TY - JOUR
T1 - Correlating continuously captured home-based digital biomarkers of daily function with postmortem neurodegenerative neuropathology
AU - Hantke, Nathan C.
AU - Kaye, Jeffrey
AU - Mattek, Nora
AU - Wu, Chao Yi
AU - Dodge, Hiroko H.
AU - Beattie, Zachary
AU - Woltjer, Randy
N1 - Publisher 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.
PY - 2023/6
Y1 - 2023/6
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0286812
DO - 10.1371/journal.pone.0286812
M3 - Article
C2 - 37289845
AN - SCOPUS:85161828190
SN - 1932-6203
VL - 18
JO - PloS one
JF - PloS one
IS - 6 June
M1 - e0286812
ER -