Linking cognitive and behavioral reserve: Evidence from the CAN-PROTECT study.

INTRODUCTION: Changes to the brain due to Alzheimer's disease and other age-related neuropathologies may present with cognitive and behavioral symptoms, even during preclinical and prodromal stages. While cognitive reserve is known to mitigate cognitive decline in the preclinical stages of Alzheimer's disease, links between cognitive reserve and behavioral symptoms remain unclear. This study investigates the relationship between cognitive reserve and mild behavioral impairment (MBI), a neurodegenerative behavioral prodrome. METHODS: We analyzed cross-sectional data from 1204 participants in the Canadian Platform for Research Online to Investigate Health, Quality of Life, Cognition, Behavior, Function, and Caregiving in Aging (CAN-PROTECT) study. A cognitive reserve score (CRS) was generated based on education, occupation, and personal cognitive reserve proxies. MBI presence (MBI+) and MBI global and domain symptom severity were evaluated using the self-reported MBI Checklist. Initial analyses examined the convergent validity of the CRS through associations with objective neuropsychological test performance and self-reported cognitive symptoms (Everyday Cognition [ECog-II] scale). Models were also fitted to assess MBI status and severity as functions of the CRS. RESULTS: Higher CRS was associated with better neuropsychological test scores, lower odds of subjective cognitive decline (OR = 0.86, 95% CI: [0.76, 0.98], p = .03), and lower ECog-II total score. Likewise, higher CRS was associated with lower odds of MBI+ (OR = 0.81, 95% CI: [0.71, 0.93], p = .003), and lower MBI symptom severity globally, and in impulse dyscontrol and social inappropriateness domains. DISCUSSION: We provide preliminary evidence that engagement in activities known to preserve cognitive function in aging and disease may also preserve behavioral function. Future research should disentangle possible pathways through which cognitive reserve may preserve both cognition and behavior, explore common etiologies for these symptoms, and observe outcomes longitudinally to better understand these relationships. Highlights: Education, occupation, and personal activities are cognitive reserve proxies.Cognitive reserve is linked to lower subjective cognitive decline in older persons.Cognitive reserve is linked to lower mild behavioral impairment odds and severity.

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.

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.

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.

Impact of Short-Term Computerized Cognitive Training on Cognition in Older Adults With and Without Genetic Risk of Alzheimer's Disease: Outcomes From the START Randomized Controlled Trial.

OBJECTIVES: To establish the impact of a 3-minute computerized cognitive training program (START) on cognition in older adults with and without genetic risk of Alzheimer's disease. DESIGN: Two-arm randomized controlled trial of the START program. SETTING AND PARTICIPANTS: Remote online trial in adults older than 50 taking part from home. METHODS: The trial compared the START program with placebo in 6544 people older than 50. Primary outcome was executive function measured through Trailmaking B, with other secondary cognitive measures. Genetic risk profile and ApoE4 status were determined by Illumina Array. RESULTS: START conferred benefit to executive function, attention, memory, and a composite measure, including in people with the ApoE4 genotype. CONCLUSIONS AND IMPLICATIONS: The 3-minute START task offers a means of supporting cognitive health in older adults and could be used at scale and within a precision medicine approach to reduce risk of cognitive decline in a targeted way.

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.

Is lifetime traumatic brain injury a risk factor for mild cognitive impairment in veterans compared to non-veterans?

Background: Traumatic brain injury (TBI) is prevalent in veterans and may occur at any stages of their life (before, during, or after military service). This is of particular concern, as previous evidence in the general population has identified TBI as a strong risk factor for mild cognitive impairment (MCI), a known precursor of dementia.Objectives: This study aimed to investigate whether exposure to at least one TBI across the lifetime was a risk factor for MCI in ageing UK veterans compared to non-veterans.Method: This cross-sectional study comprised of data from PROTECT, a cohort study comprising UK veterans and non-veterans aged ≥ 50 years at baseline. Veteran and TBI status were self-reported using the Military Service History Questionnaire (MSHQ) and the Brain Injury Screening Questionnaire (BISQ), respectively. MCI was the outcome of interest, and was defined as subjective cognitive impairment and objective cognitive impairment.Results: The sample population comprised of veterans (n = 701) and non-veterans (n = 12,389). TBI was a significant risk factor for MCI in the overall sample (OR = 1.21, 95% CI 1.11-1.31) compared to individuals without TBI. The prevalence of TBI was significantly higher in veterans compared to non-veterans (69.9% vs 59.5%, p < .001). There was no significant difference in the risk of MCI between veterans with TBI and non-veterans with TBI (OR = 1.19, 95% CI 0.98-1.45).Conclusion: TBI remains an important risk factor for MCI, irrespective of veteran status. The clinical implications indicate the need for early intervention for MCI prevention after TBI.

