Tablet-Based Puzzle Game Intervention for Cognitive Function and Well-Being in Healthy Adults: Pilot Feasibility Randomized Controlled Trial.

Background: Promoting cognitive health is key to maintaining cognitive and everyday functions and preventing the risk of cognitive impairment or dementia. Existing scientific evidence shows the benefits of various training modalities on cognition. One way to promote cognitive health is through engagement in cognitive activities (eg, board and video games). Objective: This study aims to investigate the benefits of dynamic adaptive casual puzzle games on cognitive function and well-being in healthy adults and older people. Methods: A total of 12 adults and older people (female participants: n=6; mean age 58.92, SD 10.28 years; range 46-75 years) were included in this pilot randomized controlled trial. This study used a crossover design with two phases (8 weeks each) and three measurement waves (pretest, midtest, and posttest). The participants were randomly allocated either to the control or experimental group. In the control group, participants read newspapers between the pre- and midtest, then switched to cognitive training with puzzle games. In the experimental group, the interventions were reversed. Baseline measurements (pretest) were collected before the intervention. The interventions were delivered on tablet computers and took place unsupervised at participants' homes. Results: The outcome measures included global cognitive function, higher cognitive function, and emotional well-being at 3 time points (pretest, midtest, and posttest) using standardized neuropsychological tests. The participants showed improvements in their visual attention and visuospatial measures after the puzzle game intervention. Conclusions: The study showed that digital games are a feasible way to train cognition in healthy adults and older people. The algorithm-based dynamic adaption allows accommodations for persons with different cognitive levels of skill. The results of the study will guide future prevention efforts and trials in high-risk populations.

The role of dyadic cognitive report and subjective cognitive decline in early ADRD clinical research and trials: Current knowledge, gaps, and recommendations.

Efficient identification of cognitive decline and Alzheimer's disease (AD) risk in early stages of the AD disease continuum is a critical unmet need. Subjective cognitive decline is increasingly recognized as an early symptomatic stage of AD. Dyadic cognitive report, including subjective cognitive complaints (SCC) from a participant and an informant/study partner who knows the participant well, represents an accurate, reliable, and efficient source of data for assessing risk. However, the separate and combined contributions of self- and study partner report, and the dynamic relationship between the two, remains unclear. The Subjective Cognitive Decline Professional Interest Area within the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment convened a working group focused on dyadic patterns of subjective report. Group members identified aspects of dyadic-report information important to the AD research field, gaps in knowledge, and recommendations. By reviewing existing data on this topic, we found evidence that dyadic measures are associated with objective measures of cognition and provide unique information in preclinical and prodromal AD about disease stage and progression and AD biomarker status. External factors including dyad (participant-study partner pair) relationship and sociocultural factors contribute to these associations. We recommend greater dyad report use in research settings to identify AD risk. Priority areas for future research include (1) elucidation of the contributions of demographic and sociocultural factors, dyad type, and dyad relationship to dyad report; (2) exploration of agreement and discordance between self- and study partner report across the AD syndromic and disease continuum; (3) identification of domains (e.g., memory, executive function, neuropsychiatric) that predict AD risk outcomes and differentiate cognitive impairment due to AD from other impairment; (4) development of best practices for study partner engagement; (5) exploration of study partner report as AD clinical trial endpoints; (6) continued development, validation, and optimization, of study partner report instruments tailored to the goals of the research and population.

A systems approach towards remote health-monitoring in older adults: Introducing a zero-interaction digital exhaust.

