The prevalence of dementia is expected to soar as the average life expectancy increases, but recent estimates suggest that the age-specific incidence of dementia is declining in high-income ...countries. Temporal trends are best derived through continuous monitoring of a population over a long period with the use of consistent diagnostic criteria. We describe temporal trends in the incidence of dementia over three decades among participants in the Framingham Heart Study.
Participants in the Framingham Heart Study have been under surveillance for incident dementia since 1975. In this analysis, which included 5205 persons 60 years of age or older, we used Cox proportional-hazards models adjusted for age and sex to determine the 5-year incidence of dementia during each of four epochs. We also explored the interactions between epoch and age, sex, apolipoprotein E ε4 status, and educational level, and we examined the effects of these interactions, as well as the effects of vascular risk factors and cardiovascular disease, on temporal trends.
The 5-year age- and sex-adjusted cumulative hazard rates for dementia were 3.6 per 100 persons during the first epoch (late 1970s and early 1980s), 2.8 per 100 persons during the second epoch (late 1980s and early 1990s), 2.2 per 100 persons during the third epoch (late 1990s and early 2000s), and 2.0 per 100 persons during the fourth epoch (late 2000s and early 2010s). Relative to the incidence during the first epoch, the incidence declined by 22%, 38%, and 44% during the second, third, and fourth epochs, respectively. This risk reduction was observed only among persons who had at least a high school diploma (hazard ratio, 0.77; 95% confidence interval, 0.67 to 0.88). The prevalence of most vascular risk factors (except obesity and diabetes) and the risk of dementia associated with stroke, atrial fibrillation, or heart failure have decreased over time, but none of these trends completely explain the decrease in the incidence of dementia.
Among participants in the Framingham Heart Study, the incidence of dementia has declined over the course of three decades. The factors contributing to this decline have not been completely identified. (Funded by the National Institutes of Health.).
Abstract Background Gender-specific risks for dementia and Alzheimer's disease (AD) starting in midlife remain largely unknown. Methods Prospectively ascertained dementia/AD and cause-specific ...mortality in Framingham Heart Study (FHS) participants was used to generate 10- to 50-year risk estimates of dementia/AD on the basis of the Kaplan–Meier method (cumulative incidence) or accounting for competing risk of death (lifetime risk LTR). Results Overall, 777 cases of incident dementia (601 AD) occurred in 7901 participants (4333 women) over 136,266 person-years. Whereas cumulative incidences were similar in women and men, LTRs were higher in women older than 85 years of age. LTR of dementia/AD at age 45 was 1 in 5 in women and 1 in 10 in men. Cardiovascular mortality was higher in men with rate ratios decreasing from approximately 6 at 45 to 54 years of age to less than 2 after age 65. Conclusion Selective survival of men with a healthier cardiovascular risk profile and hence lower propensity to dementia might partly explain the higher LTR of dementia/AD in women.
Forecasting the prevalence of dementia Schwarzinger, Michaël; Dufouil, Carole
The Lancet. Public health,
02/2022, Letnik:
7, Številka:
2
Journal Article
Dementia is a prevalent condition, affecting 5–7% of people aged 60 years and older, and a leading cause of disability in people aged 60 years and older globally. We aimed to examine the association ...between alcohol use disorders and dementia risk, with an emphasis on early-onset dementia (<65 years).
We analysed a nationwide retrospective cohort of all adult (≥20 years) patients admitted to hospital in metropolitan France between 2008 and 2013. The primary exposure was alcohol use disorders and the main outcome was dementia, both defined by International Classification of Diseases, tenth revision discharge diagnosis codes. Characteristics of early-onset dementia were studied among prevalent cases in 2008–13. Associations of alcohol use disorders and other risk factors with dementia onset were analysed in multivariate Cox models among patients admitted to hospital in 2011–13 with no record of dementia in 2008–10.
Of 31 624 156 adults discharged from French hospitals between 2008 and 2013, 1 109 343 were diagnosed with dementia and were included in the analyses. Of the 57 353 (5·2%) cases of early-onset dementia, most were either alcohol-related by definition (22 338 38·9%) or had an additional diagnosis of alcohol use disorders (10 115 17·6%). Alcohol use disorders were the strongest modifiable risk factor for dementia onset, with an adjusted hazard ratio of 3·34 (95% CI 3·28–3·41) for women and 3·36 (3·31–3·41) for men. Alcohol use disorders remained associated with dementia onset for both sexes (adjusted hazard ratios >1·7) in sensitivity analyses on dementia case definition (including Alzheimer's disease) or older study populations. Also, alcohol use disorders were significantly associated with all other risk factors for dementia onset (all p<0·0001).
Alcohol use disorders were a major risk factor for onset of all types of dementia, and especially early-onset dementia. Thus, screening for heavy drinking should be part of regular medical care, with intervention or treatment being offered when necessary. Additionally, other alcohol policies should be considered to reduce heavy drinking in the general population.
None.
