Digital Health Technologies (DHTs) enable remote, objective and frequent assessments of motor signs in people living with Parkinson’s (PwP). It remains unclear whether participant satisfaction with daily DHT interactions relates to long-term adherence and clinical outcomes. To quantify PwP’s satisfaction with daily remote DHT monitoring and its relationships with DHT adherence, motor disease severity, and anxiety and depression. Data from 710 participants living with early-stage Parkinson’s were analyzed from the PASADENA Phase IIa (NCT03100149; n=293) and PADOVA Phase IIb (NCT04777331; n=417) studies. At baseline, PASADENA participants (H&Y 1–2) were treatment-naive or on stable MAO-Bi, PADOVA participants (H&Y 1–2) were on stable L-DOPA or MAO-Bi. Remote monitoring with the Roche PD Mobile Application included active tests (AT), surveys, and passive monitoring (PM) via a study watch and phone, over 2 years (PASADENA) or 76–172 weeks (PADOVA). Towards the end of both studies (follow-up), participants completed questionnaires on DHT acceptance (Likert-scale: 1=very negative, 5=very positive) and open feedback. “Global satisfaction” with the DHT was defined as the mean Likert score from 4 comparable questions in the PASADENA and PADOVA questionnaires. Open feedback was analyzed qualitatively. Spearman’s correlations related global satisfaction levels with overall DHT adherence, self-reported motor experiences of daily living (MDS-UPDRS Part II), clinician-rated motor sign severity (MDS-UPDRS Part III) and, for PASADENA, anxiety and depression (HADS). Global satisfaction was 4.2/5 (SD=0.7) in PASADENA and 3.9/5 (SD=0.7) in PADOVA, reflecting overall positive sentiments. Most participants rated all DHT aspects positively, including study devices and app (PASADENA: 3.6±1.0; PADOVA: 3.4±1.0) and daily active testing (PASADENA: 3.9±1.3; PADOVA: 3.9±1.2). Respondents highlighted areas for improvement in open feedback, including technical issues (PASADENA: 20%; PADOVA: 29%), repetitive ATs/surveys (PASADENA and PADOVA:13%) and device usability (PASADENA: 10%; PADOVA:12%). Higher global satisfaction ratings were weakly-to-moderately associated with higher adherence levels in PASADENA (AT: ρ=0.40; PM smartphone [PMsp]: ρ=0.29; PM smartwatch [PMsw]: ρ=0.23; all P<.001) and PADOVA (AT: ρ=0.24; PMsp: ρ=0.18; PMsw: ρ=0.17; all P<.001). Global satisfaction showed negligible-to-weak and inconsistent associations (-.11≤ρ≤.14) with MDS-UPDRS Parts II and III across studies. In PASADENA, lower global satisfaction ratings were weakly associated with higher levels of anxiety (ρ=−.15, P=.02) and depression (ρ=−0.11, P=.06). Participants living with early-stage Parkinson’s were generally satisfied with daily DHT testing in clinical trials over ~1.5–3 years. Satisfaction was positively associated with adherence but not robustly with motor disease severity, anxiety and depression. Improving device design, battery life and test variety may boost satisfaction and adherence, strengthening DHT-based monitoring. ClinicalTrials.gov NCT03100149 (PASADENA), NCT04777331 (PADOVA)

Digital health technologies (DHT) offer a promising solution to the timely identification of early Alzheimer’s disease (eAD) to enable early treatment. This study evaluated the feasibility, acceptability, adherence, reliability, and preliminary clinical and content validity of the novel AD Digital Assessment Suite (AD-DAS). 123 individuals (32 healthy controls (HC), 31 amyloid-PET negative (SCDn), 30 amyloid-PET positive (SCDp) with subjective cognitive decline, and 30 early AD (eAD)) participated. AD-DAS was remotely deployed for 28 days. Remote testing was feasible (97.6% completers), acceptable (>85% “good”), and associated with high adherence (96%). Metrics showed moderate to excellent test-retest reliability (ICC 0.53–0.91), associations with clinical comparators (adjusted R2 0.01–0.24), differentiated eAD from other known groups (absolute log odds differences 0.6–3.28), and correlated with brain atrophy in expected regions. Episodic and working memory AD-DAS metrics differentiated SCDp from SCDn participants. These preliminary findings suggest that AD-DAS may be a promising tool for detecting cognitive impairments in early AD stages. This study was registered in the International Standard Randomised Controlled Trial Number (ISRCTN) registry (ID: ISRCTN17035495) on July 25, 2020.

