Neuroinflammation in Preclinical Alzheimer's Disease: A Review of Current Evidence

The pathology of sporadic Alzheimer’s disease (AD) may be present at mid-life and precede the prodromal and clinical dementia syndromes associated with the disorder by decades. Few successful therapeutic treatments exist and, as a result, attention is turning to the preclinical stages of the disease for the development of future intervention strategies. The success of such strategies will rely on well-defined biomarkers of preclinical disease to identify and monitor changes earlier in the disease course. Here, we consider whether immune function changes are potentially useful markers of preclinical disease. We have selected studies spanning epidemiological, animal, clinical and imaging research pertaining to the earliest stages of AD pathogenesis, as well as studies of non-demented adults at high AD risk. We examine changes in inflammatory markers, alongside changes in established biomarkers, to highlight their suitability as disease indicators across preclinical and prodromal stages. We conclude that further work surrounding this topic is required, calling for larger prospective epidemiological studies of preclinical disease that incorporate serial assessment designs with a wider range of inflammatory mediators. We anticipate that future benefits of work in this area include improved disease detection and modification, as well as diagnostic accuracy of trial participants, leading to more cost-effective observation and intervention studies

Emotional processing and Social Cognition in Amyotrophic Lateral Sclerosis

Building on evidence for cognitive-behavioural change in people with Amyotrophic Lateral Sclerosis (ALS), the current study uses a range of neuropsychological measures to delineate the nature and scope of reported deficits in emotional processing and social cognition in people with ALS. Compared to the healthy control group, the ALS group was impaired on composite scores indexing executive function and performance on the emotional processing and social cognition tasks. Single-case analyses revealed that ALS patients showed heterogeneous performance across the cognitive tasks

Goal-orientated cognitive rehabilitation for dementias associated with Parkinson's disease―A pilot randomised controlled trial

OBJECTIVE: To examine the appropriateness and feasibility of cognitive rehabilitation for people with dementias associated with Parkinson's in a pilot randomised controlled study. METHODS: This was a single-blind pilot randomised controlled trial of goal-oriented cognitive rehabilitation for dementias associated with Parkinson's. After goal setting, participants were randomised to cognitive rehabilitation (n = 10), relaxation therapy (n = 10), or treatment-as-usual (n = 9). Primary outcomes were ratings of goal attainment and satisfaction with goal attainment. Secondary outcomes included quality of life, mood, cognition, health status, everyday functioning, and carers' ratings of goal attainment and their own quality of life and stress levels. Assessments were at 2 and 6 months following randomisation. RESULTS: At 2 months, cognitive rehabilitation was superior to treatment-as-usual and relaxation therapy for the primary outcomes of self-rated goal attainment (d = 1.63 and d = 1.82, respectively) and self-rated satisfaction with goal attainment (d = 2.04 and d = 1.84). At 6 months, cognitive rehabilitation remained superior to treatment-as-usual (d = 1.36) and relaxation therapy (d = 1.77) for self-rated goal attainment. Cognitive rehabilitation was superior to treatment as usual and/or relaxation therapy in a number of secondary outcomes at 2 months (mood, self-efficacy, social domain of quality of life, carers' ratings of participants' goal attainment) and at 6 months (delayed recall, health status, quality of life, carer ratings of participants' goal attainment). Carers receiving cognitive rehabilitation reported better quality of life, health status, and lower stress than those allocated to treatment-as-usual. CONCLUSIONS: Cognitive rehabilitation is feasible and potentially effective for dementias associated with Parkinson's disease

Cognitive Dispersion Predicts Grip Strength Trajectories in Men but not Women in a Sample of the Oldest Old Without Dementia

Background and Objectives: Grip strength is a reliable marker of biological vitality and it typically demonstrates an expected decline in older adults. According to the common-cause hypothesis there is also a significant association between cognitive and physical function in older adults. Some specific cognitive functions have been shown to be associated with grip strength trajectories with most research solely focused on cut-off points or mean cognitive performance. In the present study we examine whether a measure of cognitive dispersion might be more informative. We therefore used an index that quantifies dispersion in cognitive scores across multiple cognitive tests, shown to be associated with detrimental outcomes in older adults. Research Design and Methods: Using repeated grip strength measures from men and women aged 80 and older, free of dementia in the OCTO-Twin study, we estimated ageing-related grip strength trajectories. We examined the association of cognitive dispersion and mean cognitive function with grip strength level and ageing-related rate of change, accounting for known risk factors. Results: Cognitive dispersion was associated with grip strength trajectories in men and the association varied by mean cognitive performance, whereas we found no association in women. Discussion and Implications: Our results provide evidence of a sex-specific vitality association between cognitive dispersion and ageing-related trajectories of grip strength. Our results support the call for integration of sex and gender in health promotion and intervention research

