A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.
Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress.
The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing.
Cohort studies; Cognitive ageing; Data harmonisation; Dementia; International consortium; Mild cognitive impairment
Persons with vascular disorders are at higher risk of cognitive decline.
To determine whether caffeine may be associated with cognitive decline reduction in elderly at high vascular risk.
We included 2475 women aged 65+ years in the Women’s Antioxidant Cardiovascular Study, a randomized trial of antioxidants and B vitamins for cardiovascular disease secondary prevention. We ascertained regular caffeine intake at baseline (1995–1996) using a validated 116 item-food frequency questionnaire. From 1998–2000 to 2005–2006, we administered four telephone cognitive assessments at two-year intervals evaluating global cognition, verbal memory and category fluency. The primary outcome was the change in global cognitive score, which was the average of the z-scores of all tests. We used generalized linear models for repeated measures that were adjusted for various sociodemographic, health and lifestyle factors to evaluate the difference in cognitive decline rates across quintiles of caffeine intake.
We observed significantly slower rates of cognitive decline with increasing caffeine intake (p-trend=0.02). The rate difference between the highest and lowest quintiles of usual caffeine intake (> 371 versus < 30 mg/day) was equivalent to that observed between those who were 7 years apart in age (p=0.006). Consumption of caffeinated coffee was significantly related to slower cognitive decline (p-trend=0.05), but not other caffeinated products (e.g., decaf, tea, cola, chocolate). We conducted interaction analyses and observed stronger associations in women assigned to vitamin B supplementation (p-interaction = 0.02).
Caffeine intake was related to moderately better cognitive maintenance over 5 years in older women with vascular disorders.
Cognition; Aging; Caffeine; Cohort studies; Risk factors; Epidemiology
Hypnotics are widely used by the elderly, and their impact on mortality remains controversial. The inconsistent findings could be due to methodological limitations, notably the lack of control for underlying sleep symptoms or illness associated with hypnotic use, for example, insomnia symptoms and excessive daytime sleepiness, depression and anxiety. Our objective was to examine the association between the use of hypnotics and mortality risk in a large cohort of community-dwelling elderly, taking into account a wide range of potential competing risks including sociodemographic characteristics, lifestyle, and chronic disorders as well as underlying psychiatric disorders and sleep complaints.
Analyses were carried out on 6,696 participants aged 65 years or older randomly recruited from three French cities and free of dementia at baseline. Adjusted Cox proportional hazards models with delayed entry, and age of the participants as the time scale, were used to determine the association between hypnotic use and 12-year survival.
At baseline, 21.7% of the participants regularly used at least one hypnotic. During follow-up, 1,307 persons died, 480 from cancer and 344 from cardiovascular disease. Analyses adjusted for study center, age and gender showed a significantly greater risk of all-cause and cardiovascular-related mortality with hypnotics, particularly benzodiazepines, and this increased with the number of hypnotics used. None of these associations were significant in models adjusting for sociodemographic and lifestyle characteristics, chronic disorders including cardiovascular pathologies, sleep and psychiatric disorders. Results remained unchanged when duration of past hypnotic intake or persistent versus intermittent use during follow-up were taken into account.
When controlling for a large range of potential confounders, the risk of mortality was not significantly associated with hypnotic use regardless of the type and duration. Underlying psychiatric disorders appear to be the principal confounders of the observed association.
Cohort studies; Elderly; Hypnotics; Mortality; Sleep disorders
The aim of this prospective cohort study was to evaluate the effects of lipid lowering agent (LLA) intake on cognitive function in 6830 community-dwelling elderly persons. Cognitive performance (global cognitive functioning, visual memory, verbal fluency, psychomotor speed and executive function), clinical diagnosis of dementia, and fibrate and statin use, were evaluated at baseline, and 2, 4, and 7 year follow-up. Multivariate Cox models were stratified by gender and adjusted for sociodemographic characteristics, mental and physical health including vascular risk factors, and genetic vulnerability (apolipoprotein E and cholesteryl ester transfer protein). For women but not men, fibrate use was specifically associated with an increased risk over 7 years of decline in visual memory only (HR=1.29, 95%CI=1.09–1.54, p=0.004), and did not increase risk for incident dementia. This association was independent of genetic vulnerability related to ApoE and Cholesteryl Exchange Transfer Protein polymorphisms and occurred only in women with higher LDL-cholesterol levels and treated with fibrate (HR=1.39, 95%CI=1.08–1.79, p=0.01) and not in those with lower LDL-cholesterol levels irrespective of fibrate treatment. For both sexes, no significant associations were found between statins (irrespective of their lipophilicity) and either cognitive decline or dementia incidence. This prospective study, adjusting for multiple confounders, found no evidence that LLA given in late life reduced the risk of cognitive decline and dementia, but did raise the possibility that women with treatment-resistant high LDL-cholesterol may be at increased risk of decline in visual memory.
