Sports-related concussion not associated with long-term cognitive or behavioural deficits: the PROTECT-TBI study.

BACKGROUND: The cognitive effects of sports-related concussion (SRC) have been the subject of vigorous debate but there has been little research into long-term outcomes in non-athlete populations. METHODS: This cohort study of UK community-dwelling adults (aged 50-90 years) was conducted between November 2015 and November 2020, with up to 4 years annual follow-up (n=15 214). Lifetime history of concussions was collected at baseline using the Brain Injury Screening Questionnaire. The first analysis grouped participants by type of concussion (no concussion, only SRC, only non-SRC (nSRC), mixed concussions (both SRC and nSRC)) and the second grouped the participants by number (0, 1, 2 or 3+ SRC or nSRC). Mixed models were used to assess the effect of concussion on outcomes including four cognitive domains and one behavioural measure (Mild Behavioural Impairment-C). RESULTS: Analysis of the included participants (24% male, mean age=64) at baseline found that the SRC group had significantly better working memory (B=0.113, 95% CI 0.038, 0.188) and verbal reasoning (B=0.199, 95% CI 0.092, 0.306) compared with those without concussion. Those who had suffered one SRC had significantly better verbal reasoning (B=0.111, 95% CI 0.031, 0.19) and attention (B=0.115, 95% CI 0.028, 0.203) compared with those with no SRC at baseline. Those with 3+ nSRCs had significantly worse processing speed (B=-0.082, 95% CI -0.144 to -0.019) and attention (B=-0.156, 95% CI -0.248 to -0.063). Those with 3+ nSRCs had a significantly worse trajectory of verbal reasoning with increasing age (B=-0.088, 95% CI -0.149 to -0.026). CONCLUSIONS: Compared with those reporting no previous concussions, those with SRC had no cognitive or behavioural deficits and seemed to perform better in some tasks. As indicated by previous studies, sports participation may confer long-term cognitive benefits.

The relationship between playing musical instruments and cognitive trajectories: Analysis from a UK ageing cohort.

BACKGROUND: The accumulation of age-associated cognitive deficits can lead to Mild Cognitive Impairment (MCI) and dementia. This is a major public health issue for the modern ageing population, as it impairs health, independence and overall quality of life. Keeping the brain active during life has been associated with an increased cognitive reserve, therefore reducing the risk of cognitive impairment in older age. Previous research has identified a potential relationship between musicality and cognition. OBJECTIVES: Explore the relationship between musicality and cognitive function in a large cohort of older adults. METHODS: This was a nested study within the PROTECT-UK cohort, which collects longitudinal computerised assessments of cognitive function in adults over 40. Participants were invited to complete the validated Edinburgh Lifetime Musical Experience Questionnaire (ELMEQ) to assess their musical experience and lifetime exposure to music. Linear regression analysis was performed using cognitive data from PROTECT-UK. RESULTS: Analysis identified an association between musicality and cognition in this cohort. Playing a musical instrument was associated with significantly better performance in working memory and executive function. Significant associations were also found between singing and executive function, and between overall musical ability and working memory. CONCLUSIONS: Our findings confirm previous literature, highlighting the potential value of education and engagement in musical activities throughout life as a means of harnessing cognitive reserve as part of a protective lifestyle for brain health.

Mild Behavioral Impairment and Quality of Life in Community Dwelling Older Adults.

OBJECTIVES: Mild behavioral impairment (MBI) is a dementia risk indicator in older adults characterized by later-life emergent and persistent neuropsychiatric symptoms. Quality of life (QoL) is a multi-dimensional concept encompassing physical, spiritual, and emotional well-being. QoL aims to measure and quantify perceptions of individual health, well-being, standard of living, personal fulfillment, and satisfaction. As MBI symptoms may arise from early-stage neurodegenerative disease, MBI may contribute to declining QoL before dementia onset. In this study, we investigated the relationship between symptoms of MBI and QoL in older adults. METHODS: The sample comprised 1107 individuals aged ≥ 50 years from the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behavior, Function, and Caregiving in Aging (CAN-PROTECT). Multivariable linear regressions were used to model the associations between MBI symptom severity (exposure), measured using the MBI Checklist (MBI-C), and QoL (outcome) assessed by the EuroQol-5D (EQ-5D, higher score = poorer QoL) and the novel Quality of Life and Function Five Domain Scale (QFS-5) (QFS-5, lower score = poorer QoL). Covariates were age, sex, cognition, education, ethnocultural origin, marital status, employment status, high blood pressure, heart disease, and diabetes. Moderation analysis explored potential sex differences. A sensitivity analysis was performed removing anxiety/depression items from the EQ-5D score. RESULTS: Across the sample (mean age = 64.4 ± 7.2, 79.4% female) every 1-point increase in MBI-C score was associated with a 0.06-point standard deviation (SD) increase in EQ-5D score (95% confidence interval (CI): 0.05-0.06, p < 0.001) and 0.08 SD decrease in QFS-5 score (95% CI: -0.09 to -0.08, p < 0.001). Neither association depended on sex (p = 0.59 and p = 0.41, respectively). The association remained significant after removing anxiety/depression items from the EQ-5D score (ß = 0.04, 95% CI: 0.03- 0.04, p < 0.001). CONCLUSIONS: The study shows that MBI is associated with poorer QoL, independent of sex, on two QoL scales. We addressed depression/anxiety items in the EQ-5D as a potential confounder for the observed MBI-QoL association by conducting a sensitivity analysis that excluded those items from the EQ-5D total score and by employing a novel measure of QoL (QFS-5) that excludes psychiatric symptoms from measurement of QoL. Associations of MBI with the novel QFS-5 were similar to associations between MBI and the EQ-5D. Finding interventions to reduce the burden of MBI symptoms might improve quality of life.