A digital biomarker for remote self-assessment of Alzheimer’s Diseases: development and validatio

Background: Online data-collection provide an opportunity for Alzheimer's Disease research to collect large datasets crucial for understanding important public health concerns. However, the reliability of online tasks as compared to those administered in the lab is poorly examined. Our goal is to validate an online version of the short-term memory-binding task (STMBT), a potential digital biomarker sensitive to Alzheimer’s Disease (Parra et al., 2010), to understand if data collected online in two environments, at-home and in the lab, is comparable. Method: We created an online version of the STMBT task using Psytoolkit (Stoet 2010; Stoet 2017). Development involved piloting, group and user discussions to explore how such a novel tool could be best presented for self-assessment. Useful insights led to refinement of the online tool (i.e., instruction videos, images, and text). The validation stage involves test-retest reliability assessment of cognitively fit participants (aged >40 years) who complete the two conditions of this paradigm (i.e., shape only and binding). Task Environment (home and in the lab) and conditions (shape and binding) were fully counterbalanced. Measures of general cognitive abilities, anxiety and at-home environment were also taken. Result: Recruitment is on-going, but preliminary data (n=10) has already proved informative. A repeated measures ANOVA looking at task-accuracy with factors of Environment (home vs. lab) and Condition (shape vs. binding) revealed no significant effects of Environment: F(1, 9) = 0.308, p = .591; Condition: F(1, 9) = 2.202, p = .172); or Interaction: F(1, 9) = 0.308, p = .591). For the shape condition, all participants performed near ceiling regardless of testing environment. In the binding condition, we observed good-to-excellent test-retest reliability between environments using single measures interclass correlation (ICC = 0.954, CI 0.83-0.99, (F(9, 9) = 39.62, p <.001). Conclusion: These preliminary results indicate the STMBT can provide reliable data when self-administered using an online version of the task which has important implications for public health researchers. For our fully powered sample, we will provide summary of other measures

The development and validation of a digital biomarker for remote assessment of Alzheimer's diseases risk

Background: Digital cognitive assessment is becoming increasingly widespread in ageing research and care, especially since the COVID19 pandemic. Remote online collection provides opportunities for ageing and dementia professionals to collect larger datasets, increase the diversity of research participants and patients and offer cost-effective screening and monitoring methods for clinical practice and trials. However, the reliability of self-administered at-home tests compared to their lab-based counterparts often goes unexamined, compromising the validity of adopting such measures. Objective: Our aim is to validate a self-administered web-based version of the visual short-term memory binding task (VSTMBT), a potential digital biomarker sensitive to Alzheimer’s Disease processes, suitable for use on personal devices. Methods: A final cross-sectional sample of 37 older-adult (51 – 77 years) participants without dementia completed our novel self-administered version of the VSTMBT, both at home on a personal device and in the lab, under researcher-controlled conditions. Results: ANOVA and Bayesian T-test found no significant differences between the task when it was remotely self-administered by participants at home compared to when it was taken under controlled lab conditions. Conclusions: These results indicate the VSTMBT can provide reliable data when self administered at-home using an online version of the task and on a personal device. This finding has important implications for remote screening and monitoring practices of older adults, as well as supporting clinical practices serving diverse patient communities. Future work will assess remote administration in older adults with cognitive impairment and diverse socio-economic and ethno-cultural backgrounds as well as a bench-to-bedside application

The development and validation of a digital biomarker for remote assessment of Alzheimer's Diseases Risk.

