aging

One cause of cognitive decline with age

July, 2010

The discovery that a particular type of dendritic spine is lost with age not only provides a target for therapy, but also emphasizes the importance of building skills and expertise when young.

A rhesus monkey study has revealed which dendritic spines are lost with age, providing a new target for therapies to help prevent age-association cognitive impairment. It appears that it is the thin, dynamic spines in the dorsolateral prefrontal cortex, which are key to learning new things, establishing rules, and planning, that are lost. Learning of a new task was correlated with both synapse density and average spine size, but was most strongly predicted by the head volume of thin spines. There was no correlation with size or density of the large, mushroom-shaped spines, which were very stable across age and probably mediate long-term memories, enabling the retention of expertise and skills learned early in life. There was no correlation with any of these spine characteristics once the task was learned. The findings underscore the importance of building skills and broad expertise when young.

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Teenage physical activity reduces risk of cognitive impairment later

July, 2010

A large long-running study reveals that physical activity is always important for women wanting to prevent cognitive impairment in old age, but being active in adolescence is most important.

A large longitudinal study, comparing physical activity at teenage, age 30, age 50, and late life against cognition of 9,344 women, has revealed that women who are physically active at any point have a lower risk of cognitive impairment in late-life compared to those who are inactive, but teenage physical activity is the most important. When age, education, marital status, diabetes, hypertension, depressive symptoms, smoking, and BMI were accounted for, only teenage physical activity status remained significantly associated with cognitive performance in old age. Although becoming active later in life didn’t make up for being inactive in adolescence, it did significantly reduce the risk of cognitive impairment compared to those who remained physically inactive. The findings are a strong argument for greater effort in increasing physical activity in today's youth.

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Animal studies indicate caffeine may slow dementia and cognitive decline but human studies less conclusive

July, 2010
  • Several recent studies and reviews suggest that the benefits of caffeine for age-related cognitive impairment and dementia are limited. It may be that the association only exists for women.

A special supplement in the Journal of Alzheimer's Disease focuses on the effects of caffeine on dementia and age-related cognitive decline. Here are the highlights:

A mouse study has found memory restoration and lower levels of amyloid-beta in Alzheimer’s mice following only 1-2 months of caffeine treatment. The researchers talk of “ a surprising ability of moderate caffeine intake to protect against or treat AD”, and define moderate intake as around 5 cups of coffee a day(!).

A review of studies into the relation between caffeine intake, diabetes, cognition and dementia, concludes that indications that coffee/caffeine consumption is associated with a decreased risk of Type 2 diabetes and possibly also with a decreased dementia risk, cannot yet be confirmed with any certainty.

A study involving 351 older adults without dementia found the association between caffeine intake and cognitive performance disappeared once socioeconomic status was taken into account.

A study involving 641 older adults found caffeine consumption was significantly associated with less cognitive decline for women only. Supporting this, white matter lesions were significantly fewer in women consuming more than 3 units of caffeine per day (after adjustment for age) than in women consuming less.

A Portuguese study involving 648 older adults found that caffeine intake was associated with a lower risk of cognitive decline in women, but not significantly in men.

A review of published studies examining the relation between caffeine intake and cognitive decline or dementia shows a trend towards a protective effect of caffeine, but because of the limited number of epidemiological studies, and the methodological differences between them, is unable to come up with a definitive conclusion.

A review of published epidemiological studies looking at the association between caffeine intake and Parkinson’s Disease confirms that higher caffeine intake is associated with a lower risk of developing Parkinson’s Disease (though this association may be stronger for men than women). Other studies provide evidence of caffeine’s potential in treatment, improving both the motor deficits and non-motor symptoms of Parkinson’s.

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Arendash, G.W. & Cao, C. Caffeine and Coffee as Therapeutics Against Alzheimer’s Disease. Journal of Alzheimer's Disease, 20 (Supp 1), 117-126.
Biessels, G.J. Caffeine, Diabetes, Cognition, and Dementia. Journal of Alzheimer's Disease, 20 (Supp 1), 143-150.
Kyle, J., Fox, H.C. & Whalley, L.J. Caffeine, Cognition, and Socioeconomic Status. Journal of Alzheimer's Disease, 20 (Supp 1), 151-159.
Ritchie, K. et al. Caffeine, Cognitive Functioning, and White Matter Lesions in the Elderly: Establishing Causality from Epidemiological Evidence. Journal of Alzheimer's Disease, 20 (Supp 1), 161-161
Santos, C. et al. Caffeine Intake is Associated with a Lower Risk of Cognitive Decline: A Cohort Study from Portugal. Journal of Alzheimer's Disease, 20 (Supp 1), 175-185.
Santos, C. et al. Caffeine Intake and Dementia: Systematic Review and Meta-Analysis. Journal of Alzheimer's Disease, 20 (Supp 1), 187-204.
Costa, J. et al. Caffeine Exposure and the Risk of Parkinson’s Disease: A Systematic Review and Meta-Analysis of Observational Studies. Journal of Alzheimer's Disease, 20 (Supp 1), 221-238.
Prediger, R.D.S. Effects of Caffeine in Parkinson’s Disease: From Neuroprotection to the Management of Motor and Non-Motor Symptoms. Journal of Alzheimer's Disease, 20 (Supp 1), 205-220.

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Extending lifespan has mixed effects on learning and memory

July, 2010

Although roundworm research suggesting different effects at different ages is concerned with genetic manipulation, we may speculate that restricting your food intake is a bad idea for young adults but good for the old, while reducing sugar may be better for the young than it is for the old.

