Patricia A Boyle1,2, Lei Yu1,3, Sue E Leurgans1,3, Robert S Wilson1,2,3, Ron Brookmeyer4, Julie A Schneider1,3,5, David A Bennett1,3. 1. Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL. 2. Department of Behavioral Sciences, Rush University Medical Center, Chicago, IL. 3. Department of Neurological Sciences, Rush University Medical Center, Chicago, IL. 4. Department of Biostatistics, University of California at Los Angeles, CA. 5. Department of Pathology, Rush University Medical Center, Chicago, IL.
Abstract
OBJECTIVE: The degree to which Alzheimer's versus other neuropathologies contribute to the risk of Alzheimer's dementia is unknown. We examined the risk of Alzheimer's dementia attributable to pathologic AD and 8 other neuropathologies. METHODS: Participants (n = 1,161) came from 2 clinical-pathological studies of aging. Multivariable logistic regression models examined associations of 8 neuropathological indices with Alzheimer's dementia and quantified the percentage of cases attributable to each. Furthermore, because some dementia cases are not driven by common neuropathologies, we re-estimated the attributable risks after empirically adjusting for such cases. RESULTS: Of 1,161 persons, 512 (44.1%) had Alzheimer's dementia at time of death. With the exception of microinfarcts, all neuropathological indices were independently associated with greater odds of Alzheimer's dementia. Two hundred ten (41.0%) Alzheimer's dementia cases were attributable to pathological AD. Separately, 8.9% were attributable to macroscopic infarcts, 10.8% to Lewy bodies, 5.2% to hippocampal sclerosis, 11.7% to transactive response DNA-binding protein 43, 8.1% to cerebral amyloid angiopathy, 6.0% to atherosclerosis, and 5.2% to arteriolosclerosis. A total of 83.3% of cases were attributable to all 8 indices combined. However, after further adjustment for cases driven by other factors, a total of 67.5% of cases were attributable to all 8 neuropathologic indices combined. INTERPRETATION: Pathological AD accounts for a considerable percentage of Alzheimer's dementia cases, but multiple other neuropathologies also contribute. In total, just over two-thirds of Alzheimer's dementia cases are attributable to common age-related neuropathologies, suggesting that other disease and resilience factors are important. ANN NEUROL 2019;85:114-124.
OBJECTIVE: The degree to which Alzheimer's versus other neuropathologies contribute to the risk of Alzheimer's dementia is unknown. We examined the risk of Alzheimer's dementia attributable to pathologic AD and 8 other neuropathologies. METHODS:Participants (n = 1,161) came from 2 clinical-pathological studies of aging. Multivariable logistic regression models examined associations of 8 neuropathological indices with Alzheimer's dementia and quantified the percentage of cases attributable to each. Furthermore, because some dementia cases are not driven by common neuropathologies, we re-estimated the attributable risks after empirically adjusting for such cases. RESULTS: Of 1,161 persons, 512 (44.1%) had Alzheimer's dementia at time of death. With the exception of microinfarcts, all neuropathological indices were independently associated with greater odds of Alzheimer's dementia. Two hundred ten (41.0%) Alzheimer's dementia cases were attributable to pathological AD. Separately, 8.9% were attributable to macroscopic infarcts, 10.8% to Lewy bodies, 5.2% to hippocampal sclerosis, 11.7% to transactive response DNA-binding protein 43, 8.1% to cerebral amyloid angiopathy, 6.0% to atherosclerosis, and 5.2% to arteriolosclerosis. A total of 83.3% of cases were attributable to all 8 indices combined. However, after further adjustment for cases driven by other factors, a total of 67.5% of cases were attributable to all 8 neuropathologic indices combined. INTERPRETATION: Pathological AD accounts for a considerable percentage of Alzheimer's dementia cases, but multiple other neuropathologies also contribute. In total, just over two-thirds of Alzheimer's dementia cases are attributable to common age-related neuropathologies, suggesting that other disease and resilience factors are important. ANN NEUROL 2019;85:114-124.
Authors: Richard J Caselli; Blake T Langlais; Amylou C Dueck; Yinghua Chen; Yi Su; Dona E C Locke; Bryan K Woodruff; Eric M Reiman Journal: Alzheimers Dement Date: 2020-01-06 Impact factor: 21.566
Authors: Anke Hüls; Chloe Robins; Karen N Conneely; Rachel Edgar; Philip L De Jager; David A Bennett; Aliza P Wingo; Michael P Epstein; Thomas S Wingo Journal: Biol Psychiatry Date: 2021-02-03 Impact factor: 13.382
Authors: Orit H Lesman-Segev; Renaud La Joie; Leonardo Iaccarino; Iryna Lobach; Howard J Rosen; Sang Won Seo; Mustafa Janabi; Suzanne L Baker; Lauren Edwards; Julie Pham; John Olichney; Adam Boxer; Eric Huang; Marilu Gorno-Tempini; Charles DeCarli; Mackenzie Hepker; Ji-Hye L Hwang; Bruce L Miller; Salvatore Spina; Lea T Grinberg; William W Seeley; William J Jagust; Gil D Rabinovici Journal: Ann Neurol Date: 2020-12-07 Impact factor: 10.422
Authors: Leonardo Iaccarino; Renaud La Joie; Lauren Edwards; Amelia Strom; Daniel R Schonhaut; Rik Ossenkoppele; Julie Pham; Taylor Mellinger; Mustafa Janabi; Suzanne L Baker; David Soleimani-Meigooni; Howard J Rosen; Bruce L Miller; William J Jagust; Gil D Rabinovici Journal: Cereb Cortex Date: 2021-01-01 Impact factor: 5.357
Authors: Brittney L Blevins; Harry V Vinters; Seth Love; Donna M Wilcock; Lea T Grinberg; Julie A Schneider; Rajesh N Kalaria; Yuriko Katsumata; Brian T Gold; Danny J J Wang; Samantha J Ma; Lincoln M P Shade; David W Fardo; Anika M S Hartz; Gregory A Jicha; Karin B Nelson; Shino D Magaki; Frederick A Schmitt; Merilee A Teylan; Eseosa T Ighodaro; Panhavuth Phe; Erin L Abner; Matthew D Cykowski; Linda J Van Eldik; Peter T Nelson Journal: Acta Neuropathol Date: 2020-10-24 Impact factor: 17.088