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This dataset contains the sex stratified and interaction summary statistics memory and memory slopes published in Eissman, et al, 2022 (Brain, PMID: 35552371). Cognitive and pathology data were harmonized across two datasets with autopsy measures of amyloid (ROS/MAP and ACT) and two datasets with amyloid PET (A4 and ADNI). Resilience phenotypes were calculated using a latent variable modeling approach, modeling better than expected cognition for a given level of amyloid pathology. Cognitive resilience took into account amyloid levels, age, and sex. Global cognitive resilience further incorporated education into the residual cognitive resilience. Genotype data in each study underwent standard quality control and imputation onto the TOPMed reference panel (genome build 38). GWAS on both resilience phenotypes were performed including all samples as well as subsetted to only cognitively normal samples to evaluate resilience at the preclinical stage of disease.

All GWAS described were performed in males, in females, and with a sex-interaction and were run in the combined autopsy dataset and in the combined PET dataset for all resilience phenotypes. Sex-stratified GWAS covaried for age and the first three genetic principal components. The sex-interaction GWAS also covaried for sex and included a single nucleotide polymorphism (SNP) × sex interaction term. GWAS results were then meta-analysed across cohorts using a fixed-effects model with beta and standard error input (GWAMA v2.2.2). The above models were also run identically in the sample restricted to cognitively normal individuals, with the fixed effects meta-analyses implementing the minor allele frequencies calculated based on these individuals only. Additionally, an identical GWAS and meta-analysis pipeline as described above was implemented with the X-chromosome genetic data for the sex-stratified models. All meta-analysis results were restricted to SNPs present in both the autopsy and the PET dataset.

Available Filesets

NameAccessionLatest ReleaseDescription
Sex Differences Resilience: Full Summary Statistics (application needed)fsa000095NG00161.v1Full Summary Statistics
Sex Differences Resilience: P-values only (open access)fsa000096NG00161.v1P-values only

View the File Manifest for a full list of files released in this dataset.

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Acknowledgment statement for any data distributed by NIAGADS:

Data for this study were prepared, archived, and distributed by the National Institute on Aging Alzheimer’s Disease Data Storage Site (NIAGADS) at the University of Pennsylvania (U24-AG041689), funded by the National Institute on Aging.

Use the study-specific acknowledgement statements below (as applicable):

For investigators using any data from this dataset:

Please cite/reference the use of NIAGADS data by including the accession NG00161.

For investigators using Sex differences in the genetic architecture of cognitive resilience to Alzheimer's disease – Eissman, et al. 2022 (sa000045) data:

This research was supported in part by K01-AG049164, R01-AG059716, R21-AG05994, K12-HD043483, K24-AG046373, HHSN311201600276P, S10-OD023680, R01-AG034962, R01-NS100980, R01-AG056534, P30-AG010161, P30-AG072975, R01-AG057914, R01-AG015819, R01-AG017917, R13-AG030995, U01-AG061356, U01-AG006781, U19-AG066567, K99/R00-AG061238, U01-AG046152, U01-AG068057, UL1-TR000445, T32-GM080178, R01-AG073439, U24-AG074855, P20-AG068082 (Vanderbilt Alzheimer’s Disease Research Center), and the Vanderbilt Memory & Alzheimer’s Center. Data collection was supported through funding by NIA grants P50-AG016574, P50-AG005136, R01-AG032990, U01-AG046139, R01-AG018023, U01-AG006576, U01-AG006781, U01-AG006786, R01-AG025711, R01-AG017216, R01-AG003949, P30-AG019610, U01-AG024904, U01-AG032984, U24-AG041689, R01-AG046171, RF1-AG051550, 3U01-AG024904-09S4, NINDS grant R01-NS080820, CurePSP Foundation, and support from Mayo Foundation.

The Brain and Body Donation Program is supported by the National Institute of Neurological Disorders and Stroke (U24-NS072026 National Brain and Tissue Resource for Parkinson’s Disease and Related Disorders), the National Institute on Aging (P30-AG019610 Arizona Alzheimer’s Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer’s Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson's Disease Consortium) and the Michael J. Fox Foundation for Parkinson’s Research. Data were generated as part of the CommonMind Consortium supported by funding from Takeda Pharmaceuticals Company Limited, F. Hoffman-La Roche Ltd and NIH grants R01-MH085542, R01-MH093725, R01-AG074012, P50-MH066392, P50-MH080405, R01-MH097276, R01-MH075916, P50-M096891, P50-MH084053S1, R37-MH057881, AG02219, AG05138, MH06692, R01-MH110921, R01-MH109677, R01-MH109897, U01-MH103392, and contract HHSN271201300031C through IRP NIMH. Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01-AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer's Association; Alzheimer's Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc; Biogen Inc Cambridge, MA 02139, provided support for genotyping of the A4 Study cohort; Bristol-Myers Squibb Company; CereSpir, Inc; Cogstate; Eisai Inc; Elan Pharmaceuticals, Inc; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC; Johnson & Johnson Pharmaceutical Research & Development LLC; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( Additional data collection and sharing for this project was funded by the Alzheimer's Disease Metabolomics Consortium (National Institute on Aging R01-AG046171, RF1-AG051550 and 3U01-AG024904-09S4).

Eissman, J.M., et al. Sex differences in the genetic architecture of cognitive resilience to Alzheimer’s disease. Brain. 2022 Jul. doi: 10.1093/brain/awac177 PubMed link