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.

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.

A closed max-t test for multiple comparisons of areas under the ROC curve.

Comparing areas under the ROC curve (AUCs) is a popular approach to compare prognostic biomarkers. The aim of this paper is to present an efficient method to control the family-wise error rate when multiple comparisons are performed. We suggest to combine the max-t test and the closed testing procedures. We build on previous work on asymptotic results for ROC curves and on general multiple testing methods to efficiently take into account both the correlations between the test statistics and the logical constraints between the null hypotheses. The proposed method results in an uniformly more powerful procedure than both the single-step max-t test procedure and popular stepwise extensions of the Bonferroni procedure, such as Bonferroni-Holm. As demonstrated in this paper, the method can be applied in most usual contexts, including the time-dependent context with right censored data. We show how the method works in practice through a motivating example where we compare several psychometric scores to predict the t-year risk of Alzheimer's disease. The example illustrates several multiple testing settings and demonstrates the advantage of using the proposed methods over common alternatives. R code has been made available to facilitate the use of the methods by others.

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.

Trajectory of Quality of Life Before and After Entering a Nursing Home: A Longitudinal Study.

OBJECTIVES: The objective of this longitudinal study was to compare the trajectory of subjective quality of life in 2 groups of older adults: those who entered a nursing home and those who remained living in the community with similar clinical conditions. METHOD: PAQUID is a prospective population-based study. It included, at baseline, 3777 community-dwelling participants aged 65 years and over. Participants were followed-up for up to 27 years. Among people living at home at baseline, 2 groups were compared: participants who entered a nursing home over a 20-year follow-up (n = 528) and those who remained community dwellers (n = 2273). We used latent process mixed models to estimate the relationship between mean trajectory of subjective quality of life and admission into a nursing home. We computed univariate and multivariate models taking into account potential confounders (age, gender, education, income, comorbidities, dementia, disability and depression). RESULTS: Nursing home placement was significantly associated with a drop in quality of life between the last visit before and after institutionalization. Nevertheless, we found no difference in quality of life trajectory after this initial drop. CONCLUSION: Older adults exhibit an acute drop in quality of life after nursing home admission, probably reflecting the associated psychological distress. Even though their quality of life does not go back to pre-admission levels, the residents do not show a steeper decline when compared to the "natural" evolution of quality of life in older adults living in the community, which suggests a relative adaptation to their new living conditions.

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.

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.

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.

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.

Vision Impairment and Adverse Health Conditions in Congolese Older People: A Population-Based Study.

INTRODUCTION: In sub-Saharan Africa, many older people experience vision impairment (VI) and its adverse health outcomes. In this study, we examined separately the association between VI and each adverse health conditions (cognitive disorders, vision-related quality of life [VRQoL], and daily functioning interference [DFI]) among Congolese older people. We also explored whether VI had a significant effect on VRQoL components in our population. METHOD: We performed cross-sectional analyses on data from 660 Congolese people aged ≥65 years who participated in the 2013 survey of the EPIDEMCA population-based cohort study. VI was defined as having a near visual acuity <20/40 (assessed at 30 cm using a Parinaud chart). Cognitive disorders were assessed using neuropsychological tests and neurological examinations. VRQoL was assessed using a reduced version of the National Eye Institute Visual Function Questionnaire (VFQ-22) and DFI using 11 items of participation restrictions and activity limitations. Regarding our main objective, each association was explored separately using multivariable logistic and linear regression models. Additionally, the effects of VI on each VRQoL components were explored using univariable linear regression models. RESULTS: VI was not associated with cognitive disorders after adjustment for residence area (adjusted odds ratio = 1.7; 95% confidence interval [CI]: 0.6; 4.7), but it was associated with a low VRQoL score (adjusted ß = -12.4; 95% CI: -17.5; -7.3) even after controlling for several covariates. An interaction between VI and age (p = 0.007) was identified, and VI was associated with DFI only among people aged >73 years (adjusted ß = 0.5; 95% CI: 0.2; 0.8). Our exploratory analysis showed that all components of VRQoL decreased with a decrease in visual acuity (corrected p ≤ 0.05). CONCLUSION: VI was associated with poor VRQoL and high DFI. Residence area seems to play a confounding role in the association between VI and cognitive disorders. Our findings suggest that targeting interventions on vision could reduce DFI among older people and improve their well-being.