Fibrate; Statin; Cognitive aging; Alzheimer's disease; Elderly; Apolipoprotein E; Cholesteryl Exchange Transfer Protein; Prospective cohort.
Retinal vascular caliber has been linked with increased cardiovascular risk and is predictive of cardiovascular pathology, including stroke and coronary heart disease. Oxidative stress, as well as inflammatory mechanisms, plays a major role in the pathogenesis and progression of atherosclerosis, plaque rupture and vascular thrombotic propensity. The purpose of this study is to explore the relationship between retinal vascular calibers and biomarkers of oxidative stress and inflammation, in subjects free of cardiovascular pathology.
Patients and Methods
Cross-sectional analysis from a community-dwelling cohort comprising 1224 individuals aged 60 years and over, without a history of coronary or peripheral artery disease or stroke. Retinal vascular caliber was measured from fundus photographs using semi-automated standardized imaging software. Oxidative stress was evaluated using plasma superoxide dismutase 2 and glutathione peroxidase (GPx-3) activities, and inflammatory state was assessed using plasma high sensitivity C-reactive protein (hsCRP) and orosomucoid.
In a multivariate model controlling for cardiovascular risk factors, larger retinal arteriolar caliber was independently related to higher level of GPx-3 activity (p = 0.003) whereas larger venular caliber was associated with higher levels of hsCRP (p = 0.0001) and orosomucoid (p = 0.01).
In the present study, biomarkers of oxidative stress regulation and inflammation were independently associated with retinal vascular calibers. This suggests that an assessment of retinal vessels may offer early and non-invasive detection of subclinical vascular pathology.
Evidence suggests a role for estrogen in depression but the involvement of estrogen receptor (ER) polymorphisms remains unknown.
To determine the association between ER polymorphisms and late-life depression and the modifying effect of hormone treatment (HT).
Depression was assessed using the Mini-International Neuropsychiatric Interview, according to DSM-IV criteria and the Centre for Epidemiologic Studies-Depression Scale. The association between ER-α and ER-β polymorphisms with severe depression was examined in 6017 community-dwelling elderly using multivariate logistic regression.
In women, the ER-α rs2234693 and rs9340799 polymorphisms were significantly associated with the risk of late-life depression. The A allele of ER-β rs1256049 increased the risk of depression, but only for non-current users of HT. In men, only the ER-β rs4986938 polymorphism showed a weak association with depression risk.
ER polymorphisms are associated with severe late-life depression risk in women only.
Age Factors; Aged; Aged, 80 and over; Alleles; Depressive Disorder, Major; epidemiology; genetics; Effect Modifier, Epidemiologic; Estrogen Replacement Therapy; Female; Gene Frequency; Genetic Predisposition to Disease; epidemiology; Genotype; Humans; Logistic Models; Longitudinal Studies; Male; Multivariate Analysis; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Postmenopause; psychology; Psychiatric Status Rating Scales; Receptors, Estrogen; genetics
To study, in a sample of French Family Practitioners (FPs), beliefs and attitudes toward depression and how they vary according to training received in mental health.
The Depression Attitude Questionnaire (DAQ) was completed by 468 FPs from all regions of France, recruited by pharmaceutical company representatives to attend focus groups on the management of depression in general practice.
A three factor model was derived from the DAQ, accounting for 37.7% of the total variance. The correlations between individual items of each component varied from 0.4 to 0.65 with an overall internal consistency of 0.47 (Cronbach’s alpha). FPs had an overall neutral position on component 1, professional ease, a positive view on the origins of depression and its amenability to change (component 2), and a belief in the necessity of medication and the benefit of antidepressant therapy (component 3). Training in mental health, specifically through continuing medical education and postgraduate psychiatric hospital training, was significantly and positively associated with both professional ease and a medication approach to treating depression.
this study is the first description of the beliefs and attitudes of French FPs towards depression using a standardized measure, the DAQ, despite the instrument’s limited psychometric properties. It shows the positive effect of training in mental health on attitudes towards depression.
Adult; Attitude of Health Personnel; Depressive Disorder; psychology; therapy; Education, Medical, Continuing; Family Practice; methods; Female; France; Health Knowledge, Attitudes, Practice; Humans; Male; Mental Health Services; Middle Aged; Physicians, Family; education; Principal Component Analysis; Psychometrics; methods; Questionnaires
Patient-reported outcome measures (PROMs) are intended to reflect outcomes relevant to patients. They are increasingly used for healthcare quality improvement. To produce valid measures, patients should be involved in the development process but it is unclear whether this usually includes people with low literacy skills or learning disabilities. This potential exclusion raises concerns about whether these groups will be able to use these measures and participate in quality improvement practices.
