Women can bear a bigger burden: ante- and post-mortem evidence for reserve in the face of tau
Leonardino A. Digma, John Madsen, Robert A. Rissman, Diane M. Jacobs, James Brewer, Sarah J. Banks, Alzheimer’s Disease Neuroimaging Initiative, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William J. Jagust, John Q. Trojanowki, Arthur W Toga, Laurel Beckett, Robert C Green, Andrew J. Saykin, John C. Morris, Leslie M. Shaw, Enchi Liu, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Harvey, Michael Donohue, Matt A. Bernstein, Nick C. Fox, Paul M. Thompson, Norbert Schuff, Charles DeCarli, Bret Borowski, Jeff Gunter, Matthew L. Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, Nigel J. Cairns, Erin Householder, Lisa Taylor Reinwald, Virginia M.‐Y. Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Zaven Kachaturian, R.T. Frank, Peter J. Snyder, Susan Molchan, Jeffrey Kaye, Joseph F. Quinn, Betty Lind, Raina Carter, Sara Dolen, Lon S. Schneider, Sonia Pawluczyk, Mauricio Beccera, Liberty Teodoro, Bryan M. Spann, James Brewer, Helen Vanderswag, Adam Fleisher, Judith L. Heidebrink, Joanne Lord, Ronald Petersen, Sara S. Mason, Colleen S. Albers, David S. Knopman, Kris Johnson, Rachelle S. Doody, Javier Villanueva Meyer, Munir Chowdhury, Susan Rountree, Mimi Dang, Yaakov Stern, Lawrence S. Honig, Karen L. Bell, Beau M. Ances, John C. Morris, Maria Carroll, Sue Leon, Erin Householder, Mark A. Mintun, Stacy Schneider
Abstract
Abstract In this study, we aimed to assess whether women are able to withstand more tau before exhibiting verbal memory impairment. Using data from 121 amyloid-β-positive Alzheimer’s Disease Neuroimaging Initiative participants, we fit a linear model with Rey Auditory Verbal Learning Test score as the response variable and tau-PET standard uptake value ratio as the predictor and took the residuals as an estimate of verbal memory reserve for each subject. Women demonstrated higher reserve (i.e. residuals), whether the Learning (t = 2.78, P = 0.006) or Delay (t = 2.14, P = 0.03) score from the Rey Auditory Verbal Learning Test was used as a measure of verbal memory ability. To validate these findings, we examined 662 National Alzheimer’s Coordinating Center participants with a C2/C3 score (Consortium to Establish a Registry for Alzheimer’s Disease) at autopsy. We stratified our National Alzheimer’s Coordinating Center sample into Braak 1/2, Braak 3/4 and Braak 5/6 subgroups. Within each subgroup, we compared Logical Memory scores between men and women. Men had worse verbal memory scores within the Braak 1/2 (Logical Memory Immediate: β = −5.960 ± 1.517, P < 0.001, Logical Memory Delay: β = −5.703 ± 1.677, P = 0.002) and Braak 3/4 (Logical Memory Immediate: β = −2.900 ± 0.938, P = 0.002, Logical Memory Delay: β = −2.672 ± 0.955, P = 0.006) subgroups. There were no sex differences in Logical Memory performance within the Braak 5/6 subgroup (Logical Memory Immediate: β = −0.314 ± 0.328, P = 0.34, Logical Memory Delay: β = −0.195 ± 0.287, P = 0.50). Taken together, our results point to a sex-related verbal memory reserve.