Sensitive and scalable biomarkers are critical for tracking progression during the prodromal phase of Parkinson's disease, particularly in idiopathic REM sleep behavior disorder (iRBD). We evaluated the Roche PD Mobile Application version 2, a smartphone-based platform, in 51 individuals with polysomnography-confirmed iRBD, 89 patients with early Parkinson's disease, and 22 healthy controls over 12 months. Participants completed daily active tasks generating validated digital summary measures. Adherence was high (73%). Baseline digital bradykinesia scores discriminated between groups (p < 0.001) and were higher in phenoconverters versus non-converters (p = 0.003; Cohen's d = 1.10). Over 50 weeks, bradykinesia (Cohen's d = 0.50) and speech (Cohen's d = 0.79) scores worsened significantly. Sample size modeling showed that digital bradykinesia required 132 participants per arm to detect a 50% treatment effect, fewer than the best-performing clinical measure. These findings support digital bradykinesia as a sensitive endpoint for prodromal Parkinson's disease trials.

Basal ganglia (BG) dysfunction is the hallmark of several neurological and neuropsychiatric disorders. BG dysfunction impairs cost-benefit decision-making, a brain computational process of trading off between reward and costs, and may underlie clinical observations of neuropsychiatric symptoms such as amotivation, impulsivity, and risk-taking. There is an unmet need for a remote digital monitoring tool for cost-benefit decision-making that can be administered repeatedly by a patient at home to provide a longitudinal proxy of basal ganglia functioning to inform clinical practice and drug development efforts. This report describes a data-driven and iterative prototyping effort of a smartphone-based, cost-benefit, decision-making test battery developed to measure basal ganglia functioning in three cost domains: effort, delay, and risk. Via an iterative process consisting of multiple rounds of data collection with online community-based samples, we aimed to establish feasibility, proof-of-concept, test-retest reliability over up to 4.5 months, and convergent validity with relevant clinical symptoms, namely apathy and impulsivity. We converted a lab-based, decision-making test battery to a URL-based test administered on private smartphones. An online pool of n = 879 volunteers aged 40-80 years participated. Using a data-driven approach, we iteratively (6 rounds) refined and shortened the test to a prototype with a target participant burden of less than 5 minutes while preserving its psychometric properties. Proof of concept, test-retest reliability (intraclass correlation coefficients (ICCs)), and convergent validity with the Starkstein Apathy Scale (SAS) and Barrat Impulsiveness Scale (BIS-11) were established for the final version. Consistent monotonic effects of cost levels in all cost domains were observed, demonstrating proof of concept. Measures of motivation, impulsivity, and risk-taking showed good to excellent test-retest reliability (ICCs 0.69 – 0.97). Metrics of impulsivity showed convergent validity with its clinical anchor, BIS-11 (t = -2.83, p = 0.005)), and the metric of motivation showed convergent validity with SAS (t = -2.29, p = 0.022). This accessible, short, scalable, and replicable digital smartphone-based decision-making test battery may represent an efficient and robust means to estimate cost-benefit decision-making associated with basal ganglia functioning and its changes over time. This is not a RCT

Introduction: Prasinezumab was shown to potentially delay motor progression in individuals with early-stage Parkinson's disease (PD) who were either treatment-naive or on monoamine oxidase type B inhibitor (MAOBi) therapy in the PASADENA study. We report the rationale, design, and baseline patient characteristics of the PADOVA study, designed to evaluate prasinezumab in an early-stage PD population receiving standard-of-care (SOC) symptomatic medications. Methods: PADOVA (NCT04777331) is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, in which individuals with early-stage PD on SOC stable symptomatic monotherapy (levodopa or MAO-Bi) receive intravenous prasinezumab 1500 mg every 4 weeks. The primary endpoint is time to confirmed motor progression, defined as >= 5 points increase from baseline on the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III in practically defined OFF-medication state. Results: 586 participants were enrolled between May 5th, 2021 and March 22nd, 2023. At baseline, 74.2 % and 25.8 % of participants were receiving levodopa and MAO-Bi, respectively. Mean age was 64.2 years and 63.5 % were male. Mean time from diagnosis was 18.6 months, 85 % of participants were in Hoehn & Yahr (H&Y) Stage 2, and mean MDS-UPDRS Part III score was 24.5. Compared with the PASADENA population, PADOVA participants were older (similar to 5 years), with longer disease duration (similar to 8 months), and slightly more advanced based on H&Y stage (10 % more in Stage 2) and MDS-UPDRS Part III (similar to 3 points more). Conclusions: PADOVA has successfully recruited an early-stage PD population to test the effect of prasinezumab when added to background SOC.