Taking PROMs for chronic obstructive pulmonary disease (COPD) as an exemplar condition, our review determined the inclusion of people with low literacy skills and learning disabilities in research developing, validating, and using 12 PROMs for COPD patients. The studies included in our review were based on those identified in two existing systematic reviews and our update of this search.
People with low literacy skills and/or learning disabilities were excluded from the development of PROMs in two ways: explicitly through the participant eligibility criteria and, more commonly, implicitly through recruitment or administration methods that would require high-level reading and cognitive abilities. None of the studies mentioned efforts to include people with low literacy skills or learning disabilities.
Our findings suggest that people with low literacy skills or learning disabilities are left out of the development of PROMs. Given that implicit exclusion was most common, researchers and those who administer PROMs may not even be aware of this problem. Without effort to improve inclusion, unequal quality improvement practices may become embedded in the health system.
White matter lesions (WML) increase the risk of dementia. The relevance of WML location is less clear. We sought to determine whether a particular WML profile, based on the density and location of lesions, could be associated with an increased risk of mild cognitive impairment (MCI) or dementia over the following 7 years.
In 426 healthy subjects from a cohort of community-dwelling people aged 65 years and over (ESPRIT Project), standardized cognitive and neurological evaluations were repeated after 2, 4 and 7 years. Patterns of WML were computed with a supervised data mining approach (decision trees) using the regional WML volumes (frontal, parietal, temporal, and occipital regions) and the total WML volume estimated at baseline. Cox proportional hazard models were then constructed to study the association between WML patterns and risk of MCI/dementia.
Total WML volume and percentage of WML in the temporal region proved to be the best predictors of progression to MCI and dementia. Specifically, severe total WML load with a high proportion of lesions in the temporal region was significantly associated with the risk of developing MCI or dementia.
Above a certain threshold of damage, a pattern of WML clustering in the temporal region identifies individuals at increased risk of MCI or dementia. As this WML pattern is observed before the onset of clinical symptoms, it may facilitate the detection of patients at risk of MCI/dementia.
To examine 1) the associations between history of cardio-cerebrovascular diseases (CVD) and insomnia complaints and excessive daytime sleepiness (EDS), and 2) the relationships between sleep complaints and future CVD in persons over 65.
CVD was assessed at baseline and during two, four, and six-year follow-up in 5494 non-demented subjects. Self-reported insomnia complaints (poor sleep quality, difficulty in initiating sleep, difficulty in maintening sleep, and early morning awakening), EDS and sleep medication use were evaluated at baseline. Logistic regression models and Cox proportional hazard models, with delayed entry and age of participants as the time scale, were adjusted for socio-demographic, lifestyle and clinical variables.
At baseline, 748 participants had a past-history of CVD. A past-history of CVD was associated with EDS (OR = 1.28 95%CI = [1.05–1.57]) and the number of insomnia complaints (OR = 1.26 95%CI = [1.03–1.55] for 1–2 insomnia complaints; OR = 1.32 95%CI = [1.03–1.71] for ≥3 complaints). In longitudinal analyses, neither the four components of insomnia nor the number of insomnia complaints were significantly associated with first or recurrent CVD events (n = 391 events). EDS was independently associated with future CVD events even after adjusting for prescribed sleep medication and past-history of CVD (HR = 1.35 95%CI = [1.06–1.71]).
Our results suggest that the relationships between sleep complaints and CVD could be complex. Insomnia complaints are more likely a consequence of CVD, whereas EDS appears to be a determinant of CVD independently of past-history of CVD. EDS screening may thus constitute a means of detecting persons at high risk of CVD.
Patient reported outcome measures (PROMs) are self-report measures of health status increasingly promoted for use in healthcare quality improvement. However people with low literacy skills or learning disabilities may find PROMs hard to complete. Our study investigated stakeholder views on the accessibility and use of PROMs to develop suggestions for more inclusive practice.
Taking PROMs recommended for chronic obstructive pulmonary disease (COPD) as an example, we conducted 8 interviews with people with low literacy skills and/or learning disabilities, and 4 focus groups with 20 health professionals and people with COPD. Discussions covered the format and delivery of PROMs using the EQ-5D and St George Respiratory Questionnaire as prompts. Thematic framework analysis focused on three main themes: Accessibility, Ease of Use, and Contextual factors.
