Aron S Buchman1, Lei Yu2, Patricia A Boyle2, Julie A Schneider2, Philip L De Jager2, David A Bennett2. 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.
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.
Authors: Joshua M Shulman; Lei Yu; Aron S Buchman; Denis A Evans; Julie A Schneider; David A Bennett; Philip L De Jager Journal: JAMA Neurol Date: 2014-04 Impact factor: 18.302
Authors: Robert J Dawe; Sue E Leurgans; Jingyun Yang; Joshua M Bennett; Jeffrey M Hausdorff; Andrew S Lim; Chris Gaiteri; David A Bennett; Aron S Buchman Journal: J Gerontol A Biol Sci Med Sci Date: 2018-04-17 Impact factor: 6.053
Authors: Aron S Buchman; Lei Yu; Robert S Wilson; Andrew Lim; Robert J Dawe; Chris Gaiteri; Sue E Leurgans; Julie A Schneider; David A Bennett Journal: Neurology Date: 2019-01-16 Impact factor: 9.910
Authors: Annie Robitaille; Ardo van den Hout; Robson J M Machado; David A Bennett; Iva Čukić; Ian J Deary; Scott M Hofer; Emiel O Hoogendijk; Martijn Huisman; Boo Johansson; Andriy V Koval; Maaike van der Noordt; Andrea M Piccinin; Judith J M Rijnhart; Archana Singh-Manoux; Johan Skoog; Ingmar Skoog; John Starr; Lisa Vermunt; Sean Clouston; Graciela Muniz Terrera Journal: Alzheimers Dement Date: 2018-02-01 Impact factor: 21.566
Authors: Yen Ying Lim; Jason Hassenstab; Carlos Cruchaga; Alison Goate; Anne M Fagan; Tammie L S Benzinger; Paul Maruff; Peter J Snyder; Colin L Masters; Ricardo Allegri; Jasmeer Chhatwal; Martin R Farlow; Neill R Graff-Radford; Christoph Laske; Johannes Levin; Eric McDade; John M Ringman; Martin Rossor; Stephen Salloway; Peter R Schofield; David M Holtzman; John C Morris; Randall J Bateman Journal: Brain Date: 2016-08-12 Impact factor: 13.501
Authors: Lei Yu; Vladislav A Petyuk; Chris Gaiteri; Sara Mostafavi; Tracy Young-Pearse; Raj C Shah; Aron S Buchman; Julie A Schneider; Paul D Piehowski; Ryan L Sontag; Thomas L Fillmore; Tujin Shi; Richard D Smith; Philip L De Jager; David A Bennett Journal: Ann Neurol Date: 2018-07-03 Impact factor: 10.422
Authors: Patricia A Boyle; Lei Yu; Robert S Wilson; Sue E Leurgans; Julie A Schneider; David A Bennett Journal: Ann Neurol Date: 2018-01-14 Impact factor: 10.422