Data from the PROTECT study, a longitudinal study comprising over 25,000 middle-aged and ageing adults in the UK, were used in this first UK comparative study to explore the association between a lifetime history of traumatic brain injury (TBI) and mild cognitive impairment (MCI) in UK veterans and non-veterans.Lifetime TBI was more prevalent in veterans compared to non-veterans. TBI events in military veterans could be attributed to non-military events.Exposure to a history of TBI irrespective of veteran status increased the risk of MCI by 21% compared to adults with no history of TBI.The risk of MCI did not significantly differ between veterans and non-veterans with TBI.

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.

Proof-of-concept recall-by-genotype study of extremely low and high Alzheimer's polygenic risk reveals autobiographical deficits and cingulate cortex correlates.

BACKGROUND: Genome-wide association studies demonstrate that Alzheimer's disease (AD) has a highly polygenic architecture, where thousands of independent genetic variants explain risk with high classification accuracy. This AD polygenic risk score (AD-PRS) has been previously linked to preclinical cognitive and neuroimaging features observed in asymptomatic individuals. However, shared variance between AD-PRS and neurocognitive features are small, suggesting limited preclinical utility. METHODS: Here, we recruited sixteen clinically asymptomatic individuals (mean age 67; range 58-76) with either extremely low / high AD-PRS (defined as at least 2 standard deviations from the wider sample mean (N = 4504; N EFFECTIVE = 90)) with comparable age sex and education level. We assessed group differences in autobiographical memory and T1-weighted structural neuroimaging features. RESULTS: We observed marked reductions in autobiographical recollection (Cohen's d = - 1.66; P FDR = 0.014) and midline structure (cingulate) thickness (Cohen's d = - 1.55, P FDR = 0.05), with no difference in hippocampal volume (P > 0.3). We further confirm the negative association between AD-PRS and cingulate thickness in a larger study with a comparable age (N = 31,966, ß = - 0.002, P = 0.011), supporting the validity of our approach. CONCLUSIONS: These observations conform with multiple streams of prior evidence suggesting alterations in cingulate structures may occur in individuals with higher AD genetic risk. We were able to use a genetically informed research design strategy that significantly improved the efficiency and power of the study. Thus, we further demonstrate that the recall-by-genotype of AD-PRS from wider samples is a promising approach for the detection, assessment, and intervention in specific individuals with increased AD genetic risk.

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.

Cognitive trajectories: exploring the predictive role of subjective cognitive decline and awareness of age-related changes for cognitive functioning.

Background: We investigated whether aspects of subjective cognitive aging, including awareness of age-related gains and losses in cognition (AARC-gains, AARC-losses) and subjective cognitive decline (SCD), predict change in objective cognitive function as measured by verbal reasoning (VR) and working memory (WM). Methods: We used longitudinal data for 3,299 cognitively healthy UK residents aged 65+. We used data on AARC and SCD assessed in 2019, and cognitive tasks assessed in 2019, 2020, and 2021. We used latent growth curve modeling, latent class growth analysis, and growth mixture modeling. Results: For VR, multiple growth trajectories were not evident. Mean VR at baseline was 37.45; this remained stable over time. Higher AARC-gains in cognition (mean intercept = -0.23; 95%CI: -0.31; -0.16), higher AARC-losses in cognition (mean intercept = -0.37; 95%CI: -0.46; -0.28), and lower SCD (mean intercept = 2.92; 95%CI: 2.58; 3.58) were associated with poorer VR at baseline. A three-class growth mixture model-class varying best represented trajectories of WM. In Class 1 (N = 182) mean WM at baseline was 31.20; this decreased by 2.48 points each year. In Class 2 (N = 119) mean WM at baseline was 23.12; this increased by 3.28 points each year. In Class 3 (N = 2,998) mean WM at baseline was 30.11; and it remained stable. Higher AARC-gains (Odds Ratio = 1.08; 95%CI: 1.03; 1.14) and AARC-losses (Odds Ratio = 1.10; 95%CI: 1.04; 1.16) in cognition predicted greater likelihood of being in Class 2 than Class 3. Conclusion: Although both higher AARC-gains and AARC-losses indicate poorer concurrent cognition, higher AARC-gains may be a resource that facilitates future cognitive improvement.

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.

Cognitive decline in older adults in the UK during and after the COVID-19 pandemic: a longitudinal analysis of PROTECT study data.