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.

Distinct Hippocampal Subfields Atrophy in Older People With Vascular Brain Injuries.

BACKGROUND AND PURPOSE: Many neurological or psychiatric diseases affect the hippocampus during aging. The study of hippocampal regional vulnerability may provide important insights into the pathophysiological mechanisms underlying these processes; however, little is known about the specific impact of vascular brain damage on hippocampal subfields atrophy. METHODS: To analyze the effect of vascular injuries independently of other pathological conditions, we studied a population-based cohort of nondemented older adults, after the exclusion of people who were diagnosed with neurodegenerative diseases during the 14-year clinical follow-up period. Using an automated segmentation pipeline, 1.5T-magnetic resonance imaging at inclusion and 4 years later were assessed to measure both white matter hyperintensities and hippocampal subfields volume. Annualized rates of white matter hyperintensity progression and annualized rates of hippocampal subfields atrophy were then estimated in each participant. RESULTS: We included 249 participants in our analyses (58% women, mean age 71.8, median Mini-Mental State Evaluation 29). The volume of the subiculum at baseline was the only hippocampal subfield volume associated with total, deep/subcortical, and periventricular white matter hyperintensity volumes, independently of demographic variables and vascular risk factors (ß=-0.17, P=0.011; ß=-0.25, P=0.020 and ß=-0.14, P=0.029, respectively). In longitudinal measures, the annualized rate of subiculum atrophy was significantly higher in people with the highest rate of deep/subcortical white matter hyperintensity progression, independently of confounding factors (ß=-0.32, P=0.014). CONCLUSIONS: These cross-sectional and longitudinal findings highlight the links between vascular brain injuries and a differential vulnerability of the subiculum within the hippocampal loop, unbiased of the effect of neurodegenerative diseases, and particularly when vascular injuries affect deep/subcortical structures.

Correction: Whole exome sequencing study identifies novel rare and common Alzheimer's-Associated variants involved in immune response and transcriptional regulation.

A correction to this paper has been published and can be accessed via a link at the top of the paper.

Whole exome sequencing study identifies novel rare and common Alzheimer's-Associated variants involved in immune response and transcriptional regulation.

The Alzheimer's Disease Sequencing Project (ADSP) undertook whole exome sequencing in 5,740 late-onset Alzheimer disease (AD) cases and 5,096 cognitively normal controls primarily of European ancestry (EA), among whom 218 cases and 177 controls were Caribbean Hispanic (CH). An age-, sex- and APOE based risk score and family history were used to select cases most likely to harbor novel AD risk variants and controls least likely to develop AD by age 85 years. We tested ~1.5 million single nucleotide variants (SNVs) and 50,000 insertion-deletion polymorphisms (indels) for association to AD, using multiple models considering individual variants as well as gene-based tests aggregating rare, predicted functional, and loss of function variants. Sixteen single variants and 19 genes that met criteria for significant or suggestive associations after multiple-testing correction were evaluated for replication in four independent samples; three with whole exome sequencing (2,778 cases, 7,262 controls) and one with genome-wide genotyping imputed to the Haplotype Reference Consortium panel (9,343 cases, 11,527 controls). The top findings in the discovery sample were also followed-up in the ADSP whole-genome sequenced family-based dataset (197 members of 42 EA families and 501 members of 157 CH families). We identified novel and predicted functional genetic variants in genes previously associated with AD. We also detected associations in three novel genes: IGHG3 (p = 9.8 × 10-7), an immunoglobulin gene whose antibodies interact with ß-amyloid, a long non-coding RNA AC099552.4 (p = 1.2 × 10-7), and a zinc-finger protein ZNF655 (gene-based p = 5.0 × 10-6). The latter two suggest an important role for transcriptional regulation in AD pathogenesis.

Self-Reported Vision Impairment and Frailty among Older People with Low Cognitive Performance in Central Africa: EPIDEMCA Population-Based Study.

