Age-specific Incidence Of Dementia Research Articles

Population-level interventions for the primary prevention of dementia: a complex evidence review

BackgroundDementia is a leading, global public health challenge. Recent evidence supporting a decrease in age-specific incidence of dementia in high-income countries (HICs) suggests that risk reduction is possible through improved life-course public health. Despite this, efforts to date have been heavily focused on individual-level approaches, which are unlikely to significantly reduce dementia prevalence or inequalities in dementia. In order to inform policy, we identified the population-level interventions for dementia risk reduction with the strongest evidence base. MethodsWe did this complex, multistage, evidence review to summarise the empirical, interventional evidence for population-level interventions to reduce or control each of the 12 modifiable life-course risk factors for dementia identified by the Lancet commission. We conducted a series of structured searches of peer-reviewed and grey literature databases (eg, Medline, Trip database, Cochrane library, Campbell Collaboration, the WHO, and Google Scholar), in January, March, and June, 2023. Search terms related to risk factors, prevention, and population-level interventions, without language restrictions. We extracted evidence of effectiveness and key contextual information to aid consideration and implementation of interventions by policymakers. We performed a narrative synthesis and evidence grading, and we derived a population-level dementia risk reduction intervention framework, structured by intervention type. This study is registered with PROSPERO, ID:CRD42023396193. FindingsWe identified clear and consistent evidence for the effectiveness of 26 population-level interventions to reduce the prevalence of nine of the risk factors, of which 23 have been empirically evaluated in HICs, and 16 in low-income and middle-income countries. We identified interventions that acted through fiscal levers (n=5; eg, removing primary school fees), marketing or advertising levers (n=5; eg, plain packaging of tobacco products), availability levers (n=8; eg, cleaner fuel replacement programmes for cooking stoves), and legislative levers (n=8; eg, mandated provision of hearing protective equipment at noisy workplaces). We were not able to recommend any interventions for diabetes (other than indirectly through action on obesity and physical inactivity), depression, or social isolation. InterpretationThis complex evidence review provides policymakers and public health professionals with an evidence-based framework to help develop and implement population-level approaches for dementia risk reduction that could significantly reduce the population's risk of dementia and reduce health inequalities. FundingNone.

Correlation between cardiovascular risk factors and cognitive decline.

The number of people suffering from dementia in the world is progressively increasing due to the expansion of the geriatric population in which this clinical condition is more frequent. The appearance of a variable degree of cognitive decline up to full-blown dementia does not, however, represent the inevitable fate of those who age, as the studies conducted in the centenarians clearly indicate. Indeed, the age-specific incidence of dementia has progressively decreased in many geographical areas, probably due to an improvement in lifestyles and health care. In fact, a growing number of scientific evidence shows how chronic exposure over the course of life, starting from young adulthood, to various risk factors—arterial hypertension, diabetes mellitus, obesity, tobacco smoke, sleep disorders—contribute significantly to the development of cognitive decline and dementia in the course of senescence. These risk factors, in fact, can trigger and amplify the various neuropathological mechanisms underlying the development of decline, progressively reducing the functional reserve of the brain. Although definitive evidence deriving from ad hoc intervention studies is not currently available, it is legitimate to assert that the early control of cardiovascular risk factors can represent today the most effective tool for the prevention of dementia.

Midlife dyslipidaemia as a modifiable risk factor for later-life dementia

Since the risk of developing dementia increases with age and the number of older individuals continues to grow worldwide, the prevalence of dementia is predicted to increase substantially unless effective prevention strategies are developed.1 Interestingly, in the USA and many countries in western Europe, age-specific incidence of dementia has been stable or declining in recent birth cohorts, suggesting that improvements in modifiable risk factors, such as education, health care, and lifestyle, might decrease the risk of developing dementia.

Epidemiology of Vascular Dementia.