Accessibility included issues concerning the questionnaire format, and suggestions for improvement included larger font sizes and more white space. Ease of Use included discussion about PROMs’ administration. While health professionals suggested PROMs could be completed in waiting rooms, patients preferred settings with more privacy and where they could access help from people they know. Contextual Factors included other challenges and wider issues associated with completing PROMs. While health professionals highlighted difficulties created by the system in managing patients with low literacy/learning disabilities, patient participants stressed that understanding the purpose of PROMs was important to reduce intimidation.
Adjusting PROMs’ format, giving an explicit choice of where patients can complete them, and clearly conveying PROMs’ purpose and benefit to patients may help to prevent inequality when using PROMs in health services.
Patient reported outcome measures; Quality improvement; Chronic obstructive pulmonary disease; Low literacy; Learning disabilities
Epidemiological studies indicate that significant decreases in the incidence of Alzheimer's disease (AD) may be obtained by targeting multiple middle-age risk factors. However, as dementia is unlikely to be diagnosed for decades, short-term outcome measures are required. AD biomarker changes precede clinical symptoms by many years, but their sensitivity to mid-life change remains unknown.
Methods and analysis
PREVENT is a prospective cohort study examining biomarker status at mid-life in at least 150 individuals genetically at high, medium or low risk of late-onset AD. Participants are children of individuals with or without a diagnosed AD allocated to high, medium and low-risk groups according to parental clinical status and ApoE genotype. The biomarkers examined over 2 years are plasma and CSF Aβ42 amyloid, Tau and pTau, proinflammatory cytokines, acute-phase proteins, medial temporal-lobe atrophy, white matter lesion volume, cognitive performance related to transentorhinal and hippocampal functioning and hypothalamic−pituitary−adrenal and sympathetic axes regulation.
Ethics and dissemination
Detected pathologies are communicated to the participant's general practitioner with their permission. Risk status by genotype would not be revealed. The results of the study would be published in peer-reviewed journals and validated biomarkers used to construct a randomised controlled intervention study.
Geriatric Medicine; Epidemiology
Resilience is the ability of individuals to adapt positively in the face of trauma. Little is known, however, about lifetime factors affecting resilience.
We assessed the effects of psychiatric disorder and lifetime trauma history on the resilience self-evaluation using the Connor-Davidson Resilience Scale (CD-RISC-10) in a high-risk-women sample. Two hundred and thirty eight community-dwelling women, including 122 participants in a study of breast cancer survivors and 116 participants without previous history of cancer completed the CD-RISC-10. Lifetime psychiatric symptoms were assessed retrospectively using two standardized psychiatric examinations (Mini International Neuropsychiatric Interview and Watson's Post-Traumatic Stress Disorder Inventory).
Multivariate logistic regression adjusted for age, education, trauma history, cancer, current psychiatric diagnoses, and psychoactive treatment indicated a negative association between current psychiatric disorder and high resilience compared to low resilience level (OR = 0.44, 95% CI [0.21–0.93]). This was related to anxiety and not mood disorder. A positive and independent association with a trauma history was also observed (OR = 3.18, 95% CI [1.44–7.01]).
Self-evaluation of resilience is influenced by both current anxiety disorder and trauma history. The independent positive association between resilience and trauma exposure may indicate a “vaccination” effect. This finding need to be taken into account in future studies evaluating resilience in general or clinical populations.
Disability is a common condition in the elderly and has been associated with prevalent coronary heart disease (CHD) and with shorter longevity. However, whether disability predicts the occurrence of CHD has been less studied.
To prospectively assess the association between disability and incident fatal and non-fatal CHD among older adults free of cardiovascular disease (CVD). Design and Settings: The Three-City (3C) Study is a French multicentre prospective population-based cohort of 9294 elderly subjects (3469 men and 5645 women) aged 65 and over at baseline between 1999 to 2001 and followed-up during 6 years.
7354 participants with no history of CVD and with available information on disability status. Disability was assessed at baseline with a three levels of a hierarchical scale : no disability, mild disability (mobility only), moderate or severe disability (mobility plus activities of daily living and/or instrumental activities of daily living).
Main Outcome Measure
Incident fatal and non-fatal coronary events (angina pectoris, myocardial infarction, revascularization procedures and CHD death).
At baseline, the mean level of the risk factors increased gradually with the severity of disability. After a median follow-up of 5.2 years, 264 first coronary events including 55 fatal events occurred. Participants with moderate or severe disability had a 1.8-fold (95%CI: 1.1–2.9) increased risk of overall CHD compared to non-disabled subjects in multivariate analysis, while those with mild disability were not at increased CHD risk. The association was found for fatal CHD only, for which the risk increased gradually with the severity of disability (mild disability: HR = 1.8, 95%CI: 0.9–3.8; moderate/severe disability: HR = 4.5, 95%CI: 1.8–11.3; p for trend = 0.002).
