Impact of interventions scenarios targeting three main vascular risk factors on the future burden of dementia in France.

The epidemiological and societal burden of dementia is expected to increase in the coming decades due to the world population aging. In this context, the evaluation of the potential impact of intervention scenarios aiming at reducing the prevalence of dementia risk factors is an active area of research. However, such studies must account for the associated changes in mortality and the dependence between the risk factors. Using micro-simulations, this study aims to estimate the changes in dementia burden in France in 2040 according to intervention scenarios targeting the prevention or treatment of hypertension, diabetes and physical inactivity. Accounting for their communality and their effects on mortality, the results show that the disappearance of hypertension, diabetes and physical inactivity in France in 2020 could decrease dementia prevalence by 33% among men and 26% among women in 2040 and increase the life expectancy without dementia at age 65 by 3.4 years (men) and 2.6 years (women). Among the three factors, the prevention of hypertension would be the most efficient. These projections rely on current estimates of the risk of dementia and death associated with risk factors. Thanks to the R package developed they could be refined for different countries or different interventions and updated with new estimates.

Measuring Digital Vaccine Literacy: Development and Psychometric Assessment of the Digital Vaccine Literacy Scale.

BACKGROUND: The use of the internet to look for information about vaccines has skyrocketed in the last years, especially with the COVID-19 pandemic. Digital vaccine literacy (DVL) refers to understanding, trust, appraisal, and application of vaccine-related information online. OBJECTIVE: This study aims to develop a tool measuring DVL and assess its psychometric properties. METHODS: A 7-item online questionnaire was administered to 848 French adults. Different psychometric analyses were performed, including descriptive statistics, exploratory factor analysis, confirmatory factor analysis, and convergent and discriminant validity. RESULTS: We developed the 7-item DVL scale composed of 3 factors (understanding and trust official information; understanding and trust information in social media; and appraisal of vaccine information online in terms of evaluation of the information and its application for decision making). The mean DVL score of the baseline sample of 848 participants was 19.5 (SD 2.8) with a range of 7-28. The median score was 20. Scores were significantly different by gender (P=.24), age (P=.03), studying or working in the field of health (P=.01), and receiving regular seasonal flu shots (P=.01). CONCLUSIONS: The DVL tool showed good psychometric proprieties, resulting in a promising measure of DVL.

Socioeconomic inequalities in dementia risk among a French population-based cohort: quantifying the role of cardiovascular health and vascular events.

This study aimed to investigate the role of cardiovascular health (CVH) and vascular events as potential contributors to socioeconomic inequalities in dementia using causal mediation analyses. We used data from the Three-City Cohort, a French population-based study with 12 years of follow-up, with active search of dementia cases and validated diagnosis. Individual socioeconomic status was assessed using education, occupation and income. A CVH score as defined by the American Heart Association and incident vascular events were considered separately as mediators. We performed multi-level Cox proportional and Aalen additive hazard regression models to estimate the total effects of socioeconomic status on dementia risk. To estimate natural direct and indirect effects through CVH and vascular events, we applied two distinct weighting methods to quantify the role of CVH and vascular events: Inverse Odds Ratio Weighting (IORW) and Marginal Structural Models (MSM) respectively. Among 5581 participants, the risk of dementia was higher among participants with primary education (HR 1.60, 95%CI 1.44-1.78), blue-collar workers (HR 1.62, 95%CI 1.43-1.84) and with lower income (HR 1.23, 95%CI 1.09-1.29). Using additive models, 571 (95% CI 288-782) and 634 (95% CI 246-1020) additional cases of dementia per 100 000 person and year were estimated for primary education and blue-collar occupation, respectively. Using IORW, the CVH score mediate the relationship between education or income, and dementia (proportion mediated 17% and 26%, respectively). Yet, considering vascular events as mediator, MSM generated indirect effects that were smaller and more imprecise. Socioeconomic inequalities in dementia risk were observed but marginally explained by CVH or vascular events mediators.

Prevalence, Severity, and Clinical Management of Brain Incidental Findings in Healthy Young Adults: MRi-Share Cross-Sectional Study.