Using connected sensing devices to remotely monitor health is a promising way to help transition healthcare from a rather reactive to a more precision medicine oriented proactive approach, which could be particularly relevant in the face of rapid population ageing and the challenges it poses to healthcare systems. Sensor derived digital measures of health, such as digital biomarkers or digital clinical outcome assessments, may be used to monitor health status or the risk of adverse events like falls. Current research around such digital measures has largely focused on exploring the use of few individual measures obtained through mobile devices. However, especially for long-term applications in older adults, this choice of technology may not be ideal and could further add to the digital divide. Moreover, large-scale systems biology approaches, like genomics, have already proven beneficial in precision medicine, making it plausible that the same could also hold for remote-health monitoring. In this context, we introduce and describe a zero-interaction digital exhaust: a set of 1268 digital measures that cover large parts of a person's activity, behavior and physiology. Making this approach more inclusive of older adults, we base this set entirely on contactless, zero-interaction sensing technologies. Applying the resulting digital exhaust to real-world data, we then demonstrate the possibility to create multiple ageing relevant digital clinical outcome assessments. Paired with modern machine learning, we find these assessments to be surprisingly powerful and often on-par with mobile approaches. Lastly, we highlight the possibility to discover novel digital biomarkers based on this large-scale approach.

Clinical outcome measures in dementia with Lewy bodies trials: critique and recommendations.

The selection of appropriate outcome measures is fundamental to the design of any successful clinical trial. Although dementia with Lewy bodies (DLB) is one of the most common neurodegenerative conditions, assessment of therapeutic benefit in clinical trials often relies on tools developed for other conditions, such as Alzheimer's or Parkinson's disease. These may not be sufficiently valid or sensitive to treatment changes in DLB, decreasing their utility. In this review, we discuss the limitations and strengths of selected available tools used to measure DLB-associated outcomes in clinical trials and highlight the potential roles for more specific objective measures. We emphasize that the existing outcome measures require validation in the DLB population and that DLB-specific outcomes need to be developed. Finally, we highlight how the selection of outcome measures may vary between symptomatic and disease-modifying therapy trials.

A Sensor-Driven Visit Detection System in Older Adults' Homes: Towards Digital Late-Life Depression Marker Extraction.

Modern sensor technology is increasingly used in older adults to not only provide additional safety but also to monitor health status, often by means of sensor derived digital measures or biomarkers. Social isolation is a known risk factor for late-life depression, and a potential component of social-isolation is the lack of home visits. Therefore, home visits may serve as a digital measure for social isolation and late-life depression. Late-life depression is a common mental and emotional disorder in the growing population of older adults. The disorder, if untreated, can significantly decrease quality of life and, amongst other effects, leads to increased mortality. Late-life depression often goes undiagnosed due to associated stigma and the incorrect assumption that it is a normal part of ageing. In this work, we propose a visit detection system that generalizes well to previously unseen apartments - which may differ largely in layout, sensor placement, and size from apartments found in the semi-annotated training dataset. We find that by using a self-training-based domain adaptation strategy, a robust system to extract home visit information can be built (ROC AUC = 0.773). We further show that the resulting visit information correlates well with the common geriatric depression scale screening tool ( ρ = -0.87, p = 0.001), providing further support for the idea of utilizing the extracted information as a potential digital measure or even as a digital biomarker to monitor the risk of late-life depression.

Cognition, hallucination severity and hallucination-specific insight in neurodegenerative disorders and eye disease.

Introduction: Hallucinations occur across neurodegenerative disorders, with increasing severity, poorer cognition and impaired hallucination-specific insight associated with worse outcomes and faster disease progression. It remains unclear how changes in cognition, temporal aspects of hallucinations, hallucination-specific insight and distress relate to each other.Methods: Extant samples of patients experiencing visual hallucinations were included in the analyses: Parkinson's Disease (n = 103), Parkinson's Disease Dementia (n = 41), Dementia with Lewy Bodies (n = 27) and Eye Disease (n = 113). We explored the relationship between factors of interest with Spearman's correlations and random-effect linear models.Results: Spearman's correlation analyses at the whole-group level showed that higher hallucination-specific insight was related to higher MMSE score (rs = 0.39, p < 0.001) and less severe hallucinations (rs = -0.28, p < .01). Linear mixed-models controlling for diagnostic group showed that insight was related to higher MMSE (p < .001), to hallucination severity (p = 0.003), and to VH duration (p = 0.04). Interestingly, insight was linked to the distress component but not the frequency component of severity. No significant relationship was found between MMSE and hallucination severity in these analyses.Conclusion: Our findings highlight the importance of hallucination-specific insight, distress and duration across groups. A better understanding of the role these factors play in VH may help with the development of future therapeutic interventions trans-diagnostically.

