TY - JOUR
T1 - Sex modifies effects of imaging and CSF biomarkers on cognitive and functional outcomes
T2 - a study of Alzheimer's disease
AU - for the Alzheimer's Disease Neuroimaging Initiative
AU - Lee, Brian N.
AU - Wang, Junwen
AU - Hall, Molly A.
AU - Kim, Dokyoon
AU - Stites, Shana D.
AU - Shen, Li
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2024/1
Y1 - 2024/1
N2 - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. Two of 3 patients with AD are biologically female; therefore, the biological underpinnings of this diagnosis disparity may inform interventions slowing the AD progression. To bridge this gap, we conducted analyses of 1078 male and female participants from the Alzheimer's Disease Neuroimaging Initiative to examine associations between levels of cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes. The Chow test was used to quantify sex differences by determining if biological sex affects relationships between the studied biomarkers and outcomes. Multiple magnetic resonance imaging (whole brain, entorhinal cortex, middle temporal gyrus, fusiform gyrus, hippocampus), position emission tomography (AV45), and CSF (P-TAU, TAU) biomarkers were differentially associated with cognitive and functional outcomes. Post-hoc bootstrapped and association analyses confirmed these differential effects and emphasized the necessity of using separate, sex-stratified models. The studied imaging/CSF biomarkers may account for some of the sex-based variation in AD pathophysiology. The identified sex-varying relationships between CSF/imaging biomarkers and cognitive/functional outcomes warrant future biological investigation in independent cohorts.
AB - Alzheimer's disease (AD) is a neurodegenerative disorder characterized by memory and functional impairments. Two of 3 patients with AD are biologically female; therefore, the biological underpinnings of this diagnosis disparity may inform interventions slowing the AD progression. To bridge this gap, we conducted analyses of 1078 male and female participants from the Alzheimer's Disease Neuroimaging Initiative to examine associations between levels of cerebral spinal fluid (CSF)/neuroimaging biomarkers and cognitive/functional outcomes. The Chow test was used to quantify sex differences by determining if biological sex affects relationships between the studied biomarkers and outcomes. Multiple magnetic resonance imaging (whole brain, entorhinal cortex, middle temporal gyrus, fusiform gyrus, hippocampus), position emission tomography (AV45), and CSF (P-TAU, TAU) biomarkers were differentially associated with cognitive and functional outcomes. Post-hoc bootstrapped and association analyses confirmed these differential effects and emphasized the necessity of using separate, sex-stratified models. The studied imaging/CSF biomarkers may account for some of the sex-based variation in AD pathophysiology. The identified sex-varying relationships between CSF/imaging biomarkers and cognitive/functional outcomes warrant future biological investigation in independent cohorts.
KW - Alzheimer's disease
KW - Brain imaging
KW - Cerebral spinal fluid (CSF) biomarker
KW - Cognitive and functional outcome
KW - Sex-based disparity
UR - http://www.scopus.com/inward/record.url?scp=85175292560&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85175292560&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2023.10.002
DO - 10.1016/j.neurobiolaging.2023.10.002
M3 - Article
C2 - 37913627
AN - SCOPUS:85175292560
SN - 0197-4580
VL - 133
SP - 67
EP - 77
JO - Neurobiology of aging
JF - Neurobiology of aging
ER -