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Background By enabling frequent, sensitive, and economic remote assessment, smartphones will facilitate the detection of early cognitive decline at scale. Previous studies have sustained participant engagement with remote cognitive assessment over a week; extending this to a period of 1 month clearly provides a greater opportunity for measurement. However, as study durations are increased, the need to understand how participant burden and scientific value might be optimally balanced also increases. Objective This study explored the little but often approach to assessment employed by the Mezurio app when prompting participants to interact every day for over a month. Specifically, this study aimed to understand whether this extended duration of remote study is feasible, and which factors promote sustained participant engagement over such periods. Methods A total of 35 adults (aged 40-59 years) with no diagnosis of cognitive impairment were prompted to interact with the Mezurio smartphone app platform for up to 36 days, completing short, daily episodic memory tasks in addition to optional executive function and language tests. A subset (n=20) of participants completed semistructured interviews focused on their experience of using the app. Results Participants complied with 80% of the daily learning tasks scheduled for subsequent tests of episodic memory, with 88% of participants still actively engaged by the final task. A thematic analysis of the participants’ experiences highlighted schedule flexibility, a clear user interface, and performance feedback as important considerations for engagement with remote digital assessment. Conclusions Despite the extended study duration, participants demonstrated high compliance with the schedule of daily learning tasks and were extremely positive about their experiences. Long durations of remote digital interaction are therefore definitely feasible but only when careful attention is paid to the design of the users’ experience.

Objective: The APOE ε4 allele is an established risk factor for dementia, yet this genetic variant is associated with a mixed cognitive profile across the lifespan. This paper undertakes both a systematic and meta-analytic review of research investigating APOE-related differences in cognition in mid-adulthood, when detrimental effects of the allele may first be detectable.Method: 36 papers investigating the behavioural effects of APOE ε4 in mid-adulthood (defined as a mean sample age between 35-60 years) were reviewed. In addition, the effect of carrying an ε4 allele on individual cognitive domains was assessed in separate meta-analyses. Results:The average effect size of APOE ε4 status was non-significant across cognitive domains. Further consideration of genotype effects indicates preclinical effects of APOE ε4 may be observable in memory and executive functioning. Conclusions:The cognitive profile of APOE ε4 carriers at mid-age remains elusive. Whilst there is support for comparable performance by ε4 and non-e4 carriers in the 5 th decade, studies administering sensitive cognitive paradigms indicate a more nuanced profile of cognitive differences. Methodological issues in this field preclude strong conclusions, which future research must address, as well as considering the influence of further vulnerability factors on genotype effects.

Dementia is the most widespread form of neurodegenerative disorder and is associated with an immense societal and personal cost. Prevalence of this disorder is projected to triple worldwide by 2050 leading to an urgent need to make advances in the efficiency of both its care and therapy research. Digital technologies are a rapidly advancing field that provide a previously unavailable opportunity to alleviate challenges faced by clinicians and researchers working in this area. This clinical review aimed to summarise currently available evidence on digital technologies that can be used to monitor cognition. We identified a range of pervasive digital systems, such as smartphones, smartwatches and smart homes, to assess and assist elderly demented, prodromal and preclinical populations. Generally, the studies reported good level of agreement between the digital measures and the constructs they aimed to measure. However, most of the systems are still only in the initial stages of development with limited data on acceptability in patients. Although it is clear that the use of digital technology to monitor and support the cognitive domains affected by dementia is a promising area of development, additional research validating the efficacy, utility and cost-effectiveness of these systems in patient populations is needed.

Gallery Game, deployed within the Mezurio smartphone app, targets the processes of episodic memory first vulnerable to neurofibrillary tau-related degeneration in Alzheimer's Disease, prioritising both perirhinal and entorhinal cortex/hippocampal demands. Thirty-five healthy adults (aged 40-59 years), biased towards those at elevated familial risk of dementia, completed daily Gallery Game tasks for a month. Assessments consisted of cross-modal paired-associate learning, with subsequent tests of recognition and recall following delays ranging from one to 13 days. There was a non-linear decline in memory retention with increasing delays between learning and test, with significant forgetting first reported following delays of three and five days for paired-associate recall and recognition respectively, supporting the need for ecologically valid measures of longer-term memory. Gallery Game outcomes correlated as expected with established neuropsychological memory assessments, confirming the validity of this digital assessment of episodic memory. In addition, there was preliminary support for utilising the perirhinal-dependent pattern of semantic errors during object recognition as a marker of early impairment, justifying ongoing validation against traditional biomarkers of Alzheimer's disease.

