Stress in middle age could contribute to later dementia

Data from the Baltimore Longitudinal Study on Aging, begun in 1958, has revealed that seniors with hearing loss are significantly more likely to develop dementia than those who retain their hearing. The study involved 639 people whose hearing and cognitive abilities were tested between 1990 and 1994, then re-tested every one to two years. By 2008, 58 (9%) of them had developed dementia (37 of which were Alzheimer’s).

A two-year study involving 53 older adults (60+) has found that those with a mother who had Alzheimer's disease had significantly more brain atrophy than those with a father or no parent with Alzheimer's disease. More specifically, they had twice as much gray matter shrinkage, and about one and a half times more whole brain shrinkage per year.

This atrophy was particularly concentrated in the precuneus and parahippocampal gyrus. Those with the APOE4 gene also had more atrophy in the frontal cortex than those who didn’t carry the ‘Alzheimer’s gene’.

In a study in which 78 healthy elders were given 5 different tests and then tested for cognitive performance 18 months later, two tests combined to correctly predict nearly 80% of those who developed significant cognitive decline. These tests were a blood test to identify presence of the ‘Alzheimer’s gene’ (APOE4), and a 5-minute fMRI imaging scan showing brain activity during mental tasks.

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.

A study involving 68 healthy older adults (65-85) has compared brain activity among four groups, determined whether or not they carry the Alzheimer’s gene ApoE4 and whether their physical activity is reported to be high or low. The participants performed a task involving the discrimination of famous people, which engages 15 different functional regions of the brain. Among those carrying the gene, those with higher physical activity showed greater activation in many regions than those who were sedentary.

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.

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.

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.

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.

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.