The construct of mild cognitive impairment (MCI) has evolved over the past 10 years since the publication of the new MCI definition at the Key Symposium in 2003, but the core criteria have remained ...unchanged. The construct has been extensively used worldwide, both in clinical and in research settings, to define the grey area between intact cognitive functioning and clinical dementia. A rich set of data regarding occurrence, risk factors and progression of MCI has been generated. Discrepancies between studies can be mostly explained by differences in the operationalization of the criteria, differences in the setting where the criteria have been applied, selection of subjects and length of follow‐up in longitudinal studies. Major controversial issues that remain to be further explored are algorithmic versus clinical classification, reliability of clinical judgment, temporal changes in cognitive performances and predictivity of putative biomarkers. Some suggestions to further develop the MCI construct include the tailoring of the clinical criteria to specific populations and to specific contexts. The addition of biomarkers to the clinical phenotypes is promising but requires deeper investigation. Translation of findings from the specialty clinic to the population setting, although challenging, will enhance uniformity of outcomes. More longitudinal population‐based studies on cognitive ageing and MCI need to be performed to clarify all these issues.
This review discusses the interplay between multimorbidity (i.e. co‐occurrence of more than one chronic health condition in an individual) and functional impairment (i.e. limitations in mobility, ...strength or cognition that may eventually hamper a person's ability to perform everyday tasks). On the one hand, diseases belonging to common patterns of multimorbidity may interact, curtailing compensatory mechanisms and resulting in physical and cognitive decline. On the other hand, physical and cognitive impairment impact the severity and burden of multimorbidity, contributing to the establishment of a vicious circle. The circle may be further exacerbated by people's reduced ability to cope with treatment and care burden and physicians’ fragmented view of health problems, which cause suboptimal use of health services and reduced quality of life and survival. Thus, the synergistic effects of medical diagnoses and functional status in adults, particularly older adults, emerge as central to assessing their health and care needs. Furthermore, common pathways seem to underlie multimorbidity, functional impairment and their interplay. For example, older age, obesity, involuntary weight loss and sedentarism can accelerate damage accumulation in organs and physiological systems by fostering inflammatory status. Inappropriate use or overuse of specific medications and drug–drug and drug–disease interactions also contribute to the bidirectional association between multimorbidity and functional impairment. Additionally, psychosocial factors such as low socioeconomic status and the direct or indirect effects of negative life events, weak social networks and an external locus of control may underlie the complex interactions between multimorbidity, functional decline and negative outcomes. Identifying modifiable risk factors and pathways common to multimorbidity and functional impairment could aid in the design of interventions to delay, prevent or alleviate age‐related health deterioration; this review provides an overview of knowledge gaps and future directions.
Content List – Read more articles from the symposium: “Multimorbidity research at the cross‐roads: developing the evidence for clinical practice and health policy”.
As the world's population ages, elderly people are becoming an increasingly important group that merits special attention with regard to health and social issues. Lifestyles affect health and ...survival at all ages, but the consequences of poor lifestyle behaviors may be different for elderly people than for younger adults. They can also be heavily dependent on exposure earlier in life. Our current state of knowledge is based predominantly on studies conducted among middle-aged adults or young elderly people. Moreover, studies are sparse throughout the entire older age spectrum, from 65 to 90 years. This article summarizes the evidence regarding the impact of lifestyle behaviors on mortality among elderly people. It focuses on behaviors modifiable by individual actions and public health interventions, such as smoking, obesity and sedentary behavior, which predispose numerous people to diseases that rank among the leading causes of death, including heart disease, cancer, stroke, diabetes and dementia. These factors not only shorten life but, when they occur together, also have a major impact on survival beyond that associated with each single lifestyle factor. We propose an integrated life course model to guide research on longevity to answer questions that remain open and to find new strategies to ensure a longer and healthier life for future generations.
Abstract Aims To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous ...estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range of disorders than previously covered are needed for basic, clinical and public health research and policy decisions and to inform about the estimated number of persons affected in the EU. Method Stepwise multi-method approach, consisting of systematic literature reviews, reanalyses of existing data sets, national surveys and expert consultations. Studies and data from all member states of the European Union (EU-27) plus Switzerland, Iceland and Norway were included. Supplementary information about neurological disorders is provided, although methodological constraints prohibited the derivation of overall prevalence estimates for mental and neurological disorders. Disease burden was measured by disability adjusted life years (DALY). Results Prevalence: It is estimated that each year 38.2% of the EU population suffers from a mental disorder. Adjusted for age and comorbidity, this corresponds to 164.8 million persons affected. Compared to 2005 (27.4%) this higher estimate is entirely due to the inclusion of 14 new disorders also covering childhood/adolescence as well as the elderly. The estimated higher number of persons affected (2011: 165 m vs. 2005: 82 m) is due to coverage of childhood and old age populations, new disorders and of new EU membership states. The most frequent disorders are anxiety disorders (14.0%), insomnia (7.0%), major depression (6.9%), somatoform (6.3%), alcohol and drug dependence (> 4%), ADHD (5%) in the young, and dementia (1–30%, depending on age). Except for substance use disorders and mental retardation, there were no substantial cultural or country variations. Although many sources, including national health insurance programs, reveal increases in sick leave, early retirement and treatment rates due to mental disorders, rates in the community have not increased with a few exceptions (i.e. dementia). There were also no consistent indications of improvements with regard to low treatment rates, delayed treatment provision and grossly inadequate treatment. Disability: Disorders of the brain and mental disorders in particular, contribute 26.6% of the total all cause burden, thus a greater proportion as compared to other regions of the world. The rank order of the most disabling diseases differs markedly by gender and age group; overall, the four most disabling single conditions were: depression, dementias, alcohol use disorders and stroke. Conclusion In every year over a third of the total EU population suffers from mental disorders. The true size of “disorders of the brain” including neurological disorders is even considerably larger. Disorders of the brain are the largest contributor to the all cause morbidity burden as measured by DALY in the EU. No indications for increasing overall rates of mental disorders were found nor of improved care and treatment since 2005; less than one third of all cases receive any treatment, suggesting a considerable level of unmet needs. We conclude that the true size and burden of disorders of the brain in the EU was significantly underestimated in the past. Concerted priority action is needed at all levels, including substantially increased funding for basic, clinical and public health research in order to identify better strategies for improved prevention and treatment for disorders of the brain as the core health challenge of the 21st century.