Studies on the roundworm C. elegans have revealed that the molecules required for learning and memory are the same from C. elegans to mammals, suggesting that the basic mechanisms underlying learning and memory are ancient, and that this animal can serve as a testing ground for treatments for age-related memory loss. Intriguingly, a comparison of two known regulators of longevity — reducing calorie intake and reducing activity in the insulin-signaling pathway (achieved through genetic manipulation) — has found that these two treatments produce very different effects on memory. While dietary restriction impaired memory in early adulthood, it maintained memory with age. On the other hand, reduced insulin signaling improved early adult memory performance but failed to preserve it with age. These different effects appear to be linked to expression of CREB, a protein known to be important for long-term memory. Young roundworms with defective insulin receptors had higher levels of CREB protein, while those worms genetically altered to eat less had low levels, but the level did not diminish with age. These findings add to our understanding of why memory declines with age.

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Promise of drug therapy for age-related memory loss

July, 2010

Mouse studies suggest a way to reverse both normal age-related memory loss, and dementia.

Although research has so far been confined to mouse studies, researchers are optimistic about the promise of histone deacetylase inhibitors in reversing age-related memory loss — both normal decline, and the far more dramatic loss produced by Alzheimer’s. The latest study reveals that memory impairment in the aging mouse is associated with altered hippocampal chromatin plasticity, specifically with the failure of histone H4 lysine 12 acetylation, leading to a failure to initiate the gene expression program associated with memory consolidation. Restoring this acetylation leads to the recovery of cognitive abilities.

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Why older adults remember the good times better

March, 2010

An imaging study has found differences in brain activity that explain why older adults are better at remembering positive events.

An imaging study reveals why older adults are better at remembering positive events. The study, involving young adults (ages 19-31) and older adults (ages 61-80) being shown a series of photographs with positive and negative themes, found that while there was no difference in brain activity patterns between the age groups for the negative photos, there were age differences for the positive photos. In older adult brains, but not the younger, two emotion-processing regions (the ventromedial prefrontal cortex and the amygdala) strongly influenced the memory-encoding hippocampus.

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The secret of sharp memory in old age

March, 2010

Examination of the brains from 9 “super-aged” — people over 80 whose memory performance was at the level of 50-year-olds — has found that some of them had almost no tau tangles. Are they genetically protected, or reaping the benefits of a preventive lifestyle?

Examination of the brains from 9 “super-aged” — people over 80 whose memory performance was at the level of 50-year-olds — has found that some of them had almost no tau tangles. The accumulation of tau tangles has been thought to be a natural part of the aging process; an excess of them is linked to Alzheimer’s disease. The next step is to work out why some people are immune to tangle formation, while others appear immune to the effects. Perhaps the first group is genetically protected, while the others are reaping the benefits of a preventive lifestyle.

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The findings were presented March 23 at the 239th National Meeting of the American Chemical Society (ACS).

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Personality may influence brain shrinkage in aging

March, 2010
  • An imaging study involving 79 volunteers aged 44 to 88 has found more brain atrophy and faster rates of decline in brain regions particularly affected by aging, among those ranked high in neuroticism traits.

An imaging study involving 79 volunteers aged 44 to 88 has found lower volumes of gray matter and faster rates of decline in the frontal and medial temporal lobes of those who ranked high in neuroticism traits, compared with those who ranked high in conscientious traits. These are brain regions particularly affected by aging. The idea that this might occur derived from the well-established effects of chronic stress on the brain. This is the first study to investigate whether the rate and extent of cognitive decline with age is influenced by personality variables. Extraversion, also investigated, had no effect. The study does not, however, rule out the possibility that it is reduction in brain tissue in these areas that is affecting personality. There is increasing evidence that people tend to become more neurotic and less conscientious in early-stage Alzheimer's.

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[174] Jackson, J., Balota D. A., & Head D.
(Submitted).  Exploring the relationship between personality and regional brain volume in healthy aging.
Neurobiology of Aging. In Press, Corrected Proof,

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Memory decline linked to an inability to ignore distractions

March, 2010

A new study provides more support for the idea that cognitive decline in older adults is a product of a growing inability to ignore distractions, and that forewarning doesn't help.

A new study provides more support for the idea that cognitive decline in older adults is a product of a growing inability to ignore distractions. Moreover, the study, involving 21 older adults (60-80) shown random sequences of pictures containing faces and scenes and asked to remember only the scene or the face, reveals that being given forewarning about which specific pictures would be relevant (say the second, or the fourth) did not help. The findings suggest that the failure to suppress irrelevant information is not due to a failure in quickly assessing what is relevant, but is a related to mechanisms that occur early in the visual processing stream.

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Gene variant may protect memory and thinking skills in older people

April, 2010

The role of the dopamine-regulating COMT gene in cognitive function has been the subject of debate. Now a large study of older adults has revealed that the Met variant of the COMT gene was linked to a greater decline in cognitive function. This effect was more pronounced for African-Americans.

The role of the catechol-O-methyltransferase (COMT) gene in cognitive function has been the subject of some debate. The gene, which affects dopamine, comes in two flavors: Val and Met. One recent study found no difference between healthy carriers of these two gene variants in terms of cognitive performance, but did find differences in terms of neural activity. Another found that, although the gene did not affect Alzheimer’s risk in its own, it acted synergistically with the Alzheimer’s gene variant to do so. Now an eight-year study of nearly 3000 adults in their 70s has revealed that the Met variant of the COMT gene was linked to a greater decline in cognitive function. This effect was more pronounced for African-Americans. This is interesting because it has been the Val genotype that in other research has been shown to have a detrimental effect. It seems likely that this genotype must be considered in its context (age, race, gender, and ApoE status have all been implicated in research).

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