Wise, Amy B.

AbstractIntroductionRemote smartphone assessments of cognition, speech/language, and motor functioning in frontotemporal dementia (FTD) could enable decentralized clinical trials and improve access to research. We studied the feasibility and acceptability of remote smartphone data collection in FTD research using the ALLFTD Mobile App (ALLFTD‐mApp).MethodsA diagnostically mixed sample of 214 participants with FTD or from familial FTD kindreds (asymptomatic: CDR®+NACC‐FTLD = 0 [N = 101]; prodromal: 0.5 [N = 49]; symptomatic ≥1 [N = 51]; not measured [N = 13]) were asked to complete ALLFTD‐mApp tests on their smartphone three times within 12 days. They completed smartphone familiarity and participation experience surveys.ResultsIt was feasible for participants to complete the ALLFTD‐mApp on their own smartphones. Participants reported high smartphone familiarity, completed ∼ 70% of tasks, and considered the time commitment acceptable (98% of respondents). Greater disease severity was associated with poorer performance across several tests.DiscussionThese findings suggest that the ALLFTD‐mApp study protocol is feasible and acceptable for remote FTD research.HIGHLIGHTS The ALLFTD Mobile App is a smartphone‐based platform for remote, self‐administered data collection. The ALLFTD Mobile App consists of a comprehensive battery of surveys and tests of executive functioning, memory, speech and language, and motor abilities. Remote digital data collection using the ALLFTD Mobile App was feasible in a multicenter research consortium that studies FTD. Data was collected in healthy controls and participants with a range of diagnoses, particularly FTD spectrum disorders. Remote digital data collection was well accepted by participants with a variety of diagnoses.

AbstractBackgroundMotor disturbances are common in patients with a variety of neurodegenerative and neurological syndromes, such as Parkinson’s disease and Frontotemporal Dementia (FTD). Accurately quantifying motoric changes could enable earlier detection and monitoring of these syndromes, and remote quantification may allow for more frequent assessments and may improve access to research for underrepresented and geographically dispersed participants. With these benefits in mind, investigators from the ALLFTD consortium developed smartphone tests of balance and finger tapping speed. Here we present preliminary test‐retest reliability and associations with gold standard tests.MethodThe tasks were analyzed in two independent samples. The first was an in‐person cohort of healthy older adults (n = 7), mild cognitive impairment (MCI, n = 1) and FTD (n = 3) who completed the smartphone standing/balance and finger tapping tests (FTT) twice in person. The second sample included 31 ALLFTD participants with a range of clinical presentations (healthy older adults [n = 11], FTD [n = 5], MCI [n = 2], unknown [n = 13]) who were asked to complete the balance test three times over two weeks at home. The primary outcomes were total taps for the FTT and root mean squared acceleration for the balance test. Test‐retest reliability was calculated using an intraclass correlation coefficient (ICC); given the small sample size, outliers (n = 6) were removed from the balance test. We tested the association of smartphone FTT with the gold standard mechanical FTT and the balance task with the CDR®+NACC‐FTLD‐SB (disease severity) using Spearman’s correlations. A Wilcoxon‐sign rank test compared participants with motor features on the Progressive Supranuclear Palsy Rating Scale (PSPRS>0) to those without (PSPRS = 0).ResultThe smartphone FTT showed good test‐retest reliability (ICC = 0.78) and a strong correlation (r = 0.8,p<0.05) with mechanical FTT. The test‐retest reliability for the balance task was excellent for the remote sample (ICC = 0.97) and in‐person (ICC = 0.89) samples. In the remote sample, greater acceleration was correlated with higher CDR®+NACC‐FTLD‐SB (r = 0.7,p = 0.003), and participants with motor features on the PSPRS had higher acceleration than those without (W = 11,p = 0.04).ConclusionThese findings provide preliminary support for the reliability and validity of the ALLFTD Mobile App tests of motor function. Replication in a larger sample is required.

