Frailty Influences the Relationship between the Soluble Receptor for Advanced Glycation-End Products and Mortality in Older Adults with Diabetes Mellitus.

INTRODUCTION: Frailty is prevalent among older adults with diabetes mellitus. Elevated serum levels of the soluble receptor for advanced glycation-end products (sRAGE) predict mortality in frail older adults. The evidence that sRAGE is also related to higher mortality in older adults with diabetes mellitus is inconsistent. Therefore, this study explored if frailty status influences the relationship between sRAGE and mortality in older adults with this condition. METHODS: We analysed data of 391 participants with diabetes mellitus (median age, 76 years) from four European cohorts enrolled in the FRAILOMIC project. Frailty was evaluated at baseline using Fried's criteria. Serum sRAGE was determined by ELISA. Participants were stratified by frailty status (n = 280 non-frail and 111 frail). Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between sRAGE and mortality. RESULTS: During 6 years of follow-up, 98 participants died (46 non-frail and 52 frail). Non-survivors had significantly higher baseline levels of sRAGE than survivors (median [IQR]: 1,392 [962-2,043] pg/mL vs. 1,212 [963-1,514], p = 0.008). High serum sRAGE (>1,617 pg/mL) was associated with increased mortality in the whole diabetes sample after adjustment for relevant confounders (HR 2.06, 95% CI: 1.36-3.11, p < 0.001), and there was an interaction between sRAGE and frailty (p = 0.006). Accordingly, the association between sRAGE and mortality was stronger in the frail group compared to the non-frail group (HR 2.52, 95% CI: 1.30-4.90, p = 0.006 vs. HR 1.71, 95% CI: 0.91-3.23, p = 0.099, respectively). Likewise, Kaplan-Meier curves showed a significant difference in survival rates between frail participants with high sRAGE and those with low sRAGE (p = 0.001), whereas no survival difference was seen in the non-frail group (p = 0.09). CONCLUSIONS: Frailty status influences the relationship between sRAGE and mortality in older adults with diabetes mellitus. Determination of sRAGE in this population could be a useful tool for risk stratification.

Hospital-based palliative care referrals: determinants in older adults with cancer.

OBJECTIVES: Early palliative care improves the quality of life of older patients with cancer. This work aimed to analyse the effect of sociodemographic, geriatric, and tumour-related determinants on hospital-based palliative care (HPC) referral in older patients with cancer, taking into account competing risk of death. METHODS: Older adults with diagnosed cancer from 2014 to 2018 according to the general cancer registry of Gironde (French department) were identified in three population-based cohorts on ageing (PAQUID, 3C - Three City, AMI). Cause-specific Cox models focused on 10 usual determinants in geriatric oncology and palliative care: age, gender, living alone, place of residency, tumour prognosis, activities of daily living (ADL) and instrumental-ADL (IADL) limitations, cognitive impairment, depressive disorders, and polypharmacy. RESULTS: 131 patients with incident cancer (mean age: 86.2 years, men: 62.6%, poor cancer prognosis: 32.8%) were included, HPC occurring for 26 of them. Unfavourable cancer prognosis was a key determinant for HPC referral (HR 7.02, 95% CI 2.86 to 17.23). An altered IADL score was associated with precocious (first year) referral (HR 3.21, 95% CI 1.20 to 8.64, respectively). Women had a higher rate immediately (first week) after diagnosis (HR 8.64, 95% CI 1.27 to 87.27). CONCLUSIONS: Cancer prognosis, functional decline and gender are independent factors of HPC referral in older patients with cancer. These findings may help for a better anticipation of the healthcare pathway.

Association between Helicobacter pylori infection and incident risk of dementia: The AMI cohort.