The notion of what qualifies as vascular dementia has varied greatly since the first mention of dementia after apoplexy in ancient literature. Current insight points towards a multifactorial cause of cognitive decline at old age, in which vascular components like atherosclerosis, arterio(lo)sclerosis, (micro)infarcts, and amyloid angiopathy play an important role alongside other markers of neurodegeneration. Cerebrovascular disease will be present in most individuals with dementia, but-just like other causes-rarely a cause on its own. The consequent limitations of nosology may be alleviated by addition of a vascular component to the recently introduced amyloid/tau/neurodegeneration etiological classification system for dementia. Meanwhile, risk of dementia is increased about 2-fold after stroke, and the prevention of (recurrent) stroke remains a cornerstone in the prevention of vascular dementia. Similarly, control of cardiovascular risk factors from middle age onwards is likely to have contributed to the reported decline in the age-specific incidence of dementia over the past decades. In conjunction with experimental studies, large-scale observational evidence from imaging, genomics, metabolomics, and alike will continue to improve our understanding of the underlying pathophysiological processes. To prevent ecological fallacies, such etiological studies in patients with dementia are best served by inclusion of subjects regardless of the presumed (single) cause of their disease.

Role of Improved Vascular Health in the Declining Incidence of Dementia.

As people are living longer, the disease burden is shifting toward diseases of old age, including an increasing prevalence of dementia, most commonly because of Alzheimer disease (AD). The risk of developing dementia doubles every 5 years after the age of 65 years.1 There are currently 5.1 million Americans aged >65 years living with dementia, and this number is expected to reach 13.8 million by the year 2050.2 Despite an increasing prevalence of dementia, the FHS (Framingham Heart Study) recently showed that the age-specific incidence of dementia has steadily declined over the previous 3 decades (Figure).3 In other words, whereas the overall number of people affected by dementia will continue to increase because of population aging, an individual’s risk of developing dementia by a specific age has decreased by as much as 20% each decade over the past 30 years. Other studies have also pointed toward a declining incidence of dementia in the United States and Europe.4–6 The Health and Retirement Study also reported a decline in dementia prevalence in the United States from the year 2000 to 2012.7 Collectively, these studies provide hope that some cases of dementia can be prevented or delayed. Figure. Trends in ( A ) dementia incidence and ( B ) education and vascular risk factors over four nonoverlapping epochs in the Framingham Heart Study. The baseline examination period was from 1977 to 1983 for the first epoch, 1986 to 1991 for the second epoch, 1992 to 1998 for the third epoch, and 2004 to 2008 for the fourth epoch. Data are from Satizabal et al.3 BP indicates blood pressure; HDL-C, high-density lipoprotein cholesterol; high school, completion of high-school education; and Rx, treatment. The factors underlying changing temporal trends in dementia are not entirely clear. It is important to understand what …

Cohort effects in verbal memory function and practice effects: a population-based study.

In many developed countries, cognitive functioning (as measured by neuropsychological tests) appears to be improving over time in the population at large, in parallel with the declining age-specific incidence of dementia. Here, we investigated cohort effects in the age-associated trajectories of verbal memory function in older adults. We sought to determine whether they varied by decade of birth and, if so, whether the change would be explained by increasing educational attainment. Pooling data from two prospective US population-based studies between 1987 and 2015, we identified four birth cohorts born 1902-1911, 1912-1921, 1922-1931, and 1932-1943. Among these cohorts, we compared age-associated trajectories both of performance and of practice effects on immediate and delayed recall of a 10-item Word List. We used mixed effects models, first including birth cohorts and cohort X age interaction terms, and then controlling for education and education X age interaction. We observed significant cohort effects in performance (baseline and age-associated trajectories) in both immediate recall and delayed recall, with function improving between the earliest- and latest-born cohorts. For both tests, we also observed cohort effects on practice effects with the highest levels in the latest-born cohorts. Including education in the models did not attenuate these effects. In this longitudinal population study, across four decade-long birth cohorts, there were significant improvements in test performance and practice effects in verbal memory tests, not explained by education. Whether this reflects declining disease incidence or other secular trends awaits further investigation.

