Cited by 289Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

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Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia: The Framingham Heart Study

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Weinstein, Galit, Beiser, Alexa S., Choi, Seung Hoan, Preis, Sarah R., Chen, Tai C., Vorgas, Demetrios, Au, Rhoda, Pikula, Aleksandra, Wolf, Philip A., DeStefano, Anita L., Vasan, Ramachandran S., Seshadri, Sudha·2014·JAMA Neurology

DOI 10.1001/jamaneurol.2013.4781PMC PMC4056186

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Abstract

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.

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Authors: Weinstein, G., Beiser, A. S., Choi, S. H., Preis, S. R., Chen, T. C., Vorgas, D., Au, R., Pikula, A., Wolf, P. A., DeStefano, A. L., Vasan, R. S., & Seshadri, S.
Affiliations: Boston University (US)
Corresponding author: Seshadri, Sudha
ORCID: Weinstein, Galit
Beiser, Alexa S.
Choi, Seung Hoan
Preis, Sarah R.
Chen, Tai C.
Au, Rhoda
Pikula, Aleksandra
Wolf, Philip A.
DeStefano, Anita L.
Vasan, Ramachandran S.
Seshadri, Sudha
Venue: JAMA Neurology
Publisher: American Medical Association (AMA)
Published: 2014-01-01
Volume: 71
Issue: 1
Pages: 55
ISSN: 2168-6149 (ISSN-L)
DOI: 10.1001/jamaneurol.2013.4781
PMC: PMC4056186
OpenAlex: W2112473391
Cited by: 289
References: 53
Citations by year: 2026: 17 · 2025: 22 · 2024: 29 · 2023: 28 · 2022: 22 · 2021: 31 · 2020: 26 · 2019: 18 · 2018: 15 · 2017: 24 · 2016: 26 · 2015: 13 · 2014: 18
FWCI: 13.51
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: JAMA Neurology (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (n01hc25195-41-0-1)
National Institute on Aging (P30AG010129, AG-16495, R01AG031287, AG031287, AG08122, AG033193, R01AG016495, P30AG013846, R01AG033193, R01AG008122)
National Heart, Lung, and Blood Institute (N01‐HC25195, HL93029, N01-HC-025195, R01HL093029, U01HL096917)
National Institute of Neurological Disorders and Stroke (NS17950, R01NS017950)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords: brain-derived neurotrophic factor, serum BDNF, dementia risk, Alzheimer's disease, neurodegeneration biomarkers, Framingham Heart Study, sex differences, older adults, educational attainment, physical activity, caloric restriction, lifestyle factors, dementia prevention, synaptic plasticity, neuronal survival, long-term memory, cognitive aging, neuroinflammation, neuroprotection
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Dementia, Female, Genotype, Humans, Male, Prospective Studies, Risk, Sensitivity and Specificity, Incidence, Proportional Hazards Models, Brain-Derived Neurotrophic Factor, Polymorphism, Single Nucleotide

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Serum Brain-Derived Neurotrophic Factor and the Risk for Dementia: The Framingham Heart Study

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