Genetic variants for head size share genes and pathways with cancer.

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.

Validity and diagnostic performance of a virtual reality-based supermarket application "MEMOSHOP" for assessing episodic memory in normal and pathological aging.

Objective: MEMOSHOP is a virtual reality (VR)-based supermarket application for assessing episodic memory in aging. The aim of this study was to examine its construct validity against the gold standard paper-and-pencil neuropsychological test for clinical memory assessment in mild cognitive impairment (MCI) in older adults. Methods: Patients with isolated subjective cognitive complaints (SCCs) or MCI were recruited in the Bordeaux Memory Clinic (MEMENTO cohort). Cognitively normal elderly controls were also recruited. MEMOSHOP allows a near-ecological evaluation of episodic memory during a usual daily life activity, i.e. shopping at the supermarket. MEMOSHOP and the gold standard Free and Cued Selective Reminding Test (FCSRT: French adaptation) were administered to all participants to assess episodic memory. Non-parametric tests and receiver operating characteristic curves were computed to compare their performances. Results: Twenty-nine patients (21 females, age = 71 years ±7) and 29 matched controls were evaluated. The performance trends observed with MEMOSHOP and FCSRT on free and cued recall were associated (p < .01) and comparable (p < .0001), without any participants' groups interaction. Although easier than FCSRT in free recall for participants, MEMOSHOP demonstrated better diagnostic performance based on cued recall in isolated SCCs/MCI patients (p < .05). Conclusion: MEMOSHOP demonstrated its reliability and validity for VR-based episodic memory assessment in the early stage of MCI and is potentially of interest for use in memory clinic settings.

The role of cardiovascular health and vascular events in the relationship between excessive daytime sleepiness and dementia risk.

Many studies suggest a relationship between excessive daytime sleepiness (EDS) and dementia incidence, but the underlying mechanisms remain uncertain. The study aimed to investigate the role of cardiovascular burden in the relationship between EDS and dementia incidence over a 12-year follow-up in community-dwelling older adults. We performed analyses on 6171 subjects (aged ≥65 years) free of dementia and vascular disease at baseline. Participants self-reported EDS at baseline and an expert committee validated both prevalent and incident dementia. We defined cardiovascular burden by a low Cardiovascular Health score, constructed using the American Heart Association metrics, and incident vascular events. To explore the potential role of the cardiovascular burden in the relationship between EDS and dementia, we conducted mediation analyses with inverse odds ratio-weighted estimation, using multivariable-adjusted proportional hazard Cox and logistic regression models. Subjects with EDS had a higher risk of all-cause dementia (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.13-1.69) and dementia with vascular component (DVC) (HR 2.14, 95% CI 1.30-3.51), but not Alzheimer's disease (HR 1.18, 95% CI 0.93-1.51). Cardiovascular burden explained 5% (95% CI 4.1-5.2) and 11% (95% CI 9.7-11.3) of the relationship between EDS and all-cause dementia and DVC, respectively. These findings confirm that EDS may be implicated in the development of dementia and indicate a weaker than expected role of cardiovascular burden in the relationship between EDS and DVC.

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.

Tools for assessing social isolation and feelings of loneliness in older adults: a systematic review.

Older adults who are socially isolated or who feel lonely have a higher risk of morbidity and mortality. It is important to be able to assess them with efficient tools. The objective was to describe tools for assessing feelings of loneliness (FoL) and social isolation (SI) in older adults, and to estimate their prevalence. A systematic review was conducted including 18 studies. For FoL, the most frequently used tool was the UCLA Loneliness Scale. For SI, the most frequently used tool was the Lubben Social Network Scale. The median prevalences of FoL and SI were 24.1% and 42.5%, respectively. Both of these constructs will become more prominent in the coming decades; therefore, there is a need to identify the best tools.

Comparison of mortality and hospitalizations of older adults living in residential care facilities versus nursing homes or the community. A systematic review.