DTB Select: 5 | May 2016

Hyperkalaemia with spironolactone ● Testosterone treatment in older men and sexual function ● OTC artificial tear drops for dry eye ● Decline in age-specific incidence of dementia ● Diabetes and...

Subclinical Cardiovascular Disease and Death, Dementia, and Coronary Heart Disease in Patients 80+ Years

BackgroundThe successful prevention and treatment of coronary heart disease (CHD) and stroke has resulted in a substantial increase in longevity, with subsequent growth in the population of older people at risk for dementia. ObjectivesThe authors evaluated the relationship of coronary and other peripheral atherosclerosis to risk of death, dementia, and CHD in the very elderly. Because the extent of vascular disease differs substantially between men and women, sex- and race-specific analyses were included, with a specific focus on women with low coronary artery calcium (CAC) Agatston scores. MethodsWe evaluated the relationship between measures of subclinical cardiovascular disease (CAC, carotid intimal medial thickness, stenosis, and ankle brachial index) and risk of dementia, CHD, and total mortality in 532 participants of the Cardiovascular Health Study-Cognition Study from 1998/1999 (mean age, 80 years) to 2012/2013 (mean age, 93 years). ResultsThirty-six percent of participants had CAC scores >400. Women and African-Americans had lower CAC scores. Few men had low CAC scores. CAC score and number of coronary calcifications were directly related to age-adjusted total mortality and CHD. The age-specific incidence of dementia was higher than for CHD. Only about 25% of deaths were caused by CHD and 16% by dementia. Approximately 64% of those who died had a prior diagnosis of dementia. White women with low CAC scores had a significantly decreased incidence of dementia. ConclusionsIn subjects 80+ years of age, there is a greater incidence of dementia than of CHD. CAC, as a marker of atherosclerosis, is a determinant of mortality, and risk of CHD and myocardial infarction. White women with low CAC scores had a significantly decreased risk of dementia. A very important unanswered question, especially in the very elderly, is whether prevention of atherosclerosis and its complications is associated with less Alzheimer disease pathology and dementia. (Cardiovascular Health Study [CHS]; NCT00005133)

Incidence of Dementia over Three Decades in the Framingham Heart Study

BackgroundThe 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.MethodsParticipants 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.ResultsThe 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.ConclusionsAmong 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.)

Thiamine Metabolites and Dementia?

The determinants of amyloid deposition in the brain, increased intracerebral phosphorylated tau, hippocampal atrophy, and loss of synapses in areas of brain (the pathogenic determinants of most dementia) remain undetermined except for Mendelian genetic disorders and higher risk of both amyloid deposition and dementia among individuals who carry the apolipoprotein e4 (APOE e4) genotype, especially homozygous e4 (Kuller et al., 2015, Vardarajan et al., 2014, Leduc et al., 2010). The incidence of dementia doubles every 5 years after the age of 65 and probably 2/3 or more of incident dementia cases occur over the age of 80 (Prince et al., 2013). The increasing longevity of the population is a major determinant of the ‘epidemic of dementia’ in many countries. There is little evidence that Alzheimer's disease (AD) pathology or incidence of dementia varies substantially among countries or within countries. Better-educated individuals and those with higher IQ have lower age-specific incidence of dementia attributed to ‘brain reserve.’ An excess or restriction of an exposure in the environment, lifestyle, such as consumption of a nutrient like thiamine, could be a determinant of increased or decreased risk of an age-associated disease like dementia, specifically AD. The brain requirement of a specific nutrient, e.g. thiamine, could increase with aging, either due to loss of a cellular receptor or changes in intracellular metabolism, greater degradation of the metabolite or increase in interfering agents, e.g. drugs. A vitamin deficiency in the past, e.g. pellagra, was a ‘cause of dementia’ that was successfully treated by diet change well before the specific vitamin was identified (nicotinic acid) (Terris, 1964). There is no evidence at present that deficiency of thiamine or any other B vitamin decreases risk of dementia. However, it could be necessary to consume a specific metabolite of the vitamin to have a beneficial effect in the brain. An alternative hypothesis is that lower thiamine metabolites in patients with AD identified in the paper by Xiaoli Pan and colleagues in EBioMedicine (Pan et al., 2015) is due to changes in patients' diet after diagnosis of dementia or secondary to comorbidity after diagnosis of dementia, e.g. reverse causality. The next steps would be to compare blood levels of thiamine metabolites in longitudinal studies with available stored blood samples prior to diagnosis of dementia. If the relative risk of AD or dementia is increased in relation to thiamine metabolites independent of age and education, then small feeding experiments in humans could evaluate whether thiamine metabolites have any effect on cognition in cognitively normal, mild cognitive impairment (MCI), and dementia patients and finally test the hypothesis by feeding metabolites in larger clinical trials of both risk of dementia among those who are cognitively normal and effects on changes in cognition in MCI and possibly dementia patients. The search for a nutrient that could prevent or delay onset or even reverse pathology of AD or other pathologies associated with dementia should have high priority given the worldwide magnitude of dementia, growing incidence and prevalence, and lack of effective therapies for prevention and treatment. It is very possible that a deficiency of a nutrient could be a cause of dementia among older individuals, possibly the nutrient is important only in susceptible individuals based on unique genotype, older ages, or comorbidities.