BACKGROUND: Chronic infectious diseases are increasingly being considered as potential contributors to dementia risk. Among those infections, Helicobacter pylori, the main cause of chronic gastritis worldwide, has been suggested. As the prevalence of H. pylori infection has decreased, the main objective of this work was to reconsider the association between H. pylori infection and the risk of incident dementia, including Alzheimer's disease. METHODS: Prospective cohort of 689 older (≥65 years) agricultural workers from Southwest France. Descriptive and comparative analyses were performed according to H. pylori status determined by serology at baseline. The risk of incident dementia according to H. pylori status over a 7-year follow-up was explored by survival analyses: Kaplan-Meier curve and Cox proportional hazards models. RESULTS: Two-hundred (29.0%) participants were H. pylori-positive at baseline. Compared to H. pylori-negative participants, they showed worse cognitive performances at baseline. Eighty-five incident dementia cases were diagnosed during the follow-up period. After adjustment for age, sex, education, apolipoprotein ε4, and several cardiovascular risk factors, H. pylori remained associated with an increased risk of dementia (HR 1.70, 95% CI, 1.05-2.74). The risk was stronger for Alzheimer's disease (HR 2.85, 95% CI, 1.58-5.12). CONCLUSIONS: Despite an observed decrease in H. pylori infection prevalence, this study provides evidence for the association between H. pylori infection and dementia. These results should encourage further research on the mechanisms underlying the contribution of infectious diseases to pathological brain aging, especially the influence of gut inflammation on the brain.

Night-to-night variability in sleep and amyloid beta burden in normal aging.

INTRODUCTION: Alzheimer's disease is associated with sleep disturbances and accumulation of cerebral amyloid beta. The objective was to examine whether actigraphy-detected sleep parameters might be biomarkers for early amyloid burden. METHODS: Participants underwent a week of actigraphy and an amyloid positron emission tomography (PET) scan. Sleep duration and continuity disruption (sleep fragmentation and nocturnal awakenings) were extracted and compared between amyloid-positive and amyloid-negative participants. Then multiple linear regressions were used between mean or night-to-night intra-individual variability (standard deviation) of sleep parameters and brain amyloid burden in a voxel-wise analysis. RESULTS: Eighty-six subjects were included (80.3 ± 5.4 years; 48.8% of women). Amyloid-positive participants had a higher variability of sleep fragmentation compared to amyloid-negative participants. This parameter was associated with a higher amyloid burden in the frontal and parietal regions, and in the precuneus, in the whole sample. DISCUSSION: This study highlights the relevance of using variability in sleep continuity as a potential biomarker of early amyloid pathogenesis.

Dimensionality and invariance of ADL, IADL, BI-M2/WG-SS, and GALI in large surveys in France (2008-2014) and implications for measuring disability in epidemiology.

BACKGROUND: The epidemiological investigation and surveillance of disability requires well-constructed, invariant, and, if possible, exchangeable measures. However, the current or recommended measures have not been thoroughly investigated with respect to these issues. Here we examined the dimensional structure and invariance of four measures across sociodemographic groups: Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Budapest Initiative Mark 2 (BI-M2) and Washington Group on Disability Statistics Short Set (WG-SS), and Global Activity Limitation Indicator (GALI). METHODS: We used data from three large nationwide representative surveys conducted in France between 2008 and 2014. The surveys included these four measures and classical and modern approaches (correlations, principal component analysis, Rasch modeling) were used to assess their dimensional structure as well as their invariance through differential item functioning (DIF) for sociodemographic characteristics. Polytomous logistic regression models were used to assess gradients in health inequalities associated with these measures. RESULTS: For many items of ADL, IADL, and BI-M2/WG-SS, we consistently observed disordered response thresholds, rejection of unidimensionality, and DIF evidence for sociodemographic characteristics across the survey samples. Health inequality gradients were erratic. In addition, it was impossible to identify a common continuum for GALI, ADL, IADL, and BI-M2/WG-SS or their constituent items. CONCLUSION: This study warns against the current practice of investigating disability in epidemiology using measures that are unsuitable for epidemiological use, incommensurable, and inadequate regarding the basic requisites of dimensionality and invariance. Developing invariant measures and equating them along a common continuum to enlarge the common bases of measurement should therefore be a priority.

Association between pre-diagnosis geriatric syndromes and overall survival in older adults with cancer (the INCAPAC study).

