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.

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.

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.

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.

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.

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.

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.

Immune thrombotic thrombocytopenic purpura in older patients: prognosis and long-term survival.

Older age is associated with increased mortality in immune thrombotic thrombocytopenic purpura (iTTP). Yet, data are scarce regarding iTTP occurring among older patients. To assess clinical features and long-term impact of iTTP on mortality in older patients (>60 years old), characteristics and prognoses of adult iTTP patients enrolled in the French Reference Center for Thrombotic Microangiopathies registry between 2000 and 2016 were described according to age (<60 years old or ≥60 years old). Long-term mortality of iTTP older survivors was compared with that of non-iTTP geriatric subjects. Comparing, respectively, older iTTP patients (N = 71) with younger patients (N = 340), time from hospital admission to diagnosis was longer (P < .0001); at diagnosis, delirium (P = .034), behavior impairment (P = .045), renal involvement (P < .0001), and elevated troponin level (P = .025) were more important whereas cytopenias were less profound (platelet count, 22 × 103/mm3 [9-57] vs 13 × 103/mm3 [9-21], respectively [P = .002]; hemoglobin level, 9 g/dL [8-11] vs 8 g/dL [7-10], respectively [P = .0007]). Short- and mid-term mortalities were higher (P < .0001) and increased for every 10 years of age range. Age ≥60 years, cardiac involvement, increased plasma creatinine level, and total plasma exchange volume were independently associated with 1-month mortality. Compared with a non-iTTP geriatric population, older survivors showed an increased long-term mortality (hazard ratio = 3.44; P < .001). In conclusion, older iTTP patients have atypical neurological presentation delaying the diagnosis. Age negatively impacts short-term but also long-term mortality.

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.

Higher sRAGE Levels Predict Mortality in Frail Older Adults with Cardiovascular Disease.

INTRODUCTION: The evidence that blood levels of the soluble receptor for advanced glycation end products (sRAGE) predict mortality in people with cardiovascular diseases (CVD) is inconsistent. To clarify this matter, we investigated if frailty status influences this association. METHODS: We analysed data of 1,016 individuals (median age, 75 years) from 3 population-based European cohorts, enrolled in the FRAILOMIC project. Participants were stratified by history of CVD and frailty status. Mortality was recorded during 8 years of follow-up. RESULTS: In adjusted Cox regression models, baseline serum sRAGE was positively associated with an increased risk of mortality in participants with CVD (HR 1.64, 95% CI 1.09-2.49, p = 0.019) but not in non-CVD. Within the CVD group, the risk of death was markedly enhanced in the frail subgroup (CVD-F, HR 1.97, 95% CI 1.18-3.29, p = 0.009), compared to the non-frail subgroup (CVD-NF, HR 1.50, 95% CI 0.71-3.15, p = 0.287). Kaplan-Meier analysis showed that the median survival time of CVD-F with high sRAGE (>1,554 pg/mL) was 2.9 years shorter than that of CVD-F with low sRAGE, whereas no survival difference was seen for CVD-NF. Area under the ROC curve analysis demonstrated that for CVD-F, addition of sRAGE to the prediction model increased its prognostic value. CONCLUSIONS: Frailty status influences the relationship between sRAGE and mortality in older adults with CVD. sRAGE could be used as a prognostic marker of mortality for these individuals, particularly if they are also frail.

Validation of Short Form of Preferences for Routines Scale: Norms in Older Adults.

High level of preferences for routines is an indicator of psychological vulnerability in older adults. However, the psychometric properties of the Preferences for Routines Scale (PRS) initially validated in a small selected sample of older adults revealed a low Cronbach's α (.50) in the general elderly population. The present study aims to improve the PRS using the data from the "AMI" and "PAQUID" population-based studies. Among 718 older persons, the most discriminative items are identified using item response theory methodology. A short form of the PRS (PRS-S) included five of the ten items of the original scale and showed improved internal consistency and test-retest reliability. The factors associated with the PRS-S are similar to those found in previous studies. Norms are provided according to gender and educational level. The reduction of the number of items tends to facilitate its administration and promote its use in both clinical and epidemiologic research contexts.

The disability process: is there a place for frailty?

