Correlating continuously captured home-based digital biomarkers of daily function with postmortem neurodegenerative neuropathology.

BACKGROUND

Outcome measures available for use in Alzheimer's disease (AD) clinical trials are limited in ability to detect gradual changes. Measures of everyday function and cognition assessed unobtrusively at home using embedded sensing and computing generated "digital biomarkers" (DBs) have been shown to be ecologically valid and to improve efficiency of clinical trials. However, DBs have not been assessed for their relationship to AD neuropathology.

OBJECTIVES

The goal of the current study is to perform an exploratory examination of possible associations between DBs and AD neuropathology in an initially cognitively intact community-based cohort.

METHODS

Participants included in this study were ≥65 years of age, living independently, of average health for age, and followed until death. Algorithms, run on the continuously-collected passive sensor data, generated daily metrics for each DB: cognitive function, mobility, socialization, and sleep. Fixed postmortem brains were evaluated for neurofibrillary tangles (NFTs) and neuritic plaque (NP) pathology and staged by Braak and CERAD systems in the context of the "ABC" assessment of AD-associated changes.

RESULTS

The analysis included a total of 41 participants (M±SD age at death = 92.2±5.1 years). The four DBs showed consistent patterns relative to both Braak stage and NP score severity. Greater NP severity was correlated with the DB composite and reduced walking speed. Braak stage was associated with reduced computer use time and increased total time in bed.

DISCUSSION

This study provides the first data showing correlations between DBs and neuropathological markers in an aging cohort. The findings suggest continuous, home-based DBs may hold potential to serve as behavioral proxies that index neurodegenerative processes.

Informations de copyright

Copyright: © 2023 Hantke et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Déclaration de conflit d'intérêts

JK in the past 36 months has been directly compensated for serving on a Data Safety Monitoring Committee for Eli Lilly, the Scientific Advisory Board of Sage Bionetworks, the Roche/Genentech Scientific Advisory Committee for Digital Health Solutions in Alzheimer’s Disease, and as an external Advisory Committee member for two Alzheimer’s Disease Research Centers. He has received research support awarded to his institution (Oregon Health & Science University) from the NIH, NSF, the Department of Veterans Affairs, USC Alzheimer’s Therapeutic Research Institute, Merck, AbbVie, Eisai, Green Valley Pharmaceuticals, and Alector. He has received reimbursement through Medicare or commercial insurance plans for providing clinical assessment and care for patients. He has served on the editorial advisory board and as Associate Editor of the journal, Alzheimer’s & Dementia and as Associate Editor for the Journal of Translational Engineering in Health and Medicine. HD works as a consultant for Biogen and is supported by the following federal grants: NIH R01AG051628, R01AG056102, R01AG069782, P30AG066518, R01AG072449, P30AG008017, P30AG024978, U2CAG054397, R01AG056712, R01AG0380651, P30AG053760, U01NS100611, U2CAG057441, U01NS106670, R01AG054484, RF1AG072449. ZB and JK have a financial interest in Life Analytics, Inc., a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest has been reviewed and managed by Oregon Health & Science University. Remaining authors have no disclosures. This does not alter our adherence to PLOS ONE policies on sharing data and materials.