Living longer than expected : protective and risk factors related to human longevity

The scientific community has become increasingly interested in understanding what lies behind the continuing extension of the human lifespan. The main aim of this thesis was to better understand the association between health status, lifestyle, genetic factors and survival in advanced age. Data used in the 4 studies are gathered from the Kungsholmen Project, a longitudinal population-based study on 75 year and older participants living in Stockholm, Sweden. Study I. Dementia, cardiovascular disease (CVD), and cancer were associated with a 2- to 3-fold increased rate of all-cause mortality. The mean survival times after incident diagnosis were 4.1 years for dementia, 4.2 years for CVD, and 2.2 years for cancer. A total of 3.4 potential years of life were lost because of dementia, 3.6 of CVD, and 4.4 because of cancer. Women aged 75 to 84 years lived longer than coetaneous men after incident diagnosis of dementia because they spent 1.6 years longer than men in the severe stage of the disease. Study II. Findings suggest that APOE alleles play different roles in the survival of elderly women and men. The mortality rate was 40% lower among women, but not men, who carried the ε2 allele, compared with the ε3ε3 carriers. The ε4 allele was associated with a 50% higher rate of death only among men. Dementia, not ischemic heart and cerebrovascular diseases, accounted for the majority of the increased mortality rate in those with the ε4 allele. Study III. Maintaining a healthy lifestyle and a rich social network was positively associated with survival even among people aged 75 years and older. People who reported being physically active a minimum of once a month lived about 2 years longer than those who did not. Non-smokers 75 years and older who participated in at least 1 leisure activity a month and had good social support lived about 5 years longer than inactive smokers with poor social support. These association, although attenuated, were also found in individuals aged 85 years and older and those with chronic diseases. Study IV. Genetic risk factors were relevant for survival after age 75. Variations in 4 different genes (APOC1, APOE, IDE, and PI3K) were associated with 12–20% increased rate of mortality. However, participants with at least 1 risk allele and a healthy lifestyle had about 70% lower rate of death than those with no risk allele and an unhealthy lifestyle. Those with no risk alleles and a healthy lifestyle had 80% lower mortality rate and 6 years longer median lifespan than people with at least 1 risk allele and unhealthy lifestyle. In conclusion, survival after 75 years of age was associated with health status, lifestyle, genetic factors, and a combination of those factors. These findings may help prognostic evaluation of the duration of specific diseases. They underscore the malignant nature of dementia as a result of the long period individuals lived with the severe disease stages, especially for women. These findings also suggest that the benefit of a healthy lifestyle, healthy behavior, and social support probably last a lifetime. Moreover, allelic variations in genes were associated with higher mortality rate, but the combined effect of genetic-environmental joint exposures may lead to the attenuation of the mortality rate, indicating that people with genetic susceptibility may reduce their initial mortality rate by modifying their lifestyle. Therefore, efforts to encourage smoking cessation, physical activity, and social engagement should be continued long into late life

personality and survival in older age the role of lifestyle behaviors and health status

Objective We intended to assess the relationship between personality and survival in an older population and to explore the role of lifestyle behaviors and health status as potential mediators. Design Population-based cohort study. Setting Swedish National Study of Aging and Care in Kungsholmen, Sweden. Participants 2,298 adults aged 60 or more years, without dementia or depression, followed for 11 years. Measurements Personality (extraversion, neuroticism, and openness) was assessed with a shortened version of the NEO-Five Factor Inventory. We tested whether personality affected mortality and examined the potential mediating effect of health status (body mass index, number of chronic diseases, impairment in instrumental activities of daily living, and C-reactive protein) and lifestyle behaviors (leisure activities, social network, smoking, and alcohol consumption). Results Over 11 years of follow-up, higher levels of extraversion were associated with a 14% reduction in mortality. Examination of different combinations of personality traits showed that independent of levels of neuroticism and openness, high extraversion were associated with up to 65% lower mortality. Decomposing the effect of extraversion on mortality, we found that the majority (44%) of the beneficial effect was mediated by healthy lifestyle behaviors. Health status accounted for 5% of the association. Conclusions Extroverted people, who are characterized by higher optimism and high self-efficacy, are prone to healthier behaviors and better health, which may result in longer survival. These results highlight the importance of a healthy lifestyle in survival