BACKGROUND: frailty and disability are very common in older adults; they share some risk factors and pathophysiological mechanisms. Yet, they are different clinical entities. OBJECTIVES: this study aimed to explore a potential hierarchical relationship between frailty and disability along the continuum of the disablement process. DESIGN: prospective cohort study. SETTING: the French Three-City (3C) study. SUBJECTS: the sample included 943 participants aged 75 and older. METHODS: the Fried frailty phenotype, Instrumental Activities of Daily Living (IADL) and basic Activities of Daily Living (ADL) were used. We distinguished between four mutually excluding groups: (i) robust (no frailty and no disability); (ii) pure frailty (no disability); (iii) frailty with IADL disability (no ADL disability) and (iv) frailty with IADL and ADL disabilities. We used Cox's regression models to study the 4-year mortality risk associated with each status. RESULTS: Eight-two per cent of participants were classified according to the assumed hierarchy: 61.3% was robust, 5.4% frail, 10.5% frail and IADL-disabled and 4.8% frail, IADL and ADL-disabled. An extra group of 17% was identified with IADL-disabled individuals without frailty. This extra group was similar to pure frailty in terms of characteristics and risk of death, placing them along the continuum at an intermediate stage between robustness and the two most disabled sub-groups. CONCLUSIONS: our findings suggest that including frailty along the continuum could be relevant to describe the whole disablement process. Frailty would occur upstream of the process and might be relevant to identify an opportune time window, where specific monitoring and clinical interventions could be implemented in order to interrupt the process at a potentially more reversible stage.

Development of the Central Africa Daily Functioning Interference Scale for Dementia Diagnosis in Older Adults: The EPIDEMCA Study.

BACKGROUND: There are a few validated tools capable of assessing the dimensions essential for the diagnosis of dementia and cognitive disorders in sub-Saharan Africa. OBJECTIVES: Our aim was to develop an adapted tool, the Central African - Daily Functioning Interference (DFI) scale. METHODS: An initial 16-item scale of activity limitations and participation restrictions was completed by 301 participants with low cognitive performances to assess their level of DFI. A psychometric evaluation was performed using Item Response Theory. RESULTS: A unidimensional 10-item scale emerged with a reasonable coverage of DFI (thresholds range: -1.067 to 1.587) with good item discrimination properties (1.397-4.076) and a high reliability (Cronbach's al pha = 0.92). The cutoff for detecting 96% of those with dementia was with a latent score ≥0.035 that corresponds to the LAUNDRY limitation. CONCLUSIONS: These results provide valuable support for the reliability and internal validity of an operational 10-item scale for DFI assessment used in Central Africa for the diagnosis of dementia in the elderly.

Secular trends of mortality and dementia-free life expectancy over a 10-year period in France.

The aim of this paper was to investigate the evolution of mortality and life expectancy according to dementia in two French populations 10 years apart. Two different populations of subjects aged 65 or older included in PAQUID from 1988 to 1989 (n = 1342) and 3C from 1999 to 2000 (n = 1996) and initially not demented were followed over 10 years. Dementia was assessed using an algorithmic approach, and participants were considered to have dementia if they had an MMSE score < 24 AND a 4IADL score > 1. Illness-death models were used to compare mortality with and without dementia and to provide total life expectancy (LE), dementia-free life expectancy (DemFreeLE), life expectancy with dementia (DemLE), and survival with dementia. Mortality without dementia has decreased between the two populations among men [HR = 0.63 (0.49-0.81)] and women [HR = 0.67 (0.50-0.90)], whereas mortality with dementia has decreased for women only [HR = 0.59 (0.41-0.87)]. Total LE and DemFreeLE have increased between the 1990s and the 2000s populations (total LE: + 2.5 years; DemFreeLE: + 2.2 years); DemLE only slightly increased between the populations (DemLE: + 0.3 years). For survival with dementia, an increase in survival has been evidenced (mean survival: + 1.3 years) for women only. The improvement in DemFreeLE is promising. However, as the duration of life with dementia tends to increase for women, efforts to delay the onset of dementia should be reinforced.

Vision loss and 12-year risk of dementia in older adults: the 3C cohort study.

