المؤلفون: Nyberg, Solja T., Singh-Manoux, Archana, Pentti, Jaana, Madsen, Ida E. H., Sabia, Severine, Alfredsson, Lars, Bjorner, Jakob B., Borritz, Marianne, Burr, Hermann, Goldberg, Marcel, Heikkila, Katriina, Jokela, Markus, Knutsson, Anders, Lallukka, Tea, Lindbohm, Joni, Nielsen, Martin L., Nordin, Maria, Oksanen, Tuula, Pejtersen, Jan H., Rahkonen, Ossi, Rugulies, Reiner, Shipley, Martin J., Sipila, Pyry N., Stenholm, Sari, Suominen, Sakari, Vahtera, Jussi, Virtanen, Marianna, Westerlund, Hugo, Zins, Marie, Hamer, Mark, Batty, G. David, Kivimaki, Mika

المصدر: JAMA Internal Medicine. 180(5):760-768

مصطلحات موضوعية: life style risk factors, chronic disease, multicohort, Psychology, psykologi

الوصف: This cohort study examines disease-free life-years in participants with varying combinations of lifestyle risk factors.Question: Are different combinations of lifestyle factors associated with years lived without chronic diseases?Findings: In a multicohort study of 116 & x202f;043 participants, a statistically significant association between overall healthy lifestyle score and an increased number of disease-free life-years was noted. Of 16 different lifestyle profiles studied, the 4 that were associated with the greatest disease-free life years included body mass index lower than 25 and at least 2 of 3 factors: never smoking, physical activity, and moderate alcohol consumption.Meaning: Various healthy lifestyle profiles appear to be associated with extended gains in life lived without type 2 diabetes, cardiovascular and respiratory diseases, and cancer.Importance: It is well established that selected lifestyle factors are individually associated with lower risk of chronic diseases, but how combinations of these factors are associated with disease-free life-years is unknown.Objective: To estimate the association between healthy lifestyle and the number of disease-free life-years.Design, Setting, and Participants: A prospective multicohort study, including 12 European studies as part of the Individual-Participant-Data Meta-analysis in Working Populations Consortium, was performed. Participants included 116 & x202f;043 people free of major noncommunicable disease at baseline from August 7, 1991, to May 31, 2006. Data analysis was conducted from May 22, 2018, to January 21, 2020.Exposures: Four baseline lifestyle factors (smoking, body mass index, physical activity, and alcohol consumption) were each allocated a score based on risk status: optimal (2 points), intermediate (1 point), or poor (0 points) resulting in an aggregated lifestyle score ranging from 0 (worst) to 8 (best). Sixteen lifestyle profiles were constructed from combinations of these risk factors.Main Outcomes and Measures: The number of years between ages 40 and 75 years without chronic disease, including type 2 diabetes, coronary heart disease, stroke, cancer, asthma, and chronic obstructive pulmonary disease.Results: Of the 116 & x202f;043 people included in the analysis, the mean (SD) age was 43.7 (10.1) years and 70 & x202f;911 were women (61.1%). During 1.45 million person-years at risk (mean follow-up, 12.5 years; range, 4.9-18.6 years), 17 & x202f;383 participants developed at least 1 chronic disease. There was a linear association between overall healthy lifestyle score and the number of disease-free years, such that a 1-point improvement in the score was associated with an increase of 0.96 (95% CI, 0.83-1.08) disease-free years in men and 0.89 (95% CI, 0.75-1.02) years in women. Comparing the best lifestyle score with the worst lifestyle score was associated with 9.9 (95% CI 6.7-13.1) additional years without chronic diseases in men and 9.4 (95% CI 5.4-13.3) additional years in women (P < .001 for dose-response). All of the 4 lifestyle profiles that were associated with the highest number of disease-free years included a body-mass index less than 25 (calculated as weight in kilograms divided by height in meters squared) and at least 2 of the following factors: never smoking, physical activity, and moderate alcohol consumption. Participants with 1 of these lifestyle profiles reached age 70.3 (95% CI, 69.9-70.8) to 71.4 (95% CI, 70.9-72.0) years disease free depending on the profile and sex.Conclusions and Relevance: In this multicohort analysis, various healthy lifestyle profiles appeared to be associated with gains in life-years without major chronic diseases.