INTRODUCTION: Several population-based studies have reported disparities in overall survival (OS) among older patients with cancer. However, geriatric syndromes, known to be associated with OS in the geriatric population, were rarely studied. Thus, our aim was to identify the determinants of OS among French older adults with cancer, including geriatric syndromes before cancer diagnosis. MATERIALS AND METHODS: Using cancer registries, we identified older subjects (≥65 years) with cancer in three French prospective cohort studies on aging from the Gironde department. Survival time was calculated from the date of diagnosis to the date of all-cause death or to the date of last follow-up, whichever came first. Demographic and socioeconomic characteristics, smoking status, self-rated health, cancer-related factors (stage at diagnosis, treatment), as well as geriatric syndromes (polypharmacy, activity limitation, depressive symptomatology, and cognitive impairment or dementia) were studied. Analyses were performed using Cox proportional hazard models for the whole population, then by age group (65-84 and 85+). RESULTS: Among the 607 subjects included in the study, the median age at cancer diagnosis was 84 years. Smoking habits, activity limitations, cognitive impairment or dementia, advanced cancer stage and absence of treatment were significantly associated with lower OS in the analysis including the whole population. Women presented higher OS. Factors associated with OS differed by age group. Polypharmacy was inversely associated with OS in older adults aged 65-84 and 85 + . DISCUSSION: Our findings support that geriatric assessment is needed to identify patients at higher risk of death and that an evaluation of activity limitation in older adults is essential. Improving early detection could enable interventions to address factors (activity limitations, cognitive impairment) associated with OS, potentially reducing disparities and lead to earlier palliative care.

Psychometric properties of the Perceived Social Support Questionnaire (PSSQ), a new measure of perceived social support among older adults.

OBJECTIVE: Based on literature and available questionnaires, the present study aimed at creating and validating the Perceived Social Support Questionnaire (PSSQ): a 4-item scale assessing the perceived social support in older adults. Normative scores were also computed. METHODS: Three hundred and two participants (mean age 87.68) selected from ongoing population-based studies completed a phone interview. Among these, 247 completed a second interview 4 months later allowing assessing the questionnaire fidelity over time. RESULTS: The factor analysis evidenced two dimensions: availability of social support and satisfaction with it. Both dimensions had a satisfactory internal consistency but weak intraclass correlation coefficient. Univariate analyses revealed that age, number of calls per week and living environment marginally associated with the availability score. The satisfaction score was associated with perceived health status, sadness, depressive mood, feeling of loneliness, anxiety, and the perception of social support during the pandemic context. The norms computed were stratified on age. CONCLUSIONS: The PSSQ is a short and easy-to-administer tool allowing assessing perceived social support in older population. Despite a weak fidelity that could actually be explained by changes in perceived social support over time, the questionnaire revealed good psychometric qualities and validity.

Lessons Learned From the SoBeezy Program for Older Adults During the COVID-19 Pandemic: Experimentation and Evaluation.

BACKGROUND: The SoBeezy program is an innovative intervention aimed at promoting and fostering healthy aging and aging in place by proposing to older adults concrete solutions to face daily life, tackle loneliness, promote social participation, and reduce the digital divide, thanks to a specific, easy-to-use voice assistant (the BeeVA smart display). OBJECTIVE: This study aims to assess the acceptability of the SoBeezy program and its voice assistant and to identify potential areas of improvement. METHODS: A 12-month experimentation of the program was deployed in real-life conditions among older adults living in the community in 4 pilot cities of France. Launched during the first lockdown of the COVID-19 crisis, this multisite study aimed to assess acceptability using questionnaires and interviews conducted at baseline and at the end of the experimentation. In addition, a series of meetings were conducted with SoBeezy staff members to obtain direct feedback from the ground. RESULTS: In total, 109 older individuals were equipped with BeeVA to use the SoBeezy program; of these, 32 (29.4%) left the experimentation before its end and 69 (63.3%) completed the final questionnaires. In total, 335 interventions were conducted and 27 (39%) of the participants requested services, mainly for supportive calls and visits and assistance with shopping, transportation, and crafting-gardening. Of the whole sample, 52 (75%) considered BeeVA as a reassuring presence, and few persons (15/69, 22%) reported a negative opinion about the program. Among the participants, the voice assistant appeared easy to use (n=57, 82%) and useful (n=53, 77%). They also were positive about the BeeVA smart display and the SoBeezy intervention. CONCLUSIONS: This multisite study conducted in real-life conditions among more than 100 older adults living in the community provides enlightening results of the reality from the ground of digital tools designed for the aging population. The COVID-19 context appeared both as an opportunity, given the massive needs of the older adults during this crisis, and as limiting due to sanitary constraints. Nevertheless, the experimentation showed overall good acceptability of the voice assistant and a high level of satisfaction of the participants among those who really used the system and could be a way of improving the autonomy and well-being of older adults and their families. However, the findings also highlighted resistance to change and difficulties for the users to ask for help. The experimentation also emphasized levers for next deployments and future research. The next step will be the experimentation of the activity-sharing component that could not be tested due to the COVID-19 context.

