Rosanne L. van Den Berg

Background: Assessment of cognitive decline in the earliest stages of Alzheimer disease (AD) is important but challenging. AD is a neurodegenerative disease characterized by gradual cognitive decline. Disease stages range from preclinical AD, in which individuals are cognitively unimpaired, to mild cognitive impairment (MCI) and dementia. Digital technologies promise to enable detection of early, subtle cognitive changes. Although the field of digital cognitive biomarkers is rapidly evolving, a comprehensive overview of the reporting of psychometric properties (ie, validity, reliability, responsiveness, and clinical meaningfulness) is missing. Insight into the extent to which these properties are evaluated is needed to identify the validation steps toward implementation. Objective: This scoping review aimed to identify the reporting on quality characteristics of smartphone- and tablet-based cognitive tools with potential for remote administration in individuals with preclinical AD or MCI. We focused on both psychometric properties and practical tool characteristics. Methods: This scoping review was conducted following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. In total, 4 databases (PubMed, Embase, Web of Science, and PsycINFO) were systematically searched from January 1, 2008, to January 5, 2023. Studies were included that assessed the psychometric properties of cognitive smartphone- or tablet-based tools with potential for remote administration in individuals with preclinical AD or MCI. In total, 2 reviewers independently screened titles and abstracts in ASReview, a screening tool that combines manual and automatic screening using an active learning algorithm. Thereafter, we manually screened full texts in the web application Rayyan. For each included study, 2 reviewers independently explored the reported information on practical and psychometric properties. For each psychometric property, examples were provided narratively. Results: In total, 11,300 deduplicated studies were identified in the search. After screening, 50 studies describing 37 different digital tools were included in this review. Average administration time was 13.8 (SD 10.1; range 1-32) minutes, but for 38% (14/37) of the tools, this was not described. Most tools (31/37, 84%) were examined in 1 language. The investigated populations were mainly individuals with MCI (34/37, 92%), and fewer tools were examined in individuals with preclinical AD (8/37, 22%). For almost all tools (36/37, 97%), construct validity was assessed through evaluation of clinical or biological associations or relevant group differences. For a small number of tools, information on structural validity (3/37, 8%), test-retest reliability (12/37, 32%), responsiveness (6/37, 16%), or clinical meaningfulness (0%) was reported. Conclusions: Numerous smartphone- and tablet-based tools to assess cognition in early AD are being developed, whereas studies concerning their psychometric properties are limited. Often, initial validation steps have been taken, yet further validation and careful selection of psychometrically valid outcome scores are required to demonstrate clinical usefulness with regard to the context of use, which is essential for implementation.

INTRODUCTION: We examined semantic and phonemic fluency in individuals with subjective cognitive decline (SCD) in relation to amyloid status and clinical progression.METHODS: A total of 490 individuals with SCD (62 ± 8 years, 42% female, 28% amyloid‐positive, 17% clinical progression) completed annual fluency assessments (mean ± SD follow‐up 4.3 ± 2.9 years). Associations between fluency trajectories, amyloid status, and clinical progression were examined with linear mixed models and joint models.RESULTS: Amyloid‐positive individuals declined faster than amyloid‐negative individuals on semantic fluency (B = −0.35, p < 0.001), but not on phonemic fluency (B = −0.06, p = 0.218). An annual decline of one word in semantic and phonemic fluency was associated with 22% (hazard ratio [HR] = 1.22, p < 0.001) and 28% (HR = 1.28, p = 0.004) increased risk of clinical progression.DISCUSSION: Our results indicate that decline in semantic fluency is an early indicator of cognitive deficits in preclinical Alzheimer's disease.Highlights: Abnormal amyloid burden is associated with decline in semantic fluency. Fluency trajectories are associated with an increased risk of clinical progression. More refined measures are needed to detect the earliest language deficits.

Introduction: Digital cognitive assessments (DCAs) may facilitate early recognition of cognitive decline in the context of Alzheimer's disease (AD). While DCAs are increasingly emerging, they are often not used in practice. We assessed facilitators and barriers of using DCAs according to older individuals and patients. Methods: In five focus groups, we presented three different DCAs to older individuals with unimpaired cognition ( n = 14), subjective cognitive decline ( n = 11) and mild cognitive impairment with biomarker-confirmed AD ( n = 4) and their caregivers ( n = 2). Participants discussed facilitators and barriers that could influence the use of DCAs. Focus groups were recorded, and transcripts were analysed using thematic analysis. Results: Three main themes were identified: (1) test motivation (‘Do I want to know my brain health?’), facilitated by early disease recognition, while impeded by fear of dementia; (2) digital test suitability (‘Do I want to use a digital test?’), enabling at-home testing, while lacking personal contact; and (3) digital test characteristics (‘What makes a digital test a good test for me?’), where user-friendliness was emphasized as a key facilitator to overcome digital incompetence. Discussion: Participants recognized the added value of DCAs, and multiple factors were identified as facilitators and barriers for their use. Similar factors could be a barrier for one, yet facilitated others, underlining the need for a personalized approach. Strategies to minimize barriers and exploit facilitators would ultimately foster implementation.