Background Digital cognitive assessment is becoming increasingly widespread in ageing research and care, especially since the COVID19 pandemic. Remote online collection provides opportunities for ageing and dementia professionals to collect larger datasets, increase the diversity of research participants and patients and offer cost-effective screening and monitoring methods for clinical practice and trials. However, the reliability of self-administered at-home tests compared to their lab-based counterparts often goes unexamined, compromising the validity of adopting such measures. Objective Our aim is to validate a self-administered web-based version of the visual short-term memory binding task (VSTMBT), a potential digital biomarker sensitive to Alzheimer’s Disease processes, suitable for use on personal devices. Methods A final cross-sectional sample of 37 older-adult (51 – 77 years) participants without dementia completed our novel self-administered version of the VSTMBT, both at home on a personal device and in the lab, under researcher-controlled conditions. Results ANOVA and Bayesian T-test found no significant differences between the task when it was remotely self-administered by participants at home compared to when it was taken under controlled lab conditions. Conclusions These results indicate the VSTMBT can provide reliable data when self-administered at-home using an online version of the task and on a personal device. This finding has important implications for remote screening and monitoring practices of older adults, as well as supporting clinical practices serving diverse patient communities. Future work will assess remote administration in older adults with cognitive impairment and diverse socio-economic and ethno-cultural backgrounds as well as a bench-to-bedside application

Impact of disease, cognitive and behavioural factors on caregiver outcome in amyotrophic lateral sclerosis

Up to 50% of patients with amyotrophic lateral sclerosis (ALS) show mild to moderate cognitive-behavioural change alongside their progressive functional impairment. This study examines the relative impact of patients' disease symptoms, behavioural change and current executive function and social cognition abilities on psychosocial outcomes in spouse caregivers of people with ALS. Thirty-five spouse caregivers rated their own levels of depression and anxiety, subjective burden and marital satisfaction. Caregivers also rated their partner's everyday behaviour. The patients were assessed for disease severity and cognitive function, with composite scores derived for executive function and social cognition. Regression analyses revealed that caregiver burden was predicted by the severity of patients' limb involvement and behavioural problems. Depression was predicted by patients' limb involvement, while behavioural problems and patient age predicted caregiver anxiety. Current marital satisfaction was predicted by patient behavioural problems beyond the level of pre-illness marital satisfaction. In conclusion, the study highlights the potential impact of ALS patients' functional impairment and behavioural change on ALS caregivers' psychosocial functioning. Clinical communication with ALS families should emphasise both physical and psychological challenges presented by the disease

Health, Lifestyle, and Psycho-Social Determinants of Poor Sleep Quality During the Early Phase of the COVID-19 Pandemic: A Focus on UK Older Adults Deemed Clinically Extremely Vulnerable

Background: Several studies have assessed the impact of COVID-19-relatedlockdownson sleep quality across global populations. However, no study to date has specifically assessed at-riskpopulations, particularly those at highest risk of complications from coronavirus infection deemed “clinically-extremely-vulnerable-(COVID-19CEV)” [as defined by Public Health England, 2020].Methods: In this cross-sectional study, we surveyed 5,558 adults aged ≥50 years (of whom 523 met criteria for COVID-19CEV) during the first pandemic wave that resulted in a nationwide-lockdown (April-June 2020) with assessments of sleep quality (an adapted sleep scale that captured multiple sleep indices before and during the lockdown), health/medical, lifestyle, psychosocial and socio demographic factors. We examined associations between these variablesand sleep quality;and explored interactions of COVID-19CEV status with significant predictors of poor sleep,to identify potential moderating factors. Results: 37% of participants reported poor sleep quality which was associated with younger age, female sex and multimorbidity. Significant associations with poor sleep included health/medical factors: COVID-19 CEV status, higher BMI, arthritis, pulmonary disease, and mental health disorders; and the following lifestyle and psychosocial factors: living alone, higher alcohol consumption, an unhealthy diet and higher depressive and anxiety symptoms. Moderators of the negative relationship between COVID-19 CEV status and good sleep quality were marital status, loneliness, anxiety and diet. Within this subgroup, less anxious and less lonely males, as well as females with healthier diets, reported better sleep. Conclusions: Sleep quality in older adults was compromised during the sudden unprecedented nation-wide lockdown due to distinct modifiable factors. An important contribution of our study is the assessment of a “clinically-extremely-vulnerable” population and the sex differences identified within this group. Male and female older adults deemed COVID-19 CEV may benefit from targeted mental health and dietary interventions, respectively. This work extends the available evidence on the notable impact of lack of social interactions during the COVID-19 pandemic on sleep, and provides recommendations towards areas for future work, including research into vulnerability factors impacting sleep disruption and COVID-19-related complications. Study results may inform tailored interventions targeted at modifiable risk factors to promote optimal sleep; additionally, providing empirical data to support health policy development in this area