The RESIST Study: Examining Cognitive Change in Rheumatoid Arthritis Patients with Mild Cognitive Impairment Being Treated with a TNF-Inhibitor Compared to a Conventional Synthetic Disease-Modifying Anti-Rheumatic Drug.

Background: Evidence suggests that TNF inhibitors (TNFi) used to treat rheumatoid arthritis (RA) may protect against Alzheimer's disease progression by reducing inflammation. Objective: To investigate whether RA patients with mild cognitive impairment (MCI) being treated with a TNFi show slower cognitive decline than those being treated with a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). Methods: 251 participants with RA and MCI taking either a csDMARD (N = 157) or a TNFi (N = 94) completed cognitive assessments at baseline and 6-month intervals for 18 months. It was hypothesized that those taking TNFis would show less decline on the primary outcome of Free and Cued Selective Reminding Test with Immediate Recall (FCSRT-IR) and the secondary outcome of Montreal Cognitive Assessment (MoCA). Results: No significant changes in FCSRT-IR scores were observed in either treatment group. There was no significant difference in FCSRT-IR between treatment groups at 18 months after adjusting for baseline (mean difference = 0.5, 95% CI = -1.3, 2.3). There was also no difference in MoCA score (mean difference = 0.4, 95% CI = -0.4, 1.3). Conclusions: There was no cognitive decline in participants with MCI being treated with TNFis and csDMARDs, raising the possibility both classes of drug may be protective. Future studies should consider whether controlling inflammatory diseases using any approach is more important than a specific therapeutic intervention.

Investigating the prevalence of cognitive impairment and dementia in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA): the Harmonised Cognitive Assessment Protocol (HCAP) cross-sectional substudy.

INTRODUCTION: The Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) study is the largest study of ageing in Northern Ireland (NI). The Harmonised Cognitive Assessment Protocol (HCAP) is a substudy of NICOLA designed to assess cognitive impairment and dementia in individuals aged 65 and over. The NICOLA-HCAP substudy is funded by the National Institute on Aging as part of a network for enhancing cross-national research within a worldwide group of population-based, longitudinal studies of ageing, all of which are centred around the US-based Health and Retirement Study. METHODS AND ANALYSIS: The NICOLA-HCAP study will draw on the main NICOLA cohort (of 8283 participants) and randomly sample 1000 participants aged 65 and over to take part in the substudy. Participants will complete a series of cognitive tests (n=19) via a computer-assisted personal interview administered in their home (or alternatively within the research centre) and will be asked to nominate a family member or friend to complete an additional interview of validated instruments to provide information on respondent's prior and current cognitive and physical functioning and whether the individual requires help with daily activities. The objectives of the study are: to investigate the prevalence of dementia and cognitive impairment in NICOLA; harmonise scoring of the NICOLA-HCAP data to the HCAP studies conducted in Ireland, the USA and England; to explore the validity of dementia estimates; and investigate the risk factors for dementia and cognitive impairment. ETHICS AND DISSEMINATION: The study received ethical approval from the Faculty of Medicine, Health and Life Sciences Research Ethics Committee, Queen's University Belfast. We will provide data from the Northern Irish HCAP to the research community via data repositories such as the Dementias Platform UK and Gateway to Global Aging to complement existing public data resources and support epidemiological research by others. Findings will also be disseminated through peer-reviewed publications and at international conferences.

Older adults' experiences of taking up a new community-based leisure activity to promote brain health: A focus group study.

INTRODUCTION: An active and engaged lifestyle is supported as being beneficial for brain health. Activities comprising physical, mental and social demands, or combinations of those, are of particular interest, and have been the focus of specific interventions. Exploring how older people engage with such community-based activities, including facilitators and barriers to participation, may help improve the success of future translational activities. The purpose of this study was therefore to identify factors that enabled or hindered activity engagement by conducting focus groups with people who had been supported to take up a new activity as part of an intervention study. MATERIALS AND METHODS: Twenty-seven older adults aged 65-86 (56% female) who had completed an activity-based intervention study participated in three focus groups. Discussions explored their experiences of taking up a new activity, including facilitators and barriers to their engagement, and their perceptions of any benefits. RESULTS: Thematic analysis grouped participants' responses into five themes: positive aspects and facilitators of engagement in a new activity; challenges and barriers to engagement; ageing being a facilitator and a barrier to engagement; differential effects of activities on participants' health and wellbeing; and general project feedback (including opinions on study design). DISCUSSION AND CONCLUSIONS: Participants' experiences and expectations included positive (e.g., enjoyment, socialisation) and negative factors (e.g., lack of confidence, other commitments, class costs and poor structure), consistent with previous research on social participation and engaging with new learning opportunities. Future studies should also consider those who do not readily participate in leisure activities to address earlier barriers. It is important that older adults have access to potentially beneficial activities and local authorities should prioritise increasing their provision.

