Frailty trajectories and associated factors in the years prior to death: evidence from 14 countries in the Survey of Health, Aging and Retirement in Europe.

BACKGROUND: Age-related changes in frailty have been documented in the literature. However, the evidence regarding changes in frailty prior to death is scarce. Understanding patterns of frailty progression as individuals approach death could inform care and potentially lead to interventions to improve individual's well-being at the end of life. In this paper, we estimate the progression of frailty in the years prior to death. METHODS: Using data from 8,317 deceased participants of the Survey of Health, Ageing, and Retirement in Europe, we derived a 56-item Frailty Index. In a coordinated analysis of repeated measures of the frailty index in 14 countries, we fitted growth curve models to estimate trajectories of frailty as a function of distance to death controlling both the level and rate of frailty progression for age, sex, years to death and dementia diagnosis. RESULTS: Across all countries, frailty before death progressed linearly. In 12 of the 14 countries included in our analyses, women had higher levels of frailty close to the time of death, although they progressed at a slower rate than men (e.g. Switzerland (-0.008, SE = 0.003) and Spain (-0.004, SE = 0.002)). Older age at the time of death and incident dementia were associated with higher levels and increased rate of change in frailty, whilst higher education was associated with lower levels of frailty in the year preceding death (e.g. Denmark (0.000, SE = 0.001)). CONCLUSION: The progression of frailty before death was linear. Our results suggest that interventions aimed at slowing frailty progression may need to be different for men and women. Further longitudinal research on individual patterns and changes of frailty is warranted to support the development of personalized care pathways at the end of life.

Association of Life-Course Neighborhood Deprivation With Frailty and Frailty Progression From Ages 70 to 82 Years in the Lothian Birth Cohort 1936.

Neighborhood features have been postulated to be key predictors of frailty. However, evidence is mainly limited to cross-sectional studies without indication of long-term impact. We explored how neighborhood social deprivation (NSD) across the life course is associated with frailty and frailty progression among older Scottish adults. Participants (n = 323) were persons selected from the Lothian Birth Cohort 1936 with historical measures of NSD in childhood (1936-1955), young adulthood (1956-1975), and mid- to late adulthood (1976-2014). Frailty was measured 5 times between the ages of 70 and 82 years using the Frailty Index. Confounder-adjusted life-course models were assessed using a structured modeling approach; associations were estimated for frailty at baseline using linear regression and for frailty progression using linear mixed-effects models. Accumulation was the most appropriate life-course model for males; greater accumulated NSD was associated with higher frailty at baseline (b = 0.017, 95% confidence interval: 0.005, 0.029). Among females, the mid- to late adulthood sensitive period was the best-fitting life-course model, and higher NSD in this period was associated with widening frailty trajectories (b = 0.005, 95% confidence interval: 0.0004, 0.009). To our knowledge, this is the first investigation of the life-course impact of NSD on frailty in a cohort of older adults. Policies designed to address deprivation and inequalities across the full life course may support healthy aging.

Prevalence and predictors of Motoric Cognitive Risk syndrome in a community-dwelling older Scottish population: A longitudinal observational study.

OBJECTIVES: Motoric Cognitive Risk (MCR) is a gait-based predementia syndrome that is easy to measure and prognostic of dementia and falls. We aimed to examine the prevalence and risk factors for MCR, and assess its overlap with Mild Cognitive Impairment, Prefrailty, and Frailty, in a cohort of older Scottish adults without dementia. METHODS: In this longitudinal prospective study, we classified 690 participants (mean [SD] age 76.3 [0.8] years; wave 3) of the Lothian Birth Cohort 1936 (LBC1936) into non-MCR or MCR groups. We examined their baseline (age 69.5 [0.8] years; wave 1) risk factors for MCR at waves 3, 4, and 5 (6, 9, and 12 years later respectively). RESULTS: MCR prevalence rate ranged from 5.3% to 5.7% across the three waves. The presence of MCR was associated with older baseline age (6 and 9 years later), lower occupational socioeconomic status (6 years later), and worse scores in a range of tests of executive function (6, 9 and 12 years later). Approximately 46% of the MCR group also had Mild Cognitive Impairment, and almost everyone in the MCR group had either Prefrailty or Frailty. CONCLUSIONS: The prevalence of MCR in this Scottish cohort is lower than the pooled global average, possibly reflecting the general good health of the LBC cohort. However, it is higher than the prevalence in two neighbouring countries' cohorts, which may reflect the younger average ages of those cohorts. Future LBC1936 research should assess the risk factors associated with MCR to validate previous findings and analyse novel predictive factors, particularly socioeconomic status.

