Brain-derived neurotrophic factor influences cognitive decline in elderly

By Will Boggs MD

NEW YORK (Reuters Health) - Higher brain expression of brain-derived neurotrophic factor (BDNF) is associated with slower cognitive decline, especially among adults with dementia, researchers report.

Previous studies have suggested that BDNF influences late-life cognitive impairment and mitigates the deleterious effects of Alzheimer disease pathology in older adults.

Dr. Aron S. Buchman from Rush Alzheimer's Disease Center in Chicago and colleagues investigated the influence of BDNF gene expression on the rate of cognitive decline in their study of 535 older adults, focusing on the BDNF Val66Met polymorphism, which has been linked to Alzheimer disease and cognitive decline in some studies.

In a model adjusted for demographics, the rate of cognitive decline was reduced by 48.3% in persons with the 90th percentile of BDNF expression versus those with the 10th percentile, the researchers reported online January 27th in Neurology.

The effect of BDNF expression was strongest in individuals with dementia, weakly significant in those with mild cognitive impairment, and not significant in those with no cognitive impairment.

BDNF expression was also inversely associated with pathologic Alzheimer disease, as well as amyloid load and tangles.

Even after adjusting for the presence of neuropathology, BDNF expression remained associated with cognitive decline. In fact, higher BDNF expression reduced the effect of Alzheimer disease pathology on the rate of cognitive decline.

BDNF expression did not differ by Val66Met genotype.

"These data suggest that a higher level of brain BDNF expression is associated with slower cognitive decline and may provide reserve against the effects of Alzheimer disease pathology in older adults," the researchers conclude.

"Observation over a longer period of time and in a larger number of older individuals would likely improve the estimation of individual patterns of progressive cognitive decline and provide more details on the relationship of BDNF expression in older adults with no cognitive impairment," they add.

Dr. Michal Schnaider Beeri from The Icahn School of Medicine at Mount Sinai in New York City, who coauthored a related editorial, told Reuters Health by email, "I was surprised that BDNF expression predicted cognitive decline even after controlling for Alzheimer's neuropathology, suggesting its effects on supporting cognition are through other pathways that do not relate to amyloid and tau (the two main pathologies of Alzheimer's disease), possibly pathways that enhance cognitive and brain reserve."

"We have to be careful with over-interpreting the results of the study since this study is associational, i.e., we learned that higher BDNF expression is related to slower rate of cognitive decline in individuals with Alzheimer's disease but we cannot assert BDNF causes less cognitive decline," Dr. Beeri said. "With this in mind, since animal model studies show that brain BDNF levels increase in context of physical and mental activity (such as in enriched environments), and since mental and physical activity provide benefits overall (and do not have side effects like medications), this study further reinforces investing in such activities."

Dr. Buchman did not respond to a request for comments.

SOURCE: https://bit.ly/23ua3hq and https://bit.ly/1noHDVd

Neurology 2016.