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Apathy and APOE in mild behavioral impairment, and risk for incident dementia

INTRODUCTION: Mild behavioral impairment (MBI) is a high‐risk state for incident dementia and comprises five core domains including affective dysregulation, impulse dyscontrol, social inappropriateness, psychotic symptoms, and apathy. Apathy is among the most common neuropsychiatric symptoms (NPS) i...

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Autores principales: Vellone, Daniella, Ghahremani, Maryam, Goodarzi, Zahra, Forkert, Nils D., Smith, Eric E., Ismail, Zahinoor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763783/
https://www.ncbi.nlm.nih.gov/pubmed/36544988
http://dx.doi.org/10.1002/trc2.12370
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author Vellone, Daniella
Ghahremani, Maryam
Goodarzi, Zahra
Forkert, Nils D.
Smith, Eric E.
Ismail, Zahinoor
author_facet Vellone, Daniella
Ghahremani, Maryam
Goodarzi, Zahra
Forkert, Nils D.
Smith, Eric E.
Ismail, Zahinoor
author_sort Vellone, Daniella
collection PubMed
description INTRODUCTION: Mild behavioral impairment (MBI) is a high‐risk state for incident dementia and comprises five core domains including affective dysregulation, impulse dyscontrol, social inappropriateness, psychotic symptoms, and apathy. Apathy is among the most common neuropsychiatric symptoms (NPS) in dementia but can also develop in persons with normal cognition (NC) or mild cognitive impairment (MCI). The later‐life emergence and persistence of apathy as part of the MBI syndrome may be a driving factor for dementia risk. Therefore, we investigated MBI‐apathy–associated progression to dementia, and effect modification by sex, race, cognitive diagnosis, and apolipoprotein E (APOE) genotype. METHODS: Dementia‐free National Alzheimer's Coordinating Center participants were stratified by persistent apathy status, based on Neuropsychiatric Inventory (NPI)–Questionnaire scores at two consecutive visits. Hazard ratios (HRs) for incident dementia for MBI‐apathy and NPI‐apathy relative to no NPS, and MBI‐apathy relative to no apathy, were determined using Cox proportional hazards regressions, adjusted for baseline age, sex, years of education, race, cognitive diagnosis, and APOE genotype. Interactions with relevant model covariates were explored. RESULTS: Of the 3932 participants (3247 with NC), 354 had MBI‐apathy. Of all analytic groups, MBI‐apathy had the greatest dementia incidence (HR = 2.69, 95% confidence interval [CI]: 2.15–3.36, P < 0.001). Interaction effects were observed between cognitive diagnosis and APOE genotype with the NPS group. The contribution of apathy to dementia risk was greater in NC (HR = 5.91, 95% CI: 3.91–8.93) than in MCI (HR = 2.16, 95% CI: 1.69–2.77, interaction P < 0.001) and in all APOE genotypes, was greatest in APOE ɛ3 (HR = 4.25, 95% CI: 3.1–5.82, interaction P < 0.001). DISCUSSION: Individuals with MBI‐apathy have a markedly elevated risk for future dementia, especially when symptoms emerge in those with NC. Both cognitive status and APOE genotype are important moderators in the relationship between MBI‐apathy and incident dementia. MBI‐apathy may represent a group in whom apathy is a preclinical or prodromal manifestation of dementia and identify a precision medicine target for preventative interventions.
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spelling pubmed-97637832022-12-20 Apathy and APOE in mild behavioral impairment, and risk for incident dementia Vellone, Daniella Ghahremani, Maryam Goodarzi, Zahra Forkert, Nils D. Smith, Eric E. Ismail, Zahinoor Alzheimers Dement (N Y) Research Articles INTRODUCTION: Mild behavioral impairment (MBI) is a high‐risk state for incident dementia and comprises five core domains including affective dysregulation, impulse dyscontrol, social inappropriateness, psychotic symptoms, and apathy. Apathy is among the most common neuropsychiatric symptoms (NPS) in dementia but can also develop in persons with normal cognition (NC) or mild cognitive impairment (MCI). The later‐life emergence and persistence of apathy as part of the MBI syndrome may be a driving factor for dementia risk. Therefore, we investigated MBI‐apathy–associated progression to dementia, and effect modification by sex, race, cognitive diagnosis, and apolipoprotein E (APOE) genotype. METHODS: Dementia‐free National Alzheimer's Coordinating Center participants were stratified by persistent apathy status, based on Neuropsychiatric Inventory (NPI)–Questionnaire scores at two consecutive visits. Hazard ratios (HRs) for incident dementia for MBI‐apathy and NPI‐apathy relative to no NPS, and MBI‐apathy relative to no apathy, were determined using Cox proportional hazards regressions, adjusted for baseline age, sex, years of education, race, cognitive diagnosis, and APOE genotype. Interactions with relevant model covariates were explored. RESULTS: Of the 3932 participants (3247 with NC), 354 had MBI‐apathy. Of all analytic groups, MBI‐apathy had the greatest dementia incidence (HR = 2.69, 95% confidence interval [CI]: 2.15–3.36, P < 0.001). Interaction effects were observed between cognitive diagnosis and APOE genotype with the NPS group. The contribution of apathy to dementia risk was greater in NC (HR = 5.91, 95% CI: 3.91–8.93) than in MCI (HR = 2.16, 95% CI: 1.69–2.77, interaction P < 0.001) and in all APOE genotypes, was greatest in APOE ɛ3 (HR = 4.25, 95% CI: 3.1–5.82, interaction P < 0.001). DISCUSSION: Individuals with MBI‐apathy have a markedly elevated risk for future dementia, especially when symptoms emerge in those with NC. Both cognitive status and APOE genotype are important moderators in the relationship between MBI‐apathy and incident dementia. MBI‐apathy may represent a group in whom apathy is a preclinical or prodromal manifestation of dementia and identify a precision medicine target for preventative interventions. John Wiley and Sons Inc. 2022-12-19 /pmc/articles/PMC9763783/ /pubmed/36544988 http://dx.doi.org/10.1002/trc2.12370 Text en © 2022 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Vellone, Daniella
Ghahremani, Maryam
Goodarzi, Zahra
Forkert, Nils D.
Smith, Eric E.
Ismail, Zahinoor
Apathy and APOE in mild behavioral impairment, and risk for incident dementia
title Apathy and APOE in mild behavioral impairment, and risk for incident dementia
title_full Apathy and APOE in mild behavioral impairment, and risk for incident dementia
title_fullStr Apathy and APOE in mild behavioral impairment, and risk for incident dementia
title_full_unstemmed Apathy and APOE in mild behavioral impairment, and risk for incident dementia
title_short Apathy and APOE in mild behavioral impairment, and risk for incident dementia
title_sort apathy and apoe in mild behavioral impairment, and risk for incident dementia
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763783/
https://www.ncbi.nlm.nih.gov/pubmed/36544988
http://dx.doi.org/10.1002/trc2.12370
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