Background and Objectives: Young adults represent an increasingly large proportion of healthy volunteers in brain imaging research, but descriptions of incidental findings (IFs) in this age group are scarce. We aimed to assess the prevalence and severity of IFs on brain MRIs of healthy young research participants aged 18-35 years, and to describe the protocol implemented to handle them. Methods: The study population comprised 1,867 participants aged 22.1 ± 2.3 years (72% women) from MRi-Share, the cross-sectional brain MRI substudy of the i-Share student cohort. IFs were flagged during the MRI quality control. We estimated the proportion of participants with IFs [any, requiring medical referral, potentially serious (PSIFs) as defined in the UK biobank]: overall, by type and severity of the final diagnosis, as well as the number of IFs. Results: 78/1,867 participants had at least one IF [4.2%, 95% Confidence Interval (CI) 3.4-5.2%]. IFs requiring medical referral (n = 38) were observed in 36/1,867 participants (1.9%, 1.4-2.7%), and represented 47.5% of the 80 IFs initially flagged. Referred IFs were retrospectively classified as PSIFs in 25/1,867 participants (1.3%, 0.9-2.0%), accounting for 68.4% of anomalies referred (26/38). The most common final diagnosis was cysts or ventricular abnormalities in all participants (9/1,867; 0.5%, 0.2-0.9%) and in those with referred IFs (9/36; 25.0%, 13.6-41.3%), while it was multiple sclerosis or radiologically isolated syndrome in participants with PSIFs (5/19; 26.3%, 11.5-49.1%) who represented 0.1% (0.0-0.4%) and 0.2% (0.03-0.5%) of all participants, respectively. Final diagnoses were considered serious in 11/1,867 participants (0.6%, 0.3-1.1%). Among participants with referred IFs, 13.9% (5/36) required active intervention, while 50.0% (18/36) were put on clinical surveillance. Conclusions: In a large brain imaging study of young healthy adults participating in research we observed a non-negligible frequency of IFs. The etiological pattern differed from what has been described in older adults.

Association between the retinal vascular network with Singapore "I" Vessel Assessment (SIVA) software, cardiovascular history and risk factors in the elderly: The Montrachet study, population-based study.

PURPOSE: To identify patterns summarizing the retinal vascular network in the elderly and to investigate the relationship of these vascular patterns with cardiovascular history. METHODS: We conducted a population-based study, the Montrachet study (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases), in participants older than 75 years. The history of cardiovascular disease and a score-based estimation of their 10-year risk of cardiovascular mortality (Heart SCORE) were collected. Retinal vascular network analysis was performed by means of Singapore "I" Vessel Assessment (SIVA) software. Principal component analysis was used to condense the information contained in the high number of variables provided and to identify independent retinal vascular patterns. RESULTS: Overall, 1069 photographs (1069 participants) were reviewed with SIVA software. The mean age was 80.0 ± 3.8 years. We extracted three vascular patterns summarizing 41.3% of the vascular information. The most clinically relevant pattern, Sparse vascular network, accounted for 17.4% of the total variance. It corresponded to a lower density in the vascular network and higher variability in vessel width. Diabetic participants with hypoglycemic treatment had a sparser vascular network pattern than subjects without such treatment (odds ratio, [OR], 1.68; 95% CI, 1.04-2.72; P = 0.04). Participants with no history of cardiovascular disease who had a sparser vascular network were associated with a higher Heart SCORE (OR, 1.76; 95% CI, 1.08-2.25; P = 0.02). CONCLUSIONS: Three vascular patterns were identified. The Sparse vascular network pattern was associated with having a higher risk profile for cardiovascular mortality risk at 10 years.

Life-Course Socioeconomic Position and Hippocampal Atrophy in a Prospective Cohort of Older Adults.

OBJECTIVE: Low socioeconomic position (SEP) has been linked to an increased risk of dementia and cognitive decline. However, little is known about the association between SEP and morphologic brain changes in older age. This study examines the relationships between indicators of life-course SEP with both hippocampal volume (HcV) and HcV loss in a population-based cohort of 1328 older adults aged 65 to 80 years. METHODS: Multivariable linear regression models were used to estimate the associations of SEP with baseline HcV and the annual rate of HcV atrophy according to three life-course conceptual models: the sensitive/critical periods model (which explored SEP in specific periods: in childhood [using parental education], early adulthood [based on participants' education], and midlife [based on participants' socioprofessional group]); the accumulation-of-risk model (life-course cumulative SEP), and the social mobility model (life-course SEP trajectories). RESULTS: Participants with lower midlife SEP had smaller HcV (-0.08 cm; 95% confidence interval, -0.15 to -0.01) and 0.17% (95% confidence interval, 0.04%-0.30%) faster hippocampal atrophy than participants with higher midlife SEP. Childhood and early adulthood SEPs were not related to hippocampal measures. The accumulation-of-risk and the social mobility models revealed that the accumulation of socioeconomic disadvantage and declining socioeconomic trajectories were related to faster hippocampal atrophy. CONCLUSIONS: In this cohort of older adults, lower socioprofessional attainment in midlife and disadvantageous life-course socioeconomic position were associated with faster hippocampal atrophy, a cerebral change linked to cognitive disorders. Results support the hypothesized links between socioenvironmental exposures related to stress and/or cognitive enrichment and brain/cognitive reserve capacities.