Summary Dementia is receiving increasing attention from governments and politicians. Epidemiological research based on western European populations done 20 years ago provided key initial evidence for ...dementia policy making, but these estimates are now out of date because of changes in life expectancy, living conditions, and health profiles. To assess whether dementia occurrence has changed during the past 20–30 years, investigators of five different studies done in western Europe (Sweden Stockholm and Gothenburg, the Netherlands Rotterdam, the UK England, and Spain Zaragoza) have compared dementia occurrence using consistent research methods between two timepoints in well-defined geographical areas. Findings from four of the five studies showed non-significant changes in overall dementia occurrence. The only significant reduction in overall prevalence was found in the study done in the UK, powered and designed explicitly from its outset to detect change across generations (decrease in prevalence of 22%; p=0·003). Findings from the study done in Zaragoza (Spain) showed a significant reduction in dementia prevalence in men (43%; p=0·0002). The studies estimating incidence done in Stockholm and Rotterdam reported non-significant reductions. Such reductions could be the outcomes from earlier population-level investments such as improved education and living conditions, and better prevention and treatment of vascular and chronic conditions. This evidence suggests that attention to optimum health early in life might benefit cognitive health late in life. Policy planning and future research should be balanced across primary (policies reducing risk and increasing cognitive reserve), secondary (early detection and screening), and tertiary (once dementia is present) prevention. Each has their place, but upstream primary prevention has the largest effect on reduction of later dementia occurrence and disability.
Background
Definitions and diagnostic criteria for all medical conditions are regularly subjected to reviews and revisions as knowledge advances. In the field of Alzheimer's disease (AD) research, it ...has taken almost three decades for diagnostic nomenclature to undergo major re‐examination. The shift towards presymptomatic and pre‐dementia stages of AD has brought prevention and treatment trials much closer to each other than before.
Methods
Here we discuss: (i) the impact of diagnostic reliability on the possibilities for developing preventive strategies for AD; (ii) the scientific evidence to support moving from observation to action; (iii) ongoing intervention studies; and (iv) the methodological issues and prospects for balancing strategies for high‐risk individuals with those for broad population‐based prevention.
Results
The associations between neuropathology and cognition are still not entirely clear. In addition, the risk factors for AD dementia and the neuropathological hallmarks of AD may not necessarily be the same. Cognitive impairment has a clearer clinical significance and should therefore remain the main focus of prevention. Risk/protective factors for dementia/AD need to be studied from a life‐course perspective. New approaches in prevention trials include enrichment strategies based on genetic risk factors or beta‐amyloid biomarkers (at least four ongoing pharmacological trials), and multidomain interventions simultaneously targeting various vascular and lifestyle‐related risk factors (at least three ongoing trials). Experience from prevention programmes in other chronic diseases can provide additional methodological improvements.
Conclusions
Building infrastructures for international collaborations is necessary for managing the worldwide public health problem of AD and dementia. The International Database on Aging and Dementia (IDAD) and the European Dementia Prevention Initiative (EDPI) are examples of ongoing international efforts aiming to improve the methodology of preventive studies and provide the basis for larger intervention trials.
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Objective. We aimed to disentangle the effect of chronic multimorbidity and disability on 3‐year functional decline and survival in the elderly.
Design. Prospective cohort study with a mean of ...follow‐up of 2.8 years.
Setting. Swedish elderly persons from the Kungsholmen Project (1987–2000).
Subjects. A total of 1099 subjects, 77–100 years old, living in the community and institutions.
Main outcome measurements. Medical diagnoses (based on clinical examination, drug use, medical records and blood tests), and functional assessment (according to Katz Index) at baseline were investigated in relation to functional decline and death occurring during follow‐up.
