aging

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.

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.

Inflammation in the brain appears to be a key contributor to age-related memory problems, and it may be that this has to do with the dysregulation of microglia that, previous research has shown, occurs with age. As these specialized support cells in the brain do normally when there’s an infection, with age microglia start to produce excessive cytokines, some of which result in the typical behaviors that accompany illness (sleepiness, appetite loss, cognitive deficits and depression).

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.

Findings from the long-running Religious Orders Study, from 354 Catholic nuns and priests who were given annual cognitive tests for up to 13 years before having their brains examined post-mortem, has revealed that even the very early cognitive impairments we regard as normal in aging are associated with dementia pathology. Although pathology in the form of neurofibrillary tangles, Lewy bodies, and cerebral infarctions were all associated with rapid decline, they were also associated with “normal” mild impairment.

Type 2 diabetes is known to increase the risk of cognitive impairment in old age. Now analysis of data from 41 older diabetics (aged 55-81) and 458 matched controls in the Victoria Longitudinal Study has revealed that several other factors make it more likely that an older diabetic will develop cognitive impairment. These factors are: having higher (though still normal) blood pressure, having gait and balance problems, and/or reporting yourself to be in bad health regardless of actual problems.

Reports on cognitive decline with age have, over the years, come out with two general findings: older adults do significantly worse than younger adults; older adults are just as good as younger adults. Part of the problem is that there are two different approaches to studying this, each with their own specific bias. You can keep testing the same group of people as they get older — the problem with this is that they get more and more practiced, which mitigates the effects of age.

Following on from indications that gum disease might be a risk factor for dementia, analysis of data from 152 subjects in the Danish Glostrop Aging Study has revealed that periodontal inflammation at age 70 was strongly associated with lower cognitive scores (on the Digit Symbol Test). Those with periodontal inflammation were nine times more likely to test in the lower range compared to those with little or no periodontal inflammation. A larger follow-up study, among a more ethnically diverse range of subjects, is planned. I hope they also plan to extend the cognitive testing.

A two-year study involving 271 older adults (70+) with mild cognitive impairment has found that the rate of brain atrophy in those taking folic acid (0.8 mg/d), vitamin B12 (0.5 mg/d) and vitamin B6 (20 mg/d), was significantly slower than in those taking a placebo, with those taking the supplements experiencing on average 30% less brain atrophy. Higher rates of atrophy were associated with lower cognitive performance. Moreover those who with the highest levels of homocysteine at the beginning of the trial benefited the most, with 50% less brain shrinkage.

Commercial use is a long way off, but research with mice offers hope for a ‘smart drug’ that doesn’t have the sort of nasty side-effects that, for example, amphetamines have. The mice, genetically engineered to produce dramatically less (70%) kynurenic acid, had markedly better cognitive abilities. The acid, unusually, is produced not in neurons but in glia, and abnormally high levels are produced in the brains of people with disorders such as schizophrenia, Alzheimer's and Huntington's. More acid is also typically produced as we get older.