middle-aged

Adverse changes in sleep duration associated with cognitive decline in middle-aged adults

May, 2011

A large long-running study has found that middle-aged adults whose night’s sleep had decreased from 6-8 hours or increased from 7-8 hours performed worse on some cognitive tests.

From the Whitehall II study, data involving 5431 older participants (45-69 at baseline) has revealed a significant effect of midlife sleep changes on later cognitive function. Sleep duration was assessed at one point between 1997 and 1999, and again between 2002 and 2004. A decrease in average night’s sleep from 6, 7, or 8 hours was significantly associated with poorer scores on tests of reasoning, vocabulary, and the MMSE. An increase from 7 or 8 hours (but not from 6 hours) was associated with lower scores on these, as well as on tests of phonemic and semantic fluency. Short-term verbal memory was not significantly affected. The magnitude of these effects was equivalent to a 4–7 year increase in age.

Around 8% of participants showed an increase from 7-8 hours of sleep over the five-year period (7.4% of women; 8.6% of men), while around a quarter of women and 18% of men decreased their sleep amount from 6-8 hours. About 58% of men and 50% of women reported no change in sleep duration during the study period. Some 27% of the participants were women.

The optimal amount of sleep (in terms of highest cognitive performance) was 7 hours for women, closely followed by 6 hours. For men, results were similar at 6, 7 and 8 hours.

Analysis took into account age, sex, education and occupational status. The Whitehall II study is a large, long-running study involving British civil servants. Sleep duration was assessed simply by responses to the question "How many hours of sleep do you have on an average week night?"

A very large Chinese study, involving 28,670 older adults (50-85), of whom some 72% were women, also supports an inverted U-shaped association between sleep duration and cognitive function, with 7-8 hours sleep associated with the highest scores on a delayed word recall test.

I would speculate that this finding of an effect of short-term verbal memory (in contrast to that of the Whitehall study) may reflect a group distinction in terms of education and occupation. The Whitehall study is the more homogenous (mostly white-collar), with participants probably averaging greater cognitive reserve than the community-based Chinese study. The findings suggest that memory is slower to be affected, rather than not affected.

Reference: 

Ferrie JE; Shipley MJ; Akbaraly TN; Marmot MG; Kivimäki M; Singh-Manoux A. Change in sleep duration and cognitive function: findings from the Whitehall II study. SLEEP 2011;34(5):565-573.

Xu L; Jiang CQ; Lam TH; Liu B; Jin YL; Zhu T; Zhang WS; Cheng KK; Thomas GN. Short or long sleep duration is associated with memory impairment in older Chinese: the Guangzhou Biobank Cohort Study. SLEEP 2011;34(5):575-580.

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Long term exposure to pesticides linked to cognitive decline

April, 2011

A French study of vineyard workers points to lower cognitive performance and cognitive decline in those chronically exposed to pesticides.

A study involving 614 middle-aged vineyard workers has found that those who were exposed to pesticides were five times as likely to perform more poorly on cognitive tests compared to those not exposed, and twice as likely to show cognitive decline over a two-year period.

Participants were in their 40s and 50s and had worked for at least 20 years in the agricultural sector. One in five had never been exposed to pesticides as part of their job; over half had been directly exposed, and the remainder had been possibly or certainly indirectly exposed. Educational level, age, sex, alcohol consumption, smoking, psychotropic drug use and depressive symptoms were taken into account.

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Metabolic syndrome linked to memory loss in older people

March, 2011

Three more studies point to the increased risk of memory loss in older adults with cardiovascular problems.

The new label of ‘metabolic syndrome’ applies to those having three or more of the following risk factors: high blood pressure, excess belly fat, higher than normal triglycerides, high blood sugar and low high-density lipoprotein (HDL) cholesterol (the "good" cholesterol). Metabolic syndrome has been linked to increased risk of heart attack.

