CoChat
Sign Up
Cited by 161Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

Sex Differences in Cognitive Decline in Subjects with High Likelihood of Mild Cognitive Impairment due to Alzheimer’s disease

Open access
Sohn, Dongwha, Shpanskaya, Katie, Lucas, Joseph E., Petrella, Jeffrey R., Saykin, Andrew J., Tanzi, Rudolph E., Samatova, Nagiza F., Doraiswamy, P. Murali·2018·Scientific Reports
DOI 10.1038/s41598-018-25377-wPMC PMC5945611
Open this paper in CoChat — free accountOpen PDF

Abstract

Sex differences in Alzheimer’s disease (AD) biology and progression are not yet fully characterized. The goal of this study is to examine the effect of sex on cognitive progression in subjects with high likelihood of mild cognitive impairment (MCI) due to Alzheimer’s and followed up to 10 years in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cerebrospinal fluid total-tau and amyloid-beta (Aβ42) ratio values were used to sub-classify 559 MCI subjects (216 females, 343 males) as having “high” or “low” likelihood for MCI due to Alzheimer’s. Data were analyzed using mixed-effects models incorporating all follow-ups. The worsening from baseline in Alzheimer’s Disease Assessment Scale-Cognitive score (mean, SD) (9 ± 12) in subjects with high likelihood of MCI due to Alzheimer’s was markedly greater than that in subjects with low likelihood (1 ± 6, p < 0.0001). Among MCI due to AD subjects, the mean worsening in cognitive score was significantly greater in females (11.58 ± 14) than in males (6.87 ± 11, p = 0.006). Our findings highlight the need to further investigate these findings in other populations and develop sex specific timelines for Alzheimer’s disease progression.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1038/s41598-018-25377-w

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Females with MCI or AD dementia show greater cognitive decline and are outperformed by males in several cognitive domains.

    “Research has shown that females with MCI or AD dementia shows greater cognitive decline and are outperformed by males in several cognitive domains. 68 , 69”

    From Unraveling sex differences in Alzheimer's disease and related endophenotypes with brain proteomes (2025) · cites this paper as [68]

    The Results section reports significantly greater ADAS-Cog11 worsening in females than males with a high likelihood of MCI due to AD. The Introduction describes faster decline after MCI or AD onset as emerging evidence, but this study did not examine AD dementia. The Discussion says other cognitive domains still need examination, so it does not establish that males outperform females in several domains. Page numbers are unavailable in our copy. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