INTRODUCTION: Very little is known about the impact of vision impairment (VI) on physical health in late-life in sub-Saharan Africa populations, whereas many older people experience it. We investigated the association between self-reported VI and frailty in Central African older people with low cognitive performance. METHODS: It was cross-sectional analysis of data from the Epidemiology of Dementia in Central Africa (EPIDEMCA) population-based study. After screening for cognitive impairment, older people with low cognitive performance were selected. Frailty was assessed using the Study of Osteoporotic Fracture index. Participants who met one of the 3 parameters assessed (unintentional weight loss, inability to do 5 chair stands, and low energy level) were considered as pre-frail, and those who met 2 or more parameters were considered as frail. VI was self-reported. Associations were investigated using multinomial logistic regression models. RESULTS: Out of 2,002 older people enrolled in EPIDEMCA, 775 (38.7%) had low cognitive performance on the screening test. Of them, 514 participants (sex ratio: 0.25) had available data on VI and frailty and were included in the analyses. In total, 360 (70%) self-reported VI. Prevalence of frailty was estimated at 64.9% [95% confidence interval: 60.9%-69.1%] and 23.7% [95% CI: 20.1%-27.4%] for pre-frailty. After full adjustment, self-reported VI was associated with frailty (adjusted odds ratio = 2.2; 95% CI: 1.1-4.3) but not with pre-frailty (adjusted odds ratio = 1.8; 95% CI: 0.9-3.7). CONCLUSION: In Central African older people with low cognitive performance, those who self-reported VI were more likely to experience frailty. Our findings suggest that greater attention should be devoted to VI among this vulnerable population in order to identify early frailty onset and provide adequate care management.

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.

Apolipoprotein E ϵ4 allele and neuropsychiatric symptoms among older adults in Central Africa (EPIDEMCA study).

OBJECTIVES: To evaluate the association between neuropsychiatric symptoms and apolipoprotein E (APOE) ϵ4 allele among older people in Central African Republic (CAR) and the Republic of Congo (ROC). DESIGN: Multicenter population-based study following a two-phase design. SETTING: From 2011 to 2012, rural and urban areas of CAR and ROC. PARTICIPANTS: People aged 65 and over. MEASUREMENTS: Following screening using the Community Screening Interview for Dementia, participants with low cognitive scores (CSI-D ≤ 24.5) underwent clinical assessment. Dementia diagnosis followed the DSM-IV criteria and Peterson's criteria were considered for Mild Cognitive Impairment (MCI). Neuropsychiatric symptoms were evaluated through the brief version of the Neuropsychiatric Inventory (NPI-Q). Blood samples were taken from all consenting participants before APOE genotyping was performed by polymerase chain reaction (PCR). Logistic regression models were used to evaluate the association between the APOE ϵ4 allele and neuropsychiatric symptoms. RESULTS: Overall, 322 participants had complete information on both neuropsychiatric symptoms and APOE status. Median age was 75.0 years and 81.1% were female. Neuropsychiatric symptoms were reported by 192 participants (59.8%) and at least 1 APOE ϵ4 allele was present in 135 (41.9%). APOE ϵ4 allele was not significantly associated with neuropsychiatric symptoms but showed a trend toward a protective effect in some models. CONCLUSION: This study is the first one investigating the association between APOE ϵ4 and neuropsychiatric symptoms among older people in sub-Saharan Africa (SSA). Preliminary findings indicate that the APOE ϵ4 allele was not associated with neuropsychiatric symptoms. Further research seems, however, needed to investigate the protective trend found in this study.

Plasma amyloid ß levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants.

INTRODUCTION: There is increasing interest in plasma amyloid beta (Aß) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aß levels may elucidate important biological processes that determine plasma Aß measures. METHODS: We included 12,369 non-demented participants from eight population-based studies. Imputed genetic data and measured plasma Aß1-40, Aß1-42 levels and Aß1-42/Aß1-40 ratio were used to perform genome-wide association studies, and gene-based and pathway analyses. Significant variants and genes were followed up for their association with brain positron emission tomography Aß deposition and AD risk. RESULTS: Single-variant analysis identified associations with apolipoprotein E (APOE) for Aß1-42 and Aß1-42/Aß1-40 ratio, and BACE1 for Aß1-40. Gene-based analysis of Aß1-40 additionally identified associations for APP, PSEN2, CCK, and ZNF397. There was suggestive evidence for interaction between a BACE1 variant and APOE ε4 on brain Aß deposition. DISCUSSION: Identification of variants near/in known major Aß-processing genes strengthens the relevance of plasma-Aß levels as an endophenotype of AD.