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Correlating Continuously Captured Home-based Digital Biomarkers of Daily Function with Postmortem Neurodegenerative Neuropathology

Overview
Journal PLoS One
Date 2023 Jun 8
PMID 37289845
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Abstract

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.

References
1.
Ferman T, Boeve B, Smith G, Lin S, Silber M, Pedraza O . Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies. Neurology. 2011; 77(9):875-82. PMC: 3162640. DOI: 10.1212/WNL.0b013e31822c9148. View

2.
Seelye A, Mattek N, Howieson D, Austin D, Wild K, Dodge H . Embedded Online Questionnaire Measures Are Sensitive to Identifying Mild Cognitive Impairment. Alzheimer Dis Assoc Disord. 2015; 30(2):152-9. PMC: 4715793. DOI: 10.1097/WAD.0000000000000100. View

3.
Serrano-Pozo A, Qian J, Muzikansky A, Monsell S, Montine T, Frosch M . Thal Amyloid Stages Do Not Significantly Impact the Correlation Between Neuropathological Change and Cognition in the Alzheimer Disease Continuum. J Neuropathol Exp Neurol. 2016; 75(6):516-26. PMC: 6250207. DOI: 10.1093/jnen/nlw026. View

4.
Kaye J, Mattek N, Dodge H, Campbell I, Hayes T, Austin D . Unobtrusive measurement of daily computer use to detect mild cognitive impairment. Alzheimers Dement. 2013; 10(1):10-7. PMC: 3872486. DOI: 10.1016/j.jalz.2013.01.011. View

5.
Farias S, Mungas D, Reed B, Cahn-Weiner D, Jagust W, Baynes K . The measurement of everyday cognition (ECog): scale development and psychometric properties. Neuropsychology. 2008; 22(4):531-44. PMC: 2877034. DOI: 10.1037/0894-4105.22.4.531. View