BACKGROUND: Although the long-term health effects of COVID-19 are increasingly recognised, the societal restrictions during the COVID-19 pandemic hold the potential for considerable detriment to cognitive and mental health, particularly because major dementia risk factors-such as those related to exercise and dietary habits-were affected during this period. We used longitudinal data from the PROTECT study to evaluate the effect of the pandemic on cognition in older adults in the UK. METHODS: For this longitudinal analysis, we used computerised neuropsychology data from individuals aged 50 years and older participating in the PROTECT study in the UK. Data were collected from the same participants before the COVID-19 pandemic (March 1, 2019-Feb 29, 2020) and during its first (March 1, 2020-Feb 28, 2021) and second (March 1, 2021-Feb 28, 2022) years. We compared cognition across the three time periods using a linear mixed-effects model. Subgroup analyses were conducted in people with mild cognitive impairment and in people who reported a history of COVID-19, and an exploratory regression analysis identified factors associated with changes in cognitive trajectory. FINDINGS: Pre-pandemic data were included for 3142 participants, of whom 1696 (54·0%) were women and 1446 (46·0%) were men, with a mean age of 67·5 years (SD 9·6, range 50-96). Significant worsening of executive function and working memory was observed in the first year of the pandemic across the whole cohort (effect size 0·15 [95% CI 0·12-0·17] for executive function and 0·51 [0·49-0·53] for working memory), in people with mild cognitive impairment (0·13 [0·07-0·20] and 0·40 [0·36-0·47]), and in people with a history of COVID-19 (0·24 [0·16-0·31] and 0·46 [0·39-0·53]). Worsening of working memory was sustained across the whole cohort in the second year of the pandemic (0·47; 0·44-0·49). Regression analysis indicated that cognitive decline was significantly associated with reduced exercise (p=0·0049; executive function) and increased alcohol use (p=0·049; working memory) across the whole cohort, as well as depression (p=0·011; working memory) in those with a history of COVID-19 and loneliness (p=0·0038; working memory) in those with mild cognitive impairment. In the second year of the pandemic, reduced exercise continued to affect executive function across the whole cohort, and associations were sustained between worsening working memory and increased alcohol use (p=0·0040), loneliness (p=0·042), and depression (p=0·014) in those with mild cognitive impairment, and reduced exercise (p=0·0029), loneliness (p=0·031) and depression (p=0·036) in those with a history of COVID-19. INTERPRETATION: The COVID-19 pandemic resulted in a significant worsening of cognition in older adults, associated with changes in known dementia risk factors. The sustained decline in cognition highlights the need for public health interventions to mitigate the risk of dementia-particularly in people with mild cognitive impairment, in whom conversion to dementia within 5 years is a substantial risk. Long-term intervention for people with a history of COVID-19 should be considered to support cognitive health. FUNDING: National Institute for Health and Care Research.

Testing Bidirectionality in Associations of Awareness of Age-Related Gains and Losses With Physical, Mental, and Cognitive Functioning Across 1 Year: The Role of Age.

OBJECTIVES: The bidirectionality between self-perceptions of aging and health-related outcomes may depend on age group. Therefore, we tested such bidirectionality among individuals in late midlife (50-64 years), young-old age (65-74 years), and old-old age (75+ years), taking advantage of the construct of Awareness of Age-Related Change (AARC) and its 2-dimensionality in terms of AARC-gains and AARC-losses. Various conceptualizations of physical, mental, and cognitive functioning were used as outcomes. METHODS: Data from 2 measurement occasions (2019 and 2020) from the UK PROTECT study for individuals in late midlife (N = 2,385), young-old age (N = 2,430), and old-old age (N = 539) were used. Data on self-reported functional difficulties, depression, anxiety, and performance on four computerized cognitive tasks (i.e., verbal reasoning, paired associate learning, self-ordered search, and digit span) providing a score for verbal reasoning and a score for working memory were analyzed using cross-lagged panel models. RESULTS: Across all 3 age groups, the bidirectional associations of AARC-gains with indicators of functioning were not significant, whereas higher AARC-losses significantly predicted slightly greater functional difficulties and higher depression and anxiety levels. Higher AARC-losses predicted slightly poorer Verbal Reasoning only in old-old age and poorer Working Memory predicted slightly higher AARC-losses only in young-old age. The remaining associations of AARC-losses with cognitive tasks were not statistically significant. DISCUSSION: In accordance with previous research targeting other indicators of self-perceptions of aging, this study supported a stronger impact of AARC-losses on indicators of physical functioning and mental health than vice versa from midlife to old-old age.