Abstract There is increasing evidence that subjective cognitive decline (SCD) in individuals with unimpaired performance on cognitive tests may represent the first symptomatic manifestation of ...Alzheimer's disease (AD). The research on SCD in early AD, however, is limited by the absence of common standards. The working group of the Subjective Cognitive Decline Initiative (SCD-I) addressed this deficiency by reaching consensus on terminology and on a conceptual framework for research on SCD in AD. In this publication, research criteria for SCD in pre-mild cognitive impairment (MCI) are presented. In addition, a list of core features proposed for reporting in SCD studies is provided, which will enable comparability of research across different settings. Finally, a set of features is presented, which in accordance with current knowledge, increases the likelihood of the presence of preclinical AD in individuals with SCD. This list is referred to as SCD plus.
Abstract
Background
Alzheimer’s disease and related dementia (ADRD) are characterized by multiple and progressive anatomo-clinical changes including accumulation of abnormal proteins in the brain, ...brain atrophy and severe cognitive impairment. Understanding the sequence and timing of these changes is of primary importance to gain insight into the disease natural history and ultimately allow earlier diagnosis. Yet, modeling changes over disease course from cohort data is challenging as the usual timescales (time since inclusion, chronological age) are inappropriate and time-to-clinical diagnosis is available on small subsamples of participants with short follow-up durations prior to diagnosis. One solution to circumvent this challenge is to define the disease time as a latent variable.
Methods
We developed a multivariate mixed model approach that realigns individual trajectories into the latent disease time to describe disease progression. In contrast with the existing literature, our methodology exploits the clinical diagnosis information as a partially observed and approximate reference to guide the estimation of the latent disease time. The model estimation was carried out in the Bayesian Framework using Stan. We applied the methodology to the MEMENTO study, a French multicentric clinic-based cohort of 2186 participants with 5-year intensive follow-up. Repeated measures of 12 ADRD markers stemmed from cerebrospinal fluid (CSF), brain imaging and cognitive tests were analyzed.
Results
The estimated latent disease time spanned over twenty years before the clinical diagnosis. Considering the profile of a woman aged 70 with a high level of education and
APOE4
carrier (the main genetic risk factor for ADRD), CSF markers of tau proteins accumulation preceded markers of brain atrophy by 5 years and cognitive decline by 10 years. However we observed that individual characteristics could substantially modify the sequence and timing of these changes, in particular for CSF level of A
$$\beta _{42}$$
β
42
.
Conclusion
By leveraging the available clinical diagnosis timing information, our disease progression model does not only realign trajectories into the most homogeneous way. It accounts for the inherent residual inter-individual variability in dementia progression to describe the long-term anatomo-clinical degradations according to the years preceding clinical diagnosis, and to provide clinically meaningful information on the sequence of events.
Trial registration
clinicaltrials.gov, NCT01926249. Registered on 16 August 2013.
ObjectiveDescribe demographical, social and psychological correlates of willingness to receive a COVID-19 vaccine.SettingSeries of online surveys undertaken between March and October ...2020.ParticipantsA total of 25 separate national samples (matched to country population by age and sex) in 12 different countries were recruited through online panel providers (n=25 334).Primary outcome measuresReported willingness to receive a COVID-19 vaccination.ResultsReported willingness to receive a vaccine varied widely across samples, ranging from 63% to 88%. Multivariate logistic regression analyses reveal sex (female OR=0.59, 95% CI 0.55 to 0.64), trust in medical and scientific experts (OR=1.28, 95% CI 1.22 to 1.34) and worry about the COVID-19 virus (OR=1.47, 95% CI 1.41 to 1.53) as the strongest correlates of stated vaccine acceptance considering pooled data and the most consistent correlates across countries. In a subset of UK samples, we show that these effects are robust after controlling for attitudes towards vaccination in general.ConclusionsOur results indicate that the burden of trust largely rests on the shoulders of the scientific and medical community, with implications for how future COVID-19 vaccination information should be communicated to maximise uptake.
Vascular risk factors have been proposed as important targets for the prevention of dementia. As lipid fractions represent easily modifiable targets, we examined the longitudinal relationship of ...baseline lipid fractions with 13-y incident dementia and its subtypes (Alzheimer disease AD and mixed or vascular dementia) in older community-dwelling persons.