Digital health technology (DHT) tools for Parkinson’s disease (PD) e.g., smartphones and wearables were used for remote and frequent measurement of motor signs in the phase 2 PASADENA study of the anti-alpha-synuclein monoclonal antibody prasinezumab. 316 early-stage PD participants were randomized to placebo, 1500 mg, or 4500 mg prasinezumab for 52 weeks; placebo participants were re-randomized to prasinezumab for the ensuing 52 weeks. Patients performed daily smartphone motor “active tests”, and were passively monitored by smartphone/smartwatch throughout the day over 2 y. Change from baseline analyses censored data at dopaminergic treatment start. Bilateral speeded tapping variability and hand-turning, U-turn speed, passively monitored hand movement power, and summary Simple Sum scores progressed numerically less in prasinezumab-treated vs placebo at week 52. All findings except hand-turning persisted at week 104. DHT sensor-based outcome measures may contribute to quantifying disease progression in clinical research of early-stage, dopaminergic treatment-naïve PD. Clinical Trial Registry Name: ClinicalTrials.gov; Clinical Trial Registry ID: NCT03100149; registered 2017-03-29.

Prasinezumab, a monoclonal antibody that binds aggregated alpha-synuclein, is being investigated as a potential disease-modifying therapy in early-stage Parkinson's disease. Although in the PASADENA phase 2 study, the primary endpoint (Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) sum of Parts I + II + III) was not met, prasinezumab-treated individuals exhibited slower progression of motor signs than placebo-treated participants (MDS-UPDRS Part III). We report here an exploratory analysis assessing whether prasinezumab showed greater benefits on motor signs progression in prespecified subgroups with faster motor progression. Prasinezumab's potential effects on disease progression were assessed in four prespecified and six exploratory subpopulations of PASADENA: use of monoamine oxidase B inhibitors at baseline (yes versus no); Hoehn and Yahr stage (2 versus 1); rapid eye movement sleep behavior disorder (yes versus no); data-driven subphenotypes (diffuse malignant versus nondiffuse malignant); age at baseline (>= 60 years versus <60 years); sex (male versus female); disease duration (>12 months versus <12 months); age at diagnosis (>= 60 years versus <60 years); motor subphenotypes (akinetic-rigid versus tremor-dominant); and motor subphenotypes (postural instability gait dysfunction versus tremor-dominant). In these subpopulations, the effect of prasinezumab on slowing motor signs progression (MDS-UPDRS Part III) was greater in the rapidly progressing subpopulations (for example, participants who were diffuse malignant or taking monoamine oxidase B inhibitors at baseline). This exploratory analysis suggests that, in a trial of 1-year duration, prasinezumab might reduce motor progression to a greater extent in individuals with more rapidly progressing Parkinson's disease. However, because this was a post hoc analysis, additional randomized clinical trials are needed to validate these findings.

Abstract Digital health technology (DHT) tools for Parkinson’s disease (PD) such as smartphones and wearable sensors enable remote and frequent measurement of motor signs which may facilitate research on novel treatments for PD. Here, we report the effect of the anti-alpha-synuclein monoclonal antibody prasinezumab on two-year motor sign progression in an early-stage PD population as measured with the Roche PD Mobile Application DHT. 316 early-stage PD participants of the phase 2 PASADENA study (NCT03100149) were randomized to treatment with placebo, 1500 mg, or 4500 mg prasinezumab for 52 weeks (Part 1); and placebo treated patients in Part 1 were re-randomized to 1500 mg or 4500 mg prasinezumab for the ensuing 52 weeks (Part 2, delayed-start group). Patients performed daily motor ‘active tests’ on provisioned study smartphones, carried the phone and wore a smartwatch throughout the day for passive monitoring, over two years. Change from baseline on 17 pre-specified individual sensor features and a summary Simple Sum score were analyzed with linear random slope and intercept models or mixed models for repeated measures, censoring patient data following the start of dopaminergic treatment. Adherence to active testing averaged 5.7 and 5.0 days/week in Parts 1 and 2, respectively. Bilateral speeded tapping variability and hand turning, U-turn speed, the power of passively monitored non-gait hand movements, and the Simple Sum score progressed less in prasinezumab-treated vs placebo at week 52. All findings except hand turning persisted at week 104. While the primary outcome for Part 1 PASADENA (MDS-UPDRS sum of Parts I, II and III) showed no significant difference from placebo, exploratory sensor-based outcome measures showed reduced motor sign progression in prasinezumab-treated individuals with early-stage PD.