The citation lists haven’t been fetched yet

References 36 · Cited by 161

Research works printed but not linked: 26

  1. [1]Snyder HM Sex biology contributions to vulnerability to Alzheimer’s disease: A think tank convened by the Women’s Alzheimer’s Research Initiative Alzheimer’s Dement. 2016 12 1186 1196 10.1016/j.jalz.2016.08.004 27692800 PMC10341380 · DOI · Paper page
  2. [5]Mielke MM Vemuri P Rocca WA Clinical epidemiology of Alzheimer’s disease: assessing sex and gender differences J. Clin. Epidemiol. 2014 6 37 48 10.2147/CLEP.S37929 PMC3891487 24470773 · DOI · Paper page
  3. [6]Lin KA Doraiswamy PM When Mars versus Venus is not a cliche: gender differences in the neurobiology of Alzheimer’s disease Front. Neurol. 2014 5 288 10.3389/fneur.2014.00059 25628598 PMC4290582 · DOI
  4. [7]Beery AK Zucker I Sex bias in neuroscience and biomedical research Neurosci. Biobehav. Rev. 2011 35 565 572 10.1016/j.neubiorev.2010.07.002 20620164 PMC3008499 · DOI · Paper page
  5. [8]Seshadri S Lifetime risk of dementia and Alzheimer’s disease The impact of mortality on risk estimates in the Framingham Study Neurology 1997 49 1498 1504 10.1212/WNL.49.6.1498 9409336 · DOI · Paper page
  6. [9]Paganini-Hill A Henderson VW Estrogen deficiency and risk of Alzheimer’s disease in women Am. J. Epidemiol. 1994 140 256 261 10.1093/oxfordjournals.aje.a117244 8030628 · DOI
  7. [10]Finch CE Shams S Apolipoprotein E and sex bias in cerebrovascular aging of men and mice Trends Neurosci. 2016 39 625 637 10.1016/j.tins.2016.07.002 27546867 PMC5040339 · DOI
  8. [11]Bretsky P Evidence for an interaction between apolipoprotein E genotype, gender, and Alzheimer disease Alzheimer Dis. Assoc. Disord. 1999 13 216 221 10.1097/00002093-199910000-00007 10609670 · DOI
  9. [12]Altmann A Tian L Henderson VW Greicius MD Sex modifies the APOE‐related risk of developing Alzheimer disease Ann. Neurol. 2014 75 563 573 10.1002/ana.24135 24623176 PMC4117990 · DOI · Paper page
  10. [14]Lin KA Marked gender differences in progression of mild cognitive impairment over 8 years Alzheimer’s & dementia: translational research & clinical interventions 2015 1 103 110 PMC4593067 26451386
  11. [15]Barnes LL Sex differences in the clinical manifestations of Alzheimer disease pathology Arch. Gen. Psychiatry 2005 62 685 691 10.1001/archpsyc.62.6.685 15939846 · DOI · Paper page
  12. [16]Irvine K Laws KR Gale TM Kondel TK Greater cognitive deterioration in women than men with Alzheimer’s disease: a meta analysis J. Clin. Exp. Neuropsychol. 2012 34 989 998 10.1080/13803395.2012.712676 22913619 · DOI · Paper page
  13. [17]Maylor EA Gender and sexual orientation differences in cognition across adulthood: Age is kinder to women than to men regardless of sexual orientation Arc. Sex. Behav. 2007 36 235 249 10.1007/s10508-006-9155-y 17351741 · DOI
  14. [18]Roberts, R. O. et al. The incidence of MCI differs by subtype and is higher in men The Mayo Clinic Study of Aging. Neurology WNL. 0b013e3182452862 (2012). PMC3280046 22282647
  15. [19]Berchtold NC Gene expression changes in the course of normal brain aging are sexually dimorphic Proc. Natl. Acad. Sci. USA 2008 105 15605 15610 10.1073/pnas.0806883105 18832152 PMC2563070 · DOI · Paper page
  16. [20]Fleisher A Sex, apolipoprotein E ε4 status, and hippocampal volume in mild cognitive impairment Arch. Neurol. 2005 62 953 957 10.1001/archneur.62.6.953 15956166 · DOI
  17. [21]Skup M Sex differences in grey matter atrophy patterns among AD and aMCI patients: Results from ADNI Neuroimage 2011 56 890 906 10.1016/j.neuroimage.2011.02.060 21356315 PMC3085726 · DOI
  18. [23]Koran MEI Wagener M Hohman TJ Sex differences in the association between AD biomarkers and cognitive decline Brain Imaging Behav. 2017 11 205 213 10.1007/s11682-016-9523-8 26843008 PMC4972701 · DOI · Paper page
  19. [24]Weiner MW Impact of the Alzheimer’s disease neuroimaging initiative, 2004 to 2014 Alzheimer’s Dement. 2015 11 865 884 10.1016/j.jalz.2015.04.005 26194320 PMC4659407 · DOI
  20. [28]Saykin AJ Genetic studies of quantitative MCI and AD phenotypes in ADNI: Progress, opportunities, and plans Alzheimer’s Dement. 2015 11 792 814 10.1016/j.jalz.2015.05.009 26194313 PMC4510473 · DOI
  21. [29]Reuter M Schmansky NJ Rosas HD Fischl B Within-Subject Template Estimation for Unbiased Longitudinal Image Analysis Neuroimage 2012 61 4 1402 1418 10.1016/j.neuroimage.2012.02.084 22430496 PMC3389460 · DOI · Paper page
  22. [30]Lampert EJ Choudhury KR Hostage CA Petrella JR Doraiswamy PM Prevalence of Alzheimer’s pathologic endophenotypes in asymptomatic and mildly impaired first-degree relatives PLoS One 2013 8 e60747 10.1371/journal.pone.0060747 23613741 PMC3629168 · DOI
  23. [31]Li, X. et al. Ratio of Aβ42/P-tau181p in CSF is associated with aberrant default mode network in AD. Scientific reports3 (2013). PMC3581831 23439248
  24. [32]Ritchie, C. et al. CSF tau and the CSF tau/ABeta ratio for the diagnosis of Alzheimer’s disease dementia and other dementias in people with mild cognitive impairment (MCI). The Cochrane Library (2017). PMC6464349 28328043
  25. [33]Atluri G Complex biomarker discovery in neuroimaging data: Finding a needle in a haystack NeuroImage Clin. 2013 3 123 131 10.1016/j.nicl.2013.07.004 24179856 PMC3791294 · DOI
  26. [34]Rollo JL Unraveling the mechanistic complexity of Alzheimer’s disease through systems biology Alzheimer’s Dement. 2016 12 708 718 10.1016/j.jalz.2015.10.010 26703952 · DOI