Effectiveness of an Ambient Assisted Living (HomeAssist) Platform for Supporting Aging in Place of Older Adults With Frailty: Protocol for a Quasi-Experimental Study.

BACKGROUND: Ambient assisted living (AAL) technologies are viewed as a promising way to prolong aging in place, particularly when they are designed as closely as possible to the needs of the end users. However, very few evidence-based results have been provided to support its real value, notably for frail older adults who have a high risk of autonomy loss as well as entering a nursing home. OBJECTIVE: We hypothesized that the benefit from an AAL with a user-centered design is effective for aging in place for frail older adults in terms of everyday functioning (instrumental activities of daily-life scale). In addition, our secondary hypotheses are that such an AAL decreases or neutralizes the frailty process and reduces the rates of institutionalization and hospitalization and that it improves the psychosocial health of participants and their caregivers when compared with the control condition. We also assume that a large proportion of equipped participants will have a satisfactory experience and will accept a subscription to an internet connection to prolong their participation. METHODS: HomeAssist (HA) is an AAL platform offering a large set of apps for 3 main age-related need domains (activities of daily-living, safety, and social participation), relying on a basic set of entities (sensors, actuators, tablets, etc). The HA intervention involves monitoring based on assistive services to support activities related to independent living at home. The study design is quasi-experimental with a duration of 12 months, optionally extensible to 24 months. Follow-up assessments occurred at 0, 12, and 24 months. The primary outcome measures are related to everyday functioning. Secondary outcome measures include indices of frailty, cognitive functioning, and psychosocial health of the participants and their caregivers. Every 6 months, user experience and attitudes toward HA are also collected from equipped participants. Concomitantly, data on HA use will be collected. All measures of the study will be tested based on an intention-to-treat approach using a 2-tailed level of significance set at α=.05, concerning our primary and secondary efficacy outcomes. RESULTS: Descriptive analyses were conducted to characterize the recruited equipped participants compared with the others (excluded and refusals) on the data available at the eligibility visit, to describe the characteristics of the recruited sample at baseline, as well as those of the dropouts. Finally, recruitment at 12 months included equipped participants (n=73), matched with control participants (n=474, from pre-existing cohorts). The results of this study will be disseminated through scientific publications and conferences. This will provide a solid basis for the creation of a start-up to market the technology. CONCLUSIONS: This trial will inform the real-life efficacy of HA in prolonging aging in place for frail older adults and yield an informed analysis of AAL use and adoption in frail older individuals. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/33351.

Individual dynamic prediction of clinical endpoint from large dimensional longitudinal biomarker history: a landmark approach.