These data suggest that the association of disability with incident CHD is mostly due to an association with fatal CHD in community-dwelling elderly subjects.
Activities of Daily Living; Aged; Coronary Disease; epidemiology; etiology; Disabled Persons; classification; statistics & numerical data; Female; France; epidemiology; Geriatric Assessment; Hospitalization; statistics & numerical data; Humans; Incidence; Kaplan-Meier Estimate; Logistic Models; Male; Proportional Hazards Models; Prospective Studies; Questionnaires; Risk Assessment; Risk Factors; Severity of Illness Index; Urban Health; statistics & numerical data; epidemiology; elderly; risk factors; disability; coronary heart disease; atherosclerosis.
To investigate the respective associations and clinical usefulness of the metabolic syndrome (MetS) and its individual components to predict the risk of first coronary heart disease (CHD) events in elderly.
The Three-City is a French prospective multisite community-based cohort.
Three large French cities: Bordeaux, Dijon and Montpellier.
7612 subjects aged 65 and over who were free of CHD at baseline.
Main outcome measures
The MetS was defined by the 2005 National Cholesterol Education Program Adult Treatment Panel III criteria.
During a median follow-up of 5.2 years, 275 first CHD events were adjudicated. The MetS was associated with increased risks of total (adjusted HR: 1.78; 95% CI 1.39 to 2.28), fatal (HR: 2.40; 95% CI 1.41 to 4.09) and non-fatal (HR: 1.64; 95% CI 1.24 to 2.17) CHD events. The association with total CHD was significant in women (HR: 2.56; 95% CI 1.75 to 3.75) but not in men (HR: 1.39; 95% CI 0.99 to 1.94; p for interaction=0.012). When in the same multivariable model, hyperglycemia and abdominal adiposity in women, hyperglycemia, lower HDL cholesterol and abdominal adiposity (inverse association) in men were the components significantly associated with CHD. The components of the MetS but not the MetS itself improved risk prediction beyond traditional risk factors (NRI= 9.35%, p<0;001).
The MetS is a risk marker for CHD in community-dwelling elderly subjects but may not be useful for CHD risk prediction purposes compared to its individual components.
Metabolic syndrome; coronary heart disease; elderly; risk stratification; psychology/psychiatry; epidemiology
Given the increasing prevalence of both metabolic syndrome (MetS) and depressive symptoms during old age, we aimed to examine prospectively the association between MetS and the onset of depressive symptoms according to different age-groups in a large, general elderly population.
RESEARCH DESIGN AND METHODS
This was a prospective cohort study of 4,446 men and women aged 65–91 years who were free of depression or depressive symptoms at baseline (the Three-City Study, France). MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. New onset of depressive symptoms (the Center for Epidemiologic Studies Depression Scale score ≥16 and use of antidepressant treatment) was assessed at 2- and 4-year follow-ups.
After adjusting for a large range of potential confounders, we observed MetS to be associated with 1.73-fold (95% CI 1.02–2.95) odds for new-onset depressive symptoms in the youngest age-group (65–70 years at baseline), independently of cardiovascular diseases. No such association was seen in older age-groups.
Our findings suggest that the link between MetS and depressive symptoms evidenced until now in middle-aged people can be extended to older adults but not to the oldest ones. Additional research is needed to examine if a better management of MetS prevents depressive symptoms in people aged 65–70 years.
The association between hormone treatment (HT) and mortality remains controversial. This study aimed to determine whether the risk of mortality associated with HT use varies depending on the specific characteristics of treatment and genetic variability in terms of the estrogen receptor.
A prospective, population-based study of 5135 women aged 65 years and older who were recruited from three cities in France and followed over six years. Detailed information related to HT use was obtained and five estrogen receptor polymorphisms were genotyped. The total follow-up was 25,436 person-years and during this time 352 women died. Cancer (36.4%) and cardiovascular disease (19.3%) were the major causes of death. Cox proportional hazards models adjusted for age, education, centre, living situation, comorbidity, depression, physical and mental incapacities, indicated no significant association between HT and mortality, regardless of the type or duration of treatment, or the age at initiation. However, the association between HT and all-cause or cancer-related mortality varied across women, with significant interactions identified with three estrogen receptor polymorphisms (p-values = 0.004 to 0.03) in adjusted analyses. Women carrying the C allele of ESR1 rs2234693 had a decreased risk of all-cause mortality with HT (HR: 0.42, 95% CI: 0.18–0.97), while in stark contrast, those homozygous for the T allele had a significantly increased risk of cancer-related mortality (HR: 3.18, 95% CI: 1.23–8.20). The findings were similar for ESR1 rs9340799 and ESR2 rs1271572.
