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  • 1. Kivimaki, Mika
    et al.
    Singh-Manoux, Archana
    Pentti, Jaana
    Sabia, Severine
    Nyberg, Solja T.
    Alfredsson, Lars
    Goldberg, Marcel
    Knutsson, Anders
    Koskenvuo, Markku
    Koskinen, Aki
    Kouvonen, Anne
    Nordin, Maria
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Oksanen, Tuula
    Strandberg, Timo
    Suominen, Sakari B.
    Theorell, Tores
    Vahtera, Jussi
    Vaananen, Ari
    Virtanen, Marianna
    Westerholm, Peter
    Westerlund, Hugo
    Zins, Marie
    Seshadri, Sudha
    Batty, G. David
    Sipila, Pyry N.
    Shipley, Martin J.
    Lindbohm, Joni V.
    Ferrie, Jane E.
    Jokela, Markus
    Physical inactivity, cardiometabolic disease, and risk of dementia: an individual-participant meta-analysis2019In: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 365, article id l1495Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE To examine whether physical inactivity is a risk factor for dementia, with attention to the role of cardiometabolic disease in this association and reverse causation bias that arises from changes in physical activity in the preclinical (prodromal) phase of dementia. DESIGN Meta-analysis of 19 prospective observational cohort studies. DATA SOURCES The Individual-Participant-Data Meta-analysis in Working Populations Consortium, the Inter-University Consortium for Political and Social Research, and the UK Data Service, including a total of 19 of a potential 9741 studies. REVIEW METHOD The search strategy was designed to retrieve individual-participant data from prospective cohort studies. Exposure was physical inactivity; primary outcomes were incident all-cause dementia and Alzheimer's disease; and the secondary outcome was incident cardiometabolic disease (that is, diabetes, coronary heart disease, and stroke). Summary estimates were obtained using random effects meta-analysis. RESULTS Study population included 404 840 people (mean age 45.5 years, 57.7% women) who were initially free of dementia, had a measurement of physical inactivity at study entry, and were linked to electronic health records. In 6.0 million person-years at risk, we recorded 2044 incident cases of all-cause dementia. In studies with data on dementia subtype, the number of incident cases of Alzheimer's disease was 1602 in 5.2 million person-years. When measured < 10 years before dementia diagnosis (that is, the preclinical stage of dementia), physical inactivity was associated with increased incidence of all-cause dementia (hazard ratio 1.40, 95% confidence interval 1.23 to 1.71) and Alzheimer's disease (1.36, 1.12 to 1.65). When reverse causation was minimised by assessing physical activity >= 10 years before dementia onset, no difference in dementia risk between physically active and inactive participants was observed (hazard ratios 1.01 (0.89 to 1.14) and 0.96 (0.85 to 1.08) for the two outcomes). Physical inactivity was consistently associated with increased risk of incident diabetes (hazard ratio 1.42, 1.25 to 1.61), coronary heart disease (1.24, 1.13 to 1.36), and stroke (1.16, 1.05 to 1.27). Among people in whom cardiometabolic disease preceded dementia, physical inactivity was non-significantly associated with dementia (hazard ratio for physical activity assessed > 10 before dementia onset 1.30, 0.79 to 2.14). CONCLUSIONS In analyses that addressed bias due to reverse causation, physical inactivity was not associated with all-cause dementia or Alzheimer's disease, although an indication of excess dementia risk was observed in a subgroup of physically inactive individuals who developed cardiometabolic disease.

  • 2. Kivimäki, Mika
    et al.
    Luukkonen, Ritva
    Batty, G. David
    Ferrie, Jane E.
    Pentti, Jaana
    Nyberg, Solja T.
    Shipley, Martin J.
    Alfredsson, Lars
    Fransson, Eleonor I.
    Goldberg, Marcel
    Knutsson, Anders
    Koskenvuo, Markku
    Kuosma, Eeva
    Nordin, Maria
    Umeå University, Faculty of Social Sciences, Department of Psychology. Division of Epidemiology, Stress Research Institute, Stockholm University, Stockholm, Sweden.
    Suominen, Sakari B.
    Theorell, Töres
    Vuoksimaa, Eero
    Westerholm, Peter
    Westerlund, Hugo
    Zins, Marie
    Kivipelto, Miia
    Vahtera, Jussi
    Kaprio, Jaakko
    Singh-Manoux, Archana
    Umeå University, Faculty of Social Sciences, Department of Psychology. Department of Epidemiology and Public Health, University College London, London, UK; Population-based Epidemiologic Cohort Unit, UMS 011, Inserm, Villejuif, France.
    Jokela, Markus
    Umeå University, Faculty of Social Sciences, Department of Psychology. Institute of Behavioral Sciences, University of Helsinki, Helsinki, Finland.
    Body mass index and risk of dementia: Analysis of individual-level data from 1.3 million individuals2018In: Alzheimer's & Dementia, ISSN 1552-5260, E-ISSN 1552-5279, Vol. 14, no 5, p. 601-609Article in journal (Refereed)
    Abstract [en]