Longitudinal assessment of global and regional rate of grey matter atrophy in 1,172 healthy older adults: modulation by sex and age.

To characterize the neuroanatomical changes in healthy older adults is important to differentiate pathological from normal brain structural aging. The present study investigated the annualized rate of GM atrophy in a large sample of older participants, focusing on the hippocampus, and searching for modulation by age and sex. In this 4-year longitudinal community cohort study, we used a VBM analysis to estimate the annualized rate of GM loss, at both the global and regional levels, in 1,172 healthy older adults (65-82 years) scanned at 1.5T. The global annualized rate of GM was -4.0 cm3/year (-0.83%/year). The highest rates of regional GM loss were found in the frontal and parietal cortices, middle occipital gyri, temporal cortex and hippocampus. The rate of GM atrophy was higher in women (-4.7 cm3/year, -0.91%/year) than men (-3.3 cm3/year, -0.65%/year). The global annualized rate of GM atrophy remained constant throughout the age range of the cohort, in both sexes. This pattern was replicated at the regional level, with the exception of the hippocampi, which showed a rate of GM atrophy that accelerated with age (2.8%/year per year of age) similarly for men and women. The present study reports a global and regional description of the annualized rate of grey matter loss and its evolution after the age of 65. Our results suggest greater anatomical vulnerability of women in late life and highlight a specific vulnerability of the hippocampus to the aging processes after 65 years of age.

20-Year prevalence projections for dementia and impact of preventive policy about risk factors.

Incidence of dementia increases sharply with age and, because of the increase in life expectancy, the number of dementia cases is expected to rise dramatically over time. Some studies suggest that controlling some modifiable risk factors for dementia like diabetes or hypertension could lower its incidence. However, as treating these vascular factors would also reduce mortality risk, the actual impact of such public-health intervention on dementia prevalence is not known. Accounting for the impact of dementia and risk factors on mortality, the aim of this work was (1) to compute projections of age- and-sex specific prevalence of dementia in France from 2010 to 2030, (2) to evaluate how public-health interventions targeting risk factors for dementia could change these projections. Age-and-sex specific incidence of dementia and mortality of demented subjects were estimated from the Paquid population-based cohort using a semi-parametric illness-death model. Future global mortality rates and population sizes were obtained from national demographic projections. Under the assumption that life expectancy will increase by 3.5 years for men and 2.8 years for women by 2030, the number of subjects with dementia was estimated to increase by about 75% from 2010 to 2030 with a 200% increase after 90 years of age. Therapeutic intervention on the whole population reducing high blood pressure prevalence would lead to a decrease in both dementia incidence rates and mortality and would have a modest impact on the number of dementia cases. On the other hand, a preventive dementia treatment targeting ApoE4 carriers would probably not improve survival and hence would decrease dementia prevalence by 15-25%.

Prediction model of Parkinson's disease based on antiparkinsonian drug claims.

Drug claims databases are increasingly available and provide opportunities to investigate epidemiologic questions. The authors used computerized drug claims databases from a social security system in 5 French districts to predict the probability that a person had Parkinson's disease (PD) based on patterns of antiparkinsonian drug (APD) use. Clinical information for a population-based sample of persons using APDs in 2007 was collected. The authors built a prediction model using demographic variables and APDs as predictors and investigated the additional predictive benefit of including information on dose and regularity of use. Among 1,114 APD users, 320 (29%) had PD and 794 (71%) had another diagnosis as determined by study neurologists. A logistic model including information on cumulative APD dose and regularity of use showed good performance (c statistic = 0.953, sensitivity = 92.5%, specificity = 86.4%). Predicted PD prevalence (among persons aged ≥18 years) was 6.66/1,000; correcting this estimate using sensitivity/specificity led to a similar figure (6.04/1,000). These data demonstrate that drug claims databases can be used to estimate the probability that a person is being treated for PD and that information on APD dose and regularity of use improves models' performances. Similar approaches could be developed for other conditions.

Incidence of ischaemic stroke according to income level among older people: the 3C study.

