•Exploring the effects of long-term exposure to air pollution on dementia incidence.•PM2.5 level was associated with Alzheimer’s disease and vascular dementia incidence.•No association was detected ...between NO2 or black carbon exposure and dementia risk.•PM2.5 might be a modifiable risk factor of the main forms of dementia.
Emerging epidemiological evidence suggests a relationship between exposure to air pollution and dementia. However, most of the existing studies relied on health administrative databases for the diagnosis of dementia. In a large French population-based cohort (the 3C Study), we assessed the effects of particulate matter ≤2.5 µm (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) on the risk of dementia diagnosed with reliable tools.
Participants aged ≥65 years were recruited between 1999 and 2001 and followed for 12 years. At baseline and every 2 years, dementia was suspected on the basis of the neuropsychological and neurological examination and confirmed by an independent committee of clinicians. Exposure to NO2, BC and PM2.5 at the participants’ residential address was estimated using land use regression models. For each pollutant and year of follow-up, the 10-year moving average of past exposure was estimated. Multilevel spatial random-effects Cox proportional hazards models were used in which exposure was included as a time-varying variable. Analyses were adjusted for individual (age, sex, education, APOE4 genotype, health behaviours) and contextual (neighbourhood deprivation index) confounders.
At baseline, the median age of the 7066 participants was 73.4 years, and 62% were women. The median follow-up duration was 10.0 years during which 791 participants developed dementia (n = 541 Alzheimer’s disease (AD) and n = 155 vascular/mixed dementia (VaD)). The 10-year moving average of PM2.5 concentrations ranged from 14.6 to 31.3 µg/m3.
PM2.5 concentration was positively associated with dementia risk: HR = 1.20, 95% CI (1.08–1.32) for all-cause dementia, 1.20 (1.09–1.32) for AD, and 1.33 (1.05–1.68) for VaD per 5 µg/m3 PM2.5 increase. No association was detected between NO2 or BC exposure and dementia risk.
In this large cohort of older adults, long-term PM2.5 exposure was associated with increased dementia incidence. Reducing PM2.5 emissions might lessen the burden of dementia in aging populations.
Venous thromboembolism (VTE), the third leading cause of cardiovascular mortality, is a complex thrombotic disorder with environmental and genetic determinants. Although several genetic variants have ...been found associated with VTE, they explain a minor proportion of VTE risk in cases. We undertook a meta-analysis of genome-wide association studies (GWASs) to identify additional VTE susceptibility genes. Twelve GWASs totaling 7,507 VTE case subjects and 52,632 control subjects formed our discovery stage where 6,751,884 SNPs were tested for association with VTE. Nine loci reached the genome-wide significance level of 5 × 10−8 including six already known to associate with VTE (ABO, F2, F5, F11, FGG, and PROCR) and three unsuspected loci. SNPs mapping to these latter were selected for replication in three independent case-control studies totaling 3,009 VTE-affected individuals and 2,586 control subjects. This strategy led to the identification and replication of two VTE-associated loci, TSPAN15 and SLC44A2, with lead risk alleles associated with odds ratio for disease of 1.31 (p = 1.67 × 10−16) and 1.21 (p = 2.75 × 10−15), respectively. The lead SNP at the TSPAN15 locus is the intronic rs78707713 and the lead SLC44A2 SNP is the non-synonymous rs2288904 previously shown to associate with transfusion-related acute lung injury. We further showed that these two variants did not associate with known hemostatic plasma markers. TSPAN15 and SLC44A2 do not belong to conventional pathways for thrombosis and have not been associated to other cardiovascular diseases nor related quantitative biomarkers. Our findings uncovered unexpected actors of VTE etiology and pave the way for novel mechanistic concepts of VTE pathophysiology.
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•Air pollution may have deleterious effects on the central nervous system.•In aging, it is important to determine if air pollution exposure accelerates cognitive decline.•We studied ...exposure to three air pollutants: PM2.5, NO2 and black carbon.•Exposure to PM2.5 was associated with accelerated cognitive decline in our cohort.
Growing epidemiological evidence suggests an adverse relationship between exposure to air pollutants and cognitive decline. However, there is still some heterogeneity in the findings, with inconsistent results depending on the pollutant and the cognitive domain considered. We wanted to determine whether air pollution was associated with global and domain-specific cognitive decline.
