BMC Geriatr

Background Physical activity may decrease the risk of dementia; however, previous cohort studies seldom investigated the different types of physical activity and household activities. Our objective was to analyze the links between two physical activity types and dementia in older people. Methods The study used data from the prospective observational Three-city cohort and included 1550 community-dwelling individuals aged 72 to 87 without dementia at baseline. Physical activity was assessed with the Voorrips questionnaire. Two sub-scores were calculated to assess household/transportation activities and leisure/sport activities. Restricted cubic spline and proportional hazard Cox models were used to estimate the non-linear exposure-response curve for the dementia risk and the appropriate activity level thresholds. Models were adjusted for possible confounders, including socio-demographic variables, comorbidities, depressive symptoms and APOE genotype. Results The median age was 80 years, and 63.6% of participants were women. After a median follow-up of 4.6 years, dementia was diagnosed in 117 participants (7.6%). An inverse J-shaped association was found between household/transportation physical activity sub-score and dementia risk, which means that the risk is lowest for the moderately high values and then re-increases slightly for the highest values. The results remained significant when this sub-score was categorized in three classes (low, moderate, and high), with hazard ratios (95% confidence interval) of 0.55 (0.35–0.87) and 0.62 (0.38–1.01) for moderate and high activity levels, respectively. No significant effect was found for leisure/sport activities. Conclusions The 5-year risk of dementia was significantly and negatively associated with the household/transportation activity level, but not with the leisure and sport activity sub-score. This highlights the importance of considering all physical activity types in 72 years or older people

Alzheimers Dement

Introduction: The aims of this study are to examine the evolution of clinical dementia diagnosis over 3 decades and to investigate secular trends of dementia. Methods: Four cohorts covering a period from 1988 to 2013 were used: the Personnes Agees Quid and Three-City-Bordeaux studies, and the Cognitive Function and Aging Study (CFAS) I and II. Mini-Mental State Examination scores at clinical diagnosis were evaluated over a 24-year follow-up period in French studies. An algorithmic approach was applied to CFAS I and II to provide dementia prevalence and incidence estimates. Results: A significant increase of the Mini-Mental State Examination score at diagnosis was observed until 2000 and a significant decrease after. We reported a prevalence of 8.8% for CFAS I (1990-1993) compared with a prevalence of 6.5% in CFAS II (2008-2011). The 2-year incidence rate was estimated at 31.2/1000 (95% confidence interval = 28.0-34.8) for CFAS I and 15.0/1000 (95% confidence interval = 13.5-16.7) for CFAS II. Discussion: Applying a stable algorithm to different cohorts across time can provide a robust method for time trends estimation

Recommendations for ICT use in Alzheimer's Disease assessment: Monaco CTAD expert meeting

International audienceAlzheimer disease (AD) and other related dementia represent a major challenge for health care systems within the aging population. It is therefore important to develop better instruments for assessing disease severity and disease progression to optimize patient's care and support to care provide rs, and also provide better tools for clinical research. In this area, Information and Communication Technologies (ICT) are of particular interest. Such techniques enable accurate and standardized assessments of patients' performance and actions in real time and real life situations. The aim of this article is to provide basic recommendation concerning the development and the use of ICT for Alzheimer's disease and related disorders. During he ICT and Mental Health workshop (CTAD meeting held in Monaco on the 30th October 2012) an expert panel was set up to prepare the first recommendations for the use of ICT in dementia research. The expert panel included geriatrician, epidemiologist, neurologist, psychiatrist, psychologist, ICT engineers, representatives from the industry and patient association. The recommendations are divided into three sections corresponding to 1/ the clinical targets of interest for the use of ICT, 2/ the cond itions, the type of sensors and the outputs (scores) that could be used and obtained, 3/ finally the last section concerns specifically the use of ICT within clinical trials