Residential care facility may provide a transition between living at home and a nursing home for dependent older people or an alternative to nursing homes. The objective of this review was to compare mortality and hospitalizations of older adults living in residential care facilities with those living in nursing homes or in the community. We searched Medline, Scopus and Web of Science from inception to December 2022. Fifteen cohort studies with 6 months to 10 years of follow-up were included. The unadjusted relative risk (RR) of mortality was superior in nursing homes than in residential care facilities in 6 of 7 studies (from 1.3 to 1.68). Conversely, the unadjusted relative risk of hospitalizations was higher in residential care facilities in 6 studies (from 1.3 to 3.37). Studies conducted on persons with dementia found mixed results, the only study adjusted for co-morbidities observing no difference on these two endpoints. Compared with home, unadjusted relative risks were higher in residential care facilities for mortality in 4 studies (from 1.34 à 10.1) and hospitalizations in 3 studies (from 1.12 to 1.62). Conversely, the only study that followed older adults initially living at home over a 10-year period found a reduced risk of heavy hospital use (RR = 0.68) for those who temporarily resided in a residential care facilities. There is insufficient evidence to determine whether residential care facilities might be an alternative to nursing homes for older people with similar clinical characteristics (co-morbidities and dementia). Nevertheless, given the high rate of hospitalizations observed in residential care facilities, the medical needs of residents should be better explored.

Health trajectories of elderly living in French senior housing: a longitudinal perspective.

Senior housing for older adults could be an alternative or a transitional care model between home care and nursing home care. Using two longitudinal cohorts of community dwellers aged 65 years or older, we compared risks of mortality and of nursing homes admission between older adults who did or did not move to senior housing over time. In the 3C study (n = 2104, 17 years of follow-up), 143 (6.8%) participants moved into a senior housing during the follow-up. This move was associated with a lower risk of mortality (hazard ratio (HR): 0.64; 95% confidence interval (CI) 0.46-0.77) and a higher risk of nursing home admissions (HR: 1.54 (1.10-2.15)). The risks of hospitalizations (HR: 0.54 (0.40-0.73)) and falls (HR: 0.63 (0.50-0.79)) were lower. In the PAQUID study (n = 3777, 27 years of follow-up), 161 (4.3%) participants moved into a senior housing. This move was also associated with a lower mortality risk (HR: 0.72 (0.58-0.88)) and a higher risk of nursing home admissions (HR: 1.39 (1.05-1.86)). Our results showing lower risks of mortality suggest that senior housing may be a relevant model for vulnerable older adults.

Correlates of Health-Related Quality of Life in Community-Dwelling Older Adults in Guadeloupe (French West Indies): Results from the KASADS Study.

OBJECTIVES: The aim of this study was to determine the correlates of health-related quality of life (HRQoL) in community-dwelling older adults in Guadeloupe. METHODS: We used the Karukera Study of Aging-Drugs Storage (KASADS), an observational, cross-sectional study on community-dwelling older people living in Guadeloupe. A visual analogue scale ranging from 0 to 100 was used to assess HRQoL. RESULTS: The study sample consisted of 115 patients aged 65 years or older; 67.8% were women. Participants were 76 (±7.8) years old with a mean HRQoL of 66.2 (±20.3). The correlates of HRQoL were complaints of pain (p < 0.001) and IADL dependency (p = 0.030) after adjustment. We found no significant interactions between HRQoL and other variables such as marital status, socio-educational level and cognitive decline. CONCLUSIONS: Pain and IADL dependency were independently associated with lower HRQoL in community-dwelling older people in Guadeloupe.

The Health Care Trajectories of Older People in Foster Families: Protocol for an Observational Study.

BACKGROUND: With aging of the population, the search for alternative models of care adapted to older people with dependency is necessary. In this setting, foster families (1-3 older people per family) could be an alternative to nursing homes, residential care facilities, or community- and home-based care. OBJECTIVE: The KArukera Study of Ageing in Foster Families is a prospective cohort study designed to investigate the care pathways of older people with dependency in foster care over a year. The 1-year hospitalization rate (main objective), cost of hospitalization, incidence of mortality, prevalence of geriatric syndromes, and quality of life of residents will be assessed. Quality of life and burnout of their respective foster caregivers will also be studied. METHODS: This study cohort will include 250 older people living in foster families in Guadeloupe (French West Indies), as well as their respective foster caregivers. Both older people and caregivers will be interviewed concurrently on site at three time points: (1) at baseline, (2) at 6 months, and (3) at 12 months. For older people, we will collect anthropometric measures, cognitive impairment, depressive and anxiety symptoms, functional abilities, physical frailty, information on general health status, quality of life, and care pathways (hospitalization, mortality, and medical and paramedical consultations). We will also assess the quality of life and burnout symptoms of family caregivers at each follow-up. A phone update of vital status (alive or death) and care pathways of residents will be carried out at 3 and 9 months after the baseline examination. RESULTS: Recruitment opened in September 2020 and ended in May 2021, with 109 older people recruited and 56 respective foster caregivers. The 1-year follow-up was ended in June 2022. Data analyses are ongoing and the first results are expected to be published in May 2023. CONCLUSIONS: Foster families are a potentially innovative way to accommodate dependent older people. This study could help define the clinical profile of older people adapted to foster families in the transition from frailty to dependency. The effectiveness of foster families, in terms of hospitalizations and mortality, will be compared with other models of care, particularly nursing homes. In this setting, a twin study carried out in nursing homes in Guadeloupe with similar aims and outcomes will be conducted. Beyond mortality and morbidity, the numerous outcomes will allow us to assess the evolution of geriatric syndromes over time. TRIAL REGISTRATION: ClinicalTrials.gov NCT04545775; https://clinicaltrials.gov/ct2/show/NCT04545775. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40604.

