Alzheimer's & other dementias
New findings reveal that mild cognitive impairment is more likely to develop into Alzheimer’s if vascular risk factors are present, especially if untreated.
A study following 837 people with MCI, of whom 414 (49.5%) had at least one vascular risk factor, has found that those with risk factors such as high blood pressure, diabetes, cerebrovascular disease and high cholesterol were twice as likely to develop Alzheimer's disease. Over five years, 52% of those with risk factors developed Alzheimer's, compared to 36% of those with no risk factors In total, 298 people (35.6%) developed Alzheimer's.
However, of those with vascular risk factors, those receiving full treatment for their vascular problems were 39% less likely to develop Alzheimer's disease than those receiving no treatment, and those receiving some treatments were 26% less likely to develop the disease.
Treatment of risk factors included using high blood pressure medicines, insulin, cholesterol-lowering drugs and diet control. Smoking and drinking were considered treated if the person stopped smoking or drinking at the start of the study.
 Li, J., Wang Y. J., Zhang M., Xu Z. Q., Gao C. Y., Fang C. Q., et al.
(2011). Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease.
Neurology. 76(17), 1485 - 1491.
More evidence that a moderate amount of alcohol helps protect against Alzheimer’s —but not vascular dementia or age-related cognitive decline.
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.
 Weyerer, S., Schäufele M., Wiese B., Maier W., Tebarth F., van den Bussche H., et al.
(2011). Current alcohol consumption and its relationship to incident dementia: results from a 3-year follow-up study among primary care attenders aged 75 years and older.
Age and Ageing.
Full text at http://www.oxfordjournals.org/our_journals/ageing/afr007.pdf
A two-year study involving 53 older adults (60+) has found that those with a mother who had Alzheimer's disease had significantly more brain atrophy than those with a father or no parent with Alzheimer's disease. More specifically, they had twice as much gray matter shrinkage, and about one and a half times more whole brain shrinkage per year.
This atrophy was particularly concentrated in the precuneus and parahippocampal gyrus. Those with the APOE4 gene also had more atrophy in the frontal cortex than those who didn’t carry the ‘Alzheimer’s gene’.
This adds to evidence indicating that maternal history is a far greater risk factor for Alzheimer’s than paternal history. Eleven participants reported having a mother with Alzheimer's disease, 10 had a father with Alzheimer's disease and 32 had no family history of the disease. It has been estimated that people who have first-degree relatives with Alzheimer's disease are four to 10 times more likely to develop the disease.
 Honea, R. A., Swerdlow R. H., Vidoni E. D., & Burns J. M.
(2011). Progressive regional atrophy in normal adults with a maternal history of Alzheimer disease.
Neurology. 76(9), 822 - 829.
Another study builds on earlier indications that hearing loss is a risk factor for dementia, and emphasizes the need for early intervention.
Data from the Baltimore Longitudinal Study on Aging, begun in 1958, has revealed that seniors with hearing loss are significantly more likely to develop dementia than those who retain their hearing. The study involved 639 people whose hearing and cognitive abilities were tested between 1990 and 1994, then re-tested every one to two years. By 2008, 58 (9%) of them had developed dementia (37 of which were Alzheimer’s).
Those with hearing loss at the beginning of the study were significantly more likely to have developed dementia. The degree of hearing loss also correlated with greater risk: those with mild, moderate, and severe hearing loss had twofold, threefold, and fivefold, respectively, the risk of developing dementia over time. The association was maintained after other risk factors, (high blood pressure, smoking, education, age, sex, race) were taken into account.
The reason for the association is not yet known. It’s possible that a common pathology may underlie both, or that the strain of decoding sounds over the years may make the brain more vulnerable to dementia, or that hearing loss makes people more socially isolated (a known risk factor for dementia).
The findings do suggest that hearing loss should be regarded more seriously, and not simply accepted as a natural part of growing old.
 Lin, F. R., Metter J. E., O'Brien R. J., Resnick S. M., Zonderman A. B., & Ferrucci L.
(2011). Hearing Loss and Incident Dementia.
Arch Neurol. 68(2), 214 - 220.
A long-running study has found cholesterol levels at in mid-life were not linked to later dementia in women, but marked decline in cholesterol level over the study period was.
Research into the link, if any, between cholesterol and dementia, has been somewhat contradictory. A very long-running Swedish study may explain why. The study, involving 1,462 women aged 38-60 in 1968, has found that cholesterol measured in middle or old age showed no link to dementia, but there was a connection between dementia and the rate of decline in cholesterol level. Those women whose cholesterol levels decreased the most from middle to older age were more than twice as likely to develop dementia as those whose cholesterol levels increased or stayed the same (17.5% compared to 8.9%).After 32 years, 161 women had developed dementia.
Later in life, women with slightly higher body mass index, higher levels of cholesterol and higher blood pressure tend to be healthier overall than those whose weight, cholesterol and blood pressure are too low. But it is unclear whether "too low" cholesterol, BMI and blood pressure are risk factors for dementia or simply signs that dementia is developing, for reasons we do not yet understand.
On the other hand, a recent rat study has found that consuming a high cholesterol diet for five months caused memory impairment, cholinergic dysfunction, inflammation, enhanced cortical beta-amyloid and tau and induced microbleedings — all of which is strikingly similar to Alzheimer's pathology. And this finding is consistent with a number of other studies. So it does seem clear that the story of how exactly cholesterol impacts Alzheimer’s is a complex one that we are just beginning to unravel.
In light of other research indicating that the response of men and women to various substances (eg caffeine) may be different, we should also bear in mind that the results of the Swedish study may apply only to women.
 Mielke, M. M., Zandi P. P., Shao H., Waern M., Östling S., Guo X., et al.