Face Perception and Pareidolia Production in Patients With Parkinson's Disease.

In Parkinson's disease (PD) patients, visual misperceptions are a major problem within the non-motor symptoms. Pareidolia, i.e., the tendency to perceive a specific, meaningful image in an ambiguous visual pattern, is a phenomenon that occurs also in healthy subjects. Literature suggests that the perception of face pareidolia may be increased in patients with neurodegenerative diseases. We aimed to examine, within the same experiment, face perception and the production of face pareidolia in PD patients and healthy controls (HC). Thirty participants (15 PD patients and 15 HC) were presented with 47 naturalistic photographs in which faces were embedded or not. The likelihood to perceive the embedded faces was modified by manipulating their transparency. Participants were asked to decide for each photograph whether a face was embedded or not. We found that PD patients were significantly less likely to recognize embedded faces than controls. However, PD patients also perceived faces significantly more often in locations where none were actually present than controls. Linear regression analyses showed that gender, age, hallucinations, and Multiple-Choice Vocabulary Intelligence Test (MWT) score were significant predictors of face pareidolia production in PD patients. Montreal Cognitive Assessment (MoCA) was a significant predictor for pareidolia production in PD patients in trials in which a face was embedded in another region [F (1, 13) = 24.4, p = <0.001]. We conclude that our new embedded faces paradigm is a useful tool to distinguish face perception performance between HC and PD patients. Furthermore, we speculate that our results observed in PD patients rely on disturbed interactions between the Dorsal (DAN) and Ventral Attention Networks (VAN). In photographs in which a face is present, the VAN may detect this as a behaviourally relevant stimulus. However, due to the deficient communication with the DAN in PD patients, the DAN would not direct attention to the correct location, identifying a face at a location where actually none is present.

Development of a Search Task Using Immersive Virtual Reality: Proof-of-Concept Study.

BACKGROUND: Serious games are gaining increasing importance in neurorehabilitation since they increase motivation and adherence to therapy, thereby potentially improving its outcome. The benefits of serious games, such as the possibility to implement adaptive feedback and the calculation of comparable performance measures, can be even further improved by using immersive virtual reality (iVR), allowing a more intuitive interaction with training devices and higher ecological validity. OBJECTIVE: This study aimed to develop a visual search task embedded in a serious game setting for iVR, including self-adapting difficulty scaling, thus being able to adjust to the needs and ability levels of different groups of individuals. METHODS: In a two-step process, a serious game in iVR (bird search task) was developed and tested in healthy young (n=21) and elderly (n=23) participants and in a group of patients with impaired visual exploration behavior (ie, patients with hemispatial neglect after right-hemispheric stroke; n=11). Usability, side effects, game experience, immersion, and presence of the iVR serious game were assessed by validated questionnaires. Moreover, in the group of stroke patients, the performance in the iVR serious game was also considered with respect to hemispatial neglect severity, as assessed by established objective hemispatial neglect measures. RESULTS: In all 3 groups, reported usability of the iVR serious game was above 4.5 (on a Likert scale with scores ranging from 1 to 5) and reported side effects were infrequent and of low intensity (below 1.5 on a Likert scale with scores ranging from 1 to 4). All 3 groups equally judged the iVR serious game as highly motivating and entertaining. Performance in the game (in terms of mean search time) showed a lateralized increase in search time in patients with hemispatial neglect that varied strongly as a function of objective hemispatial neglect severity. CONCLUSIONS: The developed iVR serious game, "bird search task," was a motivating, entertaining, and immersive task, which can, due to its adaptive difficulty scaling, adjust and be played by different populations with different levels of skills, including individuals with cognitive impairments. As a complementary finding, it seems that performance in the game is able to capture typical patterns of impaired visual exploration behavior in hemispatial neglect, as there is a high correlation between performance and neglect severity as assessed with a cancellation task.