Authors
Sohn, D., Shpanskaya, K., Lucas, J. E., Petrella, J. R., Saykin, A. J., Tanzi, R. E., Samatova, N. F., & Doraiswamy, P. M.
Affiliations
  • Oak Ridge National Laboratory (US)
  • Stanford Medicine (US)
  • Duke University (US)
  • Duke Medical Center (US)
  • Indiana University School of Medicine (US)
  • Harvard University (US)
Corresponding author
Doraiswamy, P. Murali
ORCID
Venue
Scientific Reports
Publisher
Springer Science and Business Media LLC
Published
2018-05-10
Volume
8
Issue
1
Pages
7490-7490
ISSN
2045-2322 (ISSN-L)
DOI
10.1038/s41598-018-25377-w
PMC
PMC5945611
OpenAlex
W2800992027
Cited by
161
References
36
Citations by year
2026: 10 · 2025: 24 · 2024: 18 · 2023: 18 · 2022: 33 · 2021: 30 · 2020: 18 · 2019: 7 · 2018: 3
FWCI
11.41
Type
journal article
Language
en
Open access
Licence
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • IUScholarWorks (Indiana University) (submittedVersion, cc-by)
Funders
  • U.S. Department of Defense (U01 AG024904, W81XWH, W81XWH-12-2-, W81XWH-12, W81XWH1220012, AG024904)
  • Foundation for the National Institutes of Health (W81XWH-12-2-0012, U01AG024904, Grant U01 AG024904, AG024904)
  • Alzheimer's Association (U01 AG024904, W81XWH-12-2-0012)
  • Bristol-Myers Squibb (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Eli Lilly and Company (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Pfizer (AG024904, W81XWH-12-2-0012, U01 AG024904)
  • Biogen (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • University of Southern California (W81XWH-12-2-0012, U01 AG024904)
  • F. Hoffmann-La Roche (W81XWH-12-2-0012, AG024904, U01 AG024904)
  • Meso Scale Diagnostics (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • Alzheimer's Disease Neuroimaging Initiative (W81XWH-12-2–0012, U01AG024904, AG024904, W81XWH-12-2-, Department of Defense award number W81XWH-12-2-0012)
  • Cure Alzheimer's Fund
  • BioClinica (U01 AG024904, W81XWH-12-2-0012, AG024904)
  • Novartis Pharmaceuticals Corporation (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • Northern California Institute for Research and Education (U01 AG024904, W81XWH-12-2-0012)
  • Eisai (W81XWH-12-2-0012, U01 AG024904, AG024904)
  • Servier (AG024904, W81XWH-12-2-0012, U01 AG024904)
  • H. Lundbeck A/S (U01 AG024904, AG024904, W81XWH-12-2-0012)
  • IXICO (AG024904, W81XWH-12-2-0012, U01 AG024904)
  • National Institutes of Health (3u01ag024904-10s2, W81XWH, W81XWH-12-2-0012, U01-AG024904, Grant U01 AG024904, AG024904)
  • Genentech (W81XWH-12-2-0012, AG024904, U01 AG024904)
  • Canadian Institutes of Health Research (U01 AG024904, W81XWH-12-2-0012)
  • National Institute on Aging (U01-AG-024904, W81XWH-12-2–0012, AG 024904, U01AG068057)
  • National Institute of Biomedical Imaging and Bioengineering (W81XWH-12-2-0012, U01 AG024904, AG024904)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords
sex differences, Alzheimer's disease, mild cognitive impairment, cognitive decline, cognitive progression, cerebrospinal fluid biomarkers, tau protein, amyloid-beta, Alzheimer's Disease Neuroimaging Initiative
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Cognition, Female, Humans, Longitudinal Studies, Male, Neuropsychological Tests, Retrospective Studies, Risk Factors, Sex Characteristics, Prevalence, Disease Progression, Neuroimaging, Cognitive Dysfunction

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review