BACKGROUND: The individual data collected throughout patient follow-up constitute crucial information for assessing the risk of a clinical event, and eventually for adapting a therapeutic strategy. Joint models and landmark models have been proposed to compute individual dynamic predictions from repeated measures to one or two markers. However, they hardly extend to the case where the patient history includes much more repeated markers. Our objective was thus to propose a solution for the dynamic prediction of a health event that may exploit repeated measures of a possibly large number of markers. METHODS: We combined a landmark approach extended to endogenous markers history with machine learning methods adapted to survival data. Each marker trajectory is modeled using the information collected up to the landmark time, and summary variables that best capture the individual trajectories are derived. These summaries and additional covariates are then included in different prediction methods adapted to survival data, namely regularized regressions and random survival forests, to predict the event from the landmark time. We also show how predictive tools can be combined into a superlearner. The performances are evaluated by cross-validation using estimators of Brier Score and the area under the Receiver Operating Characteristic curve adapted to censored data. RESULTS: We demonstrate in a simulation study the benefits of machine learning survival methods over standard survival models, especially in the case of numerous and/or nonlinear relationships between the predictors and the event. We then applied the methodology in two prediction contexts: a clinical context with the prediction of death in primary biliary cholangitis, and a public health context with age-specific prediction of death in the general elderly population. CONCLUSIONS: Our methodology, implemented in R, enables the prediction of an event using the entire longitudinal patient history, even when the number of repeated markers is large. Although introduced with mixed models for the repeated markers and methods for a single right censored time-to-event, the technique can be used with any other appropriate modeling technique for the markers and can be easily extended to competing risks setting.

Towards an approach of disability along a continuum from robustness, pre-frailty, frailty to disability.

BACKGROUND: frailty and disability are very prevalent in older age and although both are distinct clinical entities, they are commonly used indistinctly in order to identify vulnerable older adults. OBJECTIVE: to propose a hierarchical indicator between frailty and disability among older adults along a single continuum. DESIGN: population-based cohort study. SETTING: the Bordeaux Three-City Study and the Aging Multidisciplinary Investigation (AMI) cohort. SUBJECTS: the sample included 1800 participants aged 65 and older. METHODS: an additive hierarchical indicator was proposed by combining the phenotype of frailty (robustness, pre-frailty and frailty), instrumental activities of daily living (IADL) and basic activities of daily living (ADL). To test the relevance of this indicator, we estimated the 4-year mortality risk associated with each stage of the indicator. RESULTS: in total, 34.0% were Robust (n = 612), 29.9% were Pre-frail (n = 538), 3.2% were Robust with IADL-disability (n = 58), 4.6% had pure Frailty (no disability) (n = 82), 11.9% were Pre-frail + IADL (n = 215), 8.6% were Frail + IADL (n = 154) and 7.8% Frail + IADL + ADL (n = 141). After grouping grades with similar mortality risks, we obtained a five-grade hierarchical indicator ranging from robustness to severe stage of the continuum. Each state presented a gradually increasing risk of dying compared to the robust group (from Hazard Ratio (HR) = 2.20 [1.49-3.25] to 15.10 [9.99-22.82]). CONCLUSIONS: We confirmed that combining pre-frailty, frailty, IADL- and ADL-disability into a single indicator may improve our understanding of the aging process. Pre-frailty identified as the 'entry door' into the process may represent a key stage that could offer new opportunities for early, targeted, individualized and tailored interventions and care in clinical geriatrics.

Routinization: risk factor or marker of adjustment to negative health issues?

OBJECTIVES: Routinization reflects how older people cope with the health problems. It remains to be seen whether it should be considered as a risk factor of negative health outcomes, or rather, a mechanism of adjustment to health issues: mortality, institutionalization, dementia, disability, cognitive decline, depression and subjective health. METHODS: From longitudinal data of two large-scale French epidemiological studies, the study sample consists of 961 participants aged 77 years on average, living at home and with no neurocognitive disorder. The relationship between the level of routines measured by the Preferences for Routines Scale-Short form and the adverse health outcomes are studied considering the level of routines at baseline and in time-dependent using Cox proportional hazards models and Latent process mixed models. RESULTS: After adjustment for sociodemographic variables, the routinization score at baseline is not associated with any health outcomes while the routinization score as a time-dependent variable is significantly associated with an increased risk of dementia (hazard ratios (HR) = 1.08, 95% confidence intervals (CI) = 1.02-1.15, p = 0.016) and institutionalization (HR = 1.18, 95% CI = 1.03-1.36, p = 0.019), greater global cognitive decline (ß = -0.02, p = 0.001) and depressive symptoms (ß = 0.02, p = 0.023) and a decrease in subjective health (ß = 0.02, p = 0.008). CONCLUSIONS: The level of routines measured at a given time is not associated with long-term prediction of negative health outcomes, while in time-dependent, it reveals to be a significant predictor. It should be seen as a marker of adjustment process.

