Content area

Abstract

There is growing recognition regarding the importance of the exposome, or the totality of exposures one experiences across the life course, in research on Alzheimer's disease and related dementias. However, the measurement of numerous exposures at once and over time, as well as modeling their effects on dementia risk, presents significant methodological challenges. Through community engagement and consensus‐building processes integrating input from multidisciplinary panels of experts, we identified critical priority topics for methods used in studying links between the exposome and dementia risk, along with advances needed to address those priorities. We identified nine priority topics: high‐dimensional and multimodal data, measurement error, harmonization across studies, mixtures of exposures, effect heterogeneity, exposure timing, cumulative exposures, reverse causation, and sample composition. This paper describes these priority topics and highlights areas where future research or the dissemination of existing methods could advance the state of existing science.

Highlights

Inherent complexities central to the measurement and modeling of the exposome and its relationship to dementia pose methodological challenges. We identified nine priority topics, such as measurement error, mixtures of exposures, and cumulative exposures. Modeling approaches should consider complexity but provide useful simplifications when possible. Investments in the development and dissemination of innovative approaches and methodological guidance are needed.

Details

1009240
Title
Key research priorities in methodological approaches for measuring the exposome and studying its role in the development of dementia
Author
Nichols, Emma 1   VIAFID ORCID Logo  ; Keller, Kayleigh P. 2 ; Chang, Howard 3 ; Chiang, Yao‐Yi 4 ; Gross, Alden L. 5 ; Hayes‐Larson, Eleanor 6 ; Claus Henn, Birgit 7 ; Kezios, Katrina L. 8 ; Meijer, Erik 9 ; Shih, Regina A. 10 ; Szpiro, Adam A. 11 ; Weiss, Jordan 12 ; Weuve, Jennifer 8 ; Adar, Sara D. 13 ; Lee, Jinkook 14 

 Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA 
 Department of Statistics, Colorado State University, Fort Collins, Colorado, USA 
 Department of Biostatistics, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA 
 Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, USA 
 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA 
 Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA 
 Department of Environmental Health, Boston University School of Public Health, Boston, Massachusetts, USA 
 Department of Epidemiology, Boston University, Boston, Massachusetts, USA 
 Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA 
10  Department of Epidemiology, Emory Rollins School of Public Health, Atlanta, Georgia, USA 
11  Department of Biostatistics, University of Washington, Seattle, Washington, USA 
12  Optimal Aging Institute and Department of Medicine, New York University Grossman School of Medicine, New York, New York, USA 
13  Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan, USA 
14  Center for Economic and Social Research, University of Southern California, Los Angeles, California, USA, Department of Economics, University of Southern California, Los Angeles, California, USA 
Publication title
Volume
21
Issue
11
Number of pages
14
Publication year
2025
Publication date
Nov 1, 2025
Section
REVIEW ARTICLE
Publisher
John Wiley & Sons, Inc.
Place of publication
Chicago
Country of publication
United States
ISSN
1552-5260
e-ISSN
1552-5279
Source type
Scholarly Journal
Language of publication
English
Document type
Journal Article
Publication history
 
 
Online publication date
2025-11-22
Milestone dates
2025-10-20 (manuscriptRevised); 2025-11-22 (publishedOnlineFinalForm); 2025-08-22 (manuscriptReceived); 2025-10-25 (manuscriptAccepted)
Publication history
 
 
   First posting date
22 Nov 2025
ProQuest document ID
3274064165
Document URL
https://www.proquest.com/scholarly-journals/key-research-priorities-methodological-approaches/docview/3274064165/se-2?accountid=208611
Copyright
© 2025. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the "License"). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
Last updated
2025-11-22
Database
ProQuest One Academic