Prevalence of cognitive impairment in patients with rheumatoid arthritis: a cross sectional study.

OBJECTIVE: To explore the role of chronic inflammation in rheumatoid arthritis (RA) on cognition. METHODS AND ANALYSIS: Six hundred sixty-one men and women aged ≥55 years who fulfilled the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for RA were recruited from three healthcare trusts in the United Kingdom (UK) between May 2018 and March 2020. Study participants took part in interviews which captured sociodemographic information, followed by an assessment of cognition. RA specific clinical characteristics were obtained from hospital medical records. Participants were cognitively assessed using the Montreal Cognitive Assessment (MoCA) and were classified as cognitively impaired if they scored ≤27/30 points. Linear regression analyses were conducted to identify which demographic and clinical variables were potential predictors of cognitive impairment. RESULTS: The average age of participants was 67.6 years and 67% (444/661) were women. 72% (458/634; 95% CI 0.69 to 0.76) of participants were classified as cognitively impaired (MoCA≤27). Greater cognitive impairment was associated with older age (p = .006), being male (p = .041) and higher disease activity score (DAS28) (with moderate (DAS28 > 3.1) (p = 0.008) and high (DAS28 > 5.1) (p = 0.008)) compared to those in remission (DAS28 ≤ 2.6). There was no association between MoCA score and education, disease duration, RF status, anti-cyclic citrullinated peptide (anti-CCP) status, RA medication type or use of glucocorticoids or non-steroidal anti-inflammatory drugs (p > 0.05). CONCLUSION: This study suggests that cognitive impairment is highly prevalent in older adults with RA. This impairment appears to be associated with higher RA disease activity and supports the concept that chronic systemic inflammation might accelerate cognitive decline. This underlines the importance of controlling the inflammatory response.

An observational cohort study of longitudinal impacts on frailty and well-being of COVID-19 lockdowns in older adults in England and Spain.

To reduce the spread of COVID-19, governments initiated lockdowns, limiting mobility and social interaction of populations. Lockdown is linked to health issues, yet the full impact on health remains unknown, particularly in more vulnerable groups. This study examined the impact on frailty and outcomes in high and low COVID-19 risk older adults. We examined health-related behaviours and support resources participants used during lockdown(s). Lockdown impacts in two countries were compared across four time points to examine impacts of different rules. We recruited 70 participants (aged >70 years) in England and Spain. Participants were allocated to higher or lower COVID-19-risk groups based on UK NHS guidelines. They completed assessments for frailty, quality-of-life, loneliness, exercise frequency and social interaction, coping resources and perception of age-friendliness of their environment. The four assessments took place over a 7-month period. Frailty was highest at Time 1 (most severe lockdown restrictions) and significantly higher in the Spanish group. It was lower at Time 3 (lowest restrictions), but did not continue to reduce for the English participants. Perceptions of the age friendliness of the environment matched these changes. Coping resources did not mitigate changes in frailty and outcomes over time, but more frequent physical activity predicted more reduction in frailty. Lockdown had a negative impact on frailty, increasing risk of adverse events for older people, but recovery once lockdowns are eased is evidenced. Further research is required to consider longer term impacts and methods to mitigate effects of lockdown on health.

Measuring activity engagement in old age: An exploratory factor analysis.

A growing body of literature suggests that higher engagement in a range of activities can be beneficial for cognitive health in old age. Such studies typically rely on self-report questionnaires to assess level of engagement. These questionnaires are highly heterogeneous across studies, limiting generalisability. In particular, the most appropriate domains of activity engagement remain unclear. The Victoria Longitudinal Study-Activity Lifestyle Questionnaire comprises one of the broadest and most diverse collections of activity items, but different studies report different domain structures. This study aimed to help establish a generalisable domain structure of the Victoria Longitudinal Study-Activity Lifestyle Questionnaire. The questionnaire was adapted for use in a sample of UK-based older adults (336 community-dwelling adults aged 65-92 with no diagnosed cognitive impairment). An exploratory factor analysis was conducted on 29 items. The final model retained 22 of these items in a six-factor structure. Activity domains were: Manual (e.g., household repairs), Intellectual (e.g., attending a public lecture), Games (e.g., card games), Religious (e.g., attending religious services), Exercise (e.g., aerobics) and Social (e.g., going out with friends). Given that beneficial activities have the potential to be adapted into interventions, it is essential that future studies consider the most appropriate measurement of activity engagement across domains. The factor structure reported here offers a parsimonious and potentially useful way for future studies to assess engagement in different kinds of activities.