Factors associated with verbal fluency in older adults living with HIV in West Africa: A longitudinal study.

OBJECTIVE: Verbal fluency decline, observed both in aging and HIV infection, has been related to lower quality of life. This study aimed to evaluate the factors associated with categorical fluency in people living with HIV (PLHIV) aged ≥60 years living in West Africa. METHODS: In this longitudinal study, PLHIV aged ≥60 years, on antiretroviral therapy (ART) for ≥6 months were included in three clinics (two in Côte d'Ivoire, one in Senegal) participating in the West Africa International epidemiological Databases to Evaluate AIDS (IeDEA) collaboration. Categorical fluency was evaluated with the Isaacs Set Test at 60 s at baseline and 2 years later. Factors associated with verbal fluency baseline performance and annual rates of changes were evaluated using multivariate linear regression models. RESULTS: Ninety-seven PLHIV were included with 41 of them (42%) having a 2-year follow-up visit. The median age was 64 (62-67), 45.4% were female, and 89.7% had an undetectable viral load. The median annual change in categorical fluency scores was -0.9 (IQR: -2.7 to 1.8). Low baseline categorical fluency performance and its decline were associated with older age and being a female. Low educational level was associated with low baseline categorical fluency performance but not with its decline. Categorical fluency decline was also associated with marital status and hypertension. CONCLUSIONS: Among older West African PLHIV, usual socio-demographic variables and hypertension were the main factors associated with low categorical fluency performance and/or its decline. Interventions that focus on supporting cardiometabolic health are highly recommended to prevent cognitive disorders in PLHIV.

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer's disease.

Alzheimer's disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rare variants2. Here, we compared the gene-based burden of rare damaging variants in exome sequencing data from 32,558 individuals-16,036 AD cases and 16,522 controls. Next to variants in TREM2, SORL1 and ABCA7, we observed a significant association of rare, predicted damaging variants in ATP8B4 and ABCA1 with AD risk, and a suggestive signal in ADAM10. Additionally, the rare-variant burden in RIN3, CLU, ZCWPW1 and ACE highlighted these genes as potential drivers of respective AD-genome-wide association study loci. Variants associated with the strongest effect on AD risk, in particular loss-of-function variants, are enriched in early-onset AD cases. Our results provide additional evidence for a major role for amyloid-ß precursor protein processing, amyloid-ß aggregation, lipid metabolism and microglial function in AD.

Self-reported visual impairment and sarcopenia among older people in Cameroon.

Aging has been clearly associated with decline in visual and physical performance. Alteration of visual function is associated with negative health outcomes including physical frailty. We assessed the relationship between Visual Impairment (VI) and sarcopenia in older persons in Cameroon. In a cross-sectional survey conducted in Douala in 2019, sarcopenia was assessed using the SPPB (Short Physical Performance Battery) test scored from 0 to 12. The diagnosis of sarcopenia was based on SPPB test score < 9 while VI was self-reported. Of the 403 participants (50.4% male) with a mean age of 67.1 (± 6.2) years, 356 (88.3%) reported a VI while the prevalence of sarcopenia was 47.9% [95% CI 43.0-52.7]. After adjusting for several factors, VI was significantly associated with sarcopenia (OR 2.66 [95% CI 1.29-5.48]). Of the SPPB subtests, only chair stand test was negatively associated with VI (ß = - 0.45 [95% CI - 0.82 to 0.07]). Our study supports an association between VI and sarcopenia. If confirmed by further cohort studies, this result would suggest that VI could be considered as an early indicator of sarcopenia among older people in sub-Saharan Africa.

Trajectories of sleep duration and timing before dementia: a 14-year follow-up study.

