PMID- 26819457 OWN - NLM STAT- MEDLINE DCOM- 20160701 LR - 20230228 IS - 1526-632X (Electronic) IS - 0028-3878 (Print) IS - 0028-3878 (Linking) VI - 86 IP - 8 DP - 2016 Feb 23 TI - Higher brain BDNF gene expression is associated with slower cognitive decline in older adults. PG - 735-41 LID - 10.1212/WNL.0000000000002387 [doi] AB - 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. CI - (c) 2016 American Academy of Neurology. FAU - Buchman, Aron S AU - Buchman AS AD - 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. FAU - Yu, Lei AU - Yu L AD - 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. FAU - Boyle, Patricia A AU - Boyle PA AD - 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. FAU - Schneider, Julie A AU - Schneider JA AD - 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. FAU - De Jager, Philip L AU - De Jager PL AD - 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. FAU - Bennett, David A AU - Bennett DA AD - 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. LA - eng GR - RF1 AG015819/AG/NIA NIH HHS/United States GR - R01AG42210/AG/NIA NIH HHS/United States GR - R01 NS078009/NS/NINDS NIH HHS/United States GR - R01 AG043379/AG/NIA NIH HHS/United States GR - P30 AG010161/AG/NIA NIH HHS/United States GR - R01AG15819/AG/NIA NIH HHS/United States GR - R01NS78009/NS/NINDS NIH HHS/United States GR - R01 AG015819/AG/NIA NIH HHS/United States GR - R02AG36836/AG/NIA NIH HHS/United States GR - R01 AG017917/AG/NIA NIH HHS/United States GR - R01AG17917/AG/NIA NIH HHS/United States GR - U02AG46152/AG/NIA NIH HHS/United States GR - R01AG43379/AG/NIA NIH HHS/United States GR - P30AG10161/AG/NIA NIH HHS/United States GR - R01AG34374/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20160127 PL - United States TA - Neurology JT - Neurology JID - 0401060 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 7171WSG8A2 (BDNF protein, human) SB - IM CIN - Neurology. 2016 Feb 23;86(8):702-3. PMID: 26819454 MH - Aged MH - Aged, 80 and over MH - Aging/*metabolism/pathology MH - Brain/*metabolism/pathology MH - Brain-Derived Neurotrophic Factor/*biosynthesis/genetics MH - Cognition Disorders/*metabolism/pathology MH - Follow-Up Studies MH - Gene Expression Regulation MH - Humans MH - Longitudinal Studies MH - Male PMC - PMC4763800 EDAT- 2016/01/29 06:00 MHDA- 2016/07/02 06:00 PMCR- 2017/02/23 CRDT- 2016/01/29 06:00 PHST- 2015/03/25 00:00 [received] PHST- 2015/08/04 00:00 [accepted] PHST- 2016/01/29 06:00 [entrez] PHST- 2016/01/29 06:00 [pubmed] PHST- 2016/07/02 06:00 [medline] PHST- 2017/02/23 00:00 [pmc-release] AID - WNL.0000000000002387 [pii] AID - NEUROLOGY2015657007 [pii] AID - 10.1212/WNL.0000000000002387 [doi] PST - ppublish SO - Neurology. 2016 Feb 23;86(8):735-41. doi: 10.1212/WNL.0000000000002387. Epub 2016 Jan 27.