Heterogeneity of Frailty Trajectories and Associated Factors in the Lothian Birth Cohort 1936.

INTRODUCTION: Recent research suggests that the experience of frailty progression may be heterogeneous, with latent subpopulations of older adults following distinct trajectories of frailty. We aimed to investigate this notion and determine whether certain factors are associated with the membership of these subpopulations. METHODS: Data from 5 data waves collected over 12 years in participants of the Lothian Birth Cohort 1936, aged 70 at baseline, were used to derive the frailty index (FI) (NW1 = 1,091, NW5 = 431). These were used in latent class mixed modelling to estimate subpopulations of frailty trajectories. RESULTS: A quadratic latent class mixed model found 3 distinct groupings, which followed a low (61%, n = 632), medium (36%, n = 368), or high (3%, n = 28) FI trajectory. Each grouping had different intercepts and slopes, with the high grouping following the steepest trajectory indicating a rapid increase in frailty. Findings showed that in general, those in the low grouping were younger, had higher education, higher age 11 cognitive ability, and were from a higher social class than those in the medium and high groupings. DISCUSSION/CONCLUSION: Our findings demonstrate heterogeneity in frailty trajectories over 12 years in individuals aged 70 years at baseline. Membership of higher frailty trajectory groupings was associated with lower social class, less education, and lower childhood cognitive ability, indicating the potential for future interventions to target individuals who are at the greatest risk of belonging to the high frailty trajectory. Future research is required to continue this line of inquiry by exploring other risk and protective factors, and importantly, to assess whether it is possible to realign an individual's membership to a less detrimental grouping of frailty trajectory.

Mechanisms of motoric cognitive risk-Hypotheses based on a systematic review and meta-analysis of longitudinal cohort studies of older adults.

We aimed to refine the hypothesis that motoric cognitive risk (MCR), a syndrome combining measured slow gait speed and self-reported cognitive complaints, is prognostic of incident dementia and other major causes of morbidity in older age. We propose mechanisms on the relationship between motor and cognitive function and describe a roadmap to validate these hypotheses. We systematically searched major electronic databases from inception to August 2021 for original longitudinal cohort studies of adults aged ≥60 years that compared an MCR group to a non-MCR group with any health outcome. Fifteen cohorts were combined by meta-analysis. Participants with MCR were at an increased risk of cognitive impairment (adjusted hazard ratio [aHR] 1.76, 95% CI 1.49-2.08; I2  = 24.9%), dementia (aHR 2.12, 1.85-2.42; 33.1%), falls (adjusted Relative Risk 1.38, 1.15-1.66; 62.1%), and mortality (aHR 1.49, 1.16-1.91; 79.2%). The prognostic value of MCR is considerable and mechanisms underlying the syndrome are proposed.

Prevalence of Mild Cognitive Impairment in the Lothian Birth Cohort 1936.

BACKGROUND: The Lothian Birth Cohort 1936 (LBC1936) is a highly phenotyped longitudinal study of cognitive and brain ageing. Given its substantial clinical importance, we derived an indicator of mild cognitive impairment (MCI) and amnestic and nonamnestic subtypes at 3 time points. METHODS: MCI status was derived at 3 waves of the LBC1936 at ages 76 (n=567), 79 (n=441), and 82 years (n=341). A general MCI category was derived as well as amnestic MCI (aMCI) and nonamnestic MCI (naMCI). A comparison was made between MCI derivations using normative data from the LBC1936 cohort versus the general UK population. RESULTS: MCI rates showed a proportional increase at each wave between 76 and 82 years from 15% to 18%. Rates of MCI subtypes also showed a proportional increase over time: aMCI 4% to 6%; naMCI 12% to 16%. Higher rates of MCI were found when using the LBC1936 normative data to derive MCI classification rather than UK-wide norms. CONCLUSIONS: We found that MCI and aMCI rates in the LBC1936 were consistent with previous research. However, naMCI rates were higher than expected. Future LBC1936 research should assess the predictive factors associated with MCI prevalence to validate previous findings and identify novel risk factors.

