Evidence map›Paper›PMID 36314203›Full record

ArticleJournal of Alzheimer's disease : JAD2022

Sex Modifies the Associations of APOEɛ4 with Neuropsychiatric Symptom Burden in Both At-Risk and Clinical Cohorts of Alzheimer's Disease.

Andrew S Dissanayake, Yu Bin Tan, Christopher R Bowie, Meryl A Butters, Alastair J Flint, Damien Gallagher, Angela C Golas, Nathan Herrmann, Zahinoor Ismail, James L Kennedy and 14 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

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

4 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Updates and future perspectives on neuropsychiatric symptoms in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
    Review
  3. Review
  4. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

24 authors at 4 institutions in 2 countries.

Andrew S DissanayakeKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
Yu Bin TanKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
Christopher R BowieCentre for Addiction and Mental Health, Toronto, ON, Canada.
Meryl A ButtersUniversity of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
Alastair J FlintCentre for Mental Health, University Health Network, Toronto, ON, Canada.
Damien GallagherDepartment of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Angela C GolasCentre for Addiction and Mental Health, Toronto, ON, Canada.
Nathan HerrmannDepartment of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Zahinoor IsmailDepartment of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
James L KennedyCentre for Addiction and Mental Health, Toronto, ON, Canada.
Sanjeev KumarCentre for Addiction and Mental Health, Toronto, ON, Canada.
Krista L LanctotDepartment of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Linda MahDepartment of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Benoit H MulsantCentre for Addiction and Mental Health, Toronto, ON, Canada.
Bruce G PollockDepartment of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Tarek K RajjiCentre for Addiction and Mental Health, Toronto, ON, Canada.
Michael TauKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
Anika MarajDepartment of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Nathan W ChurchillKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
Debby TsuangGRECC, VA Puget Sound and Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Tom A SchweizerKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
David G MunozKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
Corinne E FischerKeenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
PACt-MD Study Group
St. Michael's Hospital · CACentre for Addiction and Mental Health · CASunnybrook Health Science Centre · CAUniversity Health Network · CA

Funding

NATIONAL ALZHEIMERS COORDINATING CENTER (NACC)U01AG016976 · NIA · UNIVERSITY OF WASHINGTON · PI KUKULL, WALTER ANTHONY · 1999 to 2020
$72.8M
THERAPEUTIC EFFECTS OF INTRA-NASAL INSULIN DETEMIRP50AG005136 · NIA · UNIVERSITY OF WASHINGTON · PI JAYADEY, SUMAN · 1985 to 2019
$57.2M
VIRUS-INDUCED BRAIN PATHOLOGYP50AG005131 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BREWER, JAMES B · 1985 to 2018
$55.4M
WASHINGTON UNIVERSITY ALZHEIMERS DISEASE RESEARCH CENTERP50AG005681 · NIA · WASHINGTON UNIVERSITY · PI MORRIS, JOHN · 1985 to 2019
$52.1M
SUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1M
Satellite Diagnostic and Treatment Clinic CoreP50AG008702 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI DE JAGER, PHILIP L · 1989 to 2019
$46.3M
TREATMENT OF DEPRESSION IN ALZHEIMER'S DISEASEP50AG005133 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BECKER, JAMES T. · 1985 to 2019
$43.0M
THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1M
VASCULAR RISK AND COGNITIVE STATUS IN A LATINO POPULATIONP50AG005142 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI ARANDA, MARIA P. · 1985 to 2019
$41.0M
VESICULAR LOCALIZATION AND FUNCTION OF PRESENILIN 1 FRAGMENTP50AG005138 · NIA · MOUNT SINAI SCHOOL OF MEDICINE OF NYU · PI SCHIMMING, CORBETT · 1985 to 2019
$37.9M
'T V ASSESSMENT - MEMORY DISORDERED PATIENTS'P50AG005146 · NIA · JOHNS HOPKINS UNIVERSITY · PI HUGANIR, RICHARD L · 1985 to 2019
$37.6M
Research Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI SAYKIN, ANDREW J · 1991 to 2020
$37.3M
NIA NIH HHS P30 AG008017NIA NIH HHS P30 AG008051NIA NIH HHS P30 AG010124NIA NIH HHS P30 AG010129NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG012300NIA NIH HHS P30 AG013846NIA NIH HHS P30 AG013854NIA NIH HHS P30 AG019610NIA NIH HHS P30 AG028383NIA NIH HHS P30 AG035982NIA NIH HHS P30 AG049638NIA NIH HHS P30 AG053760NIA NIH HHS P50 AG005131NIA NIH HHS P50 AG005133NIA NIH HHS P50 AG005134NIA NIH HHS P50 AG005136NIA NIH HHS P50 AG005138NIA NIH HHS P50 AG005142NIA NIH HHS P50 AG005146NIA NIH HHS P50 AG005681NIA NIH HHS P50 AG008702NIA NIH HHS P50 AG016573NIA NIH HHS P50 AG016574NIA NIH HHS P50 AG023501NIA NIH HHS P50 AG025688NIA NIH HHS P50 AG033514NIA NIH HHS P50 AG047266NIA NIH HHS P50 AG047270NIA NIH HHS P50 AG047366NIA NIH HHS U01 AG016976
6 · The paper itself

Abstract

backgroundRecent work suggests that APOEɛ4/4 females with Alzheimer's disease (AD) are more susceptible to developing neuropsychiatric symptoms (NPS).

objectiveTo examine the interaction of sex and APOEɛ4 status on NPS burden using two independent cohorts: 1) patients at risk for AD with mild cognitive impairment and/or major depressive disorder (n = 252) and 2) patients with probable AD (n = 7,261).

methodsRegression models examined the interactive effects of sex and APOEɛ4 on the number of NPS experienced and NPS Severity. APOEɛ3/4 and APOEɛ4/4 were pooled in the at-risk cohort due to the sample size.

resultsIn the at-risk cohort, there was a significant sex*APOEɛ4 interaction (p = 0.007) such that the association of APOEɛ4 with NPS was greater in females than in males (incident rate ratio (IRR) = 2.0). APOEɛ4/4 females had the most NPS (mean = 1.9) and the highest severity scores (mean = 3.5) of any subgroup. In the clinical cohort, APOEɛ4/4 females had significantly more NPS (IRR = 1.1, p = 0.001, mean = 3.1) and higher severity scores (b = 0.31, p = 0.015, mean = 3.7) than APOEɛ3/3 females (meanNPS = 2.9, meanSeverity = 3.3). No association was found in males.

conclusionOur study suggests that sex modifies the association of APOEɛ4 on NPS burden. APOEɛ4/4 females may be particularly susceptible to increased NPS burden among individuals with AD and among individuals at risk for AD. Further investigation into the mechanisms behind these associations are needed.

Indexed as

Alzheimer DiseaseCognitive DysfunctionMajor Depressive DisorderFemaleHumansMaleNeuropsychological TestsAlzheimer’s diseaseAPOE4behavioral and psychological symptoms of dementiabiomarkersgender differencesmajor depressive disordermild cognitive impairmentNeuropsychiatric Inventory Questionnaireneuropsychiatrypsychosis

Identifiers

PMID36314203
PMCPMC13682163
OpenAlexW4307622874

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.