Cognitive stimulation in the workplace, plasma proteins, and risk of dementia: three analyses of population cohort studies

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Cognitive stimulation in the workplace, plasma proteins, and risk of dementia : three analyses of population cohort studies

Kivimäki, Mika (author): Department of Epidemiology and Public Health, University College London, London, UK ; Clinicum, Faculty of Medicine, University of Helsinki, Finland ; Finnish Institute of Occupational Health, Helsinki, Finland,UCL, Dept Epidemiol & Publ Hlth, London, England.;Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland.;Finnish Inst Occupat Hlth, Helsinki, Finland.

Walker, Keenan A. (author): Department of Neurology, The Johns Hopkins University, Baltimore, MD, USA ; Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA,Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.;NIA, Lab Behav Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.

Pentti, Jaana (author): Clinicum, Faculty of Medicine, University of Helsinki, Finland ; Finnish Institute of Occupational Health, Helsinki, Finland ; Department of Public Health, University of Turku, Finland,Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland.;Finnish Inst Occupat Hlth, Helsinki, Finland.;Univ Turku, Dept Publ Hlth, Turku, Finland.

Theorell, Töres (author): Karolinska Institutet,Stockholms universitet,Stressforskningsinstitutet,Stockholm Univ, Stress Res Inst, Stockholm, Sweden.

Mars, Nina (author): Institute for Molecular Medicine Finland, HiLIFE, University of Helsinki, Finland,Univ Helsinki, Inst Mol Med Finland, HiLIFE, Helsinki, Finland.

Vahtera, Jussi (author): Department of Public Health, University of Turku, Finland ; Centre for Population Health Research, University of Turku and Turku University Hospital, Finland,Univ Turku, Dept Publ Hlth, Turku, Finland.;Univ Turku, Ctr Populat Hlth Res, Turku, Finland.;Turku Univ Hosp, Turku, Finland.

Suominen, Sakari (author): Högskolan i Skövde,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Department of Public Health, University of Turku, Finland,Medborgarcentrerad hälsa (MeCH), Research on Citizen Centered Health, University of Skövde (Reacch US),Univ Turku, Dept Publ Hlth, Turku, Finland.;Univ Skövde, Sch Hlth Sci, Skövde, Sweden.

Lallukka, Tea (author): Clinicum, Faculty of Medicine, University of Helsinki, Finland,Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland.

Rahkonen, Ossi (author): Clinicum, Faculty of Medicine, University of Helsinki, Finland,Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland.

Pietiläinen, Olli (author): Clinicum, Faculty of Medicine, University of Helsinki, Finland,Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland.

Koskinen, Aki (author): Finnish Institute of Occupational Health, Helsinki, Finland,Finnish Inst Occupat Hlth, Helsinki, Finland.

Väänänen, Ari (author): Finnish Institute of Occupational Health, Helsinki, Finland,Finnish Inst Occupat Hlth, Helsinki, Finland.

Kalsi, Jatinderpal K. (author): Department of Epidemiology and Public Health, University College London, UK,UCL, Dept Epidemiol & Publ Hlth, London, England.

Goldberg, Marcel (author): Inserm UMS 011, Population-Based Epidemiological Cohorts Unit, Villejuif, France ; Université de Paris, INSERM U1153, Epidemiology of Ageing and Neurodegenerative Diseases, Paris, France,INSERM, UMS 011, Populat Based Epidemiol Cohorts Unit, Villejuif, France.;Univ Paris, INSERM U1153, Epidemiol Ageing & Neurodegenerat Dis, Paris, France.

Zins, Marie (author): Inserm UMS 011, Population-Based Epidemiological Cohorts Unit, Villejuif, France ; Université de Paris, INSERM U1153, Epidemiology of Ageing and Neurodegenerative Diseases, Paris, France,INSERM, UMS 011, Populat Based Epidemiol Cohorts Unit, Villejuif, France.;Univ Paris, INSERM U1153, Epidemiol Ageing & Neurodegenerat Dis, Paris, France.

Alfredsson, Lars (author): Karolinska Institutet

Westerholm, Peter (author): Uppsala universitet,Arbets- och miljömedicin,Uppsala Univ, Dept Med Sci, Uppsala, Sweden.

Knutsson, Anders, 1942- (author): Mittuniversitetet,Institutionen för hälsovetenskap,Department of Health Sciences, Mid Sweden University, Sundsvall, Sweden,Mid Sweden Univ, Dept Hlth Sci, Sundsvall, Sweden.

Theorell, Töres (author): Stress Research Institute, Stockholm University, Sweden

Ervasti, Jenni (author): Finnish Institute of Occupational Health, Helsinki, Finland,Finnish Inst Occupat Hlth, Helsinki, Finland.

Oksanen, Tuula (author): Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland,Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.

Sipilä, Pyry N. (author): Clinicum, Faculty of Medicine, University of Helsinki, Finland,Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland.

Tabak, Adam G. (author): Department of Epidemiology and Public Health, University College London, UK ; Department of Internal Medicine and Oncology and Department of Public Health, Semmelweis University, Budapest, Hungary,UCL, Dept Epidemiol & Publ Hlth, London, England.;Semmelweis Univ, Dept Internal Med & Oncol, Budapest, Hungary.;Semmelweis Univ, Dept Publ Hlth, Budapest, Hungary.

Ferrie, Jane E. (author): Department of Epidemiology and Public Health, University College London, UK ; Bristol Medical School, University of Bristol, UK,UCL, Dept Epidemiol & Publ Hlth, London, England.;Univ Bristol, Bristol Med Sch, Bristol, Avon, England.