(2010). The 32-year relationship between cholesterol and dementia from midlife to late life.
Neurology. 75(21), 1888 - 1895.
 Ullrich, C., Pirchl M., & Humpel C.
(2010). Hypercholesterolemia in rats impairs the cholinergic system and leads to memory deficits.
Molecular and Cellular Neuroscience. 45(4), 408 - 417.
http://www.eurekalert.org/pub_releases/2010-11/aaon-mcl110210.php http://www.eurekalert.org/pub_releases/2010-11/jhmi-hci110310.php http://www.eurekalert.org/pub_releases/2010-11/e-chc112410.php
Nearly half of those with dementia with Lewy bodies were found to have had adult ADHD — three times the rate of controls and those with Alzheimer’s.
A study involving 360 patients with degenerative dementia (109 people with dementia with Lewy bodies (DLB) and 251 with Alzheimer's) and 149 matched controls, has found that 48% of those with DLB had previously suffered from adult ADHD. This compares with 15% found in both the control group and the group with Alzheimer's. DLB tends to be under-diagnosed, but is thought to account for around 10% of dementia cases in older people.
ADHD and DLB are thought to both involve the same neurotransmitter pathway problems.
 Golimstok, A., Rojas J. I., Romano M., Zurru M. C., Doctorovich D., & Cristiano E.
(2011). Previous adult attention-deficit and hyperactivity disorder symptoms and risk of dementia with Lewy bodies: a case-control study.
European Journal of Neurology. 18(1), 78 - 84.
A second study confirms the dramatic effect of being bilingual, with bilingual speakers being diagnosed with Alzheimer’s more than 4 years later than monoglots.
Clinical records of 211 patients diagnosed with probable Alzheimer's disease have revealed that those who have spoken two or more languages consistently over many years experienced a delay in the onset of their symptoms by as much as five years. It’s thought that lifelong bilingualism may contribute to cognitive reserve in the brain, enabling it to compensate for memory loss, confusion, and difficulties with problem-solving and planning.
Of the 211 patients of the Sam and Ida Ross Memory Clinic at Baycrest, 102 patients were classified as bilingual and 109 as monolingual. Bilingual patients had been diagnosed with Alzheimer's 4.3 years later than the monolingual patients on average, and had reported the onset of symptoms 5.1 years later. The groups were equivalent on measures of cognitive and occupational level, there was no apparent effect of immigration status, and there were no gender differences.
The findings confirm an earlier study from the same researchers, from the clinical records of 184 patients diagnosed with probable Alzheimer's and other forms of dementia.
 Craik, F. I. M., Bialystok E., & Freedman M.
(2010). Delaying the onset of Alzheimer disease.
Neurology. 75(19), 1726 - 1729.
A small study suggests that physical activity may be of greater benefit to those carrying the Alzheimer’s gene in protecting against cognitive decline.
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.
 Smith, J. Carson, Nielson K. A., Woodard J. L., Seidenberg M., Durgerian S., Antuono P., et al.
(2011). Interactive effects of physical activity and APOE-[epsilon]4 on BOLD semantic memory activation in healthy elders.
NeuroImage. 54(1), 635 - 644.
 Jedrziewski, K. M., Ewbank D. C., Wang H., & Trojanowski J. Q.
(2010). Exercise and cognition: Results from the National Long Term Care Survey.
Alzheimer's and Dementia. 6(6), 448 - 455.
Research with genetically engineered mice shows why the apoE4 gene is so strongly associated with Alzheimer’s, and points to strategies for countering its effects.
Carriers of the so-called ‘Alzheimer’s gene’ (apoE4) comprise 65% of all Alzheimer's cases. A new study helps us understand why that’s true. Genetically engineered mice reveal that apoE4 is associated with the loss of GABAergic interneurons in the hippocampus. This is consistent with low levels of GABA (produced by these neurons) typically found in Alzheimer’s brains. This loss was associated with cognitive impairment in the absence of amyloid beta accumulation, demonstrating it is an independent factor in the development of this disease.
The relationship with the other major characteristic of the Alzheimer’s brain, tau tangles, was not independent. When the mice’s tau protein was genetically eliminated, the mice stopped losing GABAergic interneurons, and did not develop cognitive deficits. Previous research has shown that suppressing tau protein can also prevent amyloid beta from causing memory deficits.
Excitingly, daily injections of pentobarbital, a compound that enhances GABA action, restored cognitive function in the mice.
The findings suggest that increasing GABA signaling and reducing tau are potential strategies to treat or prevent apoE4-related Alzheimer's disease.
 Andrews-Zwilling, Y., Bien-Ly N., Xu Q., Li G., Bernardo A., Yoon S Y., et al.
(2010). Apolipoprotein E4 Causes Age- and Tau-Dependent Impairment of GABAergic Interneurons, Leading to Learning and Memory Deficits in Mice.
J. Neurosci.. 30(41), 13707 - 13717.
Another small study supports earlier research suggesting that low testosterone is a risk factor for Alzheimer’s for older men.
A Chinese study involving 153 older men (55+; average age 72), of whom 47 had mild cognitive impairment, has found that 10 of those in the MCI group developed probable Alzheimer's disease within a year. These men also had low testosterone, high blood pressure, and elevated levels of the ApoE4 protein.
The findings support earlier indications that low testosterone is associated with increased risk of Alzheimer's in men, but it’s interesting to note the combination with high blood pressure and having the ApoE4 gene. I look forward to a larger study.
Chu, L-W. et al. 2010. Bioavailable Testosterone Predicts a Lower Risk of Alzheimer’s Disease in Older Men. Journal of Alzheimer's Disease, 21 (4), 1335-45.
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