    Introduction: Higher midlife body mass index (BMI) is suggested to increase the risk of dementia, but weight loss during the preclinical dementia phase may mask such effects. Methods: We examined this hypothesis in 1,349,857 dementia-free participants from 39 cohort studies. BMI was assessed at baseline. Dementia was ascertained at follow-up using linkage to electronic health records (N = 6894). We assumed BMI is little affected by preclinical dementia when assessed decades before dementia onset and much affected when assessed nearer diagnosis. Results: Hazard ratios per 5-kg/m(2) increase in BMI for dementia were 0.71 (95% confidence interval = 0.66-0.77), 0.94 (0.89-0.99), and 1.16 (1.05-1.27) when BMI was assessed 10 years, 10-20 years, and >20 years before dementia diagnosis. Conclusions: The association between BMI and dementia is likely to be attributable to two different processes: a harmful effect of higher BMI, which is observable in long follow-up, and a reverse-causation effect that makes a higher BMI to appear protective when the follow-up is short. 

  • 3. Nyberg, Solja T.
    et al.
    Batty, G. David
    Pentti, Jaana
    Virtanen, Marianna
    Alfredsson, Lars
    Fransson, Eleonor I.
    Goldberg, Marcel
    Heikkila, Katriina
    Jokela, Markus
    Knutsson, Anders
    Koskenvuo, Markku
    Lallukka, Tea
    Leineweber, Constanze
    Lindbohm, Joni V.
    Madsen, Ida E. H.
    Hanson, Linda L. Magnusson
    Nordin, Maria
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Oksanen, Tuula
    Pietilainen, Olli
    Rahkonen, Ossi
    Rugulies, Reiner
    Shipley, Martin J.
    Stenholm, Sari
    Suominen, Sakari
    Theorell, Tores
    Vahtera, Jussi
    Westerholm, Peter J. M.
    Westerlund, Hugo
    Zins, Marie
    Hamer, Mark
    Singh-Manoux, Archana
    Bell, Joshua A.
    Ferrie, Jane E.
    Kivimaki, Mika
    Obesity and loss of disease-free years owing to major non-communicable diseases: a multicohort study2018In: The Lancet Public Health, ISSN 2468-2667, Vol. 3, no 10, p. E490-E497Article in journal (Refereed)
    Abstract [en]

    Background Obesity increases the risk of several chronic diseases, but the extent to which the obesity-related loss of disease-free years varies by lifestyle category and across socioeconomic groups is unclear. We estimated the number of years free from major non-communicable diseases in adults who are overweight and obese, compared with those who are normal weight.

    Methods We pooled individual-level data on body-mass index (BMI) and non-communicable diseases from men and women with no initial evidence of these diseases in European cohort studies from the Individual-Participant-Data Meta-Analysis in Working Populations consortium. BMI was assessed at baseline (1991-2008) and non-communicable diseases (incident type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease) were ascertained via linkage to records from national health registries, repeated medical examinations, or self-report. Disease-free years from age 40 years to 75 years associated with underweight (BMI <18.5 kg/m(2)), overweight (>= 25 kg/m(2) to <30 kg/m(2)), and obesity (class I [mild] >= 30 kg/m(2) to < 35 kg/m(2); class II-III [severe] >= 35 kg/m(2)) compared with normal weight (>= 18.5 kg/m(2) to <25 kg/m(2)) were estimated.

    Findings Of 137 503 participants from ten studies, we excluded 6973 owing to missing data and 10 349 with prevalent disease at baseline, resulting in an analytic sample of 120 181 participants. Of 47 127 men, 211 (0.4%) were underweight, 21 468 (45.6%) normal weight, 20 738 (44.0%) overweight, 3982 (8.4%) class I obese, and 728 (1.5%) class II-III obese. The corresponding numbers among the 73 054 women were 1493 (2.0%), 44 760 (61.3%), 19 553 (26.8%), 5670 (7.8%), and 1578 (2.2%), respectively. During 1 328 873 person-years at risk (mean follow-up 11.5 years [range 6.3-18.6]), 8159 men and 8100 women developed at least one non-communicable disease. Between 40 years and 75 years, the estimated number of disease-free years was 29.3 (95% CI 28.8-29.8) in normal-weight men and 29.4 (28.7-30.0) in normal-weight women. Compared with normal weight, the loss of disease-free years in men was 1.8 (95% CI -1.3 to 4.9) for underweight, 1.1 (0.7 to 1.5) for overweight, 3.9 (2.9 to 4.9) for class I obese, and 8.5 (7.1 to 9.8) for class II-III obese. The corresponding estimates for women were 0.0 (-1.4 to 1.4) for underweight, 1.1 (0.6 to 1.5) for overweight, 2.7 (1.5 to 3.9) for class I obese, and 7.3 (6.1 to 8.6) for class II-III obese. The loss of disease-free years associated with class II-III obesity varied between 7.1 and 10.0 years in subgroups of participants of different socioeconomic level, physical activity level, and smoking habit.

    Interpretation Mild obesity was associated with the loss of one in ten, and severe obesity the loss of one in four potential disease-free years during middle and later adulthood. This increasing loss of disease-free years as obesity becomes more severe occurred in both sexes, among smokers and non-smokers, the physically active and inactive, and across the socioeconomic hierarchy. 

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