To analyze the longitudinal relationships between vision loss and the risk of dementia in the first 2 years, from 2 to 4 years and beyond 4 years after inclusion and to determine the roles of depressive symptomatology and engagement in cognitively stimulating activities in these associations. This study is based on the Three-City (3C) study, a population-based cohort of 7736 initially dementia-free participants aged 65 years and over with 12 years of follow-up. Near visual impairment (VI) was measured and distance visual function (VF) loss was self-reported. Dementia was diagnosed and screened over the 12-year period. At baseline, 8.7% had mild near VI, 4.2% had moderate to severe near VI, and 5.3% had distance VF loss. Among the 882 dementia cases diagnosed over the 12-year follow-up period, 140 cases occurred in the first 2 years, 149 from 2 to 4 years and 593 beyond 4 years after inclusion. In Cox multivariate analysis, moderate to severe near VI was associated with an increased risk of dementia in the first 2 years (HR 2.0, 95% CI 1.2-3.3) and from 2 to 4 years (HR 1.8, 95% CI 1.1-3.1) but the association was not significant beyond 4 years after inclusion even if pointing in similar direction (HR 1.3, 95% CI 0.95-1.9). Mild near VI was associated with an increased risk of dementia only in the first 2 years (HR 1.6, 95% CI 1.1-2.5). Moreover, self-reported distance VF loss was associated with an increased risk beyond 4 years after inclusion (HR 1.5, 95% CI 1.1-2.0) but the association was no longer significant after taking into account baseline cognitive performances. Further adjustment for engagement in cognitively stimulating activities only slightly decreased these associations. However, there was an interaction between vision loss and depressive symptomatology, with vision loss associated with dementia only among participants with depressive symptomatology. These results suggest that poor vision, in particular near vision loss, may represent an indicator of dementia risk at short and middle-term, mostly in depressed elderly people.

Patterns of circulating fat-soluble vitamins and carotenoids and risk of frailty in four European cohorts of older adults.

PURPOSE: To investigate the cross-sectional and prospective associations between patterns of serum fat-soluble micronutrients and frailty in four European cohorts of older adults 65 years of age and older. METHODS: Participants from the Three-City (Bordeaux, France), AMI (Gironde, France), TSHA (Toledo, Spain) and InCHIANTI (Tuscany, Italy) cohorts with available data on serum α-carotene, ß-carotene, lycopene, cryptoxanthin, lutein + zeaxanthin, retinol, α-tocopherol, γ-tocopherol and 25-hydroxyvitamin D3 (25(OH)D) were included. A principal component (PC) analysis was used to derive micronutrient patterns. Frailty was defined using Fried's criteria. Multivariate logistic regression models adjusted for socio-demographic and health-related covariates were performed to assess the association between micronutrient patterns and prevalent frailty in 1324 participants, and the risk of frailty in 915 initially non-frail participants. RESULTS: Three different patterns were identified: the first pattern was characterized by higher serum carotenoids and α-tocopherol levels; the second was characterized by high loadings for serum vitamins A and E levels and low loadings for carotenes level; the third one had the highest loading for serum 25(OH)D and cryptoxanthin level and the lowest loading for vitamin A and E. A significant cross-sectional association was only observed between the seconnd PC and prevalent frailty (p = 0.02). Compared to the highest quartile, participants in the lowest quartile-i.e., high carotenes and low vitamins E and A levels-had higher odds of frailty (Odds ratio = 2.2; 95% confidence interval 1.3-3.8). No association with the risk of frailty was observed. CONCLUSIONS: These findings suggest that some specific micronutrient patterns are markers but not predictors of frailty in these European cohorts of older adults.

Increased levels of soluble Receptor for Advanced Glycation End-products (RAGE) are associated with a higher risk of mortality in frail older adults.

OBJECTIVE: to evaluate the relationship between serum levels of the soluble Receptor for Advanced Glycation End-products (sRAGE) and mortality in frail and non-frail older adults. METHODS: we studied 691 subjects (141 frail and 550 non-frail) with a median age of 75 years from two population-based cohorts, the Toledo Study of Healthy Aging and the AMI study, who were enrolled to the FRAILOMIC initiative. Multivariate Cox proportional hazards regression and Kaplan-Meier survival analysis were used to assess the relationship between baseline sRAGE and mortality. RESULTS: during 6 years of follow-up 101 participants died (50 frail and 51 non-frail). Frail individuals who died had significantly higher sRAGE levels than those who survived (median [IQR]: 1563 [1015-2248] vs 1184 [870-1657] pg/ml, P = 0.006), whilst no differences were observed in the non-frail group (1262 [1056-1554] vs 1186 [919-1551] pg/ml, P = 0.19). Among frail individuals higher sRAGE levels were associated with an increased risk of death after adjustment for relevant covariates (HR = 2.72 per unit increment in ln-sRAGE, 95%CI 1.48-4.99, P = 0.001). In contrast, in non-frail individuals sRAGE showed no association with mortality. Survival curves demonstrated that among frail individuals the incidence of death was significantly higher in the top sRAGE quartile compared to the three lower quartiles (P = 0.002). Area under the ROC curve analysis demonstrated that for frail individuals, inclusion of sRAGE in the hazard model increased its predictive accuracy by ~3%. CONCLUSIONS: sRAGE is an independent predictor of mortality among frail individuals. Determination of sRAGE in frail subjects could be useful for prognostic assessment and treatment stratification.