This analysis used data from the French Three-City prospective cohort (participants aged 65 and older at recruitment and followed for up to 12 years). A battery of cognitive tests was administered at baseline and every 2 years, to assess global cognition (Mini Mental State Examination, MMSE), visual memory (Benton Visual Retention Test), semantic fluency (Isaacs Set Test) and executive functions (Trail Making Tests A and B). Exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2) and black carbon (BC) at the participants’ residential address during the 5 years before the baseline visit was estimated with land use regression models. Linear mixed models and latent process mixed models were used to assess the association of each pollutant with global and domain-specific cognitive decline.
The participants’ (n = 6380) median age was 73.4 years (IQR: 8.0), and 61.5% were women. At baseline, the median MMSE score was 28 (IQR: 3). Global cognition decline, assessed with the MMSE, was slightly accelerated among participants with higher PM2.5 exposure: one IQR increment in PM2.5 (1.5 µg/m3) was associated with accelerated decline (β: −0.0060 −0.0112; −0.0007 standard unit per year). Other associations were inconsistent in direction, and of small magnitude.
In this large population-based cohort, higher PM2.5 exposure was associated with accelerated global cognition decline. We did not detect any significant association for the specific cognitive domains or the other pollutants. Evidence concerning PM2.5 effects on cognition is growing, but more research is needed on other ambient air pollutants.
Thanks to the growing interest in personalized medicine, joint modeling of longitudinal marker and time‐to‐event data has recently started to be used to derive dynamic individual risk predictions. ...Individual predictions are called dynamic because they are updated when information on the subject's health profile grows with time. We focus in this work on statistical methods for quantifying and comparing dynamic predictive accuracy of this kind of prognostic models, accounting for right censoring and possibly competing events. Dynamic area under the ROC curve (AUC) and Brier Score (BS) are used to quantify predictive accuracy. Nonparametric inverse probability of censoring weighting is used to estimate dynamic curves of AUC and BS as functions of the time at which predictions are made. Asymptotic results are established and both pointwise confidence intervals and simultaneous confidence bands are derived. Tests are also proposed to compare the dynamic prediction accuracy curves of two prognostic models. The finite sample behavior of the inference procedures is assessed via simulations. We apply the proposed methodology to compare various prediction models using repeated measures of two psychometric tests to predict dementia in the elderly, accounting for the competing risk of death. Models are estimated on the French Paquid cohort and predictive accuracies are evaluated and compared on the French Three‐City cohort.
Sleep disturbances are common in elderly and occur frequently in dementia. The impact of excessive daytime sleepiness (EDS), insomnia complaints, sleep quality, and hypnotics on the risk of all-cause ...dementia, Alzheimer disease (AD), and dementia with vascular component (DVC) remains unclear, as does the association between sleep profile and plasma β-amyloid levels.
Analyses were carried out on 6851 participants aged 65 years and over randomly recruited from three French cities and free of dementia at baseline. A structured interview and self-questionnaire assessed sleep complaints (EDS, insomnia complaints, sleep quality) and medications at baseline. Incident cases of dementia were diagnosed systematically over a 12-year period. Multivariate Cox models were used to estimate the risk of dementia associated with the sleep complaints considered individually and globally. Plasma β-amyloid levels were measured by an xMAP-based assay technology in 984 subjects.
After adjustment for socio-demographic characteristics, lifestyle, APOE-ε4, cardiovascular factors, and depressive status, EDS had a higher risk of all-cause dementia (HR = 1.21; 95%CI = 1.01-1.46) and DVC (HR = 1.58; 95%CI = 1.07-2.32) but not AD. Persistent use of hypnotics increased the risk for all-cause dementia, specifically AD (HR = 1.28; 95%CI = 1.04-1.58), but not DVC. No association was found for insomnia complaints and sleep quality taken as individual factors or combined with EDS on the risk of dementia. No association was found between β-amyloid, sleep complaints, and incident dementia.
The results suggest a deleterious role of EDS and hypnotics on dementia. Further studies are required to elucidate the mechanisms involved in these associations and whether its management can prevent the risk of dementia.
Few studies have reported the association between air pollution exposure with different dimensions of depression. We aimed to explore this association across different dimensions of depressive ...symptoms in a large population.
Data from the enrollment phase of the French CONSTANCES cohort (2012–2020) were analyzed cross-sectionally. Annual concentrations of particulate matter with a diameter < 2.5 µm (PM2.5), black carbon (BC), and nitrogen dioxide (NO2) from the land-use regression models were assigned to the residential addresses of participants. Total depressive symptoms and its four dimensions (depressed affect, disturbed interpersonal relations, low positive affect, somatic complaints) were measured using Centre of Epidemiologic Studies Depression questionnaire (CES-D). We reported results of negative binomial regression models (reported as Incidence Rate Ratio (IRR) and 95 % confidence interval (CI) for an interquartile range (IQR) increase in exposure), for each pollutant separately. Stratified analyses were performed by sex, income, family status, education, and neighborhood deprivation.