The risk of mortality was not associated with HT duration, type or age at initiation. It was however not equal across all women, with some women appearing genetically more vulnerable to the effects of HT in terms of their estrogen receptor genotype. These findings, if confirmed in another independent study, may help explain the differential susceptibility of women to the beneficial or adverse effects of HT.
Stroke has been shown to follow a social gradient with incidence rising as socioeconomic status decreases.
To examine the relationship between socioeconomic status and ischemic stroke risk amongst older people.
The Cities of Bordeaux, Dijon and Montpellier in France.
Subjects and methods
9294 non institutionalised persons aged 65 years or more followed for 6 years.
The distribution of cardiovascular risks factors was consistent with the classical finding of more favourable risk profiles among the advantaged socioeconomic groups. 136 individuals developed a first ever ischemic stroke (incidence rate: 3.2 per 1000 py, 95% CI 2.7–3.8). The age and sex adjusted incidence of ischemic stroke increased with increasing level of income (from 2.4 to 4.1 per 1000 py, p=0.04). In the multivariable analysis adjusting for cardiovascular risk factors, the higher income group displayed a 80% increased risk of ischemic stroke compared with less wealthy participants (hazards ratio 1.77, 95% CI 1.20–2.61).
In this community-based sample of older individuals, a higher level of household income was associated with a higher risk of ischemic 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.
Aged; Aged, 80 and over; Cohort Studies; Female; Follow-Up Studies; France; Humans; Incidence; Income; Male; Multivariate Analysis; Risk Factors; Social Class; Stroke; epidemiology; aged; elderly; social class; stroke
Herpes simplex virus (HSV) reactivation has been identified as a possible risk factor for Alzheimer's disease (AD) and plasma amyloid-beta (Aβ) levels might be considered as possible biomarkers of the risk of AD. The aim of our study was to investigate the association between anti-HSV antibodies and plasma Aβ levels.
The study sample consisted of 1222 subjects (73.9 y in mean) from the Three-City cohort. IgM and IgG anti-HSV antibodies were quantified using an ELISA kit, and plasma levels of Aβ1–40 and Aβ1–42 were measured using an xMAP-based assay technology. Cross-sectional analyses of the associations between anti-HSV antibodies and plasma Aβ levels were performed by multi-linear regression.
After adjustment for study center, age, sex, education, and apolipoprotein E-e4 polymorphism, plasma Aβ1–42 and Aβ1–40 levels were specifically inversely associated with anti-HSV IgM levels (β = −20.7, P = 0.001 and β = −92.4, P = 0.007, respectively). In a sub-sample with information on CLU- and CR1-linked SNPs genotyping (n = 754), additional adjustment for CR1 or CLU markers did not modify these associations (adjustment for CR1 rs6656401, β = −25.6, P = 0.002 for Aβ1–42 and β = −132.7, P = 0.002 for Aβ1–40; adjustment for CLU rs2279590, β = −25.6, P = 0.002 for Aβ1–42 and β = −134.8, P = 0.002 for Aβ1–40). No association between the plasma Aβ1–42-to-Aβ1–40 ratio and anti-HSV IgM or IgG were evidenced.
High anti-HSV IgM levels, markers of HSV reactivation, are associated with lower plasma Aβ1–40 and Aβ1–42 levels, which suggest a possible involvement of the virus in the alterations of the APP processing and potentially in the pathogenesis of AD in human.
The aim of this study was to examine the factors associated with insomnia in community-dwelling elderly as a function of the nature and number of insomnia symptoms (IS) e.g. difficulty with initiating sleep (DIS), difficulty with maintaining sleep (DMS) and early morning awakening (EMA).
IS were assessed in a sample of 2673 men and 3213 women aged 65 years and over. The participants were administered standardized questionnaires regarding the frequency of IS and other sleep characteristics (snoring, nightmares, sleeping medication, sleepiness) as well as various socio-demographic, behavioral and clinical variables, and measures of physical and mental health.
More than 70% of men and women reported at least one IS, DMS being the most prevalent symptom in both men and women. Women reported more frequently two or three IS whereas men reported more often only one IS. Multivariate regression analyses stratified by gender showed that men and women shared numerous factors associated with IS, sleeping medication, nightmares, sleepiness, chronic diseases, and depression being independently associated with two or three IS. For both sexes, age was associated with only one IS in all age categories. Loud snoring was strongly associated with increased DMS in men only. High body mass index increased the risk for DIS in men but tended to decrease it in women. In women, hormonal replacement therapy, Mediterranean diet, caffeine and alcohol intake had a protective effect.
