Journal, 20, 2313-2320.

http://www.eurekalert.org/pub_releases/2006-09/tmsh-csr091806.php

Juices may reduce Alzheimer's disease risk

In a large epidemiological study, that followed 1836 Seattle residents for up to 10 years, it was found that those who drank three or more servings of fruit and vegetable juices per week had a 76% lower risk of developing Alzheimer’s disease than those who drank juice less than once a week. The benefit seemed greatest for those who carried the so-called “Alzheimer’s gene”. Previously, researchers suspected that antioxidant vitamins (vitamins C, E and -carotene) might help protect against Alzheimer's disease, but this has not been supported in recent clinical studies. Another class of antioxidant chemicals, polyphenols, are now suspected. Polyphenols generally exist primarily in the skins of fruits and vegetables and are particularly abundant in teas, juices and wines.

Dai, Q. et al. 2006. Fruit and Vegetable Juices and Alzheimer's Disease: The Kame Project. The American Journal of Medicine, 119 (9), 751-759.

http://www.eurekalert.org/pub_releases/2006-08/vumc-jmr082806.php
http://www.eurekalert.org/pub_releases/2006-08/ehs-ssf082806.php

Calorie restriction may help prevent Alzheimer's

A mouse study has found that beta-amyloid peptides can be reduced by restricting calorie intake, primarily through a low carbohydrate diet. Conversely, a high caloric intake based on saturated fat was shown to increase levels of beta-amyloid peptides. This is the first study to suggest that caloric restriction might inhibit the generation of beta-amyloid peptides, but there have been a number of studies providing evidence that high cholesterol, obesity, and other cardiovascular risk factors increase the likelihood of Alzheimer’s.

Qin, W. et al. 2006. Neuronal SIRT1 Activation as a Novel Mechanism Underlying the Prevention of Alzheimer Disease Amyloid Neuropathology by Calorie Restriction. Journal of Biological Chemistry, 281 (31), 21745 – 21754.

http://www.sciencedaily.com/releases/2006/06/060614113128.htm

Apples fight memory loss

The study involved adult and old mice (some engineered to develop Alzheimer's-like symptoms) being fed either a standard diet, a nutrient-deficient diet, or a nutrient-deficient diet supplemented with apple juice concentrate. The mice on the apple juice-supplemented diet showed an increased production of acetylcholine in their brains and performed significantly better on maze tests. The amount of consumption was comparable to humans drinking approximately two 8 oz. glasses of apple juice or eating 2-3 apples a day. The findings also suggest that the apple-supplemented diet was most helpful in the framework of an overall healthy diet. Acetylcholine levels declined in both adult and old mice on the nutrient-deficient diet.

Chan, A., Graves, V. & Shea, T.B. 2006. Apple juice concentrate maintains acetylcholine levels following dietary compromise. Journal of Alzheimer's Disease, 9(3), 287-291.

http://www.sciencedaily.com/releases/2006/08/060801225922.htm

Dietary supplements offer new hope for Alzheimer's patients

A "cocktail" of dietary supplements (omega-3 fatty acids, uridine and choline) has been found to dramatically increase the amount of membranes that form brain cell synapses in gerbils. The treatment is now in human clinical trials. It is hoped that such treatment may significantly delay Alzheimer's disease. The treatment offers a different approach from the traditional tactic of targeting amyloid plaques and tangles. Choline can be found in meats, nuts and eggs, and omega-3 fatty acids are found in a variety of sources, including fish, eggs, flaxseed and meat from grass-fed animals. Uridine, which is found in RNA and produced by the liver and kidney, is not obtained from the diet, although it is found in human breast milk.