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الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-183135Test
https://doi.org/10.1001/jamainternmed.2020.0618Test

المؤلفون: Nyberg, Solja T., Batty, G. David, Pentti, Jaana, Madsen, Ida E. H., Alfredsson, Lars, Bjorner, Jakob B., Borritz, Marianne, Burr, Hermann, Ervasti, Jenni, Goldberg, Marcel, Jokela, Markus, Knutsson, Anders, 1942, Koskinen, Aki, Lallukka, Tea, Lindbohm, Joni, V, Nielsen, Martin L., Oksanen, Tuula, Pejtersen, Jan H., Pietilainen, Olli, Rahkonen, Ossi, Rugulies, Reiner, Shipley, Martin J., Sipila, Pyry N., Sorensen, Jeppe K., Stenholm, Sari, Suominen, Sakari, Vaananen, Ari, Vahtera, Jussi, Virtanen, Marianna, Westerlund, Hugo, Zins, Marie, Singh-Manoux, Archana, Kivimaki, Mika

المصدر: The Lancet Regional Health. 19

مصطلحات موضوعية: Alcohol consumption, Binge drinking, Disease free life years, Chronic diseases

الوصف: Background Heavy alcohol consumption increases the risk of several chronic diseases. In this multicohort study, we estimated the number of life-years without major chronic diseases according to different characteristics of alcohol use. Methods In primary analysis, we pooled individual-level data from up to 129,942 adults across 12 cohort studies with baseline data collection on alcohol consumption, drinking patterns, and history between 1986 and 2005 (the IPD-Work Consortium). Self-reported alcohol consumption was categorised according to UK guidelines - non-drinking (never or former drinkers); moderate consumption (1-14 units); heavy consumption (>14 units per week). We further subdivided moderate and heavy drinkers by binge drinking pattern (alcohol-induced loss of consciousness). In addition, we assessed problem drinking using linked data on hospitalisations due to alcohol abuse or poisoning. Follow-up for chronic diseases for all participants included incident type 2 diabetes, coronary heart disease, stroke, cancer, and respiratory disease (asthma and chronic obstructive pulmonary disease) as ascertained via linkage to national morbidity and mortality registries, repeated medical examinations, and/or self-report. We estimated years lived without any of these diseases between 40 and 75 years of age according to sex and characteristics of alcohol use. We repeated the main analyses using data from 427,621 participants in the UK Biobank cohort study. Findings During 1.73 million person-years at risk, 22,676 participants in IPD-Work cohorts developed at least one chronic condition. From age 40 to 75 years, never-drinkers [men: 29.3 (95%CI 27.9-30.8) years, women 29.8 (29.2 - 30.4) years)] and moderate drinkers with no binge drinking habit [men 28.7 (28.4-29.0) years, women 29.6 (29.4-29.7) years] had the longest disease-free life span. A much shorter disease-free life span was apparent in participants who experienced alcohol poisoning [men 23.4 (20.9-26.0) years, women 24.0 (21.4-26.5) years] and those with self-reported heavy overall consumption and binge drinking [men: 26.0 (25.3-26.8), women 27.5 (26.4 - 28.5) years]. The pattern of results for alcohol poisoning and self-reported alcohol consumption was similar in UK Biobank. In IPD-Work and UK Biobank, differences in disease-free years between self-reported moderate drinkers and heavy drinkers were 1.5 years or less. Interpretation Individuals with alcohol poisonings or heavy self-reported overall consumption combined with a binge drinking habit have a marked 3- to 6-year loss in healthy longevity. Differences in disease-free life between categories of self-reported weekly alcohol consumption were smaller.

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الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-45886Test
https://doi.org/10.1016/j.lanepe.2022.100417Test

المؤلفون: Kivimaki, Mika, Walker, Keenan A., Pentti, Jaana, Nyberg, Solja, Mars, Nina, Vahtera, Jussi, Suominen, Sakari B., Lallukka, Tea, Rahkonen, Ossi, Pietilainen, Olli, Koskinen, Aki, Vaananen, Ari, Kalsi, Jatinderpal K., Goldberg, Marcel, Zins, Marie, Alfredsson, Lars, Westerholm, Peter J. M., Knutsson, Anders, 1942, Theorell, Tores, Ervasti, Jenni, Oksanen, Tuula, Sipila, Pyry N., Tabak, Adam G., Ferrie, Jane E., Williams, Stephen A., Livingston, Gill, Gottesman, Rebecca F., Singh-Manoux, Archana, Zetterberg, Henrik, Lindbohm, Joni, V

المصدر: The BMJ. 374

الوصف: 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 r3 -0.34, P(0.001), carbohydrate sulfotransferase 12 (CHSTC, fully adjusted r3 -0.33, P(0.001), and peptidyl-glycine alpha-amidating monooxygenase (AMD, fully adjusted r3 -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