A comprehensive approach of the determinants of use of care in dementia: the Recaredem (recourse to care in dementia) cross-sectional study.

BACKGROUND: Given the rate of the undiagnosed cases of dementia and the consequences of inappropriate care, understanding the factors that explain the use of medical and health care in dementia is a critical concern. Our objective was to identify the psychosocial and medical determinants of use of care in dementia. METHODS: The study sample consisted of 308 participants: the persons with dementia (n = 99) selected from three French population-based cohorts (i.e. PAQUID, 3C, AMI), their family caregivers (primary, n = 96, and secondary, n = 51), and their general practitioners (n = 62). Use of care in dementia was considered according to two indicators: (1) recourse to secondary care, (2) number of community and health services used. RESULTS: Multiple logistic models including sociodemographics and psychosocial variables revealed that the determinants of nonuse of care are similar both for the recourse to secondary care and for the number of community and health services used: lack of education and the contribution of the people with dementia to the decisions regarding their own care and dementia care services in the community area. In addition, satisfaction of the primary caregiver with the services used by his/her relative is associated with non-recourse to secondary care. CONCLUSIONS: Taken together, these results highlight the predominant role of psychosocial factors in the use of care in dementia and the importance of addressing this issue through an integrative approach including psychological, social, medical, and family dimensions.

Temporal Trends in the Level and Decline of Cognition and Disability in an Elderly Population: The PAQUID Study.

In line with declining trends in dementia incidence, we compared the cognitive and functional evolution of 2 "generations" of elderly individuals aged 78-88 years, who were included 10 years apart in the French Personnes Agées Quid cohort (n = 612 in 1991-1992 and n = 628 in 2001-2002) and followed-up for 12 years with assessments of cognition and disability. The impact of specific risk factors on this evolution was evaluated. Differences between the generations in baseline levels and decline over time were estimated using a joint model to account for differential attrition. Compared with the first generation, the second generation had higher performances at baseline on 4 cognitive tests (from P < 0.005). Differences in global cognition, verbal fluency, and processing speed, but not in working memory, were mostly explained by improvement in educational level. The second generation also exhibited less cognitive decline in verbal fluency and working memory. Progression of disability was less over the follow-up period for the second generation than for the first. The cognitive state of this elderly population improved, partially due to improvements in educational level.

Dietary patterns and risk of self-reported activity limitation in older adults from the Three-City Bordeaux Study.

Few studies have been interested in the relationship between dietary patterns and activity limitation in older adults yet. We analysed the association between dietary patterns and the risk of self-reported activity limitation - that is mobility restriction, limitation in instrumental activities in daily living (IADL) and in activities in daily living (ADL) - in community-dwellers aged 67+ years initially free of activity limitation in 2001-2002 and re-examined at least once over 10 years - that is 583 participants for mobility restriction, 1114 for IADL limitation and 1267 for ADL limitation. At baseline, five sex-specific dietary clusters were derived by hybrid clustering method from weekly frequency of intake of twenty food and beverage items. Self-reported mobility restriction, limitations in IADL and in ADL were assessed using the Rosow-Breslau, the Lawton-Brody and the Katz scales, respectively. Associations between dietary clusters and the risk of each activity limitation were assessed using Cox proportional hazard models. In models adjusted for socio-demographic and health-related covariates, compared with the 'Healthy' cluster the 'Biscuits and snacking' cluster was associated with a higher risk of mobility restriction (hazard ratio (HR)=3·0; 95 % CI 1·6, 5·8) and limitation in IADL (HR=2·1; 95 % CI 1·1, 4·2) in men and limitation in ADL in women (HR=2·3; 95 % CI 1·3, 4·0). In this French cohort of community-dwellers aged 67+ years, some unhealthy dietary patterns may increase the risk of activity limitation all along the disablement process in older adults.