Results. At baseline, 12.1% of participants had disability, and 52.3% were affected by multimorbidity. During follow‐up, 363 persons died and 85 worsened in functioning. The number of chronic conditions incrementally increased the risk of functional decline hazard ratio (HR) increased from 1.5 in subjects with one disease to 6.2 in persons with 4+ diseases. However, this was not the case for mortality, as the HR of death was the same for people with one disease as well as 4+ diseases (HR = 2.3). Baseline disability had the highest impact on survival, independently of number of diseases HR = 8.1; 95% confidence interval (CI) = 4.8–13.7 in subjects with one disease and HR = 7.7; 95% CI = 4.7–12.6 in those with 2+ diseases.
Conclusions. In the elderly subjects, chronic disability rather than multimorbidity emerged as the strongest negative prognostic factor for functionality and survival.
Few longitudinal studies assessed whether sleep disturbances are associated with dementia risk.
Sleep disturbances were assessed in three population-based studies (H70 study and Kungsholmen Project ...Sweden; Cardiovascular Risk Factors, Aging and Dementia study Finland). Late-life baseline analyses (3–10 years follow-up) used all three studies (N = 1446). Baseline ages ≈ 70 years (Cardiovascular Risk Factors, Aging and Dementia, H70), and ≈84 years (Kungsholmen Project). Midlife baseline (age ≈ 50 years) analyses used Cardiovascular Risk Factors, Aging and Dementia (21 and 32 years follow-up) (N = 1407).
Midlife insomnia (fully adjusted hazard ratio = 1.24, 95% confidence interval = 1.02–1.50) and late-life terminal insomnia (fully adjusted odds ratio = 1.94, 95% confidence interval = 1.08–3.49) were associated with a higher dementia risk. Late-life long sleep duration (>9 hours) was also associated with an increased dementia risk (adjusted odds ratio = 3.98, 95% confidence interval = 1.87–8.48).
Midlife insomnia and late-life terminal insomnia or long sleep duration were associated with a higher late-life dementia risk.
To determine the occurrence of neuropsychiatric symptomatology and the relation to future development of Alzheimer disease (AD) in persons with and without mild cognitive impairment (MCI).
We ...followed 185 persons with no cognitive impairment and 47 with MCI (amnestic and multidomain), ages 75 to 95, from the population-based Kungsholmen Project, Stockholm, Sweden, for 3 years. Three types of neuropsychiatric symptoms were assessed at baseline: mood-related depressive symptoms, motivation-related depressive symptoms, and anxiety-related symptomatology. AD at 3-year follow-up was diagnosed according to Diagnostic and Statistical Manual for Mental Disorders-III-R criteria.
Psychiatric symptoms occurred more frequently in persons with MCI (36.2% mood, 36.2% motivation, and 46.8% anxiety symptoms) than in cognitively intact elderly individuals (18.4% mood, 13.0% motivation, and 24.9% anxiety). Of persons with both MCI and anxiety symptoms, 83.3% developed AD over follow-up vs 6.1% of cognitively intact persons and 40.9% persons who had MCI without anxiety. Among persons with MCI, the 3-year risk of progressing to AD almost doubled with each anxiety symptom (relative risk RR = 1.8 1.2 to 2.7 per symptom). Conversely, among cognitively intact subjects, only symptoms of depressive mood were related to AD development (RR = 1.9 1.0 to 3.6 per symptom).
The predictive validity of mild cognitive impairment (MCI) for identifying future Alzheimer disease (AD) cases is improved in the presence of anxiety symptoms. Mood-related depressive symptoms (dysphoria, suicidal ideation, etc.) in preclinical AD might be related to the neuropathologic mechanism, as they appear preclinically in persons both with and without MCI.
The relation of overweight to dementia is controversial. We aimed to examine the association of midlife overweight and obesity with dementia, Alzheimer disease (AD), and vascular dementia (VaD) in ...late life, and to verify the hypothesis that genetic and early-life environmental factors contribute to the observed association.
From the Swedish Twin Registry, 8,534 twin individuals aged ≥65 (mean age 74.4) were assessed to detect dementia cases (DSM-IV criteria). Height and weight at midlife (mean age 43.4) were available in the Registry. Data were analyzed as follows: 1) unmatched case-control analysis for all twins using generalized estimating equation (GEE) models and 2) cotwin matched case-control approach for dementia-discordant twin pairs by conditional logistic regression taking into account lifespan vascular disorders and diabetes.
Among all participants, dementia was diagnosed in 350 subjects, and 114 persons had questionable dementia. Overweight (body mass index BMI >25-30) and obesity (BMI >30) at midlife were present in 2,541 (29.8%) individuals. In fully adjusted GEE models, compared with normal BMI (20-25), overweight and obesity at midlife were related to dementia with odds ratios (ORs) (95% CIs) of 1.71 (1.30-2.25) and 3.88 (2.12-7.11), respectively. Conditional logistic regression analysis in 137 dementia-discordant twin pairs led to an attenuated midlife BMI-dementia association. The difference in ORs from the GEE and the matched case-control analysis was statistically significant (p = 0.019).
Both overweight and obesity at midlife independently increase the risk of dementia, AD, and VaD. Genetic and early-life environmental factors may contribute to the midlife high adiposity-dementia association.
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