Contactless Sleep Monitoring for Early Detection of Health Deteriorations in Community-Dwelling Older Adults: Exploratory Study.

BACKGROUND: Population aging is posing multiple social and economic challenges to society. One such challenge is the social and economic burden related to increased health care expenditure caused by early institutionalizations. The use of modern pervasive computing technology makes it possible to continuously monitor the health status of community-dwelling older adults at home. Early detection of health issues through these technologies may allow for reduced treatment costs and initiation of targeted preventive measures leading to better health outcomes. Sleep is a key factor when it comes to overall health and many health issues manifest themselves with associated sleep deteriorations. Sleep quality and sleep disorders such as sleep apnea syndrome have been extensively studied using various wearable devices at home or in the setting of sleep laboratories. However, little research has been conducted evaluating the potential of contactless and continuous sleep monitoring in detecting early signs of health problems in community-dwelling older adults. OBJECTIVE: In this work we aim to evaluate which contactlessly measurable sleep parameter is best suited to monitor perceived and actual health status changes in older adults. METHODS: We analyzed real-world longitudinal (up to 1 year) data from 37 community-dwelling older adults including more than 6000 nights of measured sleep. Sleep parameters were recorded by a pressure sensor placed beneath the mattress, and corresponding health status information was acquired through weekly questionnaires and reports by health care personnel. A total of 20 sleep parameters were analyzed, including common sleep metrics such as sleep efficiency, sleep onset delay, and sleep stages but also vital signs in the form of heart and breathing rate as well as movements in bed. Association with self-reported health, evaluated by EuroQol visual analog scale (EQ-VAS) ratings, were quantitatively evaluated using individual linear mixed-effects models. Translation to objective, real-world health incidents was investigated through manual retrospective case-by-case analysis. RESULTS: Using EQ-VAS rating based self-reported perceived health, we identified body movements in bed-measured by the number toss-and-turn events-as the most predictive sleep parameter (t score=-0.435, P value [adj]=<.001). Case-by-case analysis further substantiated this finding, showing that increases in number of body movements could often be explained by reported health incidents. Real world incidents included heart failure, hypertension, abdominal tumor, seasonal flu, gastrointestinal problems, and urinary tract infection. CONCLUSIONS: Our results suggest that nightly body movements in bed could potentially be a highly relevant as well as easy to interpret and derive digital biomarker to monitor a wide range of health deteriorations in older adults. As such, it could help in detecting health deteriorations early on and provide timelier, more personalized, and precise treatment options.

Application of Eye Tracking in Puzzle Games for Adjunct Cognitive Markers: Pilot Observational Study in Older Adults.

BACKGROUND: Recent studies suggest that computerized puzzle games are enjoyable, easy to play, and engage attentional, visuospatial, and executive functions. They may help mediate impairments seen in cognitive decline in addition to being an assessment tool. Eye tracking provides a quantitative and qualitative analysis of gaze, which is highly useful in understanding visual search behavior. OBJECTIVE: The goal of the research was to test the feasibility of eye tracking during a puzzle game and develop adjunct markers for cognitive performance using eye-tracking metrics. METHODS: A desktop version of the Match-3 puzzle game with 15 difficulty levels was developed using Unity 3D (Unity Technologies). The goal of the Match-3 puzzle was to find configurations (target patterns) that could be turned into a row of 3 identical game objects (tiles) by swapping 2 adjacent tiles. Difficulty levels were created by manipulating the puzzle board size (all combinations of width and height from 4 to 8) and the number of unique tiles on the puzzle board (from 4 to 8). Each level consisted of 4 boards (ie, target patterns to match) with one target pattern each. In this study, the desktop version was presented on a laptop computer setup with eye tracking. Healthy older subjects were recruited to play a full set of 15 puzzle levels. A paper-pencil-based assessment battery was administered prior to the Match-3 game. The gaze behavior of all participants was recorded during the game. Correlation analyses were performed on eye-tracking data correcting for age to examine if gaze behavior pertains to target patterns and distractor patterns and changes with puzzle board size (set size). Additionally, correlations between cognitive performance and eye movement metrics were calculated. RESULTS: A total of 13 healthy older subjects (mean age 70.67 [SD 4.75] years; range 63 to 80 years) participated in this study. In total, 3 training and 12 test levels were played by the participants. Eye tracking recorded 672 fixations in total, 525 fixations on distractor patterns and 99 fixations on target patterns. Significant correlations were found between executive functions (Trail Making Test B) and number of fixations on distractor patterns (P=.01) and average fixations (P=.005). CONCLUSIONS: Overall, this study shows that eye tracking in puzzle games can act as a supplemental source of data for cognitive performance. The relationship between a paper-pencil test for executive functions and fixations confirms that both are related to the same cognitive processes. Therefore, eye movement metrics might be used as an adjunct marker for cognitive abilities like executive functions. However, further research is needed to evaluate the potential of the various eye movement metrics in combination with puzzle games as visual search and attentional marker.

