Boots, Elizabeth A.

AbstractBackgroundEasily accessible and self‐administered cognitive assessments that can aide early identification of individuals at risk for Alzheimer’s disease (AD) dementia are critical for timely intervention. Mayo Test Drive (MTD) is a remote, self‐administered, multi‐device compatible, web‐based cognitive assessment (Stricker et al., 2022). We investigated continuous associations between MTD and amyloid and tau PET biomarkers and compared the strength of association to PET biomarkers and in‐person cognitive measures.Method556 adults from the Mayo Clinic Study of Aging participated (mean age = 70.6; mean education = 16.0 years; 50.7% female; 97.5% white). Participants were predominantly cognitively unimpaired (95.3%; 4.7% had a consensus diagnosis of mild cognitive impairment). Participants completed (1) brain amyloid and tau PET scans, (2) in‐person neuropsychological assessment including Mayo Preclinical Alzheimer’s disease Cognitive Composite (Mayo‐PACC) and Global‐z, and (3) remote MTD comprised of the Stricker Learning Span (SLS) and the Symbols test, which are combined into an MTD composite. Multiple regressions adjusted for age, sex, and education queried associations between imaging biomarkers [amyloid meta‐region of interest (ROI), tau meta‐ROI, and tau entorhinal cortex (EC)‐ROI)] and composite and subtest scores from remote and in‐person measures. Davidson‐Mackinnon J‐test compared R‐squared values of models with remote versus in‐person composites.ResultLower performances on MTD composite and Mayo‐PACC were associated with higher amyloid meta‐ROI (p’s<.05; Table 1). MTD composite was also negatively associated with tau meta‐ROI and EC‐ROI (p’s<.05). For memory measures, SLS sum of trials was negatively associated with tau meta‐ROI (p = .01) and EC‐ROI (p<.001) with no associations between AVLT sum of trials and PET (p’s≥.06; Table 2). Among processing speed/executive function measures, worse Trails B performance was associated with higher amyloid meta‐ROI (p<.001). Symbols and Digit Symbol Coding were not associated with PET (p’s≥.29). A multivariable model with MTD explained significantly less variance (p = .04) for amyloid meta‐ROI (adjusted R‐squared = 0.165) than a multivariable model with Mayo‐PACC (adjusted R‐squared = 0.176); remote and in‐person composite measures were comparable for other associations (p’s>.05).ConclusionMTD is associated with continuous measures of amyloid and tau PET biomarkers of AD, demonstrating criterion validity for MTD. Several associations were comparable to relationships between gold‐standard in‐person neuropsychological tests and imaging biomarkers.

AbstractBackgroundBrief self‐administered cognitive assessments deployed remotely and combined with plasma biomarkers of Alzheimer’s disease (AD) are well suited to assess clinical symptoms and underlying biology in large‐scale decentralized studies. We investigated whether associations of self‐administered cognitive measures and plasma biomarkers were comparable to associations of in‐person cognitive measures and plasma biomarkers.MethodParticipants included 327 adults from the Mayo Clinic Study of Aging (mean age = 70.8; 48% female; mean education = 16.0 years; 96.9% white). Most (94.5%) were cognitively unimpaired; 5.5% had consensus diagnosis of mild cognitive impairment. Participants completed Mayo Test Drive (MTD; Stricker et al., 2022), a remote, self‐administered, multi‐device compatible web‐based cognitive assessment comprised of the Stricker Learning Span (SLS) and Symbols test that are combined into a MTD composite. Participants also completed in‐person neuropsychological assessment (global‐z; Mayo Preclinical Alzheimer’s disease Cognitive Composite [Mayo‐PACC]) and fasting venipuncture. Plasma was assayed via HD‐X simoa platform for amyloid‐beta (Aβ)‐42 and Aβ‐40 to create an Aβ42/40 ratio, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) using the N4PE Quanterix kit as well as phosphorylated‐tau protein 181 (p‐tau181). P‐tau181, GFAP, and NfL were log10‐transformed. Multiple regression analyses adjusting for age, sex, and education examined associations between plasma biomarkers and composite and subtest scores from remote and in‐person measures. Davidson‐Mackinnon J‐test compared R‐squared values of models with remote versus in‐person composites.ResultLower performances on MTD, global‐z, and Mayo‐PACC (Table 1) were associated with higher GFAP (p’s≤.02), NfL (p’s≤.003), and p‐tau181 (p’s = .04). For memory, worse SLS and AVLT sum of trials were associated with higher GFAP (p’s≤.01) and NfL (p’s≤.03). For processing speed/executive function, worse Symbols and Trails B were associated with higher p‐tau181 (p’s≤.02). Worse Trails B and Digit Symbol Coding were associated with higher NfL (p’s≤.02), and worse Digit Symbol Coding was associated with lower Aβ42/40 (p = 0.03; Table 2). A multivariable model with MTD explained significantly more variance (p = .04) for NfL (adjusted R‐squared = 0.461) than a multivariable model with Mayo‐PACC (adjusted R‐squared = 0.447); remote and in‐person composite measures were comparable for other associations (p’s>.05).ConclusionRemote and in‐person composite measures showed comparable associations with AD‐related plasma biomarkers, supporting MTD’s criterion validity.

