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Higher fronto‐parietal metabolism parallels a greater impact of amyloid and anxiety on medial temporal areas in women versus men
Author(s) -
ArenazaUrquijo Eider M,
Salvadó Gemma,
MilàAlomà Marta,
Shekari Mahnaz,
SánchezBenavides Gonzalo,
Cacciaglia Raffaele,
Minguillón Carolina,
VilorTejedor Natalia,
CrousBou Marta,
GrauRivera Oriol,
SalaVila Aleix,
Eichenlaub Udo,
Kollmorgen Gwendlyn,
SuárezCalvet Marc,
Blennow Kaj,
Zetterberg Henrik,
Gispert Juan Domingo,
Molinuevo Jose Luis,
Study ALFA,
Consortium EPAD
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.044780
Subject(s) - anxiety , cohort , medicine , psychology , clinical psychology , psychiatry
Background The higher prevalence of anxiety‐related disorders in women, as well as the lower opportunities for higher education, may explain differences in brain resilience to AD pathologies. The objectives were to (1) test sex‐differences on brain metabolism and (2) evaluate whether the effects of amyloid, tau, education and anxiety on brain metabolism and structure differ by sex. Method We included a total of 1327 non‐demented participants, 235 cognitively unimpaired adults from the ALFA+ study (50‐74 years, 66% women) and 1092 non‐demented older adults from EPAD (50‐88 years, 57% women). Participants had available Aβ42 and p‐tau CSF biomarkers (Roche NeuroToolKit robust prototype assays and Elecsys®), anxiety assessments, FDG‐PET (ALFA+) or hippocampal volumes (EPAD). First, in ALFA+, we ran voxel‐wise multiple regression models to assess the effects of sex, and sex*amyloid, sex*p‐tau, sex*education and sex*anxiety interactions on FDG‐PET scans (adjusted by age). Second, in EPAD, we ran the same models with TIV‐adjusted hippocampal volumes as outcome measures. Result In the ALFA+ cohort, there were no sex‐differences in age (p=0.09), or CSF biomarkers (all p>0.7). Women showed lower education (p=0.001) and higher anxiety scores (p<0.001) than men. In the EPAD cohort, women were younger (p=0.003), lower educated p=0.003) and showed higher anxiety levels (p=0.002); men showed lower CSF Aβ42 levels (p=0.02). In voxel‐wise multiple regression analyses (ALFA+), women showed higher FDG‐PET uptake than men in medial fronto‐parietal regions, irrespective of their age, education, anxiety and CSF biomarkers levels (Fig1). There was a sex*Aβ and sex*anxiety interaction, such that with increasing Aβ deposition or anxiety levels, women showed lower metabolism in the parahippocampus and hippocampus than men (Fig2, 3). There was no sex*p‐tau or sex*education interaction. In the EPAD cohort, we did not observe any interactions. However, sex‐stratified analyses showed an association of CSF Aβ42, p‐tau and anxiety levels with lower hippocampal volumes in women but not men (Table 1, Fig4). Conclusion Our results suggest higher fronto‐parietal metabolism coupled with lower metabolic and structural resilience in medial temporal regions in women. The effects of anxiety and AD pathologies converged in memory‐related brain areas. Brain resilience mechanisms may differ between women and men.