Objective. Several studies have reported that people with Parkinson’s disease (PD) perform poorly on tests of ‘Theory of Mind’ (ToM), suggesting impairment in the ability to understand and infer other people’s thoughts and feelings. However, few studies have sought to separate the processes involved in social reasoning from those involved in managing the inhibitory demands on these tests. In this study, we investigated the contribution of inhibition to ToM performance in PD. Methods. 18 PD patients and 22 age-matched healthy controls performed a ToM test that separates the ability to infer someone else’s perspective from the ability to inhibit one’s own. Participants also completed a battery of standard measures of social and executive functioning, including measures of inhibition. Results. The PD patients performed worse on the ToM test only when the inhibitory demands were high. When the level of inhibition required was reduced, there were no significant group differences. Furthermore, executive impairments in PD patients were limited to measures of inhibition, with disadvantages associated with poorer ToM performance in this group. Conclusions. This study provides convincing evidence that the apparent impairment observed on ToM tests in PD is explained by deficits in inhibition.

Background Functional decline in Alzheimer’s disease (AD) is typically measured using single-time point subjective rating scales, which rely on direct observation or (caregiver) recall. Remote monitoring technologies (RMTs), such as smartphone applications, wearables, and home-based sensors, can change these periodic subjective assessments to more frequent, or even continuous, objective monitoring. The aim of the RADAR-AD study is to assess the accuracy and validity of RMTs in measuring functional decline in a real-world environment across preclinical-to-moderate stages of AD compared to standard clinical rating scales. Methods This study includes three tiers. For the main study, we will include participants (n = 220) with preclinical AD, prodromal AD, mild-to-moderate AD, and healthy controls, classified by MMSE and CDR score, from clinical sites equally distributed over 13 European countries. Participants will undergo extensive neuropsychological testing and physical examination. The RMT assessments, performed over an 8-week period, include walk tests, financial management tasks, an augmented reality game, two activity trackers, and two smartphone applications installed on the participants’ phone. In the first sub-study, fixed sensors will be installed in the homes of a representative sub-sample of 40 participants. In the second sub-study, 10 participants will stay in a smart home for 1 week. The primary outcome of this study is the difference in functional domain profiles assessed using RMTs between the four study groups. The four participant groups will be compared for each RMT outcome measure separately. Each RMT outcome will be compared to a standard clinical test which measures the same functional or cognitive domain. Finally, multivariate prediction models will be developed. Data collection and privacy are important aspects of the project, which will be managed using the RADAR-base data platform running on specifically designed biomedical research computing infrastructure. Results First results are expected to be disseminated in 2022. Conclusion Our study is well placed to evaluate the clinical utility of RMT assessments. Leveraging modern-day technology may deliver new and improved methods for accurately monitoring functional decline in all stages of AD. It is greatly anticipated that these methods could lead to objective and real-life functional endpoints with increased sensitivity to pharmacological agent signal detection.

The Apolipoprotein E e4 allele is associated with greater cognitive decline with age, yet effects of this gene are also observed earlier in the lifespan. This research explores genotype differences (e2, e3, e4) in the allocation of visuospatial attention in mid-adulthood. Sixty-six volunteers, aged 45-55 years, completed two paradigms probing the active selection of information at the focus of attention (a dynamic scaling task) and perceptual capacity differences. Two methods of statistical comparison (parametric statistics, Bayesian inference) found no significant difference between e4 carriers and the homozygous e3 group on either the dynamic scaling or perceptual load task. E2 carriers, however, demonstrated less efficient visual search performance on the dynamic scaling task. The lack of an e4 difference in visuospatial attention, despite previous suggestion in the literature of genotype effects, indicates that select attentional processes are intact in e4 carriers in mid-adulthood. The association of e2 genotype with slower visual search performance complicates the premised protective effects of this allele in cognitive ageing.