The mind and motion: exploring the interplay between physical activity and Mild Behavioral Impairment in dementia-free older adults.

Physical inactivity in mid-life is a modifiable risk factor for dementia. Mild behavioral impairment (MBI) is a marker of potential neurodegenerative disease. We investigated the association between physical activity and MBI. Baseline data from the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behaviour, Function, and Caregiving in Aging (CAN-PROTECT) were used. Four categories of weekly physical activity (cardiovascular, mind-body, strength training, and physical labour) were derived from the Community Healthy Activities Model Program for Seniors questionnaire. MBI was measured using the MBI-Checklist. Multivariable negative binomial regressions modelled the association between the standardized physical activity duration and MBI severity, adjusted for age, sex, education, marital status, ethno cultural origin, occupation, hypertension, dyslipidemia, mobility, and body mass index. Every 1 SD increase in cardiovascular activity was associated with 8.42% lower MBI severity. In contrast, every 1 SD increase in physical labor duration was associated with 5.64% greater MBI severity. These associations were neither moderated by the frequency engaging in each physical activity nor by sex. Cardiovascular physical activity in older persons may reduce levels of non-cognitive dementia markers like MBI, comparable to effects seen in cognition, potentially modulating dementia risk.

Impact of the iWHELD digital person-centered care program on quality of life, agitation and psychotropic medications in people with dementia living in nursing homes during the COVID-19 pandemic: A randomized controlled trial.

INTRODUCTION: iWHELD is a digital person-centered care program for people with dementia in nursing homes adapted for remote delivery during the COVID-19 pandemic. METHODS: A 16-week two-arm cluster-randomized controlled trial in 149 UK nursing homes compared iWHELD with treatment as usual (TAU). Primary outcome was the overall quality of life with secondary outcomes of agitation and psychotropic use. RESULTS: iWHELD conferred benefit to quality of life on the primary (F = 4.3, p = 0.04) and secondary measures of quality of life (F = 6.45, p = 0.01) and reduced psychotropic medication use (χ2  = 4.08, p = 0.04) with no worsening of agitation. Benefit was seen in participants who contracted COVID-19, those with agitation at baseline, and those taking psychotropic medications. DISCUSSION: iWHELD confers benefits to quality of life and key measures of well-being, can be delivered during the challenging conditions of a pandemic, and should be considered for use alongside any emerging pharmacological treatment for neuropsychiatric symptoms. HIGHLIGHTS: iWHELD is the only remote, digital delivery nursing home training programme for dementia care iWHELD improved quality of life in people with dementia and reduced antipsychotic use without worsening of agitation Residents who contracted Covid-19 during the study also experienced benefits from iWHELD iWHELD offers a valuable, pandemic-safe tool for improving dementia care.

Microglial activation, tau and amyloid deposition in TREM2 p.R47H carriers and mild cognitive impairment patients: a multi-modal/multi-tracer PET/MRI imaging study with influenza vaccine immune challenge.

BACKGROUND: Microglia are increasingly understood to play an important role in the pathogenesis of Alzheimer's disease. The rs75932628 (p.R47H) TREM2 variant is a well-established risk factor for Alzheimer's disease. TREM2 is a microglial cell surface receptor. In this multi-modal/multi-tracer PET/MRI study we investigated the effect of TREM2 p.R47H carrier status on microglial activation, tau and amyloid deposition, brain structure and cognitive profile. METHODS: We compared TREM2 p.R47H carriers (n = 8; median age = 62.3) and participants with mild cognitive impairment (n = 8; median age = 70.7). Participants underwent two [18F]DPA-714 PET/MRI scans to assess TSPO signal, indicative of microglial activation, before and after receiving the seasonal influenza vaccination, which was used as an immune stimulant. Participants also underwent [18F]florbetapir and [18F]AV1451 PET scans to assess amyloid and tau burden, respectively. Regional tau and TSPO signal were calculated for regions of interest linked to Braak stage. An additional comparison imaging healthy control group (n = 8; median age = 45.5) had a single [18F]DPA-714 PET/MRI. An expanded group of participants underwent neuropsychological testing, to determine if TREM2 status influenced clinical phenotype. RESULTS: Compared to participants with mild cognitive impairment, TREM2 carriers had lower TSPO signal in Braak II (P = 0.04) and Braak III (P = 0.046) regions, despite having a similar burden of tau and amyloid. There were trends to suggest reduced microglial activation following influenza vaccine in TREM2 carriers. Tau deposition in the Braak VI region was higher in TREM2 carriers (P = 0.04). Furthermore, compared to healthy controls TREM2 carriers had smaller caudate (P = 0.02), total brain (P = 0.049) and white matter volumes (P = 0.02); and neuropsychological assessment revealed worse ADAS-Cog13 (P = 0.03) and Delayed Matching to Sample (P = 0.007) scores. CONCLUSIONS: TREM2 p.R47H carriers had reduced levels of microglial activation in brain regions affected early in the Alzheimer's disease course and differences in brain structure and cognition. Changes in microglial response may underlie the increased Alzheimer's disease risk in TREM2 p.R47H carriers. Future therapeutic agents in Alzheimer's disease should aim to enhance protective microglial actions.