Peak expiratory flow, walking speed and survival in older adults: An 18-year longitudinal population-based study

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Choosing Wisely? Measuring the Burden of Medications in Older Adults near the End of Life: Nationwide, Longitudinal Cohort Study

Abstract Background The burden of medications near the end of life has recently come under scrutiny, because several studies suggested that people with life-limiting illness receive potentially futile treatments. Methods We identified 511,843 older adults (>65 years) who died in Sweden between 2007 and 2013 and reconstructed their drug prescription history for each of the last 12 months of life through the Swedish Prescribed Drug Register. Decedents' characteristics at time of death were assessed through record linkage with the National Patient Register, the Social Services Register, and the Swedish Education Register. Results Over the course of the final year before death, the proportion of individuals exposed to ≥10 different drugs rose from 30.3% to 47.2% ( P Conclusion Polypharmacy increases throughout the last year of life of older adults, fueled not only by symptomatic medications but also by long-term preventive treatments of questionable benefit. Clinical guidelines are needed to support physicians in their decision to continue or discontinue medications near the end of life

effect of the interplay between genetic and behavioral risks on survival after age 75

Objectives To explore the association between genes that may be related to human mortality, taking into account the possible contribution of morbidity, and investigate whether lifestyle behaviors may attenuate genetic risk. Design Twenty-five-year population-based cohort study. Setting Kungsholmen cohort, Stockholm, Sweden. Participants Individuals aged 75 and older (N = 1,229). Measurements The associations between single-nucleotide variations in 14 genes (previously associated with mortality or to diseases linked to mortality), relevant lifestyle risk behaviors (smoking; mental, physical, or social inactivity; moderate or poor social network), and mortality were estimated using Cox regression. Results People with allelic variation in four genes related to cardiovascular diseases and metabolism were more likely to die: apolipoprotein (APO)C1 GG and AG carriers, APOE ɛ4 carriers, insulin-degrading enzyme (IDE) TC carriers, and phosphatidylinositol 3-kinase (PI3KCB) GG carriers. Individuals with multiple adverse alleles had 62% higher mortality rate than those with none. In contrast, people with no risk behaviors (low-risk profile) had 65% lower mortality rate than people with all examined risk behaviors (high-risk profile). Combining the genetic and environmental factors, it was found that, independent of genetic profile, individuals with a low-risk profile had up to 64% lower mortality rate than those with a moderate high– or high-risk profile and at least one genetic risk factor. Conclusion This study supports and expands evidence that genetic variations in APOE, IDE, and PI3KCB are associated with lower mortality rate, although lifestyle behaviors can modulate their effects

Multimorbidity Patterns and 6-Year Risk of Institutionalization in Older Persons: The Role of Social Formal and Informal Care

Abstract Objectives The aim was to evaluate patterns of multimorbidity that increase the risk of institutionalization in older persons, also exploring the potential buffering effect of formal and informal care. Design Prospective cohort study. Setting and Participants The population-based Swedish National study on Aging and Care in Kungsholmen, Stockholm, Sweden. Measures In total, 2571 community-dwelling older adults were grouped at baseline according to their underlying multimorbidity patterns, using a fuzzy c-means cluster algorithm, and followed up for 6 years to test the association between multimorbidity patterns and institutionalization. Results Six patterns of multimorbidity were identified: psychiatric diseases; cardiovascular diseases, anemia, and dementia; metabolic and sleep disorders; sensory impairments and cancer; musculoskeletal, respiratory, and gastrointestinal diseases; and an unspecific pattern including diseases of which none were overrepresented. In total, 110 (4.3%) participants were institutionalized during the follow-up, ranging from 1.7% in the metabolic and sleep disorders pattern to 8.4% in the cardiovascular diseases, anemia, and dementia pattern. Compared with the unspecific pattern, only the cardiovascular diseases, anemia, dementia pattern was significantly associated with institutionalization [relative risk ratio (RRR) = 2.23; 95% confidence interval (CI) 1.07‒4.65)], after adjusting for demographic characteristics and disability status at baseline. In stratified analyses, those not receiving formal care in the psychiatric diseases pattern (RRR 3.34; 95% CI 1.20‒9.32) and those not receiving formal or informal care in the 'cardiovascular diseases, anemia, dementia' pattern (RRR 2.99; 95% CI 1.20‒7.46; RRR 2.79; 95% CI 1.16‒6.71, respectively) had increased risks of institutionalization. Conclusions and Implications Older persons suffering from specific multimorbidity patterns have a higher risk of institutionalization, especially if they lack formal or informal care. Interventions aimed at preventing the clustering of diseases could reduce the associated burden on residential long-term care. Formal and informal care provision may be effective strategies in reducing the risk of institutionalization

walking speed drives the prognosis of older adults with cardiovascular and neuropsychiatric multimorbidity

Abstract Background We investigated the impact of multiple cardiovascular and neuropsychiatric diseases on all-cause and cause-specific mortality in older adults, considering their functional status. Methods This cohort study included 3241 participants (aged ≥60 years) in the Swedish National study of Aging and Care in Kungsholmen (SNAC-K). Number of cardiovascular and neuropsychiatric diseases was categorized as 0, 1, or ≥2. Functional impairment was defined as walking speed of Results After 3 years, compared with participants with preserved walking speed and without either cardiovascular or neuropsychiatric diseases, the multivariable-adjusted HR (95% confidence interval) of all-cause mortality for people with functional impairment in combination with 0, 1, and ≥2 cardiovascular diseases were 1.88 (1.29-2.74), 3.85 (2.60-5.70), and 5.18 (3.45-7.78), respectively. The corresponding figures for people with 0, 1, and ≥2 neuropsychiatric diseases were, respectively, 2.88 (2.03-4.08), 3.36 (2.31-4.89), and 3.68 (2.43-5.59). Among people with ≥2 cardiovascular or ≥2 neuropsychiatric diseases, those with functional impairment had an excess risk for 3-year all-cause mortality of 18/100 person-years and 17/100 person-years, respectively, than those without functional impairment. At 5 years, the association between the number of cardiovascular diseases and mortality resulted independent of functional impairment. Conclusions Functional impairment magnifies the effect of cardiovascular and neuropsychiatric multimorbidity on mortality among older adults. Walking speed appears to be a simple clinical marker for the prognosis of these two patterns of multimorbidity

Multimorbidity burden and dementia risk in older adults : The role of inflammation and genetics

Funding: Swedish National study on Aging and Care; Ministry of Health and Social Affairs; Swedish Research Council, Grant/Award Number: 2016-00981; Swedish Research Council for Health,Working Life andWelfare, Grant/Award Number: 2017-01764; Italian Ministry of Health, Grant/Award Number: PE-2016-02364885We investigate dementia risk in older adults with different disease patterns and explore the role of inflammation and apolipoprotein E (APOE) genotype. A total of 2,478 dementia-free participants with two or more chronic diseases (ie, multimorbidity) part of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) were grouped according to their multimorbidity patterns and followed to detect clinical dementia. The potential modifier effect of C-reactive protein (CRP) and apolipoprotein E (APOE) genotype was tested through stratified analyses. People with neuropsychiatric, cardiovascular, and sensory impairment/cancer multimorbidity had increased hazards for dementia compared to the unspecific (Hazard ration (HR) 1.66, 95% confidence interval [CI] 1.13-2.42; 1.61, 95% CI 1.17-2.29; 1.32, 95% CI 1.10-1.71, respectively). Despite the lack of statistically significant interaction, high CRP increased dementia risk within these patterns, and being APOE ε4 carriers heightened dementia risk for neuropsychiatric and cardiovascular multimorbidity. Individuals with neuropsychiatric, cardiovascular, and sensory impairment/cancer patterns are at increased risk for dementia and APOE ε4, and inflammation may further increase the risk. Identifying such high-risk groups might allow tailored interventions for dementia prevention

Free and cued selective reminding test predicts progression to Alzheimer's disease in people with mild cognitive impairment

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