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-42930Test
https://doi.org/10.1136/bmj.n1804Test
https://miun.diva-portal.org/smash/get/diva2:1590336/FULLTEXT01.pdfTest

المؤلفون: Kivimaki, Mika, Singh-Manoux, Archana, Pentti, Jaana, Sabia, Severine, Nyberg, Solja T., Alfredsson, Lars, Goldberg, Marcel, Knutsson, Anders, Koskenvuo, Markku, Koskinen, Aki, Kouvonen, Anne, Nordin, Maria, 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

المصدر: The BMJ. 365

الوصف: 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.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-158952Test
https://doi.org/10.1136/bmj.l1495Test
https://umu.diva-portal.org/smash/get/diva2:1318306/FULLTEXT01.pdfTest

المؤلفون: Kivimaki, Mika, Singh-Manoux, Archana, Batty, G. David, Sabia, Severine, Sommerlad, Andrew, Floud, Sarah, Jokela, Markus, Vahtera, Jussi, Beydoun, May A., Suominen, Sakari B., Koskinen, Aki, Vaananen, Ari, Goldberg, Marcel, Zins, Marie, Alfredsson, Lars, Westerholm, Peter, Knutsson, Anders, Nyberg, Solja T., Sipila, Pyry N., Lindbohm, Joni V., Pentti, Jaana, Livingston, Gill, Ferrie, Jane E., Strandberg, Timo

المصدر: JAMA Network Open. 3(9)

الوصف: This cohort study examines the association of overall consumption of alcohol and resultant loss of consciousness with risk for dementia. Question Are alcohol-induced loss of consciousness and heavy weekly alcohol consumption associated with increased risk of future dementia? Findings In this multicohort study of 131x202f;415 adults, a 1.2-fold excess risk of dementia was associated with heavy vs moderate alcohol consumption. Those who reported having lost consciousness due to alcohol consumption, regardless of their overall weekly consumption, had a 2-fold increased risk of dementia compared with people who had not lost consciousness and were moderate drinkers. Meaning The findings of this study suggest that alcohol-induced loss of consciousness is a long-term risk factor for dementia among both heavy and moderate drinkers. Importance Evidence on alcohol consumption as a risk factor for dementia usually relates to overall consumption. The role of alcohol-induced loss of consciousness is uncertain. Objective To examine the risk of future dementia associated with overall alcohol consumption and alcohol-induced loss of consciousness in a population of current drinkers. Design, Setting, and Participants Seven cohort studies from the UK, France, Sweden, and Finland (IPD-Work consortium) including 131x202f;415 participants were examined. At baseline (1986-2012), participants were aged 18 to 77 years, reported alcohol consumption, and were free of diagnosed dementia. Dementia was examined during a mean follow-up of 14.4 years (range, 12.3-30.1). Data analysis was conducted from November 17, 2019, to May 23, 2020. Exposures Self-reported overall consumption and loss of consciousness due to alcohol consumption were assessed at baseline. Two thresholds were used to define heavy overall consumption: greater than 14 units (U) (UK definition) and greater than 21 U (US definition) per week. Main Outcomes and Measures Dementia and alcohol-related disorders to 2016 were ascertained from linked electronic health records. Results Of the 131x202f;415 participants (mean [SD] age, 43.0 [10.4] years; 80x202f;344 [61.1%] women), 1081 individuals (0.8%) developed dementia. After adjustment for potential confounders, the hazard ratio (HR) was 1.16 (95% CI, 0.98-1.37) for consuming greater than 14 vs 1 to 14 U of alcohol per week and 1.22 (95% CI, 1.01-1.48) for greater than 21 vs 1 to 21 U/wk. Of the 96x202f;591 participants with data on loss of consciousness, 10x202f;004 individuals (10.4%) reported having lost consciousness due to alcohol consumption in the past 12 months. The association between loss of consciousness and dementia was observed in men (HR, 2.86; 95% CI, 1.77-4.63) and women (HR, 2.09; 95% CI, 1.34-3.25) during the first 10 years of follow-up (HR, 2.72; 95% CI, 1.78-4.15), after excluding the first 10 years of follow-up (HR, 1.86; 95% CI, 1.16-2.99), and for early-onset (<65 y: HR, 2.21; 95% CI, 1.46-3.34) and late-onset (>= 65 y: HR, 2.25; 95% CI, 1.38-3.66) dementia, Alzheimer disease (HR, 1.98; 95% CI, 1.28-3.07), and dementia with features of atherosclerotic cardiovascular disease (HR, 4.18; 95% CI, 1.86-9.37). The association with dementia was not explained by 14 other alcohol-related conditions. With moderate drinkers (1-14 U/wk) who had not lost consciousness as the reference group, the HR for dementia was twice as high in participants who reported having lost consciousness, whether their mean weekly consumption was moderate (HR, 2.19; 95% CI, 1.42-3.37) or heavy (HR, 2.36; 95% CI, 1.57-3.54). Conclusions and Relevance The findings of this study suggest that alcohol-induced loss of consciousness, irrespective of overall alcohol consumption, is associated with a subsequent increase in the risk of dementia.