Invest Ophthalmol Vis Sci

Purpose: To analyze the association between skin autofluorescence (sAF), estimating tissue accumulation of advanced glycation end-products (AGEs), and open angle glaucoma (OAG) in an elderly population. Methods: The Antioxydants, Lipides Essentiels, Nutrition and maladies OculaiRes (ALIENOR) study is an on-going epidemiologic population-based study on age-related eye diseases. In 2009 to 2010, 624 subjects, aged 74 years or older, were recruited. All subjects underwent a complete eye examination, including optic disc color photography and spectral-domain optical coherence tomography (SD-OCT) examination. Sociodemographic and medical history data were collected using standardized questionnaires. Glaucoma diagnosis was made using optic nerve head retinophotography and International Society for Epidemiologic and Geographical Ophthalmology criteria. sAF was measured with a noninvasive autofluorescence reader in 467 subjects. Results: Of subjects, 455 had complete data, 424 were classified as controls, and 31 classified as OAG. Mean age was 82.3 +/- 4.3 years, mean and median sAF were 2.8 +/- 0.7 and 2.7 arbitrary units (AU), respectively. In a multivariate analysis, higher sAF values (>/=2.7 AU) were associated with OAG (odds ratio [OR] = 2.28, 95% Confidence Interval [CI]: 1.03; 5.04). Other variables significantly associated with OAG were age (OR = 1.10, 95%CI: 1.00; 1.21), glaucoma family history (OR = 2.83, 95%CI: 1.14; 7.01) and smoking (1-20 pack-years [OR = 3.31, 95%CI: 1.18; 9.26]; >/=20 pack-years [OR = 3.85, 95%CI: 1.42; 10.46]). Conclusions: Higher level of sAF, which may act as a long-term biomarker of metabolic memory, and smoking are independently associated with an increased risk of glaucoma. Long-term accumulation of AGEs, a marker of oxidative stress, could play a role in the pathogenesis of glaucomatous chronic optic neuropathy

PLoS One

Diffusion MRI is extensively used to investigate changes in white matter microstructure. However, diffusion measures within white matter tissue can be affected by partial volume effects due to cerebrospinal fluid and white matter hyperintensities, especially in the aging brain. In previous aging studies, the cingulum bundle that plays a central role in the architecture of the brain networks supporting cognitive functions has been associated with cognitive deficits. However, most of these studies did not consider the partial volume effects on diffusion measures. The aim of this study was to evaluate the effect of free water elimination on diffusion measures of the cingulum in a group of 68 healthy elderly individuals. We first determined the effect of free water elimination on conventional DTI measures and then examined the effect of free water elimination on verbal fluency performance over 12 years. The cingulum bundle was reconstructed with a tractography pipeline including a white matter hyperintensities mask to limit the negative impact of hyperintensities on fiber tracking algorithms. We observed that free water elimination increased the ability of conventional DTI measures to detect associations between tissue diffusion measures of the cingulum and changes in verbal fluency in older individuals. Moreover, free water content and mean diffusivity measured along the cingulum were independently associated with changes in verbal fluency. This suggests that both tissue modifications and an increase in interstitial isotropic water would contribute to cognitive decline. These observations reinforce the importance of using free water elimination when studying brain aging and indicate that free water itself could be a relevant marker for age-related cingulum white matter modifications and cognitive decline

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

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

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 verbal 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. Verbal fluency was evaluated with the Isaacs Set Test at 60 seconds 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: 97 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 verbal fluency scores was -0.9 (IQR: -2.7 - 1.8). Low baseline verbal fluency performance and its decline were associated with older age and being a female. Low educational level was associated with low baseline verbal fluency performance but not with its decline. Verbal 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 verbal fluency performance and/or its decline. Interventions that focus on supporting cardiometabolic health are highly recommended to prevent cognitive disorders in PLHIV. This article is protected by copyright. All rights reserved

Seropositivity to Herpes Simplex Virus Antibodies and Risk of Alzheimer's Disease: A Population-Based Cohort Study

International audienceBACKGROUND: Herpes Simplex Virus (HSV) infection has been proposed as a possible risk factor of Alzheimer's Disease (AD) notably because it is neurotropic, ubiquitous in the general population and able to establish lifelong latency in the host. The fact that HSV was present in elderly subjects with AD suggests that the virus could be a co-factor of the disease. We investigated the risk of developing AD in anti-HSV immunoglobulin G (IgG) positive subjects (indicator of a lifelong infection to HSV) and IgM-positive subjects (indicator of primary infection or reactivation of the virus) in a longitudinal population-based cohort of elderly subjects living in the community. METHODS: Cox proportional hazard models were used to study the risk of developing AD according to the presence or not of anti-HSV IgG and IgM antibodies, assessed in the sera of 512 elderly initially free of dementia followed for 14 years. RESULTS: During the follow-up, 77 incident AD cases were diagnosed. Controlled for age, gender, educational level and Apolipoprotein E4 (APOE4) status, IgM-positive subjects showed a significant higher risk of developing AD (HR = 2.55; 95% CI [1.38-4.72]), although no significant increased risk was observed in IgG-positive subjects (HR = 1.67; 95%CI [0.75-3.73]). No modification effect with APOE4 status was found. CONCLUSION: Reactivation of HSV seropositivity is highly correlated with incident AD. HSV chronic infection may therefore be contributive to the progressive brain damage characteristic of AD