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.

Physical and mental health conditions account for variability in awareness of age-related changes.

Background: The concept of Awareness of Age-Related Changes captures people's perceptions of the positive (AARC-gains) and negative (AARC-losses) age-related changes they experience in several life domains, including their health. We investigated the cross-sectional associations of number and type of physical and mental health conditions with AARC-gains and AARC-losses. Methods: The sample comprised 3,786 middle-aged and older adults (mean age = 67.04 years; SD = 6.88) participating to the UK PROTECT study. We used hierarchical regression models to analyze whether after having included sociodemographic variables (model 1), number of physical (model 2) and of mental (model 3) health conditions explained a significant additional amount of variance in AARC-gains and AARC-losses, and whether the association between number of conditions and AARC depended on participants' age. We used multiple regression models to analyze the associations of types of physical and mental health conditions with AARC-gains and AARC-losses. Results: A higher number of physical health conditions was associated with higher AARC-gains and higher AARC-losses, but the association did not depend on participant age. After controlling for the number of physical health conditions, a higher number of mental health conditions was associated with higher AARC-losses but not with AARC-gains, and the association was stronger among older participants. Small effects were found between greater AARC-gains and current cancer and between greater AARC-losses and diagnoses of mild cognitive impairment, Parkinson's disease, arthritic condition, cancer in full remission, osteoporosis, depression, anxiety disorders, and personality disorder. The remaining health conditions were either negligibly or non-statistically related to AARC-losses. Conclusion: Middle-aged and older adults having more physical health conditions and more mental health conditions may be at higher risk of negative views on their own aging. However, specific physical health conditions, such as arthritis, and certain mental health conditions, such as depression, may make adults particularly vulnerable to negative age-related perceptions.

Late-life onset psychotic symptoms and incident cognitive impairment in people without dementia: Modification by genetic risk for Alzheimer's disease.

Introduction: Late-life onset psychosis is associated with faster progression to dementia in cognitively normal people, but little is known about its relationship with cognitive impairment in advance of dementia. Methods: Clinical and genetic data from 2750 people ≥50 years of age without dementia were analyzed. Incident cognitive impairment was operationalized using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) and psychosis was rated using the Mild Behavioral Impairment Checklist (henceforth MBI-psychosis). The whole sample was analyzed before stratification on apolipoprotein E (APOE) ε4 status. Results: In Cox proportional hazards models, MBI-psychosis had a higher hazard for cognitive impairment relative to the No Psychosis group (hazard ratio [HR]: 3.6, 95% confidence interval [CI]: 2.2-6, p < 0.0001). The hazard for MBI-psychosis was higher in APOE ε4 carriers and there was an interaction between the two (HR for interaction: 3.4, 95% CI: 1.2-9.8, p = 0.02). Discussion: Psychosis assessment in the MBI framework is associated with incident cognitive impairment in advance of dementia. These symptoms may be particularly important in the context of APOE genotype.

Bidirectional Associations of Awareness of Age-Related Change and Attitudes Toward Own Aging With Social Media Use.

OBJECTIVES: We test whether higher awareness of age-related gains (AARC-gains), lower awareness of age-related losses (AARC-losses), and more positive attitudes toward own aging (ATOA) are cross-sectionally related to more frequent social media use. We also investigate the strength and direction of the associations of AARC-gains, AARC-losses, and ATOA with social media use over 1 year, from before to after the onset of the coronavirus 2019 pandemic. METHODS: We used cross-sectional data from 8,320 individuals (mean age = 65.95 years; standard deviation = 7.01) and longitudinal data from a subsample of 4,454 individuals participating in the UK PROTECT study in 2019 and 2020. We used ordered regression models, linear regression models, and tests of interaction. Models were adjusted for age, sex, education, and employment. RESULTS: Higher AARC-gains and more positive ATOA, but not AARC-losses, were cross-sectionally associated with more frequent social media use. Social media use became more frequent at follow-up. In the longitudinal models controlling for baseline levels of the outcome variable, more frequent baseline social media use predicted increases in AARC-gains, whereas baseline AARC-gains did not significantly predict the frequency of social media use at follow-up. Baseline frequency of social media use did not significantly predict AARC-losses, nor ATOA at follow-up, whereas lower levels of AARC-losses and more positive ATOA predicted more frequent social media use at follow-up. DISCUSSION: Although effect sizes were small, decreasing negative views on aging may help increase the engagement of middle-aged and older people with social media. At the same time, fostering social media use could promote positive self-perceptions of aging.