Background: Automated analysis of natural speech is emerging as a promising digital biomarker of Alzheimer’s disease (AD). As speech is a complex process, relying on multiple interacting cognitive functions, fine‐grained analysis of speech may have the potential to capture subtle cognitive deficits in the very early stages of AD. Here, we examined the association between amyloid‐beta (Aβ) pathology and acoustic speech characteristics in a group of cognitively normal Dutch adults.Method: We included 50 cognitively normal (n = 23 Aβ‐positive, 46%) older adults from three clinical cohorts at the Alzheimer Center Amsterdam (Table 1). Aβ‐status was based on local cut‐offs for Aβ_1‐42‐concentrations in cerebrospinal‐fluid or visual inspection of amyloid positron emission tomography (PET)‐imaging. In a five day remote burst assessment, seventeen tablet‐based tasks (picture description, journal‐prompt storytelling, verbal‐fluency) were administered, with a daily administration time of approximately 10 minutes. Various acoustic features, including silent pauses, pause‐to‐word‐ratio, and perceived loudness, were extracted from the voice recordings. Mean burst scores were calculated over the five‐day period. The association between Aβ‐pathology and acoustic features was investigated using linear regression models separately for each subtask.Results: Pause‐to‐word ratio was higher in Aβ‐positive individuals in the repetitive picture description subtask (β = ‐0.05, p = 0.04) and the journaling subtask (β = ‐0.07, p = 0.03) compared to the Aβ‐negative individuals. Although statistical significance between groups was not reached for other acoustic features, a pattern was observed that the Aβ‐positive group consistently displayed more medium pauses, longer audio duration, more local jitter, higher intensity variance, a higher fundamental frequency, and fewer long pauses in all multi‐day subtasks (Figure 1).Conclusion: Our results demonstrated that Aβ‐pathology was associated with more pauses during free speech in cognitively healthy adults. This supports the notion that remote multi‐day speech assessments have the potential to monitor cognitive changes, for example in observational studies and decentralized clinical trials in preclinical AD. Next steps include examining the association between Aβ‐pathology and linguistic features using the same sample.

BACKGROUND Assessment of cognitive decline in the earliest stages of Alzheimer disease (AD) is important but challenging. AD is a neurodegenerative disease characterized by gradual cognitive decline. Disease stages range from preclinical AD, in which individuals are cognitively unimpaired, to mild cognitive impairment (MCI) and dementia. Digital technologies promise to enable detection of early, subtle cognitive changes. Although the field of digital cognitive biomarkers is rapidly evolving, a comprehensive overview of the reporting of psychometric properties (ie, validity, reliability, responsiveness, and clinical meaningfulness) is missing. Insight into the extent to which these properties are evaluated is needed to identify the validation steps toward implementation. OBJECTIVE This scoping review aimed to identify the reporting on quality characteristics of smartphone- and tablet-based cognitive tools with potential for remote administration in individuals with preclinical AD or MCI. We focused on both psychometric properties and practical tool characteristics. METHODS This scoping review was conducted following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. In total, 4 databases (PubMed, Embase, Web of Science, and PsycINFO) were systematically searched from January 1, 2008, to January 5, 2023. Studies were included that assessed the psychometric properties of cognitive smartphone- or tablet-based tools with potential for remote administration in individuals with preclinical AD or MCI. In total, 2 reviewers independently screened titles and abstracts in ASReview, a screening tool that combines manual and automatic screening using an active learning algorithm. Thereafter, we manually screened full texts in the web application Rayyan. For each included study, 2 reviewers independently explored the reported information on practical and psychometric properties. For each psychometric property, examples were provided narratively. RESULTS In total, 11,300 deduplicated studies were identified in the search. After screening, 50 studies describing 37 different digital tools were included in this review. Average administration time was 13.8 (SD 10.1; range 1-32) minutes, but for 38% (14/37) of the tools, this was not described. Most tools (31/37, 84%) were examined in 1 language. The investigated populations were mainly individuals with MCI (34/37, 92%), and fewer tools were examined in individuals with preclinical AD (8/37, 22%). For almost all tools (36/37, 97%), construct validity was assessed through evaluation of clinical or biological associations or relevant group differences. For a small number of tools, information on structural validity (3/37, 8%), test-retest reliability (12/37, 32%), responsiveness (6/37, 16%), or clinical meaningfulness (0%) was reported. CONCLUSIONS Numerous smartphone- and tablet-based tools to assess cognition in early AD are being developed, whereas studies concerning their psychometric properties are limited. Often, initial validation steps have been taken, yet further validation and careful selection of psychometrically valid outcome scores are required to demonstrate clinical usefulness with regard to the context of use, which is essential for implementation.

Background: Digital speech assessment has potential relevance in the earliest, preclinical stages of Alzheimer’s disease (AD). We evaluated the feasibility, test-retest reliability, and association with AD-related amyloid-beta (Aβ) pathology of speech acoustics measured over multiple assessments in a remote setting. Methods: Fifty cognitively unimpaired adults (Age 68 ± 6.2 years, 58% female, 46% Aβ-positive) completed remote, tablet-based speech assessments (i.e., picture description, journal-prompt storytelling, verbal fluency tasks) for five days. The testing paradigm was repeated after 2–3 weeks. Acoustic speech features were automatically extracted from the voice recordings, and mean scores were calculated over the 5-day period. We assessed feasibility by adherence rates and usability ratings on the System Usability Scale (SUS) questionnaire. Test-retest reliability was examined with intraclass correlation coefficients (ICCs). We investigated the associations between acoustic features and Aβ-pathology, using linear regression models, adjusted for age, sex and education. Results: The speech assessment was feasible, indicated by 91.6% adherence and usability scores of 86.0 ± 9.9. High reliability (ICC ≥ 0.75) was found across averaged speech samples. Aβ-positive individuals displayed a higher pause-to-word ratio in picture description (B = -0.05, p = 0.040) and journal-prompt storytelling (B = -0.07, p = 0.032) than Aβ-negative individuals, although this effect lost significance after correction for multiple testing. Conclusion: Our findings support the feasibility and reliability of multi-day remote assessment of speech acoustics in cognitively unimpaired individuals with and without Aβ-pathology, which lays the foundation for the use of speech biomarkers in the context of early AD.