A new French study, involving over 7,000 older adults (65+) has found that those with metabolic syndrome were 20% more likely to show cognitive decline on a memory test (MMSE) over a two or four year interval. They were also 13% more likely to show cognitive decline on a visual working memory test. Specifically, higher triglycerides and low HDL cholesterol were linked to poorer memory scores; diabetes (but not higher fasting blood sugar) was linked to poorer visual working memory and word fluency scores.

The findings point to the importance of managing the symptoms of metabolic syndrome.

High cholesterol and blood pressure in middle age tied to early memory problems

Another study, involving some 4800 middle-aged adults (average age 55), has found that those with higher cardiovascular risk were more likely to have lower cognitive function and a faster rate of cognitive decline over a 10-year period. A 10% higher cardiovascular risk was associated not only with increased rate of overall mental decline, but also poorer cognitive test scores in all areas except reasoning for men and fluency for women.

The cardiovascular risk score is based on age, sex, HDL cholesterol, total cholesterol, systolic blood pressure and whether participants smoked or had diabetes.

Memory problems may be sign of stroke risk

A very large study (part of the REGARDS study) tested people age 45 and older (average age 67) who had never had a stroke. Some 14,842 people took a verbal fluency test, and 17,851 people took a word recall memory test. In the next 4.5 years, 123 participants who had taken the verbal fluency test and 129 participants who had taken the memory test experienced a stroke.

Those who had scored in the bottom 20% for verbal fluency were 3.6 times more likely to develop a stroke than those who scored in the top 20%. For the memory test, those who scored in the bottom 20% were 3.5 times more likely to have a stroke than those in the top quintile.

The effect was greatest at the younger ages. At age 50, those who scored in the bottom quintile of the memory test were 9.4 times more likely to later have a stroke than those in the top quintile.

 

Together, these studies, which are consistent with many previous studies, confirm that cardiovascular problems and diabetes add to the risk of greater cognitive decline (and possible dementia) in old age. And point to the importance of treating these problems as soon as they appear.

Reference: 

[2147] Raffaitin, C., Féart C., Le Goff M., Amieva H., Helmer C., Akbaraly T. N., et al.
(2011).  Metabolic syndrome and cognitive decline in French elders.
Neurology. 76(6), 518 - 525.

The findings of the second and third studies are to be presented at the American Academy of Neurology's 63rd Annual Meeting in Honolulu April 9 to April 16, 2011

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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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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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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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Career choice may determine where frontotemporal dementia begins

October, 2010
  • An international review of patients with frontotemporal dementia has revealed that the area of the brain first affected tends to be the hemisphere least used in the individual’s occupation.

A review of brain imaging and occupation data from 588 patients diagnosed with frontotemporal dementia has found that among the dementias affecting those 65 years and younger, FTD is as common as Alzheimer's disease. The study also found that the side of the brain first attacked (unlike Alzheimer’s, FTD typically begins with tissue loss in one hemisphere) is influenced by the person’s occupation.

Using occupation scores that reflect the type of skills emphasized, they found that patients with professions rated highly for verbal skills, such as school principals, had greater tissue loss on the right side of the brain, whereas those rated low for verbal skills, such as flight engineers, had greater tissue loss on the left side of the brain. This effect was expressed most clearly in the temporal lobes of the brain. In other words, the side of the brain least used in the patient's professional life was apparently the first attacked.

These findings are in keeping with the theory of cognitive reserve, but may be due to some asymmetry in the brain that both inclines them to a particular occupational path and renders the relatively deficient hemisphere more vulnerable in later life.

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Smoking may counteract benefit of moderate drinking on stroke risk

March, 2010

A large long-running study has found that though non-smokers who consumed moderate amounts of alcohol were 37% less likely to develop stroke than non-drinkers, this association was not found among smokers.

A 12-year study following the drinking and smoking habits of 22,524 people aged 39-79 has found that in non-smokers, people who consumed moderate amounts of alcohol were 37% less likely to develop stroke than non-drinkers. This association was not found among smokers. The finding may explain the inconsistency in previous studies into the relationship between light to moderate drinking and stroke.

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The findings were presented at the American Academy of Neurology's 62nd Annual Meeting in Toronto, April 10 - 17, 2010.

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