BACKGROUND: stroke has been shown to follow a social gradient with incidence rising as socioeconomic status decreases. OBJECTIVE: to examine the relationship between socioeconomic status and ischaemic stroke risk amongst older people. SETTING: the Cities of Bordeaux, Dijon and Montpellier in France. SUBJECTS AND METHODS: nine thousand and two hundred and ninety-four non-institutionalised persons aged 65 years or more followed for 6 years. RESULTS: the distribution of cardiovascular risks factors was consistent with the classical finding of more favourable risk profiles among the advantaged socioeconomic groups. One hundred and thirty-six individuals developed a first ever ischaemic stroke (incidence rate: 3.2 per 1,000 py (person-years), 95% CI 2.7-3.8). The age- and sex-adjusted incidence of ischaemic stroke increased with increasing level of income (from 2.4 to 4.1 per 1,000 py, P = 0.04). In the multivariable analysis adjusting for cardiovascular risk factors, the higher income group displayed a 80% increased risk of ischaemic stroke compared with less wealthy participants (hazards ratio 1.77, 95% CI 1.20-2.61). CONCLUSIONS: in this community-based sample of older individuals, a higher level of household income was associated with a higher risk of ischaemic stroke, a reversal of the social gradient usually reported in younger age groups. Selective survival is one of the potential explanations for this unexpected finding.

Cognitive impairment improves the predictive validity of the phenotype of frailty for adverse health outcomes: the three-city study.

OBJECTIVES: To determine whether adding cognitive impairment to frailty improves its predictive validity for adverse health outcomes. DESIGN: Four-year longitudinal study. SETTING: The French Three-City Study. PARTICIPANTS: Six thousand thirty community-dwelling persons aged 65 to 95. MEASUREMENTS: Frailty was defined as having at least three of the following criteria: weight loss, weakness, exhaustion, slowness, and low physical activity. Subjects meeting one or two criteria were prefrail and those meeting none as nonfrail. The lowest quartile in the Mini-Mental State Examination (MMSE) and the Isaacs Set Test (IST) was used to identify subjects with cognitive impairment. The predictive validity of frailty for incident disability, hospitalization, dementia, and death was calculated first for frailty subgroups and then rerun after stratification according to the presence or absence of cognitive impairment. RESULTS: Four hundred twenty-one individuals (7%) met frailty criteria. Cognitive impairment was present in 10%, 12%, and 22% of the nonfrail, prefrail, and frail subjects, respectively. Those classified as frail scored lower on the MMSE and IST than those classified as prefrail and nonfrail. After adjustment, frail persons with cognitive impairment were significantly more likely to develop disability in activities of daily living (ADLs) and instrumental ADLs over the following 4 years. The risk of incident mobility disability and hospitalization was marginally greater. Incident dementia was greater in the groups with cognitive impairment irrespective of their frailty status. Conversely, frailty was not a significant predictor of mortality. CONCLUSION: Cognitive impairment improves the predictive validity of the operational definition of frailty, because it increases the risk of adverse health outcomes in this particular subgroup of the elderly population.

Comparison of health insurance claims and patient interviews in assessing drug use: data from the Three-City (3C) Study.

PURPOSE: Precise determination of drug exposure is fundamental in pharmacoepidemiology. Drug exposure is often presumed from health insurance claims but this may not correspond exactly to what subjects actually take. This study was designed to investigate French reimbursement databases in assessing drug use. METHODS: Between 1999 and 2001, 9294 subjects were included in the Three-City (3C) Study, a French cohort studying the relationship between vascular risk factors and dementia. Of these, 4112 subjects had data available from both clinical interviews and the reimbursement databases of the French national health insurance system. Agreement between drugs reported as used at interview and drugs reimbursed during the previous 30 or 60 days was measured with kappa coefficients. Using calculations of sensitivity (Se), specificity (Sp), positive predictive values (PPVs) and negative predictive values (NPVs), the validity of reimbursement data for the 30 or 60 days preceding the interview was investigated taking drugs reported at interview as the 'gold standard'. RESULTS: Declared drug use at interview was less well predicted by 30-day than by 60-day reimbursement data. Agreement between reimbursement data and interviews as well as validity of reimbursement data with reference to interviews were substantial for drugs used in cardiovascular diseases, diabetes, rheumatic disorders or neuropsychiatric conditions and were poor for laxatives, vitamins, vasculoprotectives, first and second line analgesics, anti-infective products or dermatologicals. CONCLUSIONS: Reimbursement data with an appropriate time frame and interviews estimate exposure to chronically used drugs similarly. Self-medication was better described with interviews whereas reimbursement data seem more useful for drugs used topically or intermittently.

Primary and secondary care consultations in elderly demented individuals in France. Results from the Three-City Study.

