Doing more with less: Women's higher brain metabolic rate compensates for early Alzheimer's pathological changes: Reserve and resilience: Opportunities and mechanisms for dementia prevention. (7th December 2020)

• Record Type: Journal Article
• Authors: Sundermann, Erin E; Maki, Pauline M; Reddy, Sarah; Bondi, Mark W; Biegon, Anat
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 10
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.037933
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Cognitively normal women have consistently shown higher brain glucose metabolism than men across the adult life span in key Alzheimer's disease (AD) related regions. The goal of our work was to examine whether these sex differences provide resilience to the effect of AD pathologies on cognition. Method: 1259 participants (44% women; aged 55‐90) from the Alzheimer's Disease Neuroimaging Initiative completed the Mini Mental Status Exam (MMSE), the Clinical Dementia Rating‐Sum of Boxes (CDR‐SOB) and neuroimaging assessments of glucose metabolism (FDG‐PET) in regions of interest (posterior cingulate, angular gyrus, inferior/middle temporal gyrus), brain volumes (T1 MRI) and cortical amyloid‐β burden (AV45‐PET). First, we examined whether sex moderates the relationship between brain glucose metabolism in the grey matter and whole brain gray matter volume (WBV) in the overall sample and within cognitively normal (CN), amnestic mild cognitive impairment (aMCI) and AD diagnostic groups. Second, we divided the AD pathological markers of cortical amyloid‐β burden and hippocampal volume (HV) into quartiles and examined sex differences in MMSE and CDR‐SOB scores within biomarker quartiles before and after adjusting for brain metabolism and the covariates of age, education, APOE4 and WBV. Result: In the overall sample and within aMCI, metabolism was higher in women versus men per unit of WBV when WBV was moderate/large but showed a steeper decrease as WBV diminished. Women showed better MMSE and CDR‐SOB scores than men ( p s<.05) at mild/moderate levels of AD brain pathology (quartiles 1‐3), particularly after adjustment for sex differences in brain volume. In contrast, men and women showed similarly poor MMSE and CDR‐SOB scores within the highest quartile of severe AD brain pathology ( p s>.05). The female cognitive advantage at mild/moderate quartiles of AD pathological markers was eliminated or markedly attenuated (41‐94%) after adjusting for brain metabolism Conclusion: More efficient neural function in women versus men may provide women greater resilience against the effects of early AD pathological changes and serve as a mechanism underlying better clinical profiles in women in early disease process and faster decline thereafter. These sex‐based mechanistic differences will have important implications for disease identification and treatment.