Williams, Stephen A. (author): SomaLogic, Boulder, CO, USA

Livingston, Gill (author): Division of Psychiatry, University College London, UK ; Camden and Islington NHS Foundation Trust, London, UK,UCL, Div Psychiat, London, England.;Camden & Islington NHS Fdn Trust, London, England.

Gottesman, Rebecca F. (author): Department of Neurology, The Johns Hopkins University, Baltimore, MD, USA,Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.

Singh-Manoux, Archana (author): Department of Epidemiology and Public Health, University College London, UK ; Université de Paris, INSERM U1153, Epidemiology of Ageing and Neurodegenerative Diseases, Paris, France,UCL, Dept Epidemiol & Publ Hlth, London, England.;Univ Paris, INSERM U1153, Epidemiol Ageing & Neurodegenerat Dis, Paris, France.

Zetterberg, Henrik, 1973 (author): Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi,Institute of Neuroscience and Physiology

Lindbohm, Joni V. (author): Department of Epidemiology and Public Health, University College London, UK ; Clinicum, Faculty of Medicine, University of Helsinki, Finland,UCL, Dept Epidemiol & Publ Hlth, London, England.;Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland.

Nyberg, Solja (author): Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland.

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Department of Epidemiology and Public Health, University College London, London, UK ; Clinicum, Faculty of Medicine, University of Helsinki, Finland ; Finnish Institute of Occupational Health, Helsinki, Finland UCL, Dept Epidemiol & Publ Hlth, London, England;Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland.;Finnish Inst Occupat Hlth, Helsinki, Finland. (creator_code:org_t)

2021-08-18
2021
English.
In: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833. ; 374

Related links:: https://doi.org/10.1...; show more...; https://his.diva-por... (primary) (Raw object); https://www.bmj.com/...; https://miun.diva-po... (primary) (Raw object); https://uu.diva-port... (primary) (Raw object); https://urn.kb.se/re...; https://doi.org/10.1...; https://urn.kb.se/re...; https://urn.kb.se/re...; https://urn.kb.se/re...; http://kipublication...; https://gup.ub.gu.se...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

OBJECTIVES: To examine the association between cognitively stimulating work and subsequent risk of dementia and to identify protein pathways for this association.DESIGN: Multicohort study with three sets of analyses.SETTING: United Kingdom, Europe, and the United States.PARTICIPANTS: Three associations were examined: cognitive stimulation and dementia risk in 107 896 participants from seven population based prospective cohort studies from the IPD-Work consortium (individual participant data meta-analysis in working populations); cognitive stimulation and proteins in a random sample of 2261 participants from one cohort study; and proteins and dementia risk in 13 656 participants from two cohort studies.MAIN OUTCOME MEASURES: Cognitive stimulation was measured at baseline using standard questionnaire instruments on active versus passive jobs and at baseline and over time using a job exposure matrix indicator. 4953 proteins in plasma samples were scanned. Follow-up of incident dementia varied between 13.7 to 30.1 years depending on the cohort. People with dementia were identified through linked electronic health records and repeated clinical examinations.RESULTS: During 1.8 million person years at risk, 1143 people with dementia were recorded. The risk of dementia was found to be lower for participants with high compared with low cognitive stimulation at work (crude incidence of dementia per 10 000 person years 4.8 in the high stimulation group and 7.3 in the low stimulation group, age and sex adjusted hazard ratio 0.77, 95% confidence interval 0.65 to 0.92, heterogeneity in cohort specific estimates I2=0%, P=0.99). This association was robust to additional adjustment for education, risk factors for dementia in adulthood (smoking, heavy alcohol consumption, physical inactivity, job strain, obesity, hypertension, and prevalent diabetes at baseline), and cardiometabolic diseases (diabetes, coronary heart disease, stroke) before dementia diagnosis (fully adjusted hazard ratio 0.82, 95% confidence interval 0.68 to 0.98). The risk of dementia was also observed during the first 10 years of follow-up (hazard ratio 0.60, 95% confidence interval 0.37 to 0.95) and from year 10 onwards (0.79, 0.66 to 0.95) and replicated using a repeated job exposure matrix indicator of cognitive stimulation (hazard ratio per 1 standard deviation increase 0.77, 95% confidence interval 0.69 to 0.86). In analysis controlling for multiple testing, higher cognitive stimulation at work was associated with lower levels of proteins that inhibit central nervous system axonogenesis and synaptogenesis: slit homologue 2 (SLIT2, fully adjusted β -0.34, P<0.001), carbohydrate sulfotransferase 12 (CHSTC, fully adjusted β -0.33, P<0.001), and peptidyl-glycine α-amidating monooxygenase (AMD, fully adjusted β -0.32, P<0.001). These proteins were associated with increased dementia risk, with the fully adjusted hazard ratio per 1 SD being 1.16 (95% confidence interval 1.05 to 1.28) for SLIT2, 1.13 (1.00 to 1.27) for CHSTC, and 1.04 (0.97 to 1.13) for AMD.CONCLUSIONS: The risk of dementia in old age was found to be lower in people with cognitively stimulating jobs than in those with non-stimulating jobs. The findings that cognitive stimulation is associated with lower levels of plasma proteins that potentially inhibit axonogenesis and synaptogenesis and increase the risk of dementia might provide clues to underlying biological mechanisms.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Public Health, Global Health, Social Medicine and Epidemiology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)

Keyword

alzheimer's disease
complexity
strain
model
Research on Citizen Centered Health, University of Skövde (Reacch US)
Medborgarcentrerad hälsa (Mech)
alzheimers-disease
complexity
strain
model
General & Internal Medicine

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art (subject category)

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Health Sciences; and Public Health Gl ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Neurosciences

Articles in the publication: The BMJ

By the university: University of Skövde; Mid Sweden University; Stockholm University; Uppsala University; Karolinska Institutet; University of Gothenburg

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