Remote data collection speech analysis in people at risk for Alzheimer's disease dementia: usability and acceptability results.

Introduction: Digital cognitive assessments are gathering importance for the decentralized remote clinical trials of the future. Before including such assessments in clinical trials, they must be tested to confirm feasibility and acceptability with the intended participant group. This study presents usability and acceptability data from the Speech on the Phone Assessment (SPeAk) study. Methods: Participants (N = 68, mean age 70.43 years, 52.9% male) provided demographic data and completed baseline and 3-month follow-up phone based assessments. The baseline visit was administered by a trained researcher and included a spontaneous speech assessment and a brief cognitive battery (immediate and delayed recall, digit span, and verbal fluency). The follow-up visit repeated the cognitive battery which was administered by an automatic phone bot. Participants were randomized to receive their cognitive test results acer the final or acer each study visit. Participants completed acceptability questionnaires electronically acer each study visit. Results: There was excellent retention (98.5%), few technical issues (n = 5), and good interrater reliability. Participants rated the assessment as acceptable, confirming the ease of use of the technology and their comfort in completing cognitive tasks on the phone. Participants generally reported feeling happy to receive the results of their cognitive tests, and this disclosure did not cause participants to feel worried. Discussion: The results from this usability and acceptability analysis suggest that completing this brief battery of cognitive tests via a telephone call is both acceptable and feasible in a midlife-to-older adult population in the United Kingdom, living at risk for Alzheimer's disease.

Trajectories of Frailty With Aging: Coordinated Analysis of Five Longitudinal Studies.

BACKGROUND AND OBJECTIVES: There is an urgent need to better understand frailty and its predisposing factors. Although numerous cross-sectional studies have identified various risk and protective factors of frailty, there is a limited understanding of longitudinal frailty progression. Furthermore, discrepancies in the methodologies of these studies hamper comparability of results. Here, we use a coordinated analytical approach in 5 independent cohorts to evaluate longitudinal trajectories of frailty and the effect of 3 previously identified critical risk factors: sex, age, and education. RESEARCH DESIGN AND METHODS: We derived a frailty index (FI) for 5 cohorts based on the accumulation of deficits approach. Four linear and quadratic growth curve models were fit in each cohort independently. Models were adjusted for sex/gender, age, years of education, and a sex/gender-by-age interaction term. RESULTS: Models describing linear progression of frailty best fit the data. Annual increases in FI ranged from 0.002 in the Invecchiare in Chianti cohort to 0.009 in the Longitudinal Aging Study Amsterdam (LASA). Women had consistently higher levels of frailty than men in all cohorts, ranging from an increase in the mean FI in women from 0.014 in the Health and Retirement Study cohort to 0.046 in the LASA cohort. However, the associations between sex/gender and rate of frailty progression were mixed. There was significant heterogeneity in within-person trajectories of frailty about the mean curves. DISCUSSION AND IMPLICATIONS: Our findings of linear longitudinal increases in frailty highlight important avenues for future research. Specifically, we encourage further research to identify potential effect modifiers or groups that would benefit from targeted or personalized interventions.

A Systematic Review of Frailty Trajectories: Their Shape and Influencing Factors.

BACKGROUND AND OBJECTIVES: Frailty describes an increased vulnerability to adverse events such as disease or injury. Combating this state remains a major challenge for geriatric research. By exploring how and why frailty changes throughout later life we will be better positioned to improve ways of identifying and treating those at high risk. RESEARCH DESIGN AND METHODS: We systematically reviewed publications that captured rate of frailty progression over time and established any associated risk or protective factors that affected this progression. We included longitudinal observational studies which quantified frailty trajectories in adults aged 50+ using any validated continuous frailty measurement tool. RESULTS: After screening 8,318 publications, 25 met our criteria. Findings show that despite a great degree of heterogeneity in the literature, progression of frailty is unquestionably affected by numerous risk and protective factors, with particular influence exhibited by social demographics, brain pathology, and physical comorbidities. DISCUSSION AND IMPLICATIONS: Findings that the gradient of frailty progression is affected by various influencing factors are valuable to clinicians and policymakers as they will help identify those at highest frailty risk and inform prevention strategies. However, the heterogeneous methodological approaches of the publications included in this review highlight the need for consensus within the field to promote more coordinated research. Improved consistency of methods will enable further data synthesis and facilitate a greater understanding of the shape of frailty over time and the influencing factors contributing to change, the results of which could have crucial implications for frailty risk reduction.