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الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-423363Test

المؤلفون: Elovainio, Marko, Komulainen, Kaisla, Sipila, Pyry N., Pulkki-Raback, Laura, Alonso, Laura Cachon, Pentti, Jaana, Nyberg, Solja, Suominen, Sakari, Vahtera, Jussi, Lipsanen, Jari, Batty, G. David, Hakulinen, Christian, Kivimaki, Mika

المصدر: WOS ; WOS:001029344500001

وصف الملف: e109-e118

العلاقة: LANCET PUBLIC HEALTH; https://www.julkari.fi/handle/10024/147026Test

الإتاحة: https://www.julkari.fi/handle/10024/147026Test

المؤلفون: Sipila, Pyry N., Heikkila, Nelli, Lindbohm, Joni, V, Hakulinen, Christian, Vahtera, Jussi, Elovainio, Marko, Suominen, Sakari, Vaananen, Ari, Koskinen, Aki, Nyberg, Solja T., Pentti, Jaana, Strandberg, Timo E., Kivimaki, Mika

المصدر: WOS ; WOS:000723826500033

وصف الملف: 1557-1567

العلاقة: LANCET INFECTIOUS DISEASES; 11; 21; https://www.julkari.fi/handle/10024/143504Test

الإتاحة: https://www.julkari.fi/handle/10024/143504Test

المؤلفون: Sipila, Pyry N., Lindbohm, Joni, V, Singh-Manoux, Archana, Shipley, Martin J., Kiiskinen, Tuomo, Havulinna, Aki S., Vahtera, Jussi, Nyberg, Solja T., Pentti, Jaana, Kivimaki, Mika

المصدر: WOS ; WOS:000623277800007 ; WOS:000626325900001

مصطلحات موضوعية: cohort studies, dementia, disease, hospitalization, risk factors

الوصف: First published 04 September 2020

وصف الملف: 1686-1695

العلاقة: ALZHEIMERS & DEMENTIA; 12; 16; https://www.julkari.fi/handle/10024/141054Test

الإتاحة: https://www.julkari.fi/handle/10024/141054Test

المؤلفون: Siikamaki, Heli M., Kivela, Pia S., Sipila, Pyry N., Kettunen, Annikaisa, Kainulainen, M. Katariina, Ollgren, Jukka P., Kantele, Anu

المصدر: WOS

وصف الملف: 239-244

العلاقة: JOURNAL OF TRAVEL MEDICINE; 18; 786KU; http://www.julkari.fi/handle/10024/109504Test; WOS:000292307800004

الإتاحة: http://www.julkari.fi/handle/10024/109504Test

المؤلفون: Kivima¨ki, Mika, Walker, Keenan A, Pentti, Jaana, Nyberg, Solja T, Mars, Nina, Vahtera, Jussi, Suominen, Sakari B, Lallukka, Tea, Rahkonen, Ossi, Pietila¨inen, Olli, Koskinen, Aki, Va¨a¨na¨nen, Ari, Kalsi, Jatinderpal K, Goldberg, Marcel, Zins, Marie, Alfredsson, Lars, Westerholm, Peter J M, Knutsson, Anders, Theorell, To¨res, Ervasti, Jenni, Oksanen, Tuula, Sipila¨, Pyry N, Tabak, Adam G, Ferrie, Jane E, Williams, Stephen A, Livingston, Gill, Gottesman, Rebecca F, Singh-Manoux, Archana, Zetterberg, Henrik, Lindbohm, Joni V

المصدر: BMJ (British Medical Journal); 2021, Vol. 374 Issue: 8 pn1804-n1804, 1p

مستخلص: ObjectivesTo examine the association between cognitively stimulating work and subsequent risk of dementia and to identify protein pathways for this association.DesignMulticohort study with three sets of analyses.SettingUnited Kingdom, Europe, and the United States.ParticipantsThree 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 measuresCognitive 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.ResultsDuring 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.ConclusionsThe 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.