Non-institutionalized persons aged 65+ y (n = 9,294) were recruited for the Three-City Study (3C Study), a population-based cohort study from the electoral rolls of the cities of Dijon, Bordeaux, and Montpellier, France, between March 1999 and March 2001. Follow-up examinations were performed every 2 y after the baseline assessment. The final study sample comprised 7,470 participants from the 3C Study (mean age ± standard deviation SD 73.8 ± 5.3 y, 61.0% women) who were prospectively followed up for up to 13 y. Fasting lipid fractions (triglycerides TGs, high-density lipoprotein cholesterol HDL-C, low-density lipoprotein cholesterol LDL-C, total cholesterol TC) were studied as continuous variables, and results are reported per SD increase of each lipid fraction. Incident dementia and its subtypes were studied as censored variables using Cox models with age as time scale. Analyses were adjusted for sex, study center, and educational level, as well as vascular risk factors and apolipoprotein E (APOE) ε4 genotype. We corrected for multiple testing, yielding a significance threshold of 0.0169. p-Values above the significance threshold but less than 0.05 were considered nominally significant. During a mean (± SD) follow-up period of 7.9 ± 3.6 y, 779 participants developed incident dementia (n = 532 AD and n = 154 mixed or vascular dementia). Higher LDL-C and TC concentrations at baseline were associated with an increased risk of AD (hazard ratio HR per SD increase = 1.13 95% CI 1.04-1.22, p = 0.0045, and HR = 1.12 1.03-1.22, p = 0.0072, respectively). These associations were largely unchanged after adjustment for vascular risk factors and were attenuated after adjustment for APOEε4 (HR per SD increase = 1.12 1.03-1.23, p = 0.0110, and HR = 1.12 1.02-1.23, p = 0.0171, respectively). Higher TG concentrations at baseline were associated with an increased risk of all dementia (HR per SD increase = 1.11 1.03-1.19, p = 0.0044) and mixed or vascular dementia (HR = 1.21 1.04-1.41, p = 0.0163). However, these associations disappeared after adjusting for vascular risk factors (HR = 1.07 0.98-1.17, p = 0.1374, and HR = 1.17 0.96-1.42, p = 0.1206, respectively). Main limitations of the study include interval censoring of incident dementia cases, potential selective survival bias, and the fact that variation in lipid concentrations during follow-up could not be accounted for in the analyses.
In a large population-based sample of older community-dwelling persons with up to 13 y of follow-up, we observed that higher LDL-C and TC concentrations were associated with an increased risk of AD. This result was independent of vascular risk factors and was attenuated after adjustment for APOEε4 carrier status. TG and HDL-C concentrations were not associated with risk of incident dementia or its subtypes after accounting for vascular risk factors.
Age-adjusted stroke incidence has decreased over the past 50 years, likely as a result of changes in the prevalence and impact of various stroke risk factors. An updated version of the Framingham ...Stroke Risk Profile (FSRP) might better predict current risks in the FHS (Framingham Heart Study) and other cohorts. We compared the accuracy of the standard (old) and of a revised (new) version of the FSRP in predicting the risk of all-stroke and ischemic stroke and validated this new FSRP in 2 external cohorts, the 3C (3 Cities) and REGARDS (Reasons for Geographic and Racial Differences in Stroke) studies.
We computed the old FSRP as originally described and a new model that used the most recent epoch-specific risk factor prevalence and hazard ratios for individuals ≥55 years of age and for the subsample ≥65 years of age (to match the age range in REGARDS and 3C studies, respectively) and compared the efficacy of these models in predicting 5- and 10-year stroke risks.
The new FSRP was a better predictor of current stroke risks in all 3 samples than the old FSRP (calibration χ
of new/old FSRP: in men: 64.0/12.1, 59.4/30.6, and 20.7/12.5; in women: 42.5/4.1, 115.4/90.3, and 9.8/6.5 in FHS, REGARDS, and 3C, respectively). In the REGARDS, the new FSRP was a better predictor among whites compared with blacks.
A more contemporaneous, new FSRP better predicts current risks in 3 large community samples and could serve as the basis for examining geographic and racial differences in stroke risk and the incremental diagnostic utility of novel stroke risk factors.
Accurate identification of individuals at high risk of dementia influences clinical care, inclusion criteria for clinical trials and development of preventative strategies. Numerous models have been ...developed for predicting dementia. To evaluate these models we undertook a systematic review in 2010 and updated this in 2014 due to the increase in research published in this area. Here we include a critique of the variables selected for inclusion and an assessment of model prognostic performance.
Our previous systematic review was updated with a search from January 2009 to March 2014 in electronic databases (MEDLINE, Embase, Scopus, Web of Science). Articles examining risk of dementia in non-demented individuals and including measures of sensitivity, specificity or the area under the curve (AUC) or c-statistic were included.
In total, 1,234 articles were identified from the search; 21 articles met inclusion criteria. New developments in dementia risk prediction include the testing of non-APOE genes, use of non-traditional dementia risk factors, incorporation of diet, physical function and ethnicity, and model development in specific subgroups of the population including individuals with diabetes and those with different educational levels. Four models have been externally validated. Three studies considered time or cost implications of computing the model.
There is no one model that is recommended for dementia risk prediction in population-based settings. Further, it is unlikely that one model will fit all. Consideration of the optimal features of new models should focus on methodology (setting/sample, model development and testing in a replication cohort) and the acceptability and cost of attaining the risk variables included in the prediction score. Further work is required to validate existing models or develop new ones in different populations as well as determine the ethical implications of dementia risk prediction, before applying the particular models in population or clinical settings.
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