Predictors of Mild Cognitive Impairment Stability, Progression, or Reversion in the Lothian Birth Cohort 1936.

BACKGROUND: Mild cognitive impairment (MCI) describes a borderland between healthy cognition and dementia. Progression to and reversion from MCI is relatively common but more research is required to understand the factors affecting this fluidity and improve clinical care interventions. OBJECTIVE: We explore these transitions in MCI status and their predictive factors over a six-year period in a highly-phenotyped longitudinal study, the Lothian Birth Cohort 1936. METHODS: MCI status was derived in the LBC1936 at ages 76 (n = 567) and 82 years (n = 341) using NIA-AA diagnostic guidelines. Progressions and reversions between healthy cognition and MCI over the follow-up period were assessed. Multinomial logistic regression assessed the effect of various predictors on the likelihood of progressing, reverting, or maintaining cognitive status. RESULTS: Of the 292 participants who completed both time points, 41 (14%) participants had MCI at T1 and 56 (19%) at T2. Over the follow-up period, 74%remained cognitively healthy, 12%transitioned to MCI, 7%reverted to healthy cognition, and 7%maintained their baseline MCI status. Findings indicated that membership of these transition groups was affected by age, cardiovascular disease, and number of depressive symptoms. CONCLUSION: Findings that higher baseline depressive symptoms increase the likelihood of reverting from MCI to healthy cognition indicate that there may be an important role for the treatment of depression for those with MCI. However, further research is required to identify prevention strategies for those at high risk of MCI and inform effective interventions that increase the likelihood of reversion to, and maintenance of healthy cognition.

Home garden use during COVID-19: Associations with physical and mental wellbeing in older adults.

The COVID-19 pandemic has affected many aspects of people's lives. Lockdown measures to reduce the spread of COVID-19 have been more stringent for those aged over 70, at highest risk for the disease. Here, we examine whether home garden usage is associated with self-reported mental and physical wellbeing in older adults, during COVID-19 lockdown in Scotland. This study analysed data from 171 individuals (mean age 84 ± 0.5 years) from the Lothian Birth Cohort 1936 study who completed an online survey approximately two months after lockdown commenced (May/June, 2020), and reported having access to a home garden. The survey also included items on garden activities (gardening, relaxing), frequency of garden usage during lockdown, and measures of self-rated physical health, emotional and mental health, anxiety about COVID-19, and sleep quality. Ordinal regression models were adjusted for sex, living alone, education, occupational social class, anxiety and depressive symptoms, body mass index, and history of diabetes and cardiovascular disease. Neither gardening nor relaxing in the garden were associated with health outcomes. However, higher frequency of garden usage during lockdown was associated with better self-rated physical health (P = 0.005), emotional and mental health (P = 0.04), sleep quality (P = 0.03), and a composite health score (P = 0.001), after adjusting for covariates. None of the garden measures were associated with perceived change in physical health, mental and emotional health, or sleep quality, from pre-lockdown levels. The results of the current study provide support for positive health benefits of spending time in a garden-though associations may be bidirectional-and suggest that domestic gardens could be a potential health resource during the COVID-19 pandemic.

Impact of COVID-19 lockdown on psychosocial factors, health, and lifestyle in Scottish octogenarians: The Lothian Birth Cohort 1936 study.