Longitudinal Study of Cognitive Decline before and after the COVID-19 Pandemic: Evidence from the PA-COVID Survey.

INTRODUCTION: Even though several studies reported good resilience capacities in older adults in the first period of the coronavirus disease 2019 (COVID-19) pandemic, in the long run, social isolation induced by the protective measures adopted by most countries may negatively impact cognitive functioning. Taking the advantage of measures collected up to 15 years before the pandemic in participants followed up in epidemiological studies, we compared cognitive decline before and after the start of the pandemic. METHODS: PA-COVID is a phone survey designed in the framework of ongoing population-based studies (PAQUID, 3-City, Approche Multidisciplinaire Intégrée cohorts). Data on social functioning and mental health were collected in participants aged 80 years and older during the pandemic. Prior to the pandemic, the participants followed up in the prospective studies completed the Mini-Mental State Examination. During the PA-COVID survey, they underwent the Telephone Interview for Cognitive Status. A score was computed with the 11 items shared by the 2 tests. Our analysis was carried out in the participants for whom a cognitive measure was available up to 15 years before the pandemic and during the pandemic (n = 263). RESULTS: Compared to the slow decline of the cognitive subscore observed during the 15 years preceding the pandemic, mixed models showed an acceleration of decline after the start of the pandemic (ß = -0.289, p value <0.001). CONCLUSIONS: With a design allowing comparing cognitive trajectory before and after the pandemic, this is the first study reporting an accelerated decline in older adults. Future COVID research in older adults will need to pay special attention to cognitive outcomes.

Simple Carbohydrate Intake and Higher Risk for Physical Frailty Over 15 Years in Community-Dwelling Older Adults.

Insulin resistance is a major mechanism involved in the onset of physical frailty (PF). Although rich carbohydrate diets may promote insulin resistance, few studies have examined their association with PF risk. This study aimed to investigate the spectrum of carbohydrate exposure, including carbohydrate intake (simple, complex, and total), glycemic load (a measure of the diet-related insulin demand), and adherence to a low-carbohydrate diet with the incident risk of PF in community-dwelling older adults. Baseline carbohydrate exposure was assessed in nonfrail participants of the Three-City Bordeaux cohort using a 24-hour dietary recall. Over 15 years of follow-up, participants were screened for PF, defined by the FRAIL scale (≥3 criteria out of Fatigue, Resistance, Ambulation, Illnesses, and weight Loss). Associations were estimated using mixed-effects logistic models adjusted for sex, age, education, smoking status, alcohol consumption, depressive symptomatology, global cognitive performances, and protein and energy intakes. The sample included 1 210 participants (62% females, mean age 76 years). Over the follow-up, 295 (24%) incident cases of PF were documented (28% in females, 18% in males). Higher intake of simple carbohydrates was significantly associated with greater odds of incident PF (per 1-SD increased: OR = 1.29; 95% CI = 1.02-1.62), specifically among males (OR = 1.52; 95% CI = 1.04-2.22). No association was observed with complex or total carbohydrate intake, glycemic load, or low-carbohydrate diet. Among the whole carbohydrate exposure, only higher consumption of simple carbohydrates in older age was associated with a higher risk of developing PF. Further studies are required to explore underlying mechanisms.

Connecting Cohorts to Diminish Alzheimer's Disease (CONCORD-AD): A Report of an International Research Collaboration Network.

