Alzheimers

Alzheimer's & other dementias

Hearing loss and dementia linked

March, 2011

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.

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Steep cholesterol decline in older women linked to Alzheimer's risk

February, 2011

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.

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Adult ADHD significantly increases risk of Lewy body dementia

February, 2011

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.

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Bilingualism delays onset of Alzheimer's symptoms

January, 2011

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.

Reference: 

[2039] Craik, F. I. M., Bialystok E., & Freedman M.
(2010).  Delaying the onset of Alzheimer disease.
Neurology. 75(19), 1726 - 1729.

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Importance of exercise for Alzheimer's gene carriers

January, 2011

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.

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How the Alzheimer’s gene works; implications for treatment

November, 2010

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.

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Low testosterone linked to Alzheimer's disease

November, 2010

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.

Reference: 

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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Vitamin B12 may reduce risk of Alzheimer's disease

November, 2010

A long-running study adds to the evidence that high levels of homocysteine increase the risk of developing Alzheimer’s, and higher levels of vitamin B12 help to bring down these levels and reduce risk.

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.

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Heavy smoking in midlife associated with dementia in later years

November, 2010

A very large long-running study has found smoking over two packs per day in middle age more than doubled the chances of developing dementia in later life.

Data from 21,123 people, surveyed between 1978 and 1985 when in their 50s and tracked for dementia from 1994 to 2008, has revealed that those who smoked more than two packs per day in middle age had more than twice the risk of developing dementia, both Alzheimer's and vascular dementia, compared to non-smokers.

A quarter of the participants (25.4%) were diagnosed with dementia during the 23 years follow-up, of whom a little over 20% were diagnosed with Alzheimer's disease and nearly 8% with vascular dementia.

Former smokers, or those who smoked less than half a pack per day, did not appear to be at increased risk. Associations between smoking and dementia did not vary by race or sex.

Smoking is a well-established risk factor for stroke, and is also known to contribute to oxidative stress and inflammation.

Reference: 

[1934] Rusanen, M., Kivipelto M., Quesenberry C. P., Zhou J., & Whitmer R. A.
(2010).  Heavy Smoking in Midlife and Long-term Risk of Alzheimer Disease and Vascular Dementia.
Arch Intern Med. archinternmed.2010.393 - archinternmed.2010.393.

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Mental activity may slow cognitive decline initially, but speed up dementia later

October, 2010

Another study has come out suggesting that the advantage of mental stimulation is to delay cognitive decline, but at the cost of faster decline later (it’s still a good bargain).

A long-running study involving 1,157 healthy older adults (65+) who were scored on a 5-point scale according to how often they participated in mental activities such as listening to the radio, watching television, reading, playing games and going to a museum, has found that this score is correlated to the rate of cognitive decline in later years.

Some 5 ½ years after this initial evaluation, 395 (34%) were found to have mild cognitive impairment and 148 (13%) to have Alzheimer’s. Participants were then tested at 3-yearly intervals for the next 6 years. The rate of cognitive decline in those without cognitive impairment was reduced by 52% for each point on the cognitive activity scale, but for those with Alzheimer's disease, the average rate of decline per year increased by 42% for each point on the cognitive activity scale. Rate of decline was unrelated to earlier cognitive activity in those with MCI (presumably they were at the balance point).

This is not terribly surprising when you think of it, if you assume that the benefit of mental stimulation is to improve your brain function so that it can better cope with the damage happening to it. But eventually it reaches the point where it can no longer compensate for that damage because it is so overwhelming.

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