Our data suggest that women may have specific predisposition factors of multiple IS which may involve both behavioral and hormonal factors. Identification and treatment of these risk factors may form the basis of an intervention program for reduction of insomnia symptoms in the elderly..
Age Factors; Aged; Aged, 80 and over; Female; France; epidemiology; Humans; Male; Prevalence; Risk Factors; Self Report; Sex Characteristics; Sex Factors; Sleep Initiation and Maintenance Disorders; diagnosis; epidemiology
Mild Cognitive Impairment (MCI) case-finding criteria have low specificity in general population studies. The present study retrospectively identifies cases of MCI and determines baseline criteria giving the highest discriminability. The ability of these criteria to increase current case-detection specificity is estimated.
A population-based cohort was recruited from electoral rolls from three French cities. Clinical and environmental characteristics were evaluated at baseline and 2 and 4 year follow-up. The clinical characterisitics of incident cases of dementia were examined retrospectively.
8919 persons over 65 without dementia (60.8% women). The mean age (SD) of the participants was 74.2 (5.6) for men and 74.4 (5.6) for women.
320 persons (3.6%) were retrospectively classified as MCI at baseline. This MCI group had poorer performance on all cognitive tests compared to the rest of the cohort and a sub-sample undergoing MRI were found to have more white matter hyperintensities. The group were also characterized by the presence of an ApoE 4 genotype (OR=2.17 CI 1.44–3.29 for men; OR=2.27 CI 1.59–3.24 for women), and IADL loss (OR=1.72 CI 1.01–3.0 for men and OR=1.49 CI 0.97–2.3 for women). Women with MCI also had high depressive symptomatology (OR=1.96; CI 1.34–2.87), anticholinergic drug use (OR=1.59; CI 1.05–2.28) and low BMI (OR=1.54; CI 1.05–2.28) and men a history of stroke (OR=2.17 CI 1.16–4.05) and glycemia (OR=1.72 CI 1.13–2.71). Addition of these characteristics to conventional MCI definitions increases their specificity.
This general population study employing a retrospective method for classifying persons with MCI identified gender-specific non-cognitive clinical variables which may increase specificity.
Activities of Daily Living; Aged; Apolipoprotein E4; genetics; Cognition Disorders; diagnosis; Dementia; diagnosis; Disease Progression; Female; Genotype; Geriatric Assessment; methods; Humans; Male; Nerve Fibers, Myelinated; pathology; Neuropsychological Tests; Retrospective Studies; Risk Factors; MCI; diagnosis; cohort studies; gender; dementia; ApoE; cardiovascular disorder
Given the increasing prevalence of both metabolic syndrome (MetS) and depressive symptoms during old age, we aimed to examine prospectively the association between MetS and onset of depressive symptoms according to different age-groups in a large general elderly population.
Research Design and Methods
Prospective cohort study of 4446 men and women aged 65 to 91 and free of depression or depressive symptoms at baseline (the Three-City study, France). MetS was defined using the NCEP-ATP III criteria. New onset of depressive symptoms (the Center for Epidemiologic Studies Depression Scale (CES-D) score≥16 and use of antidepressant treatment) was assessed at 2- and 4-year follow-ups.
After adjusting for a large range of potential confounders, we observed MetS to be associated with a 1.73-fold (95% CI: 1.02–2.95) odds for new-onset depressive symptoms in the youngest age group (65 to 70 at baseline), independently of cardiovascular diseases. No such association was seen in older age groups.
Our findings suggest that the link between MetS and depressive symptoms evidenced until now in middle-aged can be extended to older adults but not to the oldest ones. Further research is needed to examine if a better management of MetS prevents depressive symptoms in people aged 65 to 70.
Depressive symptoms; metabolic syndrome; elderly; prospective study
Background: Indexes of diet quality have been shown to be associated with decreased risk of mortality in several countries. It remains unclear if the Alternative Healthy Eating Index (AHEI), designed to provide dietary guidelines to combat major chronic diseases, is related to mortality risk.
Objective: We aimed to examine the association between adherence to the AHEI and cause-specific mortality over 18 y of follow-up in a British working population.
Design: Analyses are based on 7319 participants (mean age: 49.5 y; range: 39–63 y; 30.3% women) from the Whitehall II Study. Cox proportional hazards regression models were performed to analyze associations of the AHEI (scored on the basis of intake of 9 components: vegetables, fruit, nuts and soy, white or red meat, trans fat, polyunsaturated or saturated fat, fiber, multivitamin use, and alcohol) with mortality risk.