Wurtman, R.J., Ulus, I.H., Cansev, M., Watkins, C.J., Wang L. & Marzloff, G. 2006. Synaptic proteins and phospholipids are increased in gerbil brain by administering uridine plus docosahexaenoic acid orally. Brain Research, Available online ahead of print 21 April 2006.

http://www.eurekalert.org/pub_releases/2006-04/miot-mro042706.php

Blackcurrants may protect against Alzheimer's

A cultured cell study has found that compounds in blackcurrants strongly protect neuronal cells against the types of stress caused by dopamine and amyloid-b, a peptide associated with Alzheimer's disease. Blackcurrants and boysenberries also contain anthocyanins and polyphenolics. Those that are darker (like British blackcurrants) have more anthocyanins and are likely to be more potent. Compounds from these berries are already known to act as antioxidants, but a role in neuroprotection has not been demonstrated previously.

Ghosh, D., McGhie, T.K., Zhang, J., Adaim, A. & Skinner, M. 2006. Effects of anthocyanins and other phenolics of boysenberry and blackcurrant as inhibitors of oxidative stress and damage to cellular DNA in SH-SY5Y and HL-60 cells. Journal of the Science of Food and Agriculture, in press

http://www.eurekalert.org/pub_releases/2006-01/jws-bbb011906.php

Folates more effective in limiting Alzheimer's disease risk than antioxidants, other nutrients

Analysis of data from the Baltimore Longitudinal Study of Aging has revealed that those with higher intake of folates, vitamin E and vitamin B6 had a lower risk of developing Alzheimer’s. When the three vitamins were analyzed together, only folates were associated with a significantly decreased risk. Those who had at least 400mcg of folates a day (the recommended daily allowance) had a 55% reduction in risk of developing Alzheimer’s. Unfortunately, most people who reached that level did so by taking supplements, suggesting the difficulty of doing so through diet alone. Folates are abundant in foods such as liver, kidneys, yeast, fruits (like bananas and oranges), leafy vegetables, whole-wheat bread, lima beans, eggs and milk; however, they are often destroyed by cooking or processing. No association was found between vitamin C, carotenoids (such as beta-carotene) or vitamin B-12 intake and decreased Alzheimer's risk.

Corrada, M.M., Kawas,C.H., Hallfrisch,J., Muller,D. & Brookmeyer,R. Reduced risk of Alzheimer’s disease with high folate intake: The Baltimore Longitudinal Study of Aging. Alzheimer’s & Dementia, 1 (1), 11-18.

http://www.eurekalert.org/pub_releases/2005-08/uoc--fme081105.php

Fish oil may help prevent Alzheimer's

A study involving genetically engineered mice has found that a diet high in docosahexenoic acid, or DHA — an omega-3 fatty acid found in relatively high concentrations in cold-water fish — dramatically slowed the progression of Alzheimer's, by cutting the harmful brain plaques that mark the disease. An earlier study showed that DHA protected against damage to the "synaptic" areas where brain cells communicate and enabled mice to perform better on memory tests. Food sources of omega-3 fatty acids include fish such as salmon, halibut, mackerel and sardines, as well as almonds, walnuts, soy, and DHA-enriched eggs.

Lim, G.P., Calon, F., Morihara, T., Yang, F., Teter, B., Ubeda, O., Salem, N.Jr, Frautschy, S.A. & Cole, G.M. 2005. A Diet Enriched with the Omega-3 Fatty Acid Docosahexaenoic Acid Reduces Amyloid Burden in an Aged Alzheimer Mouse Model. Journal of Neuroscience, 25(12), 3032-3040.

http://www.eurekalert.org/pub_releases/2005-03/vrcs-foh032405.php

Fewer calories may slow Alzheimer's

Restricting the diets of genetically engineered mice by 40% over 4 weeks reduced the build-up of plaques in the brain that are linked to Alzheimer's disease by 50%. It remains to be seen whether such dietary changes would similarly affect humans. Researchers are now looking to isolate the specific factors of the diet restriction which are important.