Self-reported sleep fragmentation and sleep duration and their association with cognitive function in PROTECT, a large digital community-based cohort of people over 50.

OBJECTIVE: Sleep is vital for normal cognitive function in daily life, but is commonly disrupted in older adults. Poor sleep can be detrimental to mental and physical health, including cognitive function. This study assessed the association between self-reported short (<6 h) and long (>9 h) sleep duration and sleep fragmentation (3≥ nightly awakenings) in cognitive function. METHODS: Cross-sectional data from 8508 individuals enroled in the PROTECT study aged 50 and above formed the basis of the univariate linear regression analysis conducted on four cognitive outcomes assessing visuospatial episodic memory (VSEM), spatial working memory, verbal working memory (VWM), and verbal reasoning (VR). RESULTS: Short (ß = -0.153, 95% CI [-0.258, -0.048], p = 0.004) and long sleep duration (ß = -0.459, 95% CI [-0.826, -0.091], p = 0.014) were significantly associated with poorer cognitive performance in VWM. Long sleep duration (ß = -2.986, 95% CI [-5.453, -0.518], p = 0.018) was associated with impaired VR. Short sleep (ß = -0.133, 95% CI [-0.196, -0.069], p = <0.001) and sleep fragmentation (ß = -0.043, 95% CI [-0.085, -0.001], p = 0.043) were associated with reduced VSEM. These associations remained significant when including other established risk factors for dementia and cognitive decline (e.g., depression, hypertension). CONCLUSIONS: Our findings suggest that short and long sleep durations and fragmented sleep, may be risk factors for a decline in cognitive processes such as working memory, VR and episodic memory thus might be potential targets for interventions to maintain cognitive health in ageing.

Impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic prescribing for people with dementia in nursing home settings.

OBJECTIVES: This study aimed to determine the impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic use in people with dementia living in nursing homes. METHODS: This was a comparative analysis of baseline data from two large nursing home studies, one conducted during (COVID-iWHELD study) and one prior (WHELD study) to the pandemic. It involves data from 69 and 149 nursing homes, and 1006 and 666 participants respectively. Participants were people with established dementia (score >1 on Clinical Dementia Rating Scale). Resident data included demographics, antipsychotic prescriptions and neuropsychiatric symptoms using the Neuropsychiatric Inventory Nursing Home version. Nursing home data collected were nursing home size and staffing information. RESULTS: Overall prevalence of neuropsychiatric symptoms was unchanged from pre-pandemic prevalence. Mean antipsychotic use across the sample was 32.0%, increased from 18% pre-pandemic (Fisher's exact test p < 0.0001). At a nursing home level, the medians for the low, medium and high tertiles for antipsychotic use were 7%, 20% and 59% respectively, showing a disproportionate rise in tertile three. Residents in these homes also showed a small but significant increase in agitation. CONCLUSION: There has been a significant increase in antipsychotic prescribing in nursing homes since the COVID-19 pandemic, with a disproportionate rise in one third of homes, where median prescription rates for antipsychotics were almost 60%. Strategies are urgently needed to identify these nursing homes and introduce pro-active support to bring antipsychotic prescription rates back to pre-pandemic levels.

The Role of Awareness of Age-Related Change in the Longitudinal Association between Pain and Physical Activity.

We examined how physical pain impacts the developmental construct of Awareness of Age-Related Change (AARC-gains and AARC-losses) and, in turn, how AARC mediates and moderates the association between pain and subsequent physical activity. We used longitudinal data from 434 participants of the UK PROTECT Study (mean age = 65.5 years; SD = 6.94 years). We found that pain in 2019 predicted higher AARC-losses (ß = .07; p = .036) and less physical activity (ß = -.13; p-value = .001) in 2020. Additionally, we found that AARC-losses partially mediated, but did not moderate, the association of pain in 2019 and physical activity in 2020. AARC-losses may explain physical inactivity in middle-aged and older adults experiencing pain. Incorporating developmental constructs such as AARC into theories and empirical studies on pain and pain management may be necessary to more fully capture people's responses to pain.