Published on the BMJ website 19 August 2021 – author Serhiy Dekhtyar, assistant professor
Dementia, a devastating condition that affects nearly 50 million people worldwide, is not an inevitable part of ageing.1 It is now widely accepted that the prevention of dementia is achievable, owing to risk reductions associated with lifelong control of cardiovascular risk factors, engagement in physical activity, or prolonged education.2 The seemingly consistent protection afforded by education, although far from being fully understood,3 likely involves the beneficial impact of cognitive stimulation on the build-up of neurons, synapses, and the enrichment of reserve—the brain’s ability to withstand damage that would otherwise lead to dementia.4
In light of these hypothesised benefits, many researchers have sought to examine mental enrichment beyond schooling. Occupational based cognitive stimulation has deservedly received much interest, given the prolonged exposure to work environments throughout the life course.5 Despite considerable previous research, however, the role of work related mental enrichment in dementia has remained unclear, owing to the small size of study populations, mostly originating from northern Europe.67 Notably, the biological pathways underpinning the influence of occupational mental stimulation have not yet been described.
The linked study by Kivimäki and colleagues (doi:10.1136/bmj.n1804) is an important piece of work that addresses these gaps in a systematic way.8 Using data from the individual participant data meta-analysis in working populations (IPD-WORK), the largest ongoing multicohort project on work and health,9 these authors conducted three studies combined to investigate the association between cognitive stimulation at work and dementia (assessed in seven cohorts including nearly 108 000 people); cognitive stimulation at work and nearly 5000 plasma proteins—to explore the biological correlates of work stimulation (assessed in >2200 people from one cohort); and plasma proteins and dementia (assessed in >13 500 people from two cohorts).
In this exhaustive large sale undertaking, the authors found that, after adