Debora Rizzuto

The impact of chronic multimorbidity and disability on functional decline and survival in elderly persons. A community‐based, longitudinal study

Objective.  We aimed to disentangle the effect of chronic multimorbidity and disability on 3‐year functional decline and survival in the elderly.

Patterns of Chronic Multimorbidity in the Elderly Population

OBJECTIVES: To describe patterns of comorbidity and multimorbidity in elderly people.

Lifestyle, social factors, and survival after age 75: population based study

Objective To identify modifiable factors associated with longevity among adults aged 75 and older. Design Population based cohort study. Setting Kungsholmen, Stockholm, Sweden. Participants 1810 adults aged 75 or more participating in the Kungsholmen Project, with follow-up for 18 years. Main outcome measure Median age at death. Vital status from 1987 to 2005. Results During follow-up 1661 (91.8%) participants died. Half of the participants lived longer than 90 years. Half of the current smokers died 1.0 year (95% confidence interval 0.0 to 1.9 years) earlier than non-smokers. Of the leisure activities, physical activity was most strongly associated with survival; the median age at death of participants who regularly swam, walked, or did gymnastics was 2.0 years (0.7 to 3.3 years) greater than those who did not. The median survival of people with a low risk profile (healthy lifestyle behaviours, participation in at least one leisure activity, and a rich or moderate social network) was 5.4 years longer than those with a high risk profile (unhealthy lifestyle behaviours, no participation in leisure activities, and a limited or poor social network). Even among the oldest old (85 years or older) and people with chronic conditions, the median age at death was four years higher for those with a low risk profile compared with those with a high risk profile. Conclusion Even after age 75 lifestyle behaviours such as not smoking and physical activity are associated with longer survival. A low risk profile can add five years to women’s lives and six years to men’s. These associations, although attenuated, were also present among the oldest old (≥85 years) and in people with chronic conditions.

High Plasma Levels of Vitamin E Forms and Reduced Alzheimer's Disease Risk in Advanced Age

In this study we investigated the association between plasma levels of eight forms of vitamin E and incidence of Alzheimers disease (AD) among oldest-old individuals in a population-based setting. A dementia-free sample of 232 subjects aged 80+ years, derived from the Kungsholmen Project, was followed-up to 6 years to detect incident AD. Plasma levels of vitamin E (alpha-, beta-, gamma, and delta-tocopherol; alpha-, beta-, gamma-, and delta-tocotrienol) were measured at baseline. Vitamin E forms-AD association was analyzed with Cox proportional hazard model after adjustment for several potential confounders. Subjects with plasma levels of total tocopherols, total tocotrienols, or total vitamin E in the highest tertile had a reduced risk of developing AD in comparison to persons in the lowest tertile. Multi-adjusted hazard ratios (HRs) and 95% confidence interval (CI) were 0.55 (0.32-0.94) for total tocopherols, 0.46 (0.23-0.92) for total tocotrienols, and 0.55 (0.32-0.94) for total vitamin E. When considering each vitamin E form, the risk of developing AD was reduced only in association with high plasma levels of beta-tocopherol (HR: 0.62, 95% CI 0.39-0.99), whereas alpha-tocopherol, alpha- tocotrienol, and beta-tocotrienol showed only a marginally significant effect in the multiadjusted model [HR (95% CI): alpha-tocopherol: 0.72 (0.48-1.09); alpha-tocotrienol: 0.70 (0.44-1.11); beta-tocotrienol: 0.69 (0.45-1.06)]. In conclusion, high plasma levels of vitamin E are associated with a reduced risk of AD in advanced age. The neuroprotective effect of vitamin E seems to be related to the combination of different forms, rather than to alpha-tocopherol alone, whose efficacy in interventions against AD is currently debated.

APOE-related mortality: Effect of dementia, cardiovascular disease and gender

Allele-frequency comparisons between younger and older populations suggest an effect of apolipoprotein E gene (APOE) on mortality, not consistently confirmed by longitudinal data. Our aim was to assess the effect of APOE on survival taking into account the possible contribution of Alzheimers disease, other dementias, ischemic heart- and cerebrovascular disease (IHCD). In a community-based longitudinal study, the Kungsholmen Project, 75+ year-old individuals (n=1094) were examined, and followed for 18 years. An increased mortality-risk of 22% in those with the epsilon4 allele was detected; whereas a 28% decreased mortality-risk was detected in those with the epsilon2 allele compared to those with the epsilon3epsilon3 genotype. IHCD adjustment did not change the mortality-risk in those with the epsilon4 allele or the epsilon2 allele. Dementia accounted for the majority of the increased mortality-risk associated with the epsilon4 allele, but the protective effect of the epsilon2 allele remained. Both effects of the epsilon4 allele and the epsilon2 allele were strongly modified by gender. A 49% elevated risk for death in men was related to the epsilon4 allele, and a 36% decreased mortality-risk was found in women with the epsilon2 allele. These findings suggest different roles for the APOE alleles in survival by gender in old age.

Walking Speed, Processing Speed, and Dementia: A Population-Based Longitudinal Study

BACKGROUND Slow walking speed has been shown to predict dementia. We investigated the relation of walking speed, processing speed, and their changes over time to dementia among older adults. METHODS This study included 2,938 participants (age 60+ years) in the population-based Swedish National study on Aging and Care in Kungsholmen, Sweden, who were free from dementia and severe walking impairment at baseline. Walking speed was assessed with participants walking at their usual pace and processing speed was defined by a composite measure of standard tests (digit cancellation, trail making test-A, pattern comparison). Dementia at 3- and 6-year follow-ups was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders-IV criteria. RESULTS Of the 2,232 participants who were reassessed at least once, 226 developed dementia. Logistic regression models showed that each standard deviation slower baseline walking speed or decline in walking speed over time increased the likelihood of incident dementia (odds ratios 1.61, 95% confidence interval [CI] 1.31-1.98; and 2.58, 95% CI 2.12-3.14, respectively). Adjustment for processing speed attenuated these associations (odds ratios 1.26, 95% CI 1.01-1.58 and 1.76, 95% CI 1.33-2.34). Mixed-effects models revealed statistical interactions of time with dementia on change in walking and processing speed, such that those who developed dementia showed accelerated decline. At baseline, poorer performance in processing speed, but not in walking speed, was observed for persons who developed dementia during the study period. CONCLUSIONS Processing speed may play an important role for the association between walking speed and dementia. The slowing of walking speed appears to occur secondary to slowing of processing speed in the path leading to dementia.

Lifestyle Factors Related to Mortality and Survival: A Mini-Review

As the worlds 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.

The influence of multimorbidity on clinical progression of dementia in a population-based cohort

Introduction Co-occurrence with other chronic diseases may influence the progression of dementia, especially in case of multiple chronic diseases. We aimed to verify whether multimorbidity influenced cognitive and daily functioning during nine years after dementia diagnosis compared with the influence in persons without dementia. Methods In the Kungsholmen Project, a population-based cohort study, we followed 310 persons with incident dementia longitudinally. We compared their trajectories with those of 679 persons without dementia. Progression was studied for cognition and activities of daily life (ADLs), measured by MMSE and Katz Index respectively. The effect of multimorbidity and its interaction with dementia status was studied using individual growth models. Results The mean (SD) follow-up time was 4.7 (2.3) years. As expected, dementia related to both the decline in cognitive and daily functioning. Irrespective of dementia status, persons with more diseases had significantly worse baseline daily functioning. In dementia patients having more diseases also related to a significantly faster decline in daily functioning. Due to the combination of lower functioning in ADLs at baseline and faster decline, dementia patients with multimorbidity were about one to two years ahead of the decline of dementia patients without any co-morbidity. In persons without dementia, no significant decline in ADLs over time was present, nor was multimorbidity related to the decline rate. Cognitive decline measured with MMSE remained unrelated to the number of diseases present at baseline. Conclusion Multimorbidity was related to baseline daily function in both persons with and without dementia, and with accelerated decline in people with dementia but not in non-demented individuals. No relationship of multimorbidity with cognitive functioning was established. These findings imply a strong interconnection between physical and mental health, where the greatest disablement occurs when both somatic and mental disorders are present.

Assessing and Measuring Chronic Multimorbidity in the Older Population: A Proposal for Its Operationalization

Abstract Background Although the definition of multimorbidity as “the simultaneous presence of two or more chronic diseases” is well established, its operationalization is not yet agreed. This study aims to provide a clinically driven comprehensive list of chronic conditions to be included when measuring multimorbidity. Methods Based on a consensus definition of chronic disease, all four-digit level codes from the International Classification of Diseases, 10th revision (ICD-10) were classified as chronic or not by an international and multidisciplinary team. Chronic ICD-10 codes were subsequently grouped into broader categories according to clinical criteria. Last, we showed proof of concept by applying the classification to older adults from the Swedish National study of Aging and Care in Kungsholmen (SNAC-K) using also inpatient data from the Swedish National Patient Register. Results A disease or condition was considered to be chronic if it had a prolonged duration and either (a) left residual disability or worsening quality of life or (b) required a long period of care, treatment, or rehabilitation. After applying this definition in relation to populations of older adults, 918 chronic ICD-10 codes were identified and grouped into 60 chronic disease categories. In SNAC-K, 88.6% had ≥2 of these 60 disease categories, 73.2% had ≥3, and 55.8% had ≥4. Conclusions This operational measure of multimorbidity, which can be implemented using either or both clinical and administrative data, may facilitate its monitoring and international comparison. Once validated, it may enable the advancement and evolution of conceptual and theoretical aspects of multimorbidity that will eventually lead to better care.

Dementia After Age 75: Survival in Different Severity Stages and Years of Life Lost

Dementia is a known predictor of mortality, but little is known about disease duration. We therefore aimed to investigate the impact of dementia on survival by estimating years lived with the disease, in total and in different severity stages, and by comparing dementia to other major chronic disorders such as cancer and cardiovascular disease (CVD). During a 7.4-year follow-up of the Kungsholmen project, 371 incident dementia cases of the 1,307 dementia-free persons, aged 75+ at baseline, were clinically diagnosed (DSM-III-R criteria). Diagnoses of cancer and CVD were obtained from the national Stockholm Inpatient Registry System, active since 1969. Disease duration, hazard ratio (HR), and potential years of life lost (PYLL) were derived from Kaplan-Meier survival estimation, the Cox model, and standard life-table analysis, respectively. Dementia was a significant predictor of mortality (HR=1.7; 95% CI: 1.47-1.92) after adjustment for several covariates including comorbidity, accounting for 16% of all deaths. The mean (�SD) survival time after dementia diagnosis was 4.1 (�2.6) years, and more than 2 years were spent in moderate (14-month) and severe (12-month) stages. Women with dementia lived longer than men, as they survived longer in the severe stage (2.1 vs. 0.5 years among 75-84-year-old women compared to coetaneous men). The PYLL were 3.4 for dementia, 3.6 for CVD, and 4.4 for cancer. We found a similar impact of dementia and CVD on survival, but following diagnosis, persons with dementia, and especially women, spent half of their remaining lives in the severe disabling stages of the disease.