Case Report: Ambient Sensor Signals as Digital Biomarkers for Early Signs of Heart Failure Decompensation.

Home monitoring systems are increasingly used to monitor seniors in their apartments for detection of emergency situations. More recently, multimodal ambient sensor systems are also used to monitor digital biomarkers to detect clinically relevant health problems over longer time periods. Clinical signs of HF decompensation including increase of heart rate and respiration rate, decreased physical activity, reduced gait speed, increasing toilet use at night and deterioration of sleep quality have a great potential to be detected by non-intrusive contactless ambient sensor systems and negative changes of these parameters may be used to prevent further deterioration and hospitalization for HF decompensation. This is to our knowledge the first report about the potential of an affordable, contactless, and unobtrusive ambient sensor system for the detection of early signs of HF decompensation based on data with prospective data acquisition and retrospective correlation of the data with clinical events in a 91 year old senior with a serious heart problem over 1 year. The ambient sensor system detected an increase of respiration rate, heart rate, toilet use at night, toss, and turns in bed and a decrease of physical activity weeks before the decompensation. In view of the rapidly increasing prevalence of HF and the related costs for the health care systems and the societies, the real potential of our approach should be evaluated in larger populations of HF patients.

A Review of Multimodal Hallucinations: Categorization, Assessment, Theoretical Perspectives, and Clinical Recommendations.

Hallucinations can occur in different sensory modalities, both simultaneously and serially in time. They have typically been studied in clinical populations as phenomena occurring in a single sensory modality. Hallucinatory experiences occurring in multiple sensory systems-multimodal hallucinations (MMHs)-are more prevalent than previously thought and may have greater adverse impact than unimodal ones, but they remain relatively underresearched. Here, we review and discuss: (1) the definition and categorization of both serial and simultaneous MMHs, (2) available assessment tools and how they can be improved, and (3) the explanatory power that current hallucination theories have for MMHs. Overall, we suggest that current models need to be updated or developed to account for MMHs and to inform research into the underlying processes of such hallucinatory phenomena. We make recommendations for future research and for clinical practice, including the need for service user involvement and for better assessment tools that can reliably measure MMHs and distinguish them from other related phenomena.

Investigating a new tablet-based telerehabilitation app in patients with aphasia: a randomised, controlled, evaluator-blinded, multicentre trial protocol.

