Does the Female Advantage in Verbal Memory Contribute to Underestimating Alzheimer’s Disease Pathology in Women versus Men?

Article type: Research Article

Authors: Sundermann, Erin E.^{a; *} | Biegon, Anat^b | Rubin, Leah H.^c | Lipton, Richard B.^a | Landau, Susan^d | Maki, Pauline M.^c | for the Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA | [b] Department of Neurology, State University of New York, New York, NY, USA | [c] Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA | [d] Einstein Aging Study and the Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA | [e] Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA, USA

Correspondence: [*] Erin E. Sundermann, PhD, UCSD School of Medicine, 3350 La Jolla Village Dr. (151A), Building 13, Room 322, La Jolla, CA 92161, USA. Tel.: +1 858 552 8585 x7286; E-mail: esundermann@ucsd.edu.

Note: [1] Data used in this study were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.ucla.edu). Hence, with the exception of Susan Landau, investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or preparation of this manuscript. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: There is a growing recognition of sex differences in Alzheimer’s disease (AD). Females show an advantage over males on tests of verbal memory, which are used to diagnose AD and its precursor, amnestic mild cognitive impairment (aMCI). Women retain this advantage in aMCI despite reduced hippocampal volume and temporal lobe glucose metabolism. Here we examined whether this female advantage endures despite evidence of AD-specific pathology, cortical amyloid-β (Aβ) deposition measured with [18F]AV45 (florbetapir) positron emission tomography. Participants with normal cognition (N = 304), aMCI (N = 515), and AD dementia (N = 175) were drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Across and within diagnostic groups, we conducted linear regressions to examine the interaction of sex with cortical Aβ burden on immediate and delayed recall on the Rey Auditory Verbal Learning Test (RAVLT) adjusting for age, education, and APOE4. In the overall group, sex by cortical Aβ interaction was significant for delayed recall only. Overall, delayed recall performance was significantly better in women versus men among those with low to moderate Aβ burden, but women and men performed similarly among those with high Aβ burden. In diagnosis-stratified analyses, a significant sex by cortical Aβ interaction was observed for delayed recall in the aMCI group, but not in the normal or AD dementia groups. Thus, women maintain a verbal memory advantage over men in aMCI despite similar levels of AD pathology. Although this advantage may benefit women by delaying verbal memory impairment until more advanced pathology, it may also delay diagnosis of aMCI and treatment intervention.

Keywords: Amyloid, cognitive reserve, memory, positron-emission tomography, sex

DOI: 10.3233/JAD-160716

Journal: Journal of Alzheimer's Disease, vol. 56, no. 3, pp. 947-957, 2017