Patel, N.V., Gordon, M.N., Connor, K.E., Good, R.A., Engelman, R.W., Mason, J., Morgan, D.G., Morgan, T.E. & Finch, C.E. (in press). Caloric restriction attenuates Aβ-deposition in Alzheimer transgenic models. Neurobiology of Aging, In Press, Corrected Proof, Available online 25 November 2004.

http://www.eurekalert.org/pub_releases/2004-12/uosc-fcm121404.php

Compound in apples may help fight Alzheimer's disease

Researchers are recommending that apples may be a particularly beneficial food to protect against Alzheimer’s. A study that exposed groups of isolated rat brain cells to varying concentrations of either quercetin or vitamin C supports the theory that quercetin protects against cellular damage. A particularly good source of quercetin is apples — mainly in the skin. In general, red apples tend to have more of the antioxidant than green or yellow ones. Other foods containing high levels of quercetin include onions, which have some of the highest levels of quercetin among vegetables, as well as berries, particularly blueberries and cranberries.

The study appeared in the December 1 issue of the Journal of Agricultural and Food Chemistry.

http://www.eurekalert.org/pub_releases/2004-11/acs-ia111604.php

Tea may protect against Alzheimer’s

A study investigating the properties of coffee and green and black tea has found that both green and black tea inhibited the activity of enzymes associated with the development of Alzheimer's Disease (acetylcholinesterase and butyrylcholinesterase), but coffee had no significant effect. Green tea also obstructed the activity of beta-secretase, which plays a role in the production of protein deposits in the brain which are associated with Alzheimer's disease, and continued to have its inhibitive effect for a week, whereas black tea's enzyme-inhibiting properties lasted for only one day.

Okello, E.J., Savelev, S.U. & Perry, E.K. 2004. In vitro Anti-beta-secretase and dual anti-cholinesterase activities of Camellia sinensis L. (tea) relevant to treatment of dementia. Phytotherapy Research, 18 (8), 624-627.

http://www.eurekalert.org/pub_releases/2004-10/uonu-tci102504.php

Omega-3 fatty acid may prevent Alzheimer's disease and slow its progression

A study using genetically engineered mice has shown that a diet high in the omega-3 fatty acid DHA helps protect the brain against the memory loss and cell damage caused by Alzheimer's disease. Cheap sources of DHA include coldwater fish, like salmon, halibut, mackerel, sardines and herring. These fish consume algae, which is high in DHA. Because these fishes' oiliness makes them absorb more mercury, dioxin, PCP and other metals, however, a less risky yet more costly strategy is to consume fish oil or purified DHA supplements made from algae. Other options include DHA-rich eggs laid by chickens that eat DHA-supplemented feed.

The paper appeared in the September 2 issue of Neuron.

http://www.eurekalert.org/pub_releases/2004-09/uoc--ddp082604.php

Why diet, hormones, exercise might delay Alzheimer’s

A theory that changes in fat metabolism in the membranes of nerve cells play a role in Alzheimer's has been supported in a recent study. The study found significantly higher levels of ceramide and cholesterol in the middle frontal gyrus of Alzheimer's patients. The researchers suggest that alterations in fats (especially cholesterol and ceramide) may contribute to a "neurodegenerative cascade" that destroys neurons in Alzheimer's, and that the accumulation of ceramide and cholesterol is triggered by the oxidative stress brought on by the presence of the toxic beta amyloid peptide. The study also suggests a reason for why antioxidants such as vitamin E might delay the onset of Alzheimer's: treatment with Vitamin E reduced the levels of ceramide and cholesterol, resulting in "a significant decrease in the number of neurons killed by the beta amyloid and oxidative stress.

Cutler, R.G., Kelly, J., Storie, K., Pedersen, W.A., Tammara, A., Hatanpaa, K., Troncoso, J.C. & Mattson, M.P. 2004. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. PNAS, 101, 2070-5.

http://www.eurekalert.org/pub_releases/2004-02/aaft-nsm021004.php

Using vitamin E and C supplements together may reduce risk of Alzheimer's

A study involving 4,740 elderly (65 years or older) found the greatest reduction in both prevalence and incidence of Alzheimer's in those who used individual vitamin E and C supplements in combination, with or without an additional multivitamin. There was no significant benefit in using vitamin C alone, vitamin E alone, or vitamin C and multivitamins in combination.

