Gender Differences in Alzheimer Disease: Brain Atrophy, Histopathology Burden, and Cognition.
Multiple studies suggest that females are affected by Alzheimer disease (AD) more severely and more frequently than males. Other studies have failed to confirm this and the issue remains controversial. Difficulties include differences in study methods and male versus female life expectancy. Another element of uncertainty is that the majority of studies have lacked neuropathological confirmation of the AD diagnosis. We compared clinical and pathological AD severity in 1028 deceased subjects with full neuropathological examinations. The age of dementia onset did not differ by gender but females were more likely to proceed to very severe clinical and pathological disease, with significantly higher proportions having a Mini-Mental State Examination score of 5 or less and Braak stage VI neurofibrillary degeneration. Median neuritic plaque densities were similar in females and males with AD but females had significantly greater tangle density scores. In addition, we found that AD-control brain weight differences were significantly greater for females, even after adjustment for age, disease duration, and comorbid conditions. These findings suggest that when they are affected by AD, females progress more often to severe cognitive dysfunction, due to more severe neurofibrillary degeneration, and greater loss of brain parenchyma.
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Jessica R
JR
Filon
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Anthony J
AJ
Intorcia
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Lucia I
LI
Sue
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Elsa
E
Vazquez Arreola
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Jeffrey
J
Wilson
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Kathryn J
KJ
Davis
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Marwan N
MN
Sabbagh
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Christine M
CM
Belden
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Richard J
RJ
Caselli
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Charles H
CH
Adler
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Bryan K
BK
Woodruff
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Steven Z
SZ
Rapscak
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Geoffrey L
GL
Ahern
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Anna D
AD
Burke
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Sandra
S
Jacobson
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Holly A
HA
Shill
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Erika
E
Driver-Dunckley
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Kewei
K
Chen
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Eric M
EM
Reiman
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR).
Thomas G
TG
Beach
From the Banner Sun Health Research Institute, Sun City, Arizona (JRF, AJI, LIS, KJD, CMB, SJ, TGB, GES);Department of Economics, Arizona State University, Tempe, Arizona (EVA, JW);Neurological Institute, Phoenix, Arizona (MNS);Mayo Clinic Arizona, Scottsdale, Arizona (RJC, CHA, BKW, ED-D);Department of Neurology, University of Arizona, Tucson, Arizona (SZR, GLA);Banner Alzheimer Institute, Phoenix, Arizona (ADB, KC, EMR). Geidy.Serrano@bannerhealth.com.
Geidy E
GE
Serrano
Amyloid plaque; Brain weight; Cognition; Neuritic plaque; Neurofibrillary tangle; Phosphorylated tau