The quantification of information processing speed (IPS) and its changes over time is a cornerstone of neuropsychological assessment for early Alzheimer’s disease (eAD). Additionally, clinical practice and drug development increasingly require tools enabling the remote assessment of cognition. We previously reported the feasibility, reliability and clinical validity of a novel, smartphone-based IPS test remotely self-administered to healthy controls (HC) and individuals with subjective cognitive decline (SCD) and eAD. The present study performed whole-brain voxel-based morphometry (VBM) analyses to determine whether smartphone-based IPS performance indeed correlated with atrophy of brain regions known to support processing speed. 31 HC, 31 SCDn (amyloid-PET negative), 31 SCDp (amyloid-PET positive) and 30 eAD individuals participated in a Alzheimer’s Digital Assessment Suite (AD-DAS) Proof-of-Concept study (https://www.isrctn.com/ISRCTN17035495). Participants performed 9 IPS assessments (90s digit-symbol matching) over 28 days on provisioned smartphones. Each response sequence and digit-symbol pairing was novel and matched for difficulty within/across sessions. High-resolution anatomic, T1-weighted MRI were submitted to whole-brain VBM analyses (Computational Anatomy Toolbox, SPM12/Matlab 2021) testing whether performance (number correct) correlated with gray matter signal intensities (covariates: age, gender, years of education, study site, total intracranial volume). The statistical parametric map was thresholded at p<0.001 uncorrected (voxel-level) and family-wise error corrected p<0.05 (cluster-level). Peak voxel MNI coordinates and t-values, cluster-level p-values are reported. Poor smartphone-based IPS performance correlated with atrophy in five regions centered in: (1) right insula (57, -14, 15; t = 5.83; p<0.0001), (2) right lingual gyrus (14, -64, -8; t = 5.21; p = 0.006), (3) left hippocampus (-36, -24, -16; t = 4.83; p = 0.021), (4) left precuneus (-10, -57, 26; t = 4.73; p = 0.017), (5) right fusiform gyrus (27, -38, -15; t = 4.69; p = 0.043), replicating previous functional MRI findings with IPS (lingual gyrus, precuneus) and known neuroanatomical correlates of working memory (insula, hippocampus). These findings support the functional neuroanatomic validity of a novel smartphone-based IPS task and thus remote, clinically meaningful characterization of preclinical/early AD individuals’ IPS impairments in clinical monitoring and drug trials.