AbstractBackgroundFrontotemporal dementia (FTD) is a collection of neurodegenerative diseases affecting behavior, cognition, and motor functions. FTD treatment trials will benefit from sensitive assessments capable of detecting and longitudinally tracking cognitive changes. Remote smartphone cognitive tests may improve the sensitivity to detect and monitor cognitive decline via novel methods of data capture and more frequent assessments within ecologically valid environments, while simultaneously reducing patient burden. The first step in determining the utility of these measures is establishing their reliability. We previously reported baseline reliability estimates for the ALLFTD Mobile App cognitive tests in a small pilot sample. Here we extend these results using a larger sample and evaluate six‐month stability.MethodWe enrolled a diagnostically mixed sample of 128 participants (CDR®+NACC‐FTLD = 0 [n = 84]; CDR®+NACC‐FTLD = 0.5 [n = 21]; CDR®+NACC‐FTLD≥1 [n = 23]) from ongoing studies of healthy aging (Hillblom Network) and frontotemporal dementia (ALLFTD). Participants self‐administered five cognitive tests from the ALLFTD Mobile App on their own smartphone; they were asked to complete each test three times within two weeks. Tests included gamified versions of N‐back, Stroop, Flanker, and Go/No‐Go paradigms, and an adaptive short‐term memory test. We evaluated the internal consistency of each test’s first occurrence using Spearman‐Brown split‐half reliability (100 simulations). Test‐retest reliability over the first three baseline replicates (as available) was evaluated by calculating intraclass correlations (ICC). In a preliminary analysis, we tested the six‐month stability of test performance in nine functionally intact participants who completed baseline and follow‐up Flanker, N‐Back, and adaptive memory assessments by calculating Spearman’s rho.ResultSplit‐half reliability estimates were in the good to excellent range (r’s: 0.81–0.97). Test‐retest reliability estimates were in the adequate to excellent range (ICCs: 0.72–0.96). ICC estimates were comparable for participants with and without clinical impairment (CDR®+NACC‐FTLD = 0 (0.74–0.95) and CDR®+NACC‐FTLD >0 (0.67–0.95). Among functionally intact individuals, baseline and 6‐months scores were highly correlated (r’s: 0.76–0.93, p’s<.05).ConclusionOur findings of adequate to excellent internal consistency, test‐retest reliability, and 6‐month stability support the feasibility of remote, smartphone‐based cognitive testing among a diagnostically mixed sample typical of healthy aging and frontotemporal dementia research studies.

AbstractBackgroundRemote digital cognitive assessments validated for use in frontotemporal dementia (FTD) and other neurodegenerative diseases would benefit clinical trials and clinical care. The ALLFTD Mobile App includes several smartphone‐based measures of cognition, and prior studies have provided preliminary support for their reliability. Here we evaluate their validity by testing associations with gold standard clinical outcomes and expected neural correlates.MethodA diagnostically mixed sample of 92 participants (CDR®+NACC‐FTLD = 0 [n = 33]; CDR®+NACC‐FTLD = 0.5 [n = 15]; CDR®+NACC‐FTLD≥1 [n = 16]; unknown [n = 28]) were recruited from a UCSF healthy aging study (Hillblom Network) and a North American FTD study (ALLFTD). Participants were asked to remotely complete four ALLFTD Mobile App tests of executive functioning (EF) and a memory test on their smartphones. Gold standard clinical measures were also collected; outcomes were the UDSv3 EF composite, CVLT‐SF Total Immediate Recall (memory), and CDR®+NACC‐FTLD Box Score (disease severity). Volumetric brain MRI measurements were available for a subset (n = 37). Expected neural correlates were frontoparietal gray matter volume for EF tests and hippocampal volume for the memory test. Linear models were fitted to evaluate the association of app tests with the gold standard outcomes, controlling for education, sex, and total intracranial volume (imaging only).ResultSmartphone EF measures were strongly and positively associated with the UDS3‐EF composite (ß’s = 0.6–0.8, all p<.001). The memory test was strongly correlated with the CVLT‐SF (ß = 0.7, p<.001). Tests were less strongly associated with divergent cognitive domains (e.g., associations with a visuospatial test were ß’s = 0.1–0.3). Worse performance on all tests was significantly associated with greater disease severity (ß’s = 0.5–0.7, all p<.001). Worse app‐based EF scores were associated with lower frontoparietal volume (ß’s = 0.4–0.6, all p<.015) and worse memory scores with lower hippocampal volume (ß = 0.5, p<.001).ConclusionALLFTD Mobile App scores were strongly associated with gold standard neuropsychological tests of the same cognitive domain (i.e., convergent validity) and less associated with measures of a different domain (i.e., divergent validity). Worse performance on the smartphone tests was associated with increasing disease severity and volume loss in expected brain regions. These results provide preliminary support for the construct validity of the ALLFTD Mobile App cognitive tests.