| 1. |
- Pérez, Laura M., et al.
(författare)
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Glutathione Serum Levels and Rate of Multimorbidity Development in Older Adults
- 2020
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 75:6, s. 1089-1094
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to investigate the association between baseline levels of total serum glutathione (tGSH) and rate of chronic disease accumulation over time. The study population (n = 2,596) was derived from a population-based longitudinal study on >= 60-year-olds living in Stockholm. Participants were clinically assessed at baseline, 3- and 6-year follow-ups. Multimorbidity was measured as the number of chronic conditions from a previously built list of 60 diseases. Linear mixed models were applied to analyze the association between baseline tGSH levels and the rate of multimorbidity development over 6 years. We found that at baseline, participants with >= 4 diseases had lower tGSH levels than participants with no chronic conditions (3.3 vs 3.6 mu mol/L; p < .001). At follow-up, baseline levels of tGSH were inversely associated with the rate of multimorbidity development (beta * time: -0.044, p < .001) after adjusting for age, sex, education, levels of serum creatinine, C-reactive protein, albumin, body mass index, smoking, and time of dropout or death. In conclusion, serum levels of tGSH are inversely associated with multimorbidity development; the association exists above and beyond the link between tGSH and specific chronic conditions. Our findings support the hypothesis that tGSH is a biomarker of multisystem dysregulation that eventually leads to multimorbidity.
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| 2. |
- Calderón-Larrañaga, Amaia, et al.
(författare)
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Assessing and Measuring Chronic Multimorbidity in the Older Population : A Proposal for Its Operationalization
- 2017
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 72:10, s. 1417-1423
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundAlthough 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. MethodsBased 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.ResultsA 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.ConclusionsThis 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.
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| 3. |
- Hooshmand, Babak, et al.
(författare)
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Association of Methionine to Homocysteine Status With Brain Magnetic Resonance Imaging Measures and Risk of Dementia
- 2019
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 76:11, s. 1198-1205
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Impairment of methylation status (ie, methionine to homocysteine ratio) may be a modifiable risk factor for structural brain changes and incident dementia.OBJECTIVE To investigate the association of serum markers of methylation status and sulfur amino acids with risk of incident dementia, Alzheimer disease (AD), and the rate of total brain tissue volume loss during 6 years.DESIGN, SETTING, AND PARTICIPANTS This population-based longitudinal study was performed from March 21, 2001, to October 10, 2010, in a sample of 2570 individuals aged 60 to 102 years from the Swedish Study on Aging and Care in Kungsholmen who were dementia free at baseline and underwent comprehensive examinations and structural brain magnetic resonance imaging (MRI) on 2 to 3 occasions during 6 years. Data analysis was performed from March 1, 2018, to October 1, 2018.MAIN OUTCOMES AND MEASURES Incident dementia, AD, and the rate of total brain volume loss.RESULTS This study included 2570 individuals (mean [SD] age, 73.1 [10.4] years; 1331 [56.5%] female). The methionine to homocysteine ratio was higher in individuals who consumed vitamin supplements (median, 1.9; interquartile range [IQR], 1.5-2.6) compared with those who did not (median, 1.8; IQR, 1.3-2.3; P<.001) and increased per each quartile increase of vitamin B-12 or folate. In the multiadjusted model, an elevated baseline serum total homocysteine level was associated with an increased risk of dementia and AD during 6 years: for the highest homocysteine quartile compared with the lowest, the hazard ratios (HRs) were 1.60 (95% CI, 1.01-2.55) for dementia and 2.33 (95% CI, 1.26-4.30) for AD. In contrast, elevated concentrations of methionine were associated with a decreased risk of dementia (HR, 0.54; 95% CI, 0.36-0.81) for the highest quartile compared with the lowest. Higher values of the methionine to homocysteine ratio were significantly associated with lower risk of dementia and AD: for the fourth methionine-homocysteine quartile compared with the first quartile, the HR was 0.44 (95% CI, 0.27-0.71) for incident dementia and 0.43 (95% CI, 0.23-0.80) for AD. In the multiadjusted linear mixed models, a higher methionine to homocysteine ratio was associated with a decreased rate of total brain tissue volume loss during the study period (beta [SE] per 1-SD increase, 0.038 [0.014]; P=.007).CONCLUSIONS AND RELEVANCE The methionine to homocysteine status was associated with dementia development and structural brain changes during the 6-year study period, suggesting that a higher methionine to homocysteine ratio may be important in reducing the rate of brain atrophy and decreasing the risk of dementia in older adults.
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| 4. |
- Hooshmand, Babak, et al.