Association of Plasma Aß Peptides with Blood Pressure in the Elderly

Background Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively). Methodology/Principal Findings Plasma Aß1-40 and Aß1-42 levels were measured using an xMAP-based assay in 1,972 individuals (none of whom were taking antihypertensive drugs) from 3 independent studies: the French population-based 3C and MONA-LISA (Lille) studies (n = 627 and n = 769, respectively) and the Australian, longitudinal AIBL study (n = 576). In the combined sample, the Aß1-42/ Aß1-40 ratio was significantly and inversely associated with SBP (p = 0.03) and a similar trend was observed for DBP (p = 0.06). Using the median age (69) as a cut-off, the Aß1-42/Aß1-40 ratio was strongly associated with both SBP and DBP in elderly individuals (p = 0.002 and p = 0.03, respectively). Consistently, a high Aß1-42/ Aß1-40 ratio was associated with a lower risk of hypertension in both the combined whole sample (odds ratio [OR], 0.71; 95% confidence interval [CI], 0.56-0.90) and (to an even greater extent) in the elderly subjects (OR, 0.53; 95% CI, 0.37–0.75). Lastly, all these associations appeared to be primarily driven by the level of plasma Aß1-40. Conclusion The plasma Aß1-42/Aß1-40 ratio is inversely associated with SBP, DBP and the risk of hypertension in elderly subjects, suggesting that Aß peptides affect blood pressure in vivo. These results may be particularly relevant in Alzheimer\u27s disease, in which a high Aß1-42/Aß1-40 plasma ratio is reportedly associated with a decreased risk of incident disease

Increasing Prevalence of Myopia in Europe and the Impact of Education

Purpose To investigate whether myopia is becoming more common across Europe and explore whether increasing education levels, an important environmental risk factor for myopia, might explain any temporal trend. Design Meta-analysis of population-based, cross-sectional studies from the European Eye Epidemiology (E3) Consortium. Participants The E3 Consortium is a collaborative network of epidemiological studies of common eye diseases in adults across Europe. Refractive data were available for 61 946 participants from 15 population-based studies performed between 1990 and 2013; participants had a range of median ages from 44 to 78 years. Methods Noncycloplegic refraction, year of birth, and highest educational level achieved were obtained for all participants. Myopia was defined as a mean spherical equivalent ≤-0.75 diopters. A random-effects meta-analysis of age-specific myopia prevalence was performed, with sequential analyses stratified by year of birth and highest level of educational attainment. Main Outcome Measures Variation in age-specific myopia prevalence for differing years of birth and educational level. Results There was a significant cohort effect for increasing myopia prevalence across more recent birth decades; age-standardized myopia prevalence increased from 17.8% (95% confidence interval [CI], 17.6-18.1) to 23.5% (95% CI, 23.2-23.7) in those born between 1910 and 1939 compared with 1940 and 1979 (P = 0.03). Education was significantly associated with myopia; for those completing primary, secondary, and higher education, the age-standardized prevalences were 25.4% (CI, 25.0-25.8), 29.1% (CI, 28.8-29.5), and 36.6% (CI, 36.1-37.2), respectively. Although more recent birth cohorts were more educated, this did not fully explain the cohort effect. Compared with the reference risk of participants born in the 1920s with only primary education, higher education or being born in the 1960s doubled the myopia prevalence ratio-2.43 (CI, 1.26-4.17) and 2.62 (CI, 1.31-5.00), respectively - whereas individuals born in the 1960s and completing higher education had approximately 4 times the reference risk: a prevalence ratio of 3.76 (CI, 2.21-6.57). Conclusions Myopia is becoming more common in Europe; although education levels have increased and are associated with myopia, higher education seems to be an additive rather than explanatory factor. Increasing levels of myopia carry significant clinical and economic implications, with more people at risk of the sight-threatening complications associated with high myopia