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Neurology. 2016 Feb 23;86(8):735-41. doi: 10.1212/WNL.0000000000002387. Epub 2016 Jan 27.

Higher brain BDNF gene expression is associated with slower cognitive decline in older adults.

Author information

1
From the Rush Alzheimer's Disease Center (A.S.B., L.Y., P.A.B., J.A.S., D.A.B.), Neurological Science (A.S.B., L.Y., J.A.S., D.A.B.), Behavioral Sciences (P.A.B.), Pathology (Neuropathology) (J.A.S.), Rush University Medical Center, Chicago, IL; Program in Translational NeuroPsychiatric Genomics (P.L.D.), Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston; Harvard Medical School (P.L.D.), Boston; and Program in Medical and Population Genetics, Broad Institute (P.L.D.), Cambridge, MA. Aron_S_Buchman@rush.edu.
2
From the Rush Alzheimer's Disease Center (A.S.B., L.Y., P.A.B., J.A.S., D.A.B.), Neurological Science (A.S.B., L.Y., J.A.S., D.A.B.), Behavioral Sciences (P.A.B.), Pathology (Neuropathology) (J.A.S.), Rush University Medical Center, Chicago, IL; Program in Translational NeuroPsychiatric Genomics (P.L.D.), Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston; Harvard Medical School (P.L.D.), Boston; and Program in Medical and Population Genetics, Broad Institute (P.L.D.), Cambridge, MA.

Abstract

OBJECTIVES:

We tested whether brain-derived neurotrophic factor (BDNF) gene expression levels are associated with cognitive decline in older adults.

METHODS:

Five hundred thirty-five older participants underwent annual cognitive assessments and brain autopsy at death. BDNF gene expression was measured in the dorsolateral prefrontal cortex. Linear mixed models were used to examine whether BDNF expression was associated with cognitive decline adjusting for age, sex, and education. An interaction term was added to determine whether this association varied with clinical diagnosis proximate to death (no cognitive impairment, mild cognitive impairment, or dementia). Finally, we examined the extent to which the association of Alzheimer disease (AD) pathology with cognitive decline varied by BDNF expression.

RESULTS:

Higher brain BDNF expression was associated with slower cognitive decline (p < 0.001); cognitive decline was about 50% slower with the 90th percentile BDNF expression vs 10th. This association was strongest in individuals with dementia. The level of BDNF expression was lower in individuals with pathologic AD (p = 0.006), but was not associated with macroscopic infarcts, Lewy body disease, or hippocampal sclerosis. BDNF expression remained associated with cognitive decline in a model adjusting for age, sex, education, and neuropathologies (p < 0.001). Furthermore, the effect of AD pathology on cognitive decline varied by BDNF expression such that the effect was strongest for high levels of AD pathology (p = 0.015); thus, in individuals with high AD pathology (90th percentile), cognitive decline was about 40% slower with the 90th percentile BDNF expression vs 10th.

CONCLUSIONS:

Higher brain BDNF expression is associated with slower cognitive decline and may also reduce the deleterious effects of AD pathology on cognitive decline.

PMID:
26819457
PMCID:
PMC4763800
DOI:
10.1212/WNL.0000000000002387
[Indexed for MEDLINE]
Free PMC Article

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