Longitudinal observational cohort studies are being conducted worldwide to understand cognition, biomarkers, and the health of the aging population better. Cross-cohort comparisons and networks of registries in Alzheimer's disease (AD) foster scientific exchange, generate insights, and contribute to the evolving clinical science in AD. A scientific working group was convened with invited investigators from established cohort studies in AD, in order to form a research collaboration network as a resource to address important research questions. The Connecting Cohorts to Diminish Alzheimer's Disease (CONCORD-AD) collaboration network was created to bring together global resources and expertise, to generate insights and improve understanding of the natural history of AD, to inform design of clinical trials in all disease stages, and to plan for optimal patient access to disease-modifying therapies once they become available. The network brings together expertise and data insights from 7 cohorts across Australia, Europe, and North America. Notably, the network includes populations recruited through memory clinics as well as population-based cohorts, representing observations from individuals across the AD spectrum. This report aims to introduce the CONCORD-AD network, providing an overview of the cohorts involved, reporting the common assessments used, and describing the key characteristics of the cohort populations. Cohort study designs and baseline population characteristics are compared, and available cognitive, functional, and neuropsychiatric symptom data, as well as the frequency of biomarker assessments, are summarized. Finally, the challenges and opportunities of cross-cohort studies in AD are discussed.

Self-Rated Health and Frailty in Older Adults from the Population-Based Three-City Bordeaux Cohort.

INTRODUCTION: This study aimed to investigate whether self-rated health (SRH) predict frailty and its components among community dwellers aged 75 years and older. METHODS: We ran a cross-sectional and prospective analysis from 643 and 379 participants of the Bordeaux Center (France) of the Three-City Study, respectively. We assessed SRH using a single question with 5 response options. We defined frailty as having at least 3 out of the following 5 criteria: weight loss, exhaustion, slowness, weakness, and low energy expenditure. We used multivariate logistic regression and Cox proportional hazard models. RESULTS: At baseline, poor SRH was significantly associated with frailty (odds ratio = 5.2; 95% confidence interval [CI]: 2.9-9.5) and its components except for weakness. In the prospective analysis on nonfrail participants, poor SRH was associated with the 4-year risk of slowness (hazard ratio [HR] = 1.7; 95% CI: 1.1-2.6) but not with that of frailty (HR = 1.6; 95% CI: 0.9-2.9) or the other components. CONCLUSIONS: In a French cohort of community dwellers aged 75 years or older, poorer SRH was associated with concomitant frailty and 70% higher risk of slowness over 4 years.

Older Adults and the COVID-19 Pandemic, What About the Oldest Old? The PACOVID Population-Based Survey.

Introduction: The literature draws a mitigated picture of the psychosocial effects of the lockdown in older adults. However, the studies conducted so far are mainly based on web surveys which may involve selection bias. The PACOVID survey relies on a population-based design and addresses the attitudes, psychological and social experiences of the oldest old regarding the pandemic and lockdown and their impact. Material and Methods: Cross-sectional phone survey involving 677 persons. Baseline report on attitudes, psychological, and social experiences of the oldest old, regarding the pandemic and lockdown measures. Results: The mean age was 87.53 (SD 5.19). About 46% were living alone during the lockdown. Concerning difficulties, "none" was the most frequent answer (35.6%). For questions addressing how often they had felt sad, depressed, or lonely (CESD-scale), the most frequent answers were "never/very rarely" (58.7, 76.6, 60.8%) and 27.1% had anxious symptomatology (STAI scale). Most (92.9%) felt socially supported. Engaging in leisure activities was the most frequent coping strategy, and for numerous participants the lockdown did not represent much of a change in terms of daily routine. A very good knowledge and awareness of COVID-19 and the safety measures was observed. Comparisons with measures collected before the pandemic showed low changes in subjective health and the CES-D questions. Discussion: With a methodological design limiting selection bias, our results claim for a weakened psychosocial impact even though the participants are concerned and aware of the pandemic issues. These results highlight the resources and resilience abilities of older persons including in advancing age.

Herpes simplex virus, early neuroimaging markers and incidence of Alzheimer's disease.