Multiple imputation for estimating the risk of developing dementia and its impact on survival

Dementia, Alzheimer's disease in particular, is one of the major causes of disability and decreased quality of life among the elderly and a leading obstacle to successful aging. Given the profound impact on public health, much research has focused on the age-specific risk of developing dementia and the impact on survival. Early work has discussed various methods of estimating age-specific incidence of dementia, among which the illness-death model is popular for modeling disease progression. In this article we use multiple imputation to fit multi-state models for survival data with interval censoring and left truncation. This approach allows semi-Markov models in which survival after dementia depends on onset age. Such models can be used to estimate the cumulative risk of developing dementia in the presence of the competing risk of dementia-free death. Simulations are carried out to examine the performance of the proposed method. Data from the Honolulu Asia Aging Study are analyzed to estimate the age-specific and cumulative risks of dementia and to examine the effect of major risk factors on dementia onset and death.

Incidence and mortality of Alzheimer's disease or dementia using an illness-death model.

We present an illness-death model for studying the incidence and the prevalence of Alzheimer's disease or dementia. We argue that the illness-death model is better than a survival model for this purpose. In this model the best choice for the basic time-scale is age. Then we present extensions of this model for incorporating covariates and taking account of a possible effect of calendar time. Calendar time is introduced via a proportional intensity model. We give the likelihood for a mixed discrete-continuous observation pattern from this model: clinical status is observed at discrete visit-times while the date of death is observed exactly or right-censored. The penalized likelihood approach allows to non-parametrically estimate the transition intensities. Application on the data of the Paquid study allows to produce estimates of the age-specific incidence of dementia together with mortality rates of both demented and non-demented subjects. Then the effect of calendar time and educational level are studied. Low educational level increases the risk of dementia. The risk of dementia increases with calendar time while the mortality of demented subjects decreases. The most likely explanation of this result seems to be in a shift in the diagnosis of dementia towards earlier stages of the disease prompted by a change in the perception of dementia and the arrival of new drugs.

A penalized likelihood approach for an illness-death model with interval-censored data: application to age-specific incidence of dementia.

We consider the problem of estimating the intensity functions for a continuous time 'illness-death' model with intermittently observed data. In such a case, it may happen that a subject becomes diseased between two visits and dies without being observed. Consequently, there is an uncertainty about the precise number of transitions. Estimating the intensity of transition from health to illness by survival analysis (treating death as censoring) is biased downwards. Furthermore, the dates of transitions between states are not known exactly. We propose to estimate the intensity functions by maximizing a penalized likelihood. The method yields smooth estimates without parametric assumptions. This is illustrated using data from a large cohort study on cerebral ageing. The age-specific incidence of dementia is estimated using an illness-death approach and a survival approach.