INTRODUCTION: Aphasia is a common language disorder acquired after stroke that reduces the quality of life of affected patients. The impairment is frequently accompanied by a deficit in cognitive functions. The state-of-the-art therapy is speech and language therapy but recent findings highlight positive effects of high-frequency therapy. Telerehabilitation has the potential to enable high-frequency therapy for patients at home. This study investigates the effects of high-frequency telerehabilitation speech and language therapy (teleSLT) on language functions in outpatients with aphasia compared with telerehabilitative cognitive training. We hypothesise that patients training with high-frequency teleSLT will show higher improvement in language functions and quality of life compared with patients with high-frequency tele-rehabilitative cognitive training (teleCT). METHODS AND ANALYSIS: This study is a randomised controlled, evaluator-blinded multicentre superiority trial comparing the outcomes following either high-frequency teleSLT or teleCT. A total of 100 outpatients with aphasia will be recruited and assigned in a 1:1 ratio stratified by trial site and severity of impairment to one of two parallel groups. Both groups will train over a period of 4 weeks for 2 hours per day. Patients in the experimental condition will devote 80% of their training time to teleSLT and the remaining 20% (24 min/day) to teleCT, vice versa for patients in the control condition. The primary outcome measure is the understandability of verbal communication on the Amsterdam Nijmegen Everyday Language Test and secondary outcome measures are intelligibility of the verbal communication, impairment of receptive and expressive language functions, confrontation naming. Other outcomes measures are quality of life and acceptance (usability and subjective experience) of the teleSLT system. ETHICS AND DISSEMINATION: This study is approved by the Ethics Committee Bern (ID 2016-01577). Results will be submitted to a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03228264.

Isometric Strength Measures are Superior to the Timed Up and Go Test for Fall Prediction in Older Adults: Results from a Prospective Cohort Study.

BACKGROUND: Isometric strength measures and timed up and go (TUG) tests are both recognized as valuable tools for fall prediction in older adults. However, results from direct comparison of these two tests are lacking. We aimed to assess the potential of isometric strength measures and the different modalities of the TUG test to detect individuals at risk of falling. METHODS: This is a prospective cohort study including 24 community-dwelling older adults (≥65 years, 19 females, 88±7 years). Participants performed three variations of the TUG test (standard, counting and holding a full cup) and three isometric strength tests (handgrip, knee extension and hip flexion) at several time points (at baseline and every ~6 weeks) during a one-year follow-up. The association between these tests and the incidence of falls during the follow-up was assessed. RESULTS: Twelve participants out of 24 participants experienced falls during the follow-up. Fallers showed a significantly lower handgrip strength (-5.7 kg, 95% confidence interval: -10.4 to -1.1, p=0.019) and knee extension strength (-4.9 kg, -9.6 to -0.2, p=0.042) at follow-up, while no significant differences were found for any TUG variation. CONCLUSIONS: Handgrip and knee extension strength measures - particularly when assessed regularly over time - have the potential to serve as a simple and easy tool for detecting individuals at risk of falling as compared to functional mobility measures (ie, TUG test).

Potential of Ambient Sensor Systems for Early Detection of Health Problems in Older Adults.

Background: Home monitoring sensor systems are increasingly used to monitor seniors in their apartments for detection of emergency situations. The aim of this study was to deliver a proof-of-concept for the use of multimodal sensor systems with pervasive computing technology for the detection of clinically relevant health problems over longer time periods. Methods: Data were collected with a longitudinal home monitoring study in Switzerland (StrongAge Cohort Study) in a cohort of 24 old and oldest-old, community-dwelling adults over a period of 1 to 2 years. Physical activity in the apartment, toilet visits, refrigerator use, and entrance door openings were quantified using a commercially available passive infrared motion sensing system (Domosafety S.A., Switzerland). Heart rate, respiration rate, and sleep quality were recorded with the commercially available EMFIT QS bed sensor device (Emfit Ltd., Finland). Vital signs and contextual data were collected using a wearable sensor on the upper arm (Everion, Biovotion, Switzerland). Sensor data were correlated with health-related data collected from the weekly visits of the seniors by health professionals, including information about physical, psychological, cognitive, and behavior status, health problems, diseases, medication, and medical diagnoses. Results: Twenty of the 24 recruited participants (age 88.9 ± 7.5 years, 79% females) completed the study; two participants had to stop their study participation because of severe health deterioration, whereas two participants died during the course of the study. A history of chronic disease was present in 12/24 seniors, including heart failure, heart rhythm disturbances, pulmonary embolism, severe insulin-dependent diabetes, and Parkinson's disease. In total, 242,232 person-hours were recorded. During the monitoring period, 963 health status records were reported and repeated clinical assessments of aging-relevant indicators and outcomes were performed. Several episodes of health deterioration, including heart failure worsening and heart rhythm disturbances, could be captured by sensor signals from different sources. Conclusions: Our results indicate that monitoring of seniors with a multimodal sensor and pervasive computing system over longer time periods is feasible and well-accepted, with a great potential for detection of health deterioration. Further studies are necessary to evaluate the full range of the clinical potential of these findings.