While previous studies suggest the implication of herpes simplex virus (HSV) in the onset of Alzheimer's disease (AD), no study has investigated its association with early neuroimaging markers of AD. In the Three-City and the AMI cohorts, the associations between HSV infection and (i) hippocampal volume (n = 349), (ii) white matter alterations in the parahippocampal cingulum and fornix using diffusion tensor imaging (n = 260), and (iii) incidence of AD (n = 1599) were assessed according to APOE4 status. Regardless of APOE4 status, infected subjects presented (i) significantly more microstructural alterations of the parahippocampal cingulum and fornix, (ii) lower hippocampal volumes only when their anti-HSV IgG level was in the highest tercile-reflecting possibly more frequent reactivations of the virus (p = 0.03 for subjects with a high anti-HSV IgG level while there was no association for all infected subjects, p = 0.19), and (iii) had no increased risk of developing AD. Nevertheless, among APOE4 carriers, infected subjects presented lower hippocampal volumes, although not significant (p = 0.09), and a two or three times higher risk of developing AD (adjusted Hazard ratio (aHR) = 2.72 [1.07-6.91] p = 0.04 for infected subjects and aHR = 3.87 [1.45-10.28] p = 0.007 for infected subjects with an anti-HSV IgG level in the highest tercile) while no association was found among APOE4 noncarriers. Our findings support an association between HSV infection and AD and a potential interaction between HSV status and APOE4. This reinforces the need to further investigate the infectious hypothesis of AD, especially the associated susceptibility factors and the possibility of preventive treatments.

Living in rural area: A protective factor for a negative experience of the lockdown and the COVID-19 crisis in the oldest old population?

OBJECTIVES: Some factors influence the experience of the COVID-19 pandemic (health, loneliness, digital access...), but what about the living area? The objective was to compare between rural and urban areas, the psychological and social experiences of the older individuals with regard to the COVID-19 crisis during the first French lockdown. METHODS: The sample included participants of three existing population-based cohorts on aging. Telephone interviews conducted by psychologists focused on the lockdown period. Data collected included living environment, professional assistance, social support, contacts with relatives, difficulties encountered, health, and knowledge and representations of the epidemic. The negative experience was defined by the presence of at least two of the following items: high anxiety symptomatology, depressive symptoms, worries or difficulties during the lockdown and insufficient social support. RESULTS: The sample included 467 participants, aged on average 87.5 years (5.2), 58.9% were female and 47.1% lived in rural areas. Persons living in rural area had better social support, greater family presence, a less frequent feeling of imprisonment (OR = 0.60, 95 CI% = 0.36-0.99), 95% had a garden (vs. 56%), fewer depressive symptoms and lower anxiety scores, but also tended to lower comply with the health measures. Finally, they had an almost twofold lower risk of having a negative experience of the lockdown compared to their urban counterparts (OR = 0.55, 95% CI = 0.33-0.92, p = 0.0223). CONCLUSIONS: The oldest old living in rural area experienced the first lockdown better than the urbans. Living conditions, with access to nature, a greater social support and family presence, could have contributed to these findings.

ADL-dependent older adults were identified in medico-administrative databases.

OBJECTIVE: We aimed to develop an algorithm for the identification of basic Activities of Daily Living (ADL)-dependency in health insurance databases. STUDY DESIGN AND SETTING: We used the AMI (Aging Multidisciplinary Investigation) population-based cohort including both individual face-to-face assessment of ADL-dependency and merged health insurance data. The health insurance factors associated with ADL-dependency were identified using a LASSO logistic regression model in 1000 bootstrap samples. An external validation on a 1/97 representative sample of the French Health Insurance general population of Affiliates has been performed. RESULTS: Among 995 participants of the AMI cohort aged ≥ 65y, 114 (11.5%) were ADL-dependent according to neuropsychologists individual assessments. The final algorithm developed included: age, sex, four drug classes (dopaminergic antiparkinson drugs, antidepressants, antidiabetic agents, lipid modifying agents), three type of medical devices (medical bed, patient lifter, incontinence equipment), four medical acts (GP's consultations at home, daily and non-daily nursing at home, transport by ambulance) and four long-term diseases (stroke, heart failure, coronary heart disease, Alzheimer and other dementia). Applying this algorithm, the estimated prevalence of ADL-dependency was 12.3% in AMI and 9.5% in the validation sample. CONCLUSION: This study proposes a useful algorithm to identify ADL-dependency in the health insurance data.