(författare)
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Association of Vitamin B-12, Folate, and Sulfur Amino Acids With Brain Magnetic Resonance Imaging Measures in Older Adults A Longitudinal Population-Based Study
- 2016
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 73:6, s. 606-613
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Vitamin B-12, folate, and sulfur amino acids may be modifiable risk factors for structural brain changes that precede clinical dementia. OBJECTIVE To investigate the association of circulating levels of vitamin B-12, red blood cell folate, and sulfur amino acids with the rate of total brain volume loss and the change in white matter hyperintensity volume as measured by fluid-attenuated inversion recovery in older adults. DESIGN, SETTING, AND PARTICIPANTS The magnetic resonance imaging subsample of the Swedish National Study on Aging and Care in Kungsholmen, a population-based longitudinal study in Stockholm, Sweden, was conducted in 501 participants aged 60 years or older who were free of dementia at baseline. A total of 299 participants underwent repeated structural brain magnetic resonance imaging scans from September 17, 2001, to December 17, 2009. MAIN OUTCOMES AND MEASURES The rate of brain tissue volume loss and the progression of total white matter hyperintensity volume. RESULTS In the multi-adjusted linear mixed models, among 501 participants (300 women [59.9%]; mean [SD] age, 70.9 [9.1] years), higher baseline vitamin B-12 and holotranscobalamin levels were associated with a decreased rate of total brain volume loss during the study period: for each increase of 1 SD, beta (SE) was 0.048 (0.013) for vitamin B-12 (P < .001) and 0.040 (0.013) for holotranscobalamin (P = .002). Increased total homocysteine levels were associated with faster rates of total brain volume loss in the whole sample (beta [SE] per 1-SD increase, -0.035 [0.015]; P = .02) and with the progression of white matter hyperintensity among participants with systolic blood pressure greater than 140mmHg (beta [SE] per 1-SD increase, 0.000019 [0.00001]; P = .047). No longitudinal associations were found for red blood cell folate and other sulfur amino acids. CONCLUSIONS AND RELEVANCE This study suggests that both vitamin B-12 and total homocysteine concentrations may be related to accelerated aging of the brain. Randomized clinical trials are needed to determine the importance of vitamin B-12 supplementation on slowing brain aging in older adults.
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| 5. |
- Mangialasche, Francesca, et al.
(författare)
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Dementia prevention : current epidemiological evidence and future perspective
- 2012
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Ingår i: Alzheimer's research & therapy. - : Springer Science and Business Media LLC. - 1758-9193. ; 4:1, s. 6-
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Forskningsöversikt (refereegranskat)abstract
- Dementia, a major cause of disability and institutionalization in older people, poses a serious threat to public health and to the social and economic development of modern society. Alzheimer's disease (AD) and cerebrovascular diseases are the main causes of dementia; most dementia cases are attributable to both vascular and neurodegenerative brain damage. No curative treatment is available, but epidemiological research provides a substantial amount of evidence of modifiable risk and protective factors that can be addressed to prevent or delay onset of AD and dementia. Risk of late-life dementia is determined by exposures to multiple factors experienced over the life course, and the effect of specific risk/protective factors depends largely on age. Moreover, cumulative and combined exposure to different risk/protective factors can modify their effect on dementia/AD risk. Multidisciplinary research involving epidemiology, neuropathology, and neuroimaging has provided sufficient evidence that vascular risk factors significantly contribute to the expression and progression of cognitive decline (including dementia) but that active engagement in social, physical, and mentally stimulating activities may delay the onset of dementia. However, these findings need to be confirmed by randomized controlled trials (RCTs). A promising strategy for preventing dementia is to implement intervention programs that take into account both the life-course model and the multifactorial nature of this syndrome. In Europe, there are three ongoing multidomain interventional RCTs that focus on the optimal management of vascular risk factors and vascular diseases. The RCTs include medical and lifestyle interventions and promote social, mental, and physical activities aimed at increasing the cognitive reserve. These studies will provide new insights into prevention of cognitive impairment and dementia. Such knowledge can help researchers plan larger, international prevention trials that could provide robust evidence on dementia/AD prevention. Taking a step in this direction, researchers involved in these European RCTs recently started the European Dementia Prevention Initiative, an international collaboration aiming to improve strategies for preventing dementia.
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| 6. |
- Mangialasche, Francesca, et al.
(författare)
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High plasma levels of vitamin E forms and reduced Alzheimer's disease risk in advanced age
- 2010
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Ingår i: Journal of Alzheimer's disease : JAD. - Amsterdam, Washington : IOS Press. - 1875-8908. ; 58:3, s. 131-140
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Tidskriftsartikel (refereegranskat)abstract
- In this study we investigated the association between plasma levels of eight forms of vitamin E and incidence of Alzheimer's 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.
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| 7. |
- Mangialasche, Francesca, et al.
