Dementia Risk Lower in Patients with Cognitively Stimulating Jobs Interview with:


Prof Kivimaki

Prof Mika Kivimaki PhD
Director, Whitehall II Study
Dept. of Epidemiology
University College London What is the background for this study?

Response: The Lancet 2020 Commission on Dementia Prevention, which is the most comprehensive and up-to-date review on the evidence in this field, did not list cognitive stimulation in adulthood as a protective factor against dementia. This was because trials results are inconsistent and observational studies suggest that leisure time cognitive activity does not reduce risk of dementia.

However, it was unclear whether the reason for modest findings is that the decrease in brain plasticity with age prevents cognitive activities across adult life from conferring protection against dementia, or, in the case of interventions, that the cognitive stimulation studied has not been intensive or engaging enough to preserve cognitive function.

To address this question, we decided to focus on cognitive stimulation at work rather than leisure time cognitive activity or cognitive interventions. We thought that this approach would allow us to detect an effect, if there is one, because exposure to cognitive stimulation at work typically lasts considerably longer than cognitively stimulating hobbies or cognitive interventions.

We contacted 13 cohort studies in Europe which had data on cognitive stimulation at work. Seven had also a dementia follow-up and were selected to our analyses, a total of 107 896 dementia-free participants from the UK, France, Sweden and Finland. Follow-up of incident dementia varied between 13.7 to 30.1 years depending on the cohort. 1143 people developed dementia during this follow-up. What are the main findings?

Response: We found that the risk of dementia in old age was approximately 20% lower in individuals with cognitively stimulating jobs than in those with non-stimulating jobs. This association was stronger for Alzheimer’s disease than for other dementias.

To better understand the nature of this association, we analysed proteins levels using stored blood samples of 759 participants in high stimulating, 949 in medium stimulating, and 553 in low stimulating jobs and found clear differences in 6 proteins. Of them, three were also associated with dementia risk. According to previous animal studies, these proteins affect the way brain cells form new connections, i.e. processes called axonogenesis and synaptogenesis. If this were also the case in humans, our protein findings might provide clues to biological mechanisms underlying the association between cognitive stimulation and reduced dementia risk. What should readers take away from your report?

Response: Our observational findings support the hypothesis that cognitive stimulation in adulthood may postpone the onset of dementia. The cumulative incidence of dementia at age 80 in the high stimulation group was already observed at age 78.3 in the low stimulation group. This suggests the average delay in disease onset is about one and half years, but there is probably considerable variation in the effects of cognitive stimulation between people. What recommendations do you have for future research as a result of this work?

Response:  It would be important to study further the identified three proteins, that is, slit homologue 2 (SLIT2), carbohydrate sulfotransferase 12 (CHSTC), and peptidyl-glycine α-amidating monooxygenase (AMD) because they might more generally provide clues to search for mechanisms underlying long-term risk of dementia in humans. At this stage we do not know whether the three proteins are causally related to dementia risk. This would be an interesting future research topic because proteins are typically modifiable and therefore, in principle, can be targeted by drugs. The three proteins are likely to be associated with a wide range of biological processes beyond neural influences. It is therefore important that their effects are comprehensively examined.   

We have provided all disclosures in the paper.   


Cognitive stimulation in the workplace, plasma proteins, and risk of dementia: three analyses of population cohort studies
BMJ 2021374 doi: (Published 19 August 2021)Cite this as: BMJ 2021;374:n1804



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Last Updated on August 24, 2021 by Marie Benz MD FAAD