Evidence map›Paper›PMID 41540505›Full record

Observational studyBiology of sex differences2026

Sex differences in the relationship of biomarker change to memory decline in early Alzheimer's disease: an observational cohort study.

Erin E Sundermann, Sarah J Banks, Mark W Bondi, Maricedes Acosta Martinez, Anat Biegon, Lindsay J Rotblatt, Thomas Hildebrandt

Abstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Biology of sex differences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

7 authors.

Erin E SundermannDepartment of Psychiatry, University of California, 9500 Gilman Drive, San Diego, La JollaCA, Mail Code 8218, USA. esundermann@health.ucsd.edu.
Sarah J BanksDepartment of Neurosciences, University of California, 9500 Gilman Drive, San Diego, La JollaCA, Mail Code 0662, USA.
Mark W BondiDepartment of Psychiatry, University of California, 9500 Gilman Drive, San Diego, La JollaCA, Mail Code 8218, USA.
Maricedes Acosta MartinezDepartment of Physiology and Biophysics, Stonybrook University, 101 Nicolls Road, BST 5-180, Stony Brook, NY, USA.
Anat BiegonDepartment of Women's health, Uppsala University, Akademiska sjukhuset 751 85, Uppsala, Sweden.
Lindsay J RotblattDepartment of Psychiatry, University of California, 9500 Gilman Drive, San Diego, La JollaCA, Mail Code 8218, USA.
Thomas HildebrandtDepartment of Psychiatry, Mt. Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1230, NY, USA.

Funding

NIA NIH HHS 1R01AG074221
6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD) exhibits sex differences in pathology and cognitive trajectories. Understanding how these differences manifest across the Alzheimer's continuum can improve early detection, diagnostics, and interventions. We examined sex differences in the association between cerebrospinal fluid (CSF) pTau181/Aβ42 ratio changes and verbal memory decline across the preclinical and mild cognitive impairment (MCI) stages of AD.

methodsIn this retrospective, longitudinal, observational study, data were extracted from 401 participants (age range: 55-87.8, 98% non-Hispanic White) of the Alzheimer's Disease Neuroimaging Initiative cohort study who were classified as either preclinical AD (78 females, 73 males) or MCI (104 females, 146 males) at baseline and had CSF pTau181/Aβ42 ratio and cognitive assessment data at at-least two timepoints. Using regression models, we examined the relationship between changes in CSF pTau181/Aβ42 and verbal memory across all available time points and the moderating role of sex and AD stage over a mean follow-up period of 4 years. Verbal memory was represented by a composite z-score averaging Learning and Delayed Recall z-scores of the Rey Auditory Verbal Learning Test. Covariates included baseline age, education, and apolipoprotein E genotype.

resultsA significant sex * diagnostic group * biomarker change interaction (b=-17.47, 95%CI = 27.60 to -7.33, p = .001) indicated that sex differences in the relationship between changes in CSF pTau181/Aβ42 ratio and verbal memory differed by disease stage. While males in the preclinical AD stage showed steeper memory decline than females with increasing pTau181/Aβ42 ratios, this difference was not statistically significant. In contrast, in the MCI stage, a significant sex * biomarker change interaction (b = 10.17, 95% CI = 4.94 to 15.40, p < .001) indicated that females exhibited significantly steeper memory decline associated with increasing pTau181/Aβ42 ratios compared to males.

conclusionSex differences in the relationship between AD biomarker levels and cognitive decline vary by disease stage. Although not statistically significant, females demonstrated resilience to memory decline in the preclinical stage, whereas, in the MCI stage, they experienced significantly steeper memory loss compared to males. Results suggest that accounting for sex in biomarker-based methods of disease detection and tracking can improve early detection and intervention in both sexes.

Indexed as

Alzheimer DiseaseMemory DisordersSex FactorsAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersCognitive DysfunctionCohort StudiesFemaleHumansLongitudinal StudiesMaleMiddle AgedPeptide FragmentsRetrospective StudiesAmyloid beta-Peptidesamyloid beta-protein (1-42)BiomarkersPeptide Fragmentstau ProteinsAlzheimer’s diseaseAlzheimer’s pathologyClinical presentationCognitive reserveMild cognitive impairmentPreclinical alzheimer’s diseaseSex/genderVerbal memory

Identifiers

PMID41540505
PMCPMC12930658

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.