BACKGROUND: given the complex relationship between sleep and neurodegenerative processes, it is important to examine whether changes in sleep patterns occur prior or close to dementia onset. OBJECTIVE: to examine the relationship between sleep parameters and dementia incidence and, to characterize trajectories of sleep patterns before dementia diagnosis. DESIGN: a 14-year longitudinal study including a nested case-control study. SETTING: the French Three-City Study. SUBJECTS: overall, 1,749 cognitively healthy participants (≥65 years) for the longitudinal study and, 182 incident dementia cases and 719 controls matched by sex, age and educational level for the case-control study. METHODS: dementia cases were assessed at each visit and self-reported sleep parameters at baseline, 2, 8, 10, 12 and 14 years. Cox models were used to estimate the risk of dementia associated with baseline sleep parameters (sleep duration, time in bed (TIB), sleep timing, sleepiness and insomnia). Latent-process mixed models were performed to compare sleep trajectories according to the case-control status. RESULTS: long baseline nighttime and 24-h sleep durations (≥9 h) as well as being persistent or becoming long sleepers during follow-up were associated with dementia incidence. Trajectories of sleep durations and TIB showed faster increases in cases compared with controls up to 12 years before dementia. The mean differences [95%CI] for 24-h sleep duration between cases and controls were: 0.27 h [0.01;0.52], 0.34 [0.09;0.58] and 0.67 [0.44;0.90] at -12, -8 and -2 years, respectively. Bedtime trajectories showed an earlier bedtime in cases up to -8 years. CONCLUSION: long sleep duration and earlier bedtime may impact dementia incidence.

The "Alzheimer Village": Assessment of Alzheimer's disease representations in the general population: A cross sectional phone survey.

Introduction: In most countries, the societal view of Alzheimer's disease (AD) is very negative. The initiatives that are part of the so-called "dementia-friendly approach" aim not only at promoting well-being and dignity of persons suffering from AD but also improving the way they are regarded and their inclusion in society. Unfortunately, scarce research has been conducted to assess whether such goals can be achieved. In France, the experimental Alzheimer Village in Dax is designed as a dementia-friendly community. Due to the recent opening (2020) and the strong local media coverage of this project, a survey has been designed to determine whether the representations of AD have been impacted by such a project. Methods: The survey was conducted before and after the opening of the Alzheimer Village in the city of Dax (hosting the village) and surrounding areas, and in a control city with similar socio-demographics. The analyses intend to compare different dimensions of the representations and attitudes toward AD in the general population. Results: A total of 423 persons living in the Alzheimer Village city (37.4% were men) and 415 persons living in the control city (40.2% were men) were interviewed, resulting in 838 complete questionnaires. The main results report significantly lower rating in the perception of loss of identity (ß = -0.57, P = .014) and in the feeling of disgust for persons with AD (ß = -0.61, P = .008) in the city hosting the village after the opening of the Alzheimer Village. No significant changes were seen in the control city sample. Discussion: While societal representations of AD are very robust and difficult to change, this study suggests a modest but significant evolution of representations of AD in the surrounding areas of the Alzheimer Village. Highlights: The French Alzheimer Village is one of the very few ones in the world.This is the first study assessing the impact of an Alzheimer Village on disease representations.After the opening of the village, attitudes toward Alzheimer's disease have changed.

Prodromal characteristics of dementia with Lewy bodies: baseline results of the MEMENTO memory clinics nationwide cohort.

BACKGROUND: Isolated subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) are the prodromal phases of dementia with Lewy bodies (DLB). MEMENTO is a nationwide study of patients with SCI and MCI with clinic, neuropsychology, biology, and brain imaging data. We aimed to compare SCI and MCI patients with symptoms of prodromal DLB to others in this study at baseline. METHODS: Participants of the French MEMENTO cohort study were recruited for either SCI or MCI. Among them, 892 were included in the Lewy sub-study, designed to search specifically for symptoms of DLB. Probable prodromal DLB diagnosis (pro-DLB group) was done using a two-criteria cutoff score among the four core clinical features of DLB. This Pro-DLB group was compared to two other groups at baseline: one without any core symptoms (NS group) and the one with one core symptom (1S group). A comprehensive cognitive battery, questionnaires on behavior, neurovegetative and neurosensory symptoms, brain 3D volumetric MRI, CSF, FDG PET, and amyloid PET were done. RESULTS: The pro-DLB group comprised 148 patients (16.6%). This group showed more multidomain (59.8%) MCI with slower processing speed and a higher proportion of patients with depression, anxiety, apathy, constipation, rhinorrhea, sicca syndrome, and photophobia, compared to the NS group. The pro-DLB group had isolated lower P-Tau in the CSF (not significant after adjustments for confounders) and on brain MRI widening of sulci including fronto-insular, occipital, and olfactory sulci (FDR corrected), when compared to the NS group. Evolution to dementia was not different between the three groups over a median follow-up of 2.6 years. CONCLUSIONS: Patients with symptoms of prodromal DLB are cognitively slower, with more behavioral disorders, autonomic symptoms, and photophobia. The occipital, fronto-insular, and olfactory bulb involvement on brain MRI was consistent with symptoms and known neuropathology. The next step will be to study the clinical, biological, and imaging evolution of these patients. TRIAL REGISTRATION: Clinicaltrials.gov , NCT01926249.