BACKGROUND/AIMS: Our purpose was to analyze consultations with primary- and secondary-care physicians by demented people and identify factors that hamper or facilitate consultation. METHODS: In total, 498 demented subjects were evaluated within the Three-City Study, a population-based cohort of individuals aged >or=65 years.Primary- and secondary-care consultations (consultation with a specialist and/or treatment with anti-dementia drugs) were assessed by a neurologist or geriatrician. RESULTS: Thirty-five percent of the demented subjects did not seek advice for their cognitive problems and only 31% consulted a specialist. Consultation for primary care was principally dependent on the subjects' own awareness of the cognitive disorder and on their age. Factors associated with consultation for secondary care were younger age, higher education level, higher instrumental activities of daily living disability and awareness of the cognitive disorder by the subject, all of which predicted more frequent consultation. The level of cognitive performance had only a slight influence on primary care and none on secondary care. CONCLUSION: The failure to see a physician due to dementia, especially secondary-care practitioners, is frequent in the community, particularly in the oldest subjects.

Evaluation of the impact of memantine treatment initiation on psychotropics use: a study from the French national health care database.

BACKGROUND: Clinical studies reported that treatments for Alzheimer's disease may have an impact on behavioral and psychiatric disorders. We tested the hypothesis that memantine treatment initiation modifies psychotropic medication in real-life practice patients. METHODS: A 2-year follow-up cohort study was performed. A sample of patients treated in the general population, extracted from the database of the French national healthcare system (CNAM-TS), was examined. The sample included 4,600 memantine-treated patients (mean age 79.8 years, 69% women) randomly selected from the database of the CNAM-TS covering 69% of the French population aged 65 years and over. The follow-up rate was 95.0%. This database includes exhaustive data on drug consumption. We used interrupted time series analysis of the proportion of psychotropics users (all psychotropic drugs and specific categories) before and after onset of memantine. RESULTS: There was a 39-50% regular increase in patients treated with psychotropic drugs before memantine initiation This increasing trend stopped after memantine initiation, the proportion of psychotropic users remaining stable around 53% up to the end. The trends before and after memantine onset were significantly different (p < 0.001). CONCLUSIONS: Our results suggest a temporal relationship between the onset of memantine and the stabilization of psychotropic drugs use in this large sample of elderly patients.

An automated procedure for the assessment of white matter hyperintensities by multispectral (T1, T2, PD) MRI and an evaluation of its between-centre reproducibility based on two large community databases.

INTRODUCTION: An automated procedure for the detection, quantification, localization and statistical mapping of white matter hyperintensities (WMH) on T2-weighted magnetic resonance (MR) images is presented and validated based on the results of a between-centre reproducibility study. METHODS: The first step is the identification of white matter (WM) tissue using a multispectral (T1, T2, PD) segmentation. In a second step, WMH are identified within the WM tissue by segmenting T2 images, isolating two different classes of WMH voxels - low- and high-contrast WMH voxels, respectively. The reliability of the whole procedure was assessed by applying it to the analysis of two large MR imaging databases (n = 650 and n= 710, respectively) of healthy elderly subjects matched for demographic characteristics. RESULTS: Average overall WMH load and spatial distribution were found to be similar in the two samples, (1.81 and 1.79% of the WM volume, respectively). White matter hyperintensity load was found to be significantly associated with both age and high blood pressure, with similar effects in both samples. With specific reference to the 650 subject cohort, we also found that WMH load provided by this automated procedure was significantly associated with visual grading of the severity of WMH, as assessed by a trained neurologist. CONCLUSION: The results show that this method is sensitive, well correlated with semi-quantitative visual rating and highly reproducible.

S18Y polymorphism in the UCH-L1 gene and Parkinson's disease: evidence for an age-dependent relationship.

We studied the relationship between Parkinson's disease (PD) and the S18Y polymorphism in the UCH-L1 gene and the effect on this relationship of age at onset, smoking, and pesticides. Patients requested free health coverage for PD to the Mutualité Sociale Agricole (MSA), the French health insurance organization for people whose work is related to agriculture. Controls requested reimbursement of health expenses to the MSA. A maximum of three controls were matched to each case. Analyses included participants with both parents born in Europe. There were no differences in S18Y genotypes between patients (n = 209; 67% SS, 32% SY, 1% YY) and controls (n = 488; 66% SS, 30% SY, 4% YY). The relationship between PD and S18Y was modified by age at onset (P = 0.03). The Y allele was inversely associated with PD for patients with onset before 61 years (odds ratio [OR] = 0.53; 95% confidence interval [CI], 0.29-0.99); there was no association for older patients (62-68 years: OR = 1.21; 95% CI, 0.67-2.20; >68 years: OR = 1.24; 95% CI, 0.67-2.31). Among patients, Y carriers had a later onset than noncarriers (P = 0.04). These findings were not modified or confounded by smoking and pesticides. In this community-based case-control study, carriers of the Y allele were at decreased risk of developing PD at a young age, independently of pesticides and smoking.