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.

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.

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.

Diabetes and hypertension often go together, and both are separately associated with greater cognitive impairment and dementia risk, so it is not surprising that higher blood pressure is one of the significant factors that increases risk. The other factors are less expected, although gait and balance problems have been linked to cognitive impairment in a recent study, and they may be connected to diabetes through diabetes’ effect on nerves. Negativity about one’s health may reflect emotional factors such as anxiety, stress, or depression, although depression and well-being measures were not themselves found to be mediating effects for cognitive impairment in diabetics (Do note that this study is not investigating which factors, in general, are associated with age-related cognitive impairment; it is trying to establish which factors are specifically sensitive to cognitive impairment in older diabetics).

In the U.S., type 2 diabetes occurs in over 23% of those over 60; in Canada (where this study took place) the rate is 19%. It should be noted that the participants in this study are not representative of the general population, in that they were fairly well-educated older Canadians, most of whom have benefited from a national health care system. Moreover, the study did not have longitudinal data on these various factors, meaning that we don’t know the order of events (which health problems come first? How long between the development of the different problems?). Nevertheless, the findings provide useful markers to alert diabetics and health providers.

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.

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.

The acid is produced in our brains after we’ve eaten food containing the amino acid tryptophan, which helps us produce serotonin (turkey is a food well-known for its high tryptophan levels). But serotonin helps us feel good (low serotonin levels are linked to depression), so the trick is to block the production of kynurenic acid without reducing the levels of serotonin. The next step is therefore to find a chemical that blocks production of the acid in the glia, and can safely be used in humans. Although no human tests have yet been performed, several major pharmaceutical companies are believed to be following up on this research.