Abstract Background Easily accessible and self‐administered cognitive assessments that can aide early identification of individuals at risk for Alzheimer’s disease (AD) dementia are critical for timely intervention. Mayo Test Drive (MTD) is a remote, self‐administered, multi‐device compatible, web‐based cognitive assessment (Stricker et al., 2022). We investigated continuous associations between MTD and amyloid and tau PET biomarkers and compared the strength of association to PET biomarkers and in‐person cognitive measures. Method 556 adults from the Mayo Clinic Study of Aging participated (mean age = 70.6; mean education = 16.0 years; 50.7% female; 97.5% white). Participants were predominantly cognitively unimpaired (95.3%; 4.7% had a consensus diagnosis of mild cognitive impairment). Participants completed (1) brain amyloid and tau PET scans, (2) in‐person neuropsychological assessment including Mayo Preclinical Alzheimer’s disease Cognitive Composite (Mayo‐PACC) and Global‐z, and (3) remote MTD comprised of the Stricker Learning Span (SLS) and the Symbols test, which are combined into an MTD composite. Multiple regressions adjusted for age, sex, and education queried associations between imaging biomarkers [amyloid meta‐region of interest (ROI), tau meta‐ROI, and tau entorhinal cortex (EC)‐ROI)] and composite and subtest scores from remote and in‐person measures. Davidson‐Mackinnon J‐test compared R‐squared values of models with remote versus in‐person composites. Result Lower performances on MTD composite and Mayo‐PACC were associated with higher amyloid meta‐ROI (p’s<.05; Table 1). MTD composite was also negatively associated with tau meta‐ROI and EC‐ROI (p’s<.05). For memory measures, SLS sum of trials was negatively associated with tau meta‐ROI (p = .01) and EC‐ROI (p<.001) with no associations between AVLT sum of trials and PET (p’s = .06; Table 2). Among processing speed/executive function measures, worse Trails B performance was associated with higher amyloid meta‐ROI (p<.001). Symbols and Digit Symbol Coding were not associated with PET (p’s = .29). A multivariable model with MTD explained significantly less variance (p = .04) for amyloid meta‐ROI (adjusted R‐squared = 0.165) than a multivariable model with Mayo‐PACC (adjusted R‐squared = 0.176); remote and in‐person composite measures were comparable for other associations (p’s>.05). Conclusion MTD is associated with continuous measures of amyloid and tau PET biomarkers of AD, demonstrating criterion validity for MTD. Several associations were comparable to relationships between gold‐standard in‐person neuropsychological tests and imaging biomarkers.

Abstract Background Brief self‐administered cognitive assessments deployed remotely and combined with plasma biomarkers of Alzheimer’s disease (AD) are well suited to assess clinical symptoms and underlying biology in large‐scale decentralized studies. We investigated whether associations of self‐administered cognitive measures and plasma biomarkers were comparable to associations of in‐person cognitive measures and plasma biomarkers. Method Participants included 327 adults from the Mayo Clinic Study of Aging (mean age = 70.8; 48% female; mean education = 16.0 years; 96.9% white). Most (94.5%) were cognitively unimpaired; 5.5% had consensus diagnosis of mild cognitive impairment. Participants completed Mayo Test Drive (MTD; Stricker et al., 2022), a remote, self‐administered, multi‐device compatible web‐based cognitive assessment comprised of the Stricker Learning Span (SLS) and Symbols test that are combined into a MTD composite. Participants also completed in‐person neuropsychological assessment (global‐z; Mayo Preclinical Alzheimer’s disease Cognitive Composite [Mayo‐PACC]) and fasting venipuncture. Plasma was assayed via HD‐X simoa platform for amyloid‐beta (Aß)‐42 and Aß‐40 to create an Aß42/40 ratio, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) using the N4PE Quanterix kit as well as phosphorylated‐tau protein 181 (p‐tau181). P‐tau181, GFAP, and NfL were log10‐transformed. Multiple regression analyses adjusting for age, sex, and education examined associations between plasma biomarkers and composite and subtest scores from remote and in‐person measures. Davidson‐Mackinnon J‐test compared R‐squared values of models with remote versus in‐person composites. Result Lower performances on MTD, global‐z, and Mayo‐PACC (Table 1) were associated with higher GFAP (p’s = .02), NfL (p’s = .003), and p‐tau181 (p’s = .04). For memory, worse SLS and AVLT sum of trials were associated with higher GFAP (p’s = .01) and NfL (p’s = .03). For processing speed/executive function, worse Symbols and Trails B were associated with higher p‐tau181 (p’s = .02). Worse Trails B and Digit Symbol Coding were associated with higher NfL (p’s = .02), and worse Digit Symbol Coding was associated with lower Aß42/40 (p = 0.03; Table 2). A multivariable model with MTD explained significantly more variance (p = .04) for NfL (adjusted R‐squared = 0.461) than a multivariable model with Mayo‐PACC (adjusted R‐squared = 0.447); remote and in‐person composite measures were comparable for other associations (p’s>.05). Conclusion Remote and in‐person composite measures showed comparable associations with AD‐related plasma biomarkers, supporting MTD’s criterion validity.