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

Male Female Humans Alzheimer Disease / diagnosis Depressive Disorder, Major / genetics Cognitive Dysfunction / diagnosis Neuropsychological Tests
APOE4 Alzheimer’s disease Neuropsychiatric Inventory Questionnaire behavioral and psychological symptoms of dementia biomarkers gender differences major depressive disorder mild cognitive impairment neuropsychiatry psychosis

Journal

Journal of Alzheimer's disease : JAD
ISSN: 1875-8908
Titre abrégé: J Alzheimers Dis
Pays: Netherlands
ID NLM: 9814863

Informations de publication

Date de publication:
2022
Historique:
pubmed: 1 11 2022
medline: 15 12 2022
entrez: 31 10 2022
Statut: ppublish

Résumé

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

Sections du résumé

BACKGROUND
Recent work suggests that APOEɛ4/4 females with Alzheimer's disease (AD) are more susceptible to developing neuropsychiatric symptoms (NPS).
OBJECTIVE
To 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).
METHODS
Regression 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.
RESULTS
In 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.
CONCLUSION
Our 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.

Identifiants

DOI: 10.3233/JAD-220586 PMID: 36314203
pubmed: 36314203
pii: JAD220586
doi: 10.3233/JAD-220586
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1571-1588

Subventions

Organisme : NIA NIH HHS
ID : P50 AG016574
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG049638
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG016573
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005133
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005146
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047266
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG019610
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010161
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG035982
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005134
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010129
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG053760
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010124
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG033514
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG010133
Pays : United States
Organisme : NIA NIH HHS
ID : U01 AG016976
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005136
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG012300
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG008051
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG023501
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005681
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG028383
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG008702
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047270
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005138
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005131
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005142
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG008017
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG047366
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013854
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG025688
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG013846
Pays : United States

Auteurs

Andrew S Dissanayake (AS)

Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.

Yu Bin Tan (YB)

Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.

Christopher R Bowie (CR)

Centre for Addiction and Mental Health, Toronto, ON, Canada.
Queen's University, Kingston, ON, Canada.

Meryl A Butters (MA)

University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.

Alastair J Flint (AJ)

Centre for Mental Health, University Health Network, Toronto, ON, Canada.
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Damien Gallagher (D)

Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Neuropsychopharmacology Research Group, Sunnybrook Research Institute, Toronto, ON, Canada.

Angela C Golas (AC)

Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Nathan Herrmann (N)

Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Zahinoor Ismail (Z)

Department of Psychiatry, Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.

James L Kennedy (JL)

Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Sanjeev Kumar (S)

Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Krista L Lanctot (KL)

Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Sunnybrook Health Sciences Centre, Toronto, ON, Canada.
Neuropsychopharmacology Research Group, Sunnybrook Research Institute, Toronto, ON, Canada.

Linda Mah (L)

Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Rotman Research Institute, Baycrest Health Science Centre, Toronto, ON, Canada.

Benoit H Mulsant (BH)

Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Bruce G Pollock (BG)

Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Campbell Family Mental Health Research Institute, Division of Geriatric Psychiatry, Centre for Addiction and Mental Health, Toronto, ON, Canada.
Toronto Dementia Research Alliance, University of Toronto, Toronto, ON, Canada.

Tarek K Rajji (TK)

Centre for Addiction and Mental Health, Toronto, ON, Canada.
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Toronto Dementia Research Alliance, University of Toronto, Toronto, ON, Canada.

Michael Tau (M)

Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Unity Health, St. Michaels Hospital, University of Toronto, Toronto, Ontario, Canada.

Anika Maraj (A)

Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Unity Health, St. Michaels Hospital, University of Toronto, Toronto, Ontario, Canada.

Nathan W Churchill (NW)

Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
Unity Health, St. Michaels Hospital, University of Toronto, Toronto, Ontario, Canada.

Debby Tsuang (D)

GRECC, VA Puget Sound and Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.

Tom A Schweizer (TA)

Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
Unity Health, St. Michaels Hospital, University of Toronto, Toronto, Ontario, Canada.

David G Munoz (DG)

Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
Unity Health, St. Michaels Hospital, University of Toronto, Toronto, Ontario, Canada.

Corinne E Fischer (CE)

Keenan Research Centre for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada.
Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Unity Health, St. Michaels Hospital, University of Toronto, Toronto, Ontario, Canada.

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