(författare)
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Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults
- 2013
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Ingår i: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 48:12, s. 1428-1435
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vitamin E includes eight natural antioxidant compounds (four tocopherols and four tocotrienols), but a-tocopherol has been the main focus of investigation in studies of cognitive impairment and Alzheimer's disease. Objective: To investigate the association between serum levels of tocopherols and tocotrienols, markers of vitamin E oxidative/nitrosative damage (alpha-tocopherylquinone, 5-nitro-gamma-tocopherol) and incidence of cognitive impairment in a population-based study. Design: A sample of 140 non-cognitively impaired elderly subjects derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study was followed-up for 8 years to detect cognitive impairment, defined as development of mild cognitive impairment (MCI) or Alzheimer's dementia. The association between baseline serum vitamin E and cognitive impairment was analyzed with multiple logistic regression after adjusting for several confounders. Results: The risk of cognitive impairment was lower in subjects in the middle tertile of the alpha-tocopherol/cholesterol ratio than in those in the lowest tertile: the multiadjusted odds ratio (OR) with 95% confidence interval (CI) was 0.27 (0.10-0.78). Higher incidence of cognitive impairment was found in the middle [OR (95% CI): 3.41 (1.29-9.06)] and highest [OR (95% CI): 2.89 (1.05-7.97)] tertiles of the 5-NO2-gamma-tocopherol/gamma-tocopherol ratio. Analyses of absolute serum levels of vitamin E showed lower risk of cognitive impairment in subjects with higher levels of gamma-tocopherol, beta-tocotrienol, and total tocotrienols. Conclusions: Elevated levels of tocopherol and tocotrienol forms are associated with reduced risk of cognitive impairment in older adults. The association is modulated by concurrent cholesterol concentration. Various vitamin E forms might play a role in cognitive impairment, and their evaluation can provide a more accurate measure of vitamin E status in humans.
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| 8. |
- Marengoni, Alessandra, et al.
(författare)
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Aging with multimorbidity : A systematic review of the literature
- 2011
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Ingår i: Ageing Research Reviews. - : Elsevier BV. - 1568-1637 .- 1872-9649. ; 10:4, s. 430-439
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Forskningsöversikt (refereegranskat)abstract
- A literature search was carried out to summarize the existing scientific evidence concerning occurrence, causes, and consequences of multimorbidity (the coexistence of multiple chronic diseases) in the elderly as well as models and quality of care of persons with multimorbidity. According to pre-established inclusion criteria, and using different search strategies, 41 articles were included (four of these were methodological papers only). Prevalence of multimorbidity in older persons ranges from 55 to 98%. In cross-sectional studies, older age, female gender, and low socioeconomic status are factors associated with multimorbidity, confirmed by longitudinal studies as well. Major consequences of multimorbidity are disability and functional decline, poor quality of life, and high health care costs. Controversial results were found on multimorbidity and mortality risk. Methodological issues in evaluating multimorbidity are discussed as well as future research needs, especially concerning etiological factors, combinations and clustering of chronic diseases, and care models for persons affected by multiple disorders. New insights in this field can lead to the identification of preventive strategies and better treatment of multimorbid patients.
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| 9. |
- Marengoni, Alessandra, et al.
(författare)
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Coexisting chronic conditions in the older population : Variation by health indicators
- 2016
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Ingår i: European journal of internal medicine. - : Elsevier BV. - 0953-6205 .- 1879-0828. ; 31, s. 29-34
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Tidskriftsartikel (refereegranskat)abstract
- Background: This study analyzes the prevalence and patterns of coexisting chronic conditions in older adults.Design: Cross-sectional.Participant and setting: A sample of 3363 people >= 60 years living in Stockholm were examined from March 2001 through August 2004.Measurements: Chronic conditions were measured with: 1) multimorbidity (>= 2 concurrent chronic diseases); 2) the Cumulative Illness Rating Scale, 3) polypharmacy (>= 5 prescribed drugs), and 4) complex health problems ( chronic diseases and/or symptoms along with cognitive and/or functional limitations).Results: A total of 55.6% of 60-74 year olds and 13.4% of those >= 85 years did not have chronic conditions according to the four indicators. Multimorbidity and polypharmacy were the most prevalent indicators: 38% aged 60-74 and 76% aged >= 85 had multimorbidity; 24.3% aged 60-74 and 59% aged >= 85 had polypharmacy. Prevalence of chronic conditions as indicated by the comorbidity index and complex health problems ranged from 16.5% and 1.5% in the 60-74 year olds to 38% and 36% in the 85 + year olds, respectively. Prevalence of participants with 4 indicators was low, varying from 1.6% in those aged 60-74 to 14.9% in those aged >= 85 years. Older age was associated with higher odds of each of the 4 indicators; being a woman, with all indicators but multimorbidity; and lower educational level, only with complex health problems.Conclusions: Prevalence of coexisting chronic conditions varies greatly by health indicator used. Variation increases when age, sex, and educational level are taken into account. These findings underscore the need of different indicators to capture health complexity in older adults.
