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Assessment of Demographic, Genetic, and Imaging Variables Associated With Brain Resilience and Cognitive Resilience to Pathological Tau in Patients With Alzheimer Disease.


ABSTRACT: Importance:Better understanding is needed of the degree to which individuals tolerate Alzheimer disease (AD)-like pathological tau with respect to brain structure (brain resilience) and cognition (cognitive resilience). Objective:To examine the demographic (age, sex, and educational level), genetic (APOE-?4 status), and neuroimaging (white matter hyperintensities and cortical thickness) factors associated with interindividual differences in brain and cognitive resilience to tau positron emission tomography (PET) load and to changes in global cognition over time. Design, Setting, an Participants:In this cross-sectional, longitudinal study, tau PET was performed from June 1, 2014, to November 30, 2017, and global cognition monitored for a mean [SD] interval of 2.0 [1.8] years at 3 dementia centers in South Korea, Sweden, and the United States. The study included amyloid-?-positive participants with mild cognitive impairment or AD dementia. Data analysis was performed from October 26, 2018, to December 11, 2019. Exposures:Standard dementia screening, cognitive testing, brain magnetic resonance imaging, amyloid-? PET and cerebrospinal fluid analysis, and flortaucipir (tau) labeled with fluor-18 (18F) PET. Main Outcomes and Measures:Separate linear regression models were performed between whole cortex [18F]flortaucipir uptake and cortical thickness, and standardized residuals were used to obtain a measure of brain resilience. The same procedure was performed for whole cortex [18F]flortaucipir uptake vs Mini-Mental State Examination (MMSE) as a measure of cognitive resilience. Bivariate and multivariable linear regression models were conducted with age, sex, educational level, APOE-?4 status, white matter hyperintensity volumes, and cortical thickness as independent variables and brain and cognitive resilience measures as dependent variables. Linear mixed models were performed to examine whether changes in MMSE scores over time differed as a function of a combined brain and cognitive resilience variable. Results:A total of 260 participants (145 [55.8%] female; mean [SD] age, 69.2 [9.5] years; mean [SD] MMSE score, 21.9?[5.5]) were included in the study. In multivariable models, women (standardized ??=?-0.15, P?=?.02) and young patients (standardized ??=?-0.20, P?=?.006) had greater brain resilience to pathological tau. Higher educational level (standardized ??=?0.23, P?

SUBMITTER: Ossenkoppele R 

PROVIDER: S-EPMC7042808 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Assessment of Demographic, Genetic, and Imaging Variables Associated With Brain Resilience and Cognitive Resilience to Pathological Tau in Patients With Alzheimer Disease.

Ossenkoppele Rik R   Lyoo Chul Hyoung CH   Jester-Broms Jonas J   Sudre Carole H CH   Cho Hanna H   Ryu Young Hoon YH   Choi Jae Yong JY   Smith Ruben R   Strandberg Olof O   Palmqvist Sebastian S   Kramer Joel J   Boxer Adam L AL   Gorno-Tempini Maria L ML   Miller Bruce L BL   La Joie Renaud R   Rabinovici Gil D GD   Hansson Oskar O  

JAMA neurology 20200501 5


<h4>Importance</h4>Better understanding is needed of the degree to which individuals tolerate Alzheimer disease (AD)-like pathological tau with respect to brain structure (brain resilience) and cognition (cognitive resilience).<h4>Objective</h4>To examine the demographic (age, sex, and educational level), genetic (APOE-ε4 status), and neuroimaging (white matter hyperintensities and cortical thickness) factors associated with interindividual differences in brain and cognitive resilience to tau po  ...[more]

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