The study included 123,754 participants (mean age, 46.50 ± 13.61 years; 52.4 % women). The mean concentration of PM2.5, BC and NO2 were 17.14 µg/m3 (IQR = 4.89), 1.82 10-5/m (IQR = 0.88) and 26.58 µg/m3 (IQR = 17.41) respectively. Exposures to PM2.5, BC and NO2 were significantly associated with a higher CES-D total (IRR = 1.022; 95 % CI = 1.002: 1.042, IRR = 1.027; 95 % CI = 1.013: 1.040, and IRR = 1.029; 95 % CI = 1.015: 1.042 respectively), and with depressed affect, and somatic complaints. For all pollutants, a higher estimate was observed for depressed affect. We found stronger adverse associations for men, lower-income participants, low and middle education groups, those living in highly deprived areas, and single participants.
Our finding could assist the exploration of the etiological pathway of air pollution on depression and also considering primary prevention strategies in the areas with air pollution.
Dietary factors might modify cognitive decline that results from aging. Fatty acids, which are limiting factors in brain development, are prime candidates.
We studied the relation between erythrocyte ...membrane fatty acid composition and cognitive decline in free-living volunteers.
In 1995, erythrocyte membrane fatty acid composition was measured in 246 men and women (aged 63-74 y) from the Etude du Vieillissement Artériel (EVA) cohort. During a 4-y follow-up, cognitive abilities were assessed longitudinally with the Mini-Mental State Examination. Moderate cognitive decline was defined as a > or = 2-point decrease over the 4 y. The predictive value of fatty acid proportions on cognitive decline was assessed with a multivariate logistic model that included age, sex, education level, and initial Mini-Mental State Examination score as covariates.
Higher proportions of both stearic acid (saturated, 18:0) and total n-6 polyunsaturated fatty acids were associated with greater risk of cognitive decline; the odds ratios were 1.91 (95% CI: 1.16, 3.15) and 1.59 (95% CI: 1.04, 2.44), respectively, for 1-SD differences in fatty acid proportions. Conversely, a higher proportion of total n-3 fatty acids was associated with a lower risk of cognitive decline; the odds ratio was 0.59 (95% CI: 0.38, 0.93).
The inverse association between cognitive decline and the ratio of n-3 to n-6 fatty acids in erythrocyte membranes agrees with results obtained in some studies that assessed fatty acid intake by using dietary questionnaires. These results require confirmation but provide new rationale for studying how these modifiable risk factors might be implicated in the cognitive aging process.
We compared the prevalence of frailty among aging people living with HIV (PLHIV) with people without HIV from the ANS EP58 HAND 55-70 Study.
Cross-sectional multicentric study which consecutively ...included 200 PLHIV and 1000 people without HIV from the French national CONSTANCES cohort, matched on age, sex, and education level. PLHIV were aged 55-70 years, with a HIV viral load < 50 copies/mL and a lymphocyte T-CD4 level > 200 cells/µL for the last 24 and 12 months, respectively. We measured frailty (>2 items) and prefrailty (one or 2 items) using a proxy of the 5-item Fried score. Multivariate logistic regression was performed to assess the association between HIV and frailty/prefrailty, adjusting for demographic, social, behavioral, and comorbidity confounders.
Outcome measures were available for 192 PLHIV and 822 people without HIV. The median age was 62 years, and 84.9% were men. Among PLHIV, the median CD4 cell count was 645.5 cells/µL. Prevalence of frailty/prefrailty was 5.73%/57.3% in PLHIV vs. 1.73%/52.2% in people without HIV, respectively. HIV was associated with prefrailty/frailty odds ratio = 1.89; 95% confidence interval = 1.37 to 2.61), but after adjusting for social and behavioral factors and comorbidities, HIV was not significantly associated with prefrailty/frailty (odds ratio = 1.24; 95% confidence interval: = 0.84 to 1.81). In PLHIV only, frailty/prefrailty was associated with depressive symptomatology, kidney disease, and time since HIV infection.
Prevalence of frailty is increased in aging PLHIV with well-controlled HIV disease, but other factors than HIV are predominant, particularly depression and comorbidities.
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