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| 10. |
- Pan, Kuan-Yu, et al.
(författare)
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Psychosocial working conditions, trajectories of disability, and the mediating role of cognitive decline and chronic diseases : A population-based cohort study
- 2019
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Ingår i: PLoS Medicine. - : Public Library of Science (PLoS). - 1549-1277 .- 1549-1676. ; 16:9
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Tidskriftsartikel (refereegranskat)abstract
- Background Unfavorable psychosocial working conditions have been associated with cognitive decline and chronic diseases, both of which may subsequently accelerate functional dependence. This study aimed to investigate the association between job demand-control-support combinations and trajectories of disability in later life and to further explore the role of cognitive decline and the co-occurrence of chronic diseases in mediating this association. Methods and findings In this cohort study, 2,937 community dwellers aged 60+ years (mean age 73 +/- 10.6; 62.9% female) residing in the Kungsholmen District of Stockholm, Sweden, participated in the baseline survey (2001-2004) and were followed up to 12 years. Lifelong occupational history was obtained through a standardized interview; job demands, job control, and social support at work in the longest-held occupation were graded with a psychosocial job-exposure matrix. Job control, demands, and social support were dichotomized using the median values from the matrix, respectively, to further generate demand-control-support combinations. Disability was measured by summing the number of impaired basic and instrumental activities of daily living. Global cognitive function was assessed by Mini-Mental State Examination. Chronic conditions were ascertained by clinical examinations, medical history, and patient clinical records; the total number of chronic diseases was summed. Data were analyzed using linear mixed-effects models and mediation analysis. Age, sex, education, alcohol consumption, smoking, leisure activity engagement, early-life socioeconomic status, occupational characteristic and physical demands, and baseline cognitive function and number of chronic diseases were adjusted for in the analyses. Compared with active jobs (high control/high demands; n = 1,807), high strain (low control/high demands; n = 328), low strain (high control/low demands; n = 495), and passive jobs (low control/low demands; n = 307) were all associated with a faster rate of disability progression (beta = 0.07, 95% CI 0.02-0.13, p = 0.01; beta = 0.10, 95% CI 0.06-0.15, p < 0.001; beta = 0.11, 95% CI 0.05-0.18, p < 0.001). The association between high strain and disability progression was only shown in people with low social support at work (beta = 0.13, 95% CI 0.07-0.19, p < 0.001), but not in those with high social support (beta = 0.004, 95% CI -0.09 to 0.10, p = 0.93). Moreover, we estimated that the association between demand-control status and disability trajectories was mediated 38.5% by cognitive decline and 18.4% by accumulation of chronic diseases during the follow-up period. The limitations of this study include unmeasured confounding, self-reported work experience, and the reliance on a psychosocial job-exposure matrix that does not consider variabilities in individuals' perception on working conditions or job characteristics within occupations. Conclusions Our findings suggest that negative psychosocial working conditions during working life may accelerate disability progression in later life. Notably, social support at work may buffer the detrimental effect of high strain on disability progression. Cognitive decline and chronic-disease accumulation, and especially the former, partially mediate the association of psychosocial working conditions with trajectories of disability. Further studies are required to explore more mechanisms that underlie the association between psychosocial working conditions and disability trajectories. Author summaryWhy was this study done? Work is one of the activities that take up a considerable amount of time in our adult lives, thus potentially making it an important determinant of health, even in later life. Inability to independently carry out daily tasks (defined as disability) can affect older people's quality of life and pose a burden on caregivers and societies. A better understanding of the pathway between midlife working conditions and late-life disability may help the development of preventive strategies. What did the researchers do and find? We studied the association of psychosocial working conditions with the rate of disability progression over 12 years in a cohort of 2,937 individuals aged 60 years and older. We found that unfavorable psychosocial working conditions, including high-strain, low-strain, and passive jobs, were related to a faster rate of disability progression. The association of high-strain jobs with accelerated disability accumulation was only present among people with low social support at work. The decrement in cognitive function and increase in chronic-disease burden, and especially the former, partially explained the relationship between unfavorable working conditions and disability progression in later life. What do these findings mean? Unfavorable psychosocial working conditions during working life are related to the progression of disability in later life. Public health authorities, employers, and employees should all be aware of that. Social support at work is especially important in a high-strain work environment given its capacity to attenuate the impact of high-strain jobs on disability accumulation. Monitoring cognitive function and medical conditions of people with unfavorable working conditions is endorsed by the role of both dimensions, and especially of cognitive dysfunction, in accelerating disability progression in older age.
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