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Does brain volume explain the difference in Alzheimer’s disease diagnosis risk between men and women? Results from analyses of four research cohorts
Author(s) -
Stites Shana D.,
Dedhia Mehek
Publication year - 2021
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.054432
Subject(s) - dementia , brain size , neuroimaging , disease , medicine , alzheimer's disease , biomarker , gerontology , psychology , psychiatry , magnetic resonance imaging , biochemistry , chemistry , radiology
Background Women are more likely than men to be diagnosed Alzheimer’s disease (AD) despite recent biomarker studies demonstrating no significant difference in prevalence of AD pathology between men and women. Given that larger brain volume has been shown to be protective against progression of AD symptoms, we hypothesized that sex‐based differences in brain volume may modify the risk of AD dementia and thus explain the difference in AD diagnosis risk between males and females. Method We describe sex‐based differences in brain volume in a well‐characterized and socioculturally and clinically homogenous sample of older adults screening for a clinical trial. To test our hypotheses, we analyze cross‐sectional data from four distinct research cohorts: Rush Alzheimer’s Disease Research Center, Mayo Clinic Study of Aging, National Alzheimer’s Coordinating Center Uniform Data Set, Alzheimer’s Disease Neuroimaging Initiative. We use two‐stage general linear models with binomial family and log link to estimate risk of AD diagnosis attributable to self‐report sex and brain volume. In step two, an interaction‐term for sex and brain volume is entered to test how the main effect for self‐report sex changes. Multivariable models control for age and race. Results We will characterize sex‐based differences in brain volume in older adults using visual summaries, descriptive statistics, and estimates of effect. This information will be compared to other published estimates of sex‐based differences in brain volume. We expect that both self‐report sex and brain volume will show independent associations with AD diagnosis risk. However, in interaction analyses, brain volume will remain statistically significant while self‐report sex no longer shows an independent association with AD diagnosis risk. We will report model estimates from these analyses. Conclusion The study results will help elucidate brain volume’s role in contributing to sex‐based disparities in AD diagnosis. Results from analyses of four distinct data sources will lend strength to conclusions related to this novel hypothesis. They will also help advance knowledge about the character of sex‐based differences in cognitively typical older adults. Moreover, the results will help inform future research to elucidate AD mechanisms and discover drivers of sex‐based disparities in AD.