BACKGROUND: Little is known about effects of COVID-19 lockdown on psychosocial factors, health and lifestyle in older adults, particularly those aged over 80 years, despite the risks posed by COVID-19 to this age group. METHODS: Lothian Birth Cohort 1936 members, residing mostly in Edinburgh and the surrounding Lothians regions in Scotland, mean age 84 years (SD = 0.3), responded to an online questionnaire in May 2020 (n = 190). We examined responses (experience and knowledge of COVID-19; adherence to guidance; impact on day-to-day living; social contact; self-reported physical and mental health; loneliness; and lifestyle) and relationships between previously-measured characteristics and questionnaire outcomes. RESULTS: Four respondents experienced COVID-19; most had good COVID-19 knowledge (94.7%) and found guidance easy to understand (86.3%). There were modest declines in self-reported physical and mental health, and 48.2% did less physical activity. In multivariable regression models, adherence to guidance by leaving the house less often associated with less professional occupational class (OR = 0.71, 95%CI 0.51-0.98) and poorer self-rated general health (OR = 0.62, 95%CI 0.42-0.92). Increased internet use associated with female sex (OR = 2.32, 95%CI 1.12-4.86) and higher general cognitive ability (OR = 1.53, 95%CI 1.03-2.33). Loneliness associated with living alone (OR = 0.15, 95%CI 0.07-0.31) and greater anxiety symptoms (OR = 1.76, 95%CI 0.45-1.24). COVID-19 related stress associated with lower emotional stability scores (OR = 0.40, 95%CI 0.24-0.62). Decreased physical activity associated with less professional occupational class (OR = 1.43, 95%CI 1.04-1.96), and lower general cognitive ability (OR = 0.679, 95%CI 0.491-0.931). CONCLUSIONS: Characteristics including cognitive function, occupational class, self-rated health, anxiety, and emotional stability, may be related to risk of poorer lockdown-related psychosocial and physical outcomes.

Inflammation as a risk factor for the development of frailty in the Lothian Birth Cohort 1936.

BACKGROUND: Research suggests that frailty is associated with higher inflammation levels. We investigated the longitudinal association between chronic inflammation and frailty progression. METHODS: Participants of the Lothian Birth Cohort 1936, aged 70 at baseline were tested four times over 12 years (wave 1: n = 1091, wave 4: n = 550). Frailty was assessed by; the Frailty Index at waves 1-4 and Fried phenotype at waves 1, 3 and 4. Two blood-based inflammatory biomarkers were measured at wave 1: Fibrinogen and C-reactive protein (CRP). RESULTS: Fully-adjusted, linear mixed effects models showed higher Fibrinogen was significantly associated with higher wave 1 Frailty Index score (ß = 0.011, 95% CI[0.002,0.020], p < .05). Over 12 year follow-up, higher wave 1 CRP (ß = 0.001, 95% CI[0.000,0.002], p < .05) and Fibrinogen (ß = 0.004, 95% CI[0.001,0.007], p < .05) were significantly associated with increased Frailty Index change. For the Fried phenotype, wave 1 Pre-frail and Frail participants had higher CRP and Fibrinogen than Non-frail participants (p < .001). Logistic regression models calculated risk of worsening frailty over follow-up and we observed no significant association of CRP or Fibrinogen in minimally-adjusted nor fully-adjusted models. CONCLUSIONS: Findings showed a longitudinal association of higher wave 1 CRP and Fibrinogen on worsening frailty in the Frailty Index, but not Fried Phenotype. A possible explanation for this disparity may lie in the conceptual differences between frailty measures (a biopsychosocial vs physical approach). Future research, which further explores different domains of frailty, as well the associations between improving frailty and inflammation levels, may elucidate the pathway through which inflammation influences frailty progression. This may improve earlier identification of those at high frailty risk.

Change in Physical Activity, Sleep Quality, and Psychosocial Variables during COVID-19 Lockdown: Evidence from the Lothian Birth Cohort 1936.

(1) Objectives: The COVID-19 pandemic has disproportionately affected the lives of older people. In this study, we examine changes in physical activity, sleep quality, and psychosocial variables among older people during COVID-19 lockdown. We build on cross-sectional studies on this topic by assessing change longitudinally. We also examined whether participant characteristics including demographic, cognitive, personality, and health variables were related to more positive or negative changes during lockdown. (2) Methods: 137 older participants (mean age 84 years) from the Lothian Birth Cohort 1936 study were included in the analysis. They completed the same questionnaires assessing physical activity, sleep quality, mental wellbeing, social support, loneliness, neighbourhood cohesion, and memory problems before (mostly 2 years earlier) and again during national lockdown. (3) Results: On average, levels of physical activity were reduced (those doing minimal physical activity increased from 10% to 19%) and perceived social support increased during lockdown (effect size drm = 0.178). More positive change in the psychosocial and behavioural outcome variables during lockdown was associated with personality traits (greater intellect, emotional stability, and extraversion) and having a higher general cognitive ability. Participants with a history of cardiovascular disease, more symptoms of anxiety, or who lived alone were more likely to experience negative changes in the outcome variables during lockdown. (4) Discussion: These results provide further insight into the experiences of older people during the COVID-19 pandemic and could help to identify those at greatest risk of negative psychosocial or behavioural changes during this time.