The association between oral health and nutritional status in older adults: a cross-sectional study.

OBJECTIVES: This work aimed to describe the nutritional status of French older adults (age ≥ 90 years) and studied the association between oral health and nutritional status. METHODS: A cross-sectional study was carried out in 2014 among the participants of a cohort on cerebral and functional aging in France at their 25-year follow up (the PAQUID cohort). Nutritional status (Mini Nutritional Assessment [MNA]) and oral health status (number of decayed, missing, and filled teeth [DMFT], number of posterior occluding pairs, xerostomia [Xerostomia Inventory], and prosthetic rehabilitation) were recorded at the participants' living places by two dentists. Univariate and multivariate logistic regressions were used to explore the association between oral health and nutritional status, with adjustments for potential confounders. Odds ratios (OR) were estimated with their 95% confidence interval (CI). RESULTS: 87 participants were included in the analyses: 74.7% were females and the mean age was 94.1 years (± 3.0). Malnutrition or risk of malnutrition (MNA < 24) was present in 23 participants (26.4%), with only one having malnutrition. The mean DMFT score was 26.5 (± 5.3). The mean number of posterior occluding pairs was 1.5 (± 2.3). Twenty-one participants had xerostomia (24.1%). Only 8.1% of the participants had all their teeth or adequate dentures; 47.1% had inadequate dentures, while 44.8% had no dentures despite tooth loss. After adjustment, xerostomia (OR = 8.79; 95% CI = 2.38-39.10; p = 0.002) was found to be associated with malnutrition or risk of malnutrition. CONCLUSION: Being at risk of malnutrition was common among people ≥ 90 years old and was associated with xerostomia. NCT04065828.

Chronic pain and long-term dementia risk in older adults: Results from a 24-year longitudinal study.

INTRODUCTION: Chronic pain (CP) was associated with cognitive impairment in previous studies. However, the longitudinal association between CP and dementia remains under debate. We aimed to assess the prospective link between CP and long-term dementia risk in a population-based cohort of older participants, considering covariables linked to CP and cognitive functioning. METHODS: The study sample was selected from the PAQUID study, an ongoing cohort of older community-dwellers aged 65 years and over at baseline; Information regarding CP and analgesics consumption was collected using questionnaires. Dementia was clinically assessed every 2 years. The population was divided into 4 groups according to CP and analgesic drugs intake (CP+/A+, CP+/A-, CP-/A+, CP-/A-). An illness-death model was used to estimate the link between CP and incident dementia risk controlled for sex, educational level, comorbidities, depression, antidepressant drugs and analgesics. RESULTS: Five hundred ninety three participants (364 women) who completed a CP questionnaire, were included. They were followed-up over 24 years (mean follow-up: 11.3 years, SD 7.3). A total of 223 participants (32.5%) had CP, among them 88 (38.6%) took analgesic drugs. Compared to CP-/A- group, CP+/A+ participants had a higher risk of developing dementia in the univariate model (hazard ratio (HR) = 1.73, 95%CI:1.18-2.56; p = 0.0051). However, these results did not persist in the multivariate models (aHR = 1.23, 95%CI:0.88-1.73; p = 0.23). No significant risk for dementia were observed in CP-/A+ and CP+/A- (HR = 1.30, 95%CI:0.84-2.01; p = 0.23 and HR = 1.36, 95%CI:0.95-1.96; p = 0.09, respectively). CONCLUSION: Our results failed to show a significant relationship between the presence of CP and long-term dementia risk, suggesting that the cognitive decline associated with CP observed in the literature does not appear to be related to Alzheimer's disease or related disorders.

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.