Impacts of COVID-19 lockdowns on frailty and wellbeing in older people and those living with long-term conditions.

Lockdowns and social distancing have been important and successful strategies to limit the spread of the coronavirus disease 2019 (COVID-19) virus. However, excess deaths related to non-COVID-19 causes have been reported, suggesting issues around availability and use of health services, particularly for people with conditions needing ongoing medical support. In addition, evidence indicates that a range of age-related diseases and frailty are impacted by physical activity and social engagement, both limited in lockdown situations. It is therefore important to learn from the effects of lockdowns in order to limit any impacts, while still protecting people from the infection. This editorial summarizes two research themes at the Centre for Ageing Research at Lancaster University in the UK, one assessing impacts of lockdown for people living with a long-term neurodegenerative condition, Parkinson's disease, and one assessing longitudinal impacts on frailty and wellbeing, with older adults aged over 70, including those living with at least one long-term condition. Uncertainty related to Parkinson's disease and to COVID-19 amplified each other, and cancelled clinical appointments and limitations on physical activity had very significant impacts on wellbeing for this group. In the longitudinal study, frailty was more severe during lockdown periods. While lockdowns reduce spread of the virus, becoming frailer could make older adults more vulnerable to the effects of the virus during these periods. Regular exercise during lockdown had beneficial effects aiding recovery once restrictions relaxed. These studies suggest factors that could lessen negative impacts of future lockdowns. Maintaining physical activity and providing access to health services during periods of lockdown are suggested as priorities.

Apolipoprotein E Genotype Moderation of the Association Between Physical Activity and Brain Health. A Systematic Review and Meta-Analysis.

INTRODUCTION: Possession of one or two e4 alleles of the apolipoprotein E (APOE) gene is associated with cognitive decline and dementia risk. Some evidence suggests that physical activity may benefit carriers of the e4 allele differently. METHOD: We conducted a systematic review and meta-analysis of studies which assessed APOE differences in the association between physical activity and: lipid profile, Alzheimer's disease pathology, brain structure and brain function in healthy adults. Searches were carried out in PubMed, SCOPUS, Web of Science and PsycInfo. RESULTS: Thirty studies were included from 4,896 papers screened. Carriers of the e4 allele gained the same benefit from physical activity as non-carriers on most outcomes. For brain activation, e4 carriers appeared to gain a greater benefit from physical activity on task-related and resting-state activation and resting-state functional connectivity compared to non-carriers. Post-hoc analysis identified possible compensatory mechanisms allowing e4 carriers to maintain cognitive function. DISCUSSION: Though there is evidence suggesting physical activity may benefit e4 carriers differently compared to non-carriers, this may vary by the specific brain health outcome, perhaps limited to brain activation. Further research is required to confirm these findings and elucidate the mechanisms.

Investigating associations between personality and the efficacy of interventions for cognitive ageing: A systematic review.

The personal and societal impact of age-related cognitive decline supports the development of effective interventions. While some strategies, such as cognitive training, exercise or socio-intellectual engagement, appear beneficial, few studies have examined the association between personality and intervention efficacy. A systematic review was therefore conducted to summarise and synthesise the literature regarding the influence of personality traits on the effectiveness of non-pharmacological interventions for cognitive ageing. A systematic search of PubMed, PsycINFO and Web of Science was carried out. Of the 2100 papers identified by the search strategy, 10 studies were retained that met the relevant criteria (e.g., intervention studies with one or more cognitive outcomes and a measure of personality). Of these, two studies reported that higher levels of Openness to Experience were associated with greater improvement in memory performance after cognitive training interventions. Another found a positive association between Openness and improvement in divergent thinking following a novel group-based problem solving programme. One social intervention study reported positive moderating effects of Conscientiousness and Agreeableness, and mixed effects of Extraversion. Mixed evidence was also found regarding Need for Cognition, with one study reporting a positive association with memory improvement and another reporting less improvement in divergent thinking. Others found no evidence of personality influencing intervention outcomes. Due to the relatively small and heterogeneous sample of studies identified, any conclusions should currently be considered preliminary. These findings highlight the need for further research exploring the role of personality in intervention efficacy, so that interventions might be better tailored to individuals.