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February 23, 2016; 86 (8) Article

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

Aron S. Buchman, Lei Yu, Patricia A. Boyle, Julie A. Schneider, Philip L. De Jager, David A. Bennett
First published January 27, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002387
Aron S. Buchman
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.
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Lei Yu
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.
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Patricia A. Boyle
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.
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Julie A. Schneider
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.
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Philip L. De Jager
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.
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David A. Bennett
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.
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Citation
Higher brain BDNF gene expression is associated with slower cognitive decline in older adults
Aron S. Buchman, Lei Yu, Patricia A. Boyle, Julie A. Schneider, Philip L. De Jager, David A. Bennett
Neurology Feb 2016, 86 (8) 735-741; DOI: 10.1212/WNL.0000000000002387

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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.

GLOSSARY

AD=
Alzheimer disease;
BDNF=
brain-derived neurotrophic factor;
DLPFC=
dorsal lateral prefrontal cortex;
FPKM=
fragments per kilobase per million;
LBD=
Lewy body disease;
MCI=
mild cognitive impairment;
NCI=
no cognitive impairment

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 702

  • Supplemental data at Neurology.org

  • Received March 25, 2015.
  • Accepted in final form August 4, 2015.
  • © 2016 American Academy of Neurology
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