Zandi, P.P., Anthony, J.C., Khachaturian, A.S., Stone, S.V., Gustafson, D., Tschanz, J.T., Norton, M.C., Welsh-Bohmer, K.A. & Breitner, J.C.S. 2004. Reduced Risk of Alzheimer Disease in Users of Antioxidant Vitamin Supplements: The Cache County Study. Archives of Neurology, 61, 82-88.

http://www.eurekalert.org/pub_releases/2004-01/jaaj-uve011404.php

High-dose vitamin regime may help slow Alzheimer's

A preliminary study suggests that a regime of high doses of folic acid, B12 and B6 reduces levels of homocysteine in people with mild to moderate Alzheimer’s. A larger study, recruiting 400 participants from all over the U.S., is to be undertaken to assess whether such a vitamin regime can slow the progression of Alzheimer's disease. In the meantime, it is not advised that people take high doses of these vitamins, as there are possible side-effects, including peripheral nerve damage.

Aisen, P.S. et al. 2003. Effects of Rofecoxib or Naproxen vs Placebo on Alzheimer Disease Progression: A Randomized Controlled Trial. JAMA, 289, 2819-2826.

http://www.eurekalert.org/pub_releases/2003-03/gumc-cvs031403.php

Drinking wine may lower risk of dementia

Researchers in Copenhagen have followed up an analysis of drinking patterns for wine, beer and liquor of 1,709 people in the 1970s with an assessment of dementia in the 1990s, when participants were age 65 or older. 83 of the participants had developed dementia. Their alcohol intake was compared to that of those who did not develop dementia. It was found that those who drank wine occasionally had a lower risk of developing dementia, including Alzheimer's disease. Those who drank wine every day were no more or less likely to develop dementia than those who drank it less often. The study also found that occasional beer drinking was associated with an increased risk of developing dementia. It is important to note that eating habits were not investigated, and research suggests that wine drinkers may have better dietary habits than beer and liquor drinkers.

Truelsen, T., Thudium, D. & Grønbæk, M. 2002. Amount and type of alcohol and risk of dementia: The Copenhagen City Heart Study. Neurology, 59, 1313-1319.

http://www.eurekalert.org/pub_releases/2002-11/aaon-dwm110702.php

Eating fish cuts risk of dementia

Using data from a French epidemiological study of cognitive and functional aging, researchers found that those who ate fish or seafood at least once a week had a significantly lower risk of being diagnosed as having dementia (including Alzheimer’s) over the seven years follow-up. This confirms earlier findings from the Rotterdam Study, which had a much shorter follow-up (a mean of 2.1 years). There was an association between level of education and diet which partly, but not completely, explains this. It does appear that this is a benefit from eating fish / seafood, possibly from the fatty acids found in fish oils. There was no significant association between meat consumption and risk of dementia.

Barberger-Gateau, P., Letenneur, L., Deschamps, V., Pérès, K., Dartigues, J. & Renaud, S. 2002. Fish, meat, and risk of dementia: cohort study. BMJ, 325, 932-933.

http://www.eurekalert.org/pub_releases/2002-10/bmj-efc102302.php

Diet rich in foods with Vitamin E may reduce Alzheimer’s disease risk

Two studies have come out in favor of a diet rich in foods containing vitamin E to help protect against Alzheimer's disease. One study involved 815 Chicago residents age 65 and older with no initial symptoms of mental decline, who were questioned about their eating habits and followed for an average of about four years. When factors like age and education were taken into account, those eating the most vitamin E-rich foods had a lower risk of developing Alzheimer’s, provided they did not have the ApoE e4 allele. This was not true when vitamin E was taken as a supplement. Intake of vitamin C and beta carotene appeared protective, but not at a statistically significant level. The other study involved 5,395 people in the Netherlands age 55 and older who were followed for an average of six years. Those with high intakes of vitamins E and C were less likely to become afflicted with Alzheimer's, regardless of whether they had the gene variation. This association was most pronounced for current smokers, for whom beta carotene also seemed to be protective. A number of clinical trials are underway to further investigate these links.