PHMPL: a computer program for hazard estimation using a penalized likelihood method with interval-censored and left-truncated data

The Cox model is the model of choice when analyzing right-censored and possibly left-truncated survival data. The present paper proposes a program to estimate the hazard function in a proportional hazards model and also to treat more complex observation schemes involving general censored and left-truncated data. The hazard function estimator is defined non-parametrically as the function which maximizes a penalized likelihood, and the solution is approximated using splines. The smoothing parameter is chosen using approximate cross-validation. Confidence bands for the estimator are given. As an illustration, the age-specific incidence of dementia is estimated and one of its risk factors is studied.

Modelling age-specific risk: application to dementia.

We give up-to-date methods for estimating the age-specific incidence of a disease and for estimating the effect of risk factors. We recommend taking age as the basic time scale of the analysis; then, the hazard function can be interpreted as the age-specific incidence of the disease. This choice raises a delayed entry problem. We present three methods: the person-years method; the smoothed Nelson-Aalen estimator, and the penalized likelihood approach. When explanatory variables are available, the Poisson model and the Cox model with delayed entry may be used for estimating relative risks; the penalized likelihood approach can also be used. We apply these methods to estimate the age-specific incidence of dementia using data from a large cohort study, Paquid. This 5-year study followed a random initial sample of 3675 subjects with 190 incident cases of dementia. We compare the estimates based on the three possible methods. The estimated incidences computed separately for men and women cross and it is verified that a non-proportional hazards model for gender holds; women below 75 have a lower risk than men while women above 75 have a higher risk.

Incidence and subtypes of dementia in southern Taiwan: impact of socio-demographic factors.

To determine the incidence rate (IR) and subtypes of dementia in southern Taiwan. From a cohort of 2,915 community inhabitants aged 65 years and over, 2,507 and 2,175 subjects participated in the first- and second-year follow-up surveys, respectively. A two-phase study used the Mini-Mental State Examination in phase I and the Consortium to Establish a Registry of Alzheimer's Disease (CERAD) neuropsychological battery and the neurobehavioral examination in phase II. We applied International Classification of Diseases (ICD)-10NA criteria for dementia, National Institute of Neurological and Communication Disorders and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) guidelines for Alzheimer's disease (AD), and National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria for vascular dementia (VaD). The annual IR for total dementia was 1.28%, which increased with age from 0.77% for 65- to 74-year-olds to 6.19% for persons aged 85 years or older. AD (25 cases, 41.7%, IR=0.54%) was the most common cause of dementia, followed by VaD (19 cases, 31.7%, IR=0.41%) and mixed dementia (9 cases, 15.0%). After adjusting for sex, increasing age was significantly associated with total dementia and AD (p < 0.01). Illiteracy was associated with a marginally increased risk for total dementia (aRR=1.59, p < 0.1) as was being female for AD (aRR = 1.92, p < 0.1). The 2-year mortality rate was high among the demented (48% in total dementia, 38% in AD, and 60% in VaD). The age-specific incidence of dementia in Taiwan is approaching that of developed countries and the low prevalence of dementia (especially VaD) may be mainly due to the high mortality. Age was the major risk factor for total dementia and AD. Being female was probably a risk factor for AD, as was illiteracy for total dementia.

A Penalized Likelihood Approach for Arbitrarily Censored and Truncated Data: Application to Age-Specific Incidence of Dementia

The Cos model is the model of choice when analyzing survival data presenting only right censoring and left truncation. There is a need for methods that can accommodate more complex observation schemes involving general censoring and truncation. In addition, it is important in many epidemiological applications to have a smooth estimate of the hazard function. We show that the penalized likelihood approach gives a solution to these problems. The solution of the maximum of the penalized likelihood is approximated on a basis of splines. The smoothing parameter is estimated using approximate cross-validation; confidence bands can be given. A simulation study shows that this approach gives better results than the smoothed Nelson-Aalen estimator. We apply this method to the analysis of data from a large cohort study on cerebral aging. The age-specific incidence of dementia is estimated and risk factors of dementia studied.