seniors

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.

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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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Old bees' memory fades too

November, 2010
  • New research shows that many old bees, like many older humans, have trouble replacing out-of-date knowledge with new memories.

I love cognitive studies on bees. The whole notion that those teeny-tiny brains are capable of the navigation and communication feats bees demonstrate is so wonderful. Now a new study finds that, just like us, aging bees find it hard to remember the location of a new home.

The study builds on early lab research that demonstrated that old bees find it harder to learn floral odors. In this new study, researchers trained bees to a new nest box while their former nest was closed off. Groups composed of mature and old bees were given several days in which to learn the new home location and to extinguish the bees' memory of their unusable former nest box. The new home was then disassembled, and groups of mixed-age bees were given three alternative nest locations to choose from (including the former nest box). Some old bees (those with symptoms of senescence) preferentially went to the former nest site, despite the experience that should have told them that it was unusable.

The findings demonstrate that memory problems and increasing inflexibility with age are not problems confined to mammals.

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Walk for your brain’s sake

November, 2010

Walking helps older adults fight brain shrinkage, which is in turn associated with a reduced risk of cognitive impairment and dementia.

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).

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70-year-olds smarter than they used to be

November, 2010

Findings from a large Swedish study are consistent with the hypothesis that more education and better healthcare have produced less cognitive impairment in present-day older adults.

Beginning in 1971, healthy older adults in Gothenburg, Sweden, have been participating in a longitudinal study of their cognitive health. The first H70 study started in 1971 with 381 residents of Gothenburg who were 70 years old; a new one began in 2000 with 551 residents and is still ongoing. For the first cohort (born in 1901-02), low scores on non-memory tests turned out to be a good predictor of dementia; however, these tests were not predictive for the generation born in 1930. Those from the later cohort also performed better in the intelligence tests at age 70 than their predecessors had.

It’s suggested that the higher intelligence is down to the later cohort’s better pre and postnatal care, better nutrition, higher quality education, and better treatment of high blood pressure and cholesterol. And possibly the cognitive demands of modern life.

Nevertheless, the researchers reported that the incidence of dementia at age 75 was little different (5% in the first cohort and 4.4% in the later). However, since a substantially greater proportion of the first cohort were dead by that age (15.7% compared to 4.4% of the 2nd cohort), it seems quite probable that there really was a higher incidence of dementia in the earlier cohort.

The fact that low scores on non-memory cognitive tests were predictive in the first cohort of both dementia and death by age 75 supports this argument.

The fact that low scores on non-memory cognitive tests were not predictive of dementia or death in the later cohort is in keeping with the evidence that higher levels of education help delay dementia. We will need to wait for later findings from this study to see whether that is what is happening.

The findings are not inconsistent with those from a very large U.S. national study that found older adults (70+) are now less likely to be cognitively impaired (see below). It was suggested then also that better healthcare and more education were factors behind this decline in the rate of cognitive impairment.

Previous study:

A new nationally representative study involving 11,000 people shows a downward trend in the rate of cognitive impairment among people aged 70 and older, from 12.2% to 8.7% between 1993 and 2002. It’s speculated that factors behind this decline may be that today’s older people are much likelier to have had more formal education, higher economic status, and better care for risk factors such as high blood pressure, high cholesterol and smoking that can jeopardize their brains. In fact the data suggest that about 40% of the decrease in cognitive impairment over the decade was likely due to the increase in education levels and personal wealth between the two groups of seniors studied at the two time points. The trend is consistent with a dramatic decline in chronic disability among older Americans over the past two decades.

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Memory impairment more common in people with a history of cancer

November, 2010

A very large study has found everyday memory problems among middle-aged and elderly are more likely in those with a history of cancer.

Confirming earlier indications from small studies, a very large nationwide survey has found that people who have had cancer are 40% more likely to experience memory problems that interfere with daily functioning.

The U.S. study involved nearly 10,000 people aged 40 and older, of whom 1,305 (13.3%) reported they had cancer or a history of cancer. Of these, 14% answered yes to the question "Are you limited in any way because of difficulty remembering or because you experience periods of confusion?" Of those who did not have a history of cancer, 8% answered yes to this question.

The degree to which these memory problems are related to the treatment or to the cancer itself (or even perhaps to the experience of having cancer) is one that needs further investigation, but the researcher suggests the finding points to memory issues being more common among cancer sufferers than realized, and recommends that cognitive assessment should be a standard part of cancer treatment.

The study is noteworthy in including all cancers, rather than focusing on one. Nevertheless, I hope that we eventually see a published paper (these results were presented at conference) that also analyses the data in terms of different cancers, different treatments, and length of time since the cancer.

Earlier reports on ‘chemobrain’, and possible ways to help

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Results were presented at the Third AACR Conference on The Science of Cancer Health Disparities.

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When estrogen helps memory, and when it doesn’t

November, 2010

Recent rodent studies confirm attention and learning is more difficult for women when estrogen is high, but estrogen therapy can help menopausal women — if given during a critical window.

Recent rodent studies add to our understanding of how estrogen affects learning and memory. A study found that adult female rats took significantly longer to learn a new association when they were in periods of their estrus cycle with high levels of estrogen, compared to their ability to learn when their estrogen level was low. The effect was not found among pre-pubertal rats. The study follows on from an earlier study using rats with their ovaries removed, whose learning was similarly affected when given high levels of estradiol.

Human females have high estrogen levels while they are ovulating. These high levels have also been shown to interfere with women's ability to pay attention.

On the other hand, it needs to be remembered that estrogen therapy has been found to help menopausal and post-menopausal women. It has also been found to be detrimental. Recent research has suggested that timing is important, and it’s been proposed that a critical period exists during which hormone therapy must be administered if it is to improve cognitive function.

This finds some support in another recent rodent study, which found that estrogen replacement increased long-term potentiation (a neural event that underlies memory formation) in young adult rats with their ovaries removed, through its effects on NMDA receptors and dendritic spine density — but only if given within 15 months of the ovariectomy. By 19 months, the same therapy couldn’t induce the changes.

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Insulin sensitivity may explain link between obesity, memory problems

November, 2010

A new study suggests that the link between midlife obesity and cognitive impairment and dementia in old age may be explained by poorer insulin sensitivity.

Previous research has indicated that obesity in middle-age is linked to higher risk of cognitive decline and dementia in old age. Now a study of 32 middle-aged adults (40-60) has revealed that although obese, overweight and normal-weight participants all performed equally well on a difficult cognitive task (a working memory task called the 2-Back task), obese individuals displayed significantly lower activation in the right inferior parietal cortex. They also had lower insulin sensitivity than their normal weight and overweight peers (poor insulin sensitivity may ultimately lead to diabetes). Analysis pointed to the impaired insulin sensitivity mediating the relationship between task-related activation in that region and BMI.

This suggests that it is insulin sensitivity that is responsible for the higher risk of cognitive impairment later in life. The good news is that insulin sensitivity is able to be modified through exercise and diet.

A follow-up study to determine if a 12-week exercise intervention can reverse the differences is planned.

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