Objective: Here, we describe the results of PASADENA Part 2 at Week 104 and Part 3 Week 52 open-label extension (OLE). Background: Prasinezumab is a humanised monoclonal antibody designed to target aggregated alpha-synuclein and slow disease progression in Parkinson's disease (PD). PASADENA (NCT03100149) is multicentre, randomised, double-blind, placebo-controlled study evaluating the efficacy of prasinezumab in participants with early-stage PD. Design/Methods: Participants with early-stage PD (diagnosis ≤2 years of age at screening; Hoehn & Yahr Stages I–II) were randomised to receive intravenous prasinezumab every 4 weeks (1500 mg or 4500 mg) for approximately three years (early-start group), or placebo for 52 weeks followed by prasinezumab (1500 mg or 4500 mg) for approximately two years (delayed-start group). All 316 PASADENA participants were considered in the analysis, with participants included regardless of change in symptomatic therapy. Motor progression and motor complications were defined, respectively, as a ≥5-point increase on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III and reaching a score ≥1 point on MDS-UPDRS Part IV, and were analysed using Cox proportional hazards models. Results: Baseline characteristics were balanced between individuals in the early- and delayed-start groups. At the end of Part 2, fewer participants in the early-start group showed motor progression (80.1%) or developed motor complications (45.0%) compared with the delayed-start group (89.5% and 55.2%) (hazard ratio: 0.77 [80% confidence interval (CI) 0.65–0.91] and 0.74 [80% CI 0.60–0.92]). One-year results from Part 3 will be further described. Conclusions: The PASADENA Part 3 OLE is currently ongoing, and we aim to describe the long-term safety and efficacy on a yearly basis. Disclosure: Prof. Pagano has received personal compensation for serving as an employee of F.Hoffmann-La Roche Ltd. Prof. Pagano has stock in F.Hoffmann La Roche Ltd. Dr. Zanigni has received personal compensation for serving as an employee of Eli-Lilly and Company. Dr. Zanigni has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd. Dr. Zanigni has stock in F. Hoffmann-La Roche Ltd. Mrs. Monnet has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd. Kirsten I. Taylor has received personal compensation for serving as an employee of F. Hoffmann-La Roche Ltd. Kirsten I. Taylor has received stock or an ownership interest from F Hoffman-La Roche Ltd. Ms. Hahn has received personal compensation for serving as an employee of Excelya Germany GmbH, Freiburg, Germany. Dr. Simuni has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Acadia, Abbvie, Accorda, Adamas, Allergan, Amneal, Aptinyx, Denali, General Electric (GE), Kyowa, Neuroderm, Neurocrine, Sanofi, Sinopia, Sunovion, Roche, Takeda, Voyager, US World Meds, Parkinson's Foundation, and the Michael J. Fox Foundation for Parkinson's Research. Dr. Simuni has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Neuroderm and Sanofi. Dr. Simuni has received research support from NINDS, Parkinson's Foundation, MJFF, Biogen, Roche, Neuroderm, Sanofi, Sun Pharma, Abbvie, IMPAX and Prevail. . Dr. Marek has received personal compensation for serving as an employee of IND. Dr. Marek has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for invicro. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biohaven. Dr. Marek has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for takeda. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Alkahest. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Denali. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Astellas. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bial. Dr. Marek has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Marek has received research support from Michael J Fox Foundation. Dr. Postuma has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Roche, Biogen, Takeda, Theranexus, GE, Jazz, Curasen, Paladin, Inception Sciences, Phytopharmics, Vaxxinity, Merck. Dr. Postuma has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen/Partners. The institution of Dr. Postuma has received research support from CIHR, Weston Foundation, Webster Foundation, Roche, MJFF, Parkinson Canada, FRSQ, NIH. Dr. Pavese has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. The institution of Dr. Pavese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Bial. Dr. Pavese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AbbVie. Dr. Pavese has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Britannia. The institution of Dr. Pavese has received research support from Multiple System Atrophy Trust. The institution of Dr. Pavese has received research support from Parkinson's UK. The institution of Dr. Pavese has received research support from Independent Research Fund Denmark. The institution of Dr. Pavese has received research support from European Union. The institution of Dr. Pavese has received research support from MRC. Fabrizio Stocchi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bial, Biogen, Sunovion, Lundbeck, UCB, Zambon, Chiesi, Lusofarmaco, Abbvie, Neuroderm, Kyowa, Synegile, Roche, Britannia, Sunovion, Blue Rock. Fabrizio Stocchi has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for BIAL, Zambon, Biogen, Roche, Synegile, Sunovion. Fabrizio Stocchi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bial, Zambon, UCB, Kyowa, Sunovion. Dr. Svoboda has received personal compensation for serving as an employee of Hoffmann La Roche. Dr. Svoboda has received stock or an ownership interest from Hoffmann La Roche. Dr. Fontoura has received personal compensation for serving as an employee of F. Hoffmann La Roche. Dr. Fontoura has received stock or an ownership interest from Roche Pharmaceuticals. Rachelle Doody has nothing to disclose. Dr. Kerchner has received personal compensation for serving as an employee of F. Hoffmann-La Roche, Ltd.. Dr. Kerchner has stock in F. Hoffmann-La Roche, Ltd.. Dr. Kerchner has received publishing royalties from a publication relating to health care. Dr. Bonni has received personal compensation for serving as an employee of F.Hoffmann-La Roche Ltd. Dr. Bonni has received stock or an ownership interest from F.Hoffmann-La Roche Ltd. Tania Nikolcheva has received personal compensation for serving as an employee of F. Hoffmann La Roche. Tania Nikolcheva has received stock or an ownership interest from F. Hoffmann La Roche.