Engelhart, M.J., Geerlings, M.I., Ruitenberg, A., van Swieten, J.C., Hofman, A., Witteman, J.C.M. & Breteler, M.M.B. 2002. Dietary Intake of Antioxidants and Risk of Alzheimer Disease. JAMA, 287, 3223-3229. Morris, M.C., Evans, D.A., Bienias, J.L., Tangney, C.C., Bennett, D.A., Aggarwal, N., Wilson, R.S. & Scherr, P.A. 2002. Dietary Intake of Antioxidant Nutrients and the Risk of Incident Alzheimer Disease in a Biracial Community Study. JAMA, 287, 3230-3237.

http://www.eurekalert.org/pub_releases/2002-06/nioa-dri062102.php
http://www.eurekalert.org/pub_releases/2002-06/pn-tsr062702.php

Folic acid possibly a key factor in preventing Alzheimer's disease

Experiments with mice bred with mutant genes that cause Alzheimer's disease found that those mice fed on a diet deficient in folate had fewer neurons in the hippocampus ( a brain region critical for learning and memory that is destroyed as plaques accumulate during Alzheimer’s disease), and elevated levels of homocysteine. Researchers suspect that increased levels of homocysteine in the brain caused damage to the DNA of nerve cells in the hippocampus. In the mice fed an adequate amount of folate, nerve cells in this brain region were able to repair the damage. But in those mice fed a folate-deficient diet, nerve cells were unable to repair this damage. A human study is being planned.
Green leafy vegetables, citrus fruits and juices, whole wheat bread and dry beans are good sources of folate. In the U.S., since 1998, the Food and Drug Administration has required the addition of folic acid to enriched breads, cereals, flours, corn meals, pastas, rice, and other grain products.

Kruman, I.I., Kumaravel, T.S., Lohani, A., Pedersen, W.A., Cutler, R.G., Kruman, Y., Haughey, N., Lee, J., Evans, M. & Mattson, M.P. 2002. Folic Acid Deficiency and Homocysteine Impair DNA Repair in Hippocampal Neurons and Sensitize Them to Amyloid Toxicity in Experimental Models of Alzheimer's Disease. Journal of Neuroscience, 22, 1752-1762.

http://www.eurekalert.org/pub_releases/2002-03/nioa-fap030102.php

Physical exercise & fitness

Reduced muscle strength associated with Alzheimer's risk

A study involving 970 older adults (average age 80.3) has found that over the average 3.6 years follow-up period, those with weaker muscles had a higher risk of developing Alzheimer’s. For each one-unit increase at the beginning of the study, older adults had about a 43% decrease in the risk of developing Alzheimer's disease during follow-up (strength scores ranged from -1.6 to 3.3 units). Those in the top 10% had about a 61% reduced risk of developing Alzheimer's compared with those in the bottom 10%. The association remained even after factors such as body mass index and physical activity level were accounted for. The association also was found with mild cognitive impairment.

Boyle, P. A., Buchman, A. S., Wilson, R. S., Leurgans, S. E., & Bennett, D. A. (2009). Association of Muscle Strength With the Risk of Alzheimer Disease and the Rate of Cognitive Decline in Community-Dwelling Older Persons. Arch Neurol, 66(11), 1339-1344.

http://www.eurekalert.org/pub_releases/2009-11/jaaj-sb110509.php

Physical fitness improves memory in seniors

A study of 165 older adults (59-81) has found a significant association between physical fitness and performance on certain spatial memory tests. Fitness was also strongly correlated with hippocampus size. Although rodent studies have shown that exercise increases hippocampus size and spatial memory, this is the first study to show that in humans. The findings provide more evidence for the benefits of physical exercise in preventing memory loss in older adults.