Development and Evaluation of Maze-Like Puzzle Games to Assess Cognitive and Motor Function in Aging and Neurodegenerative Diseases.

There is currently a need for engaging, user-friendly, and repeatable tasks for assessment of cognitive and motor function in aging and neurodegenerative diseases. This study evaluated the feasibility of a maze-like Numberlink puzzle game in assessing differences in game-based measures of cognition and motor function due to age and neurodegenerative diseases. Fifty-five participants, including young (18-31 years, n = 18), older (64-79 years, n = 14), and oldest adults (86-98 years, n = 14), and patients with Parkinson's (59-76 years, n = 4) and Huntington's disease (HD; 35-66 years, n = 5) played different difficulty levels of the Numberlink puzzle game and completed usability questionnaires and tests for psychomotor, attentional, visuospatial, and constructional and executive function. Analyses of Numberlink game-based cognitive (solving time and errors) and motor [mean velocity and movement direction changes (MDC)] performance metrics revealed statistically significant differences between age groups and between patients with HD and older adults. However, patients with Parkinson's disease (PD) did not differ from older adults. Correlational analyses showed significant associations between game-based performance and movement metrics and performance on neuropsychological tests for psychomotor, attentional, visuospatial, and constructional and executive function. Furthermore, varying characteristics of the Numberlink puzzle game succeeded in creating graded difficulty levels. Findings from this study support recent suggestions that data from a maze-like puzzle game provide potential "digital biomarkers" to assess changes in psychomotor, visuoconstructional, and executive function related to aging and neurodegeneration. In particular, game-based movement measures from the maze-like puzzle Numberlink games are promising as a tool to monitor the progression of motor impairment in neurodegenerative diseases. Further studies are needed to more comprehensively establish the cognitive validity and test-retest reliability of using Numberlink puzzles as a valid cognitive assessment tool.

Visual hallucinations in neurological and ophthalmological disease: pathophysiology and management.

Visual hallucinations are common in older people and are especially associated with ophthalmological and neurological disorders, including dementia and Parkinson's disease. Uncertainties remain whether there is a single underlying mechanism for visual hallucinations or they have different disease-dependent causes. However, irrespective of mechanism, visual hallucinations are difficult to treat. The National Institute for Health Research (NIHR) funded a research programme to investigate visual hallucinations in the key and high burden areas of eye disease, dementia and Parkinson's disease, culminating in a workshop to develop a unified framework for their clinical management. Here we summarise the evidence base, current practice and consensus guidelines that emerged from the workshop.Irrespective of clinical condition, case ascertainment strategies are required to overcome reporting stigma. Once hallucinations are identified, physical, cognitive and ophthalmological health should be reviewed, with education and self-help techniques provided. Not all hallucinations require intervention but for those that are clinically significant, current evidence supports pharmacological modification of cholinergic, GABAergic, serotonergic or dopaminergic systems, or reduction of cortical excitability. A broad treatment perspective is needed, including carer support. Despite their frequency and clinical significance, there is a paucity of randomised, placebo-controlled clinical trial evidence where the primary outcome is an improvement in visual hallucinations. Key areas for future research include the development of valid and reliable assessment tools for use in mechanistic studies and clinical trials, transdiagnostic studies of shared and distinct mechanisms and when and how to treat visual hallucinations.