http://jama.jamanetwork.com/article.aspx?articleID=1861777
JAMA Neurology
Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia: The Framingham Heart Study
Importance In
animal studies, brain-derived neurotrophic factor (BDNF) has been shown
to impact neuronal survival and function and improve synaptic
plasticity and long-term memory. Circulating BDNF levels increase with
physical activity and caloric restriction, thus BDNF may mediate some of
the observed associations between lifestyle and the risk for dementia.
Some prior studies showed lower circulating BDNF in persons with
Alzheimer disease (AD) compared with control participants; however, it
remains uncertain whether reduced levels precede dementia onset.
Objective
To examine whether higher serum BDNF levels in cognitively healthy
adults protect against the future risk for dementia and AD and to
identify potential modifiers of this association.
Design, Setting, and Participants
Framingham Study original and offspring participants were followed up
from 1992 and 1998, respectively, for up to 10 years. We used Cox models
to relate BDNF levels to the risk for dementia and AD and adjusted for
potential confounders. We also ran sensitivity analyses stratified by
sex, age, and education, as well as related BDNF genetic variants to AD
risk. This community-based, prospective cohort study involved 2131
dementia-free participants aged 60 years and older (mean [SD] age, 72
[7] years; 56% women).
Main Outcomes and Measures Ten-year incidence of dementia and AD.
Results
During follow-up, 140 participants developed dementia, 117 of whom had
AD. Controlling for age and sex, each standard-deviation increment in
BDNF was associated with a 33% lower risk for dementia and AD (P = .006 and P
= .01, respectively) and these associations persisted after additional
adjustments. Compared with the bottom quintile, BDNF levels in the top
quintile were associated with less than half the risk for dementia and
AD (hazard ratio, 0.49; 95% CI, 0.28-0.85; P = .01; and hazard ratio, 0.46; 95% CI, 0.24-0.86; P
= .02, respectively). These associations were apparent only among women,
persons aged 80 years and older, and those with college degrees (hazard
ratios for AD: 0.65, [95% CI, 0.50-0.85], P = .001; 0.63 [95% CI, 0.47-0.85], P = .002; and 0.27 [95% CI, 0.11-0.65], P = .003, respectively). Brain-derived neurotrophic factor genetic variants were not associated with AD risk.
Conclusions and Relevance
Higher serum BDNF levels may protect against future occurrence of
dementia and AD. Our findings suggest a role for BDNF in the biology and
possibly in the prevention of dementia and AD, especially in select
subgroups of women and older and more highly educated persons.
JAMA Neurol. 2014;71(1):55-61. doi:10.1001/jamaneurol.2013.4781.
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