Erickson, K.I. et al.  2009. Aerobic fitness is associated with hippocampal volume in elderly humans. Hippocampus, Published online 2 January

http://www.eurekalert.org/pub_releases/2009-02/uoia-pfi022409.php

Moderate exercise helps mild cognitive impairment

An Australian study involving 138 older adults (50 years and over) with mild cognitive impairment, has found that those who undertook to achieve 2 ½ hours of physical activity each week (three 50 minute sessions), ranging from walking, ballroom dancing to swimming, for a six month period, continually out-scored the control group on cognitive tests during the 18 month testing period — showing that memory improvement was still evident a year after the supervised exercise period.

Lautenschlager, N.T. et al. 2008. Effect of Physical Activity on Cognitive Function in Older Adults at Risk for Alzheimer Disease: A Randomized Trial. Journal of the American Medical Association, 300(9), 1027-1037.

http://www.eurekalert.org/pub_releases/2008-09/ra-wtp090108.php
http://www.eurekalert.org/pub_releases/2008-09/uom-aow090108.php
http://www.eurekalert.org/pub_releases/2008-09/jaaj-emh082808.php

Exercise may slow brain shrinkage in early Alzheimer's

A study of 121 people age 60 and older, of whom 57 were in the early stages of Alzheimer's disease, has found that those with early Alzheimer's disease who were less physically fit (measured by cardiorespiratory fitness) had four times more brain shrinkage when compared to normal older adults than those who were more physically fit. The findings suggest the value of physical fitness in slowing down the progression of Alzheimer's disease. The association existed even after age, gender, severity of dementia, physical activity and frailty were accounted for. There was no relationship between higher fitness levels and brain changes in the group of people without dementia.

Burns, J.M. et al. 2008. Cardiorespiratory fitness and brain atrophy in early Alzheimer disease. Neurology, 71, 210-216.

http://www.eurekalert.org/pub_releases/2008-07/aaon-emp070808.php

Walking and moderate exercise help prevent dementia

A four-year study involving 749 older adults has found that the top one-third of participants who exerted the most energy in moderate activities such as walking were significantly less likely to develop vascular dementia than those people in the bottom one-third of the group. Contrary to some reports, no such association was found with Alzheimer’s disease.

Ravaglia, G. et al. 2007. Physical activity and dementia risk in the elderly. Findings from a prospective Italian study. Neurology, published online ahead of print December 19

http://www.eurekalert.org/pub_releases/2007-12/aaon-wam121107.php

Good physical function linked to Alzheimer's delay

A study following 2,288 older adults for six years found that those whose physical function was higher at the start of the study were three times less likely to develop dementia than were those whose physical function was lower.

Wang, L., Larson, E.B., Bowen, J.D. & van Belle, G. 2006. Performance-Based Physical Function and Future Dementia in Older People. Archives of Internal Medicine, 166, 1115-1120.

http://www.eurekalert.org/pub_releases/2006-05/ghcc-gpf051806.php

Exercise protects against Alzheimer's

A study following 1,740 seniors (aged 65 and older) over a six-year period, found that those who exercised three or more times a week had a 30 — 40% lower risk for developing dementia compared with those who exercised fewer than three times per week. Even modest amounts, such as walking 15 minutes a day, appear beneficial, and the more frail the person was, the more they benefited from regular exercise.

Larson, E.B., Wang, L., Bowen, J.D., McCormick, W.C., Teri, L., Crane, P., & Kukull, W. 2006. Exercise Is Associated with Reduced Risk for Incident Dementia among Persons 65 Years of Age and Older. Annals of Internal Medicine, 144 (2), 73-81.

http://www.eurekalert.org/pub_releases/2006-01/ghcc-eil011006.php

Exercise slows development of Alzheimer's-like brain changes in mice

Population-based studies have provided evidence that various lifestyle interventions might help slow the onset and progression of Alzheimer’s. A mouse study now provides a clue how that might work. Physical activity enhanced the learning ability of mice genetically engineered to develop amyloid plaques and decreased the level of plaque-forming beta-amyloid protein fragments in their brains. The mice were divided into mice with access to running wheels or no access. The findings are supported by another recent study that found that beta-amyloid levels decreased in the brains of another kind of transgenic mice when they were housed in groups and in environments that were enriched with running wheels, colored tunnels, and toys.