Results: After potential confounders were controlled for, participants in the top compared with the bottom third of the AHEI score showed 25% lower all-cause mortality [hazard ratio (HR): 0.76; 95% CI: 0.61, 0.95] and >40% lower mortality from cardiovascular disease (CVD; HR: 0.58; 95% CI: 0.37, 0.91). Consumption of nuts and soy and moderate alcohol intake appeared to be the most important independent contributors to decreased mortality risk. The AHEI was not associated with cancer mortality or noncancer/non-CVD mortality.
Conclusion: Our findings suggest that the encouragement of adherence to the AHEI dietary recommendations constitutes a valid and clear public health recommendation that would decrease the risk of premature death from CVD.
In this paper we aim to: (1) identify and review midlife risk factors that may contribute to the development of dementia and that may be amenable to intervention; (2) review advances made in our understanding of the most common cause of dementia, Alzheimer's disease (AD), where current pharmacological studies have aimed to modify the disease course; and (3) explore other interventions that may slow cognitive decline in those with AD.
A review of the literature was conducted to look for interventions that may modify the risk of incident dementia or that may modify symptom progression in those with diagnosed dementia.
(1) Midlife risks identified as amenable to intervention include blood pressure, diabetes, elevated cholesterol, poor psychosocial and lifestyle factors. (2) The leading drugs in development can be grouped by their principal target: anti-amyloid, anti-tau and mitochondrial stability. However to date, there have been no successes in late stage Phase III trials of putative disease-modifying drugs for AD. (3) Once the diagnosis of dementia has been made there is little that can slow the rate of decline. Possible exceptions include the use of exercise and antihypertensive medication with some nootropic medication showing promise in small trials.
(1) It is clear that there are several risk factors in midlife that may lead to a greater likelihood of developing dementia. However, there is no simple intervention to modify these risks. It seems sensible to conclude from the data that avoiding high blood pressure, controlling cholesterol and diabetes as well as maintaining a healthy diet and lifestyle may lower the risk of developing dementia. (2) The need for better outcome measures in clinical trials is evident and may, in part, explain the numerous failures in late-stage clinical trials of disease-modifying drugs. Improved diagnostic test batteries to reduce population heterogeneity in early intervention studies will be required for robust clinical trials in the future. (3) Current research indicates that there is little that can delay decline; however, future trials may wish to focus on nootropics.
ageing; Alzheimer's disease; delay; dementia; cognitive decline; prevent; risk factors
Neurobiological and clinical studies suggest that childhood maltreatment may result in functional and structural nervous system changes which predispose the individual to depression. This vulnerability appears to be modulated by a polymorphism in the serotonin linked promoter region (5-HTTLPR). Little is known however, about the persistence of this vulnerability across the life-span although clinical studies of adult populations suggest that gene-environment interaction may diminish with ageing.
Depressive symptomatology and adverse and protective childhood events were examined in a population of 942 persons aged 65 years and over, taking into account socio-demographic characteristics and proximal competing causes of depression (widowhood, recent life-events, vascular and neurological disorder, and disability). Subjects were diagnosed as depressed if they met one of three criteria: a diagnosis of major depression on the Mini International Neuropsychiatric Interview (MINI), over 16 on the CES-D or anti-depressant treatment
Exposure to traumatic events in childhood doubled the risk of late-life depression and increased the risk of repeated episodes. Not all events were found to be pathogenic; significant risk being associated with excessive sharing of parental problems, poverty, mental disorder in parents, excessive punishment, verbal abuse, humiliation and mistreatment by an adult outside the family. Interactions were observed between the 5-HTTLPR ‘L’ allele, poverty and excessive sharing of parental problems.
Certain types of childhood trauma continue to constitute risk factors for depression in old age, outweighing more proximal causes. Gene-environment vulnerability interaction is linked in older age to the L-carrying genotype, modulating the effects of general environmental conditions rather than aggressive acts on the individual, perhaps due to increased cardiac reactivity.
Adult; Adult Survivors of Child Abuse; psychology; statistics & numerical data; Age Factors; Aged; Aged, 80 and over; Child; Child of Impaired Parents; psychology; statistics & numerical data; Depressive Disorder, Major; epidemiology; genetics; Female; France; epidemiology; Genotype; Humans; Life Change Events; Longitudinal Studies; Male; Polymorphism, Genetic; Psychiatric Status Rating Scales; statistics & numerical data; Retrospective Studies; Risk Factors; Serotonin Plasma Membrane Transport Proteins; genetics; Social Environment; Stress, Psychological; depression; elderly; child abuse; 5-HTTLPR; gene-environment interaction