Trials in early Alzheimer’s disease (eAD) require the quantification of cognitive and functional progression. Compared with traditional in-clinic assessments, remote assessments via digital health technologies (DHT) enable the collection of a broader palette of cognitive and functional measures at higher frequency and in patients' home environments. However, these must demonstrate validity against standard clinical outcome measures and relevant biomarkers. To this end, the present study aims to determine the reliability, convergent clinical, and functional neuroanatomic validity of a novel DHT, the Alzheimer’s Disease Digital Assessment Suite (AD-DAS), for individuals on the AD continuum. In total, 123 participants from 2 countries across 5 sites (3 USA, 2 Spain) participated (https://www.isrctn.com/ISRCTN17035495): 32 healthy controls (HC), 31 amyloid-PET negative and 30 amyloid-PET positive subjective cognitive decline (SCDn, SCDP, respectively), and 30 eAD. All participants completed standard in-clinic neuropsychological assessments and remotely performed the AD-DAS tasks daily for 28 days without supervision. AD-DAS comprised 9 active tasks of cognitive/motor functioning and 4 survey questionnaires. Convergent and clinical validity analysis were performed using linear and proportional odds logistic regression modeling with age, sex, education, and site as covariates, respectively. Functional neuroanatomic validity was tested with voxel-based morphometry (VBM) analyses with anatomic MRIs. Outcome metrics from all AD-DAS cognitive/motor tasks correlated with their corresponding clinical comparators (ρpartial (range) = 0.16 - 0.52), supporting their convergent validity. Similarly, outcome metrics from all tasks significantly differentiated the eAD from all the other groups in the expected directions (odds ratio (range) = 0.01 - 61), supporting their clinical validity. The reliability of the outcome metrics ranged from good to excellent (interclass correlation coefficient (range) = 0.71 - 0.91). VBM analyses provided independent and largely confirmatory results, further validating the AD-DAS. The AD-DAS remote, smartphone-based assessments of cognition show good to excellent test-retest reliability, and preliminary analyses indicate that they may show convergent, clinical and exploratory functional neuroanatomic validity. Thus, these results provide a foundation for building towards the overarching goals of remote screening, prediction of progression, and monitoring of cognitive decline for future clinical trials and clinical care for preclinical and eAD.

Early stages of Alzheimer’s disease (eAD) are marked by changes in gait characteristics that may be measured using simple smartphone-based gait tasks. Here we present an assessment of cognitive-motor-interference where participants walk for 30 seconds with a smartphone placed in a running belt while counting backwards, called the 30-Second Walk Test Dual Task (30sWTDT). We report the preliminary reliability and validation of the 30sWTDT in a cohort of healthy individuals (HC), individuals with subjective cognitive decline amyloid-PET negative and positive (SCDn and SCDp, respectively) and eAD. 123 participants (32 HC, 31 SCDn, 30 SCDp and 30 eAD) were recruited as a part of a Proof-of-Concept study of the Alzheimer’s Disease Digital Assessment Suite (AD-DAS) ( https://www.isrctn.com/ISRCTN17035495 ). Participants performed 9 sessions of 30sWTDT over 28 days on provisioned smartphones. Feasibility was evaluated as the proportion of completed 30sWTDT relative to the total number of expected sessions. Two gait characteristic metrics were estimated: variability in step frequency (VSF) and the 25th percentile in step power (25SP). Intraclass correlation coefficients (ICC) tested the metrics’ reliability. Convergent validity was established as partial correlation between VSF/25SP and adjusted mean duration in Timed 25 foot Walk Test (T25WT). Clinical validity was evaluated using a proportional odds logistic regression model to differentiate between groups. Among the 97.5% of participants who completed the study (i.e., n = 120), participants completed 88.9% of all assigned 30sWTDT tasks, with no group difference in adherence. VSF and 25SP metrics showed moderate (ICC = 0.74) and good (ICC = 0.79) reliability, respectively. Both metrics significantly distinguished between HC and all other study groups (odds ratio = [0.012,0.029]), and were associated with T25WT adjusted mean duration (adjusted r2 = [0.09,0.069]). Preliminary findings demonstrate that a smartphone-based 30sWTDT can be successfully self-administered by cognitively healthy participants and individuals on the eAD continuum. Participants show high adherence in an ecologically valid environment. 30sWTDT differentiated HC from all other groups with subjective or objective cognitive problems, indicating a lack of specificity of gait characteristics to differentiate between increasing levels of cognitive impairment. These findings require replication in larger independent datasets.