Adlard, P.A., Perreau, V.M., Pop, V. & Cotman, C.W. 2005. Voluntary Exercise Decreases Amyloid Load in a Transgenic Model of Alzheimer's Disease. Journal of Neuroscience, 25, 4217-4221.

http://www.eurekalert.org/pub_releases/2005-04/nioa-esd042605.php

 

Drugs

Estrogen use before 65 linked to reduced risk of Alzheimer's disease

Data from the Women’s Health Initiative Memory Study looked at prior hormone use in 7,153 healthy women ages 65-79 before they enrolled in the WHI Memory Study, and followed their cognitive health over an average of five years. In that time, 106 of the women developed Alzheimer’s disease or dementia. The study found women who used any form of estrogen hormone therapy before the age of 65 were nearly 50% less likely to develop Alzheimer’s disease or dementia than women who did not use hormone therapy before age 65, but women who began estrogen-only therapy after the age of 65 had roughly a 50% increased risk of developing dementia. The risk jumped to nearly double for women using estrogen-plus-progestin hormone therapy.

The findings were presented at the American Academy of Neurology’s 59th Annual Meeting in Boston, April 28 – May 5, 2007.

http://www.eurekalert.org/pub_releases/2007-05/aaon-eub041007.php

Low dose aspirin does not protect women against cognitive decline

Evidence that aspirin and other anti-inflammatory drugs may protect against dementia has been inconclusive. Now a large, long-running study involving 6,377 women aged 65 years or more, over ten years, has found that those who took low dose aspirin (100 mg on alternate days) performed at similar levels to a placebo group on cognitive tests. However, there was evidence of benefit in one very specific area of cognition: category fluency.

Kang, J-E., Cirrito, J.R., Dong, H., Csernansky, J.G. & Holtzman, D.M. 2007. Acute stress increases interstitial fluid amyloid-beta via corticotropin-releasing factor and neuronal activity. Proceedings of the National Academy of Science, 104 (25), 10673-10678.

http://www.eurekalert.org/pub_releases/2007-04/bmj-lda042607.php

Common painkillers may help protect against Alzheimer’s disease

Observations that people who take anti-inflammatory medications over several years have a lower risk of later developing Alzheimer's disease have received support from an exciting new study which has revealed that common over-the-counter pain medications (such as ibuprofen and naproxen) bind to amyloid plaques, and may help dissolve existing plaques and prevent the formation of new ones. Amyloid plaques are one of the definitive hallmarks of Alzheimer's disease.

Agdeppa, E.D., Kepe, V., Petri, A., Satyamurthy, N., Liu, J., Huang, S.-C., Small, G.W., Cole, G.M. & Barrio, J.R. 2003. In vitro detection of (S)-naproxen and ibuprofen binding to plaques in the Alzheimer's brain using the positron emission tomography molecular imaging probe 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile, Neuroscience, 117(3), 723-730.

http://www.eurekalert.org/pub_releases/2003-03/uoc--urd031203.php

Regular long-term use of aspirin may reduce the risk of Alzheimer’s

A large-scale study of 5,092 older adults has found that regular use of aspirin and other non-steroidal anti-inflammatory drugs may reduce the incidence of dementia in elderly people, but only when taken for more than two years, and provided the use occurred well before the onset of dementia.

Zandi, P.P., Anthony, J.C., Hayden, K.M., Mehta, K., Mayer, L. & Breitner, J.C.S. 2002. Reduced incidence of AD with NSAID but not H2 receptor antagonists: The Cache County Study. Neurology, 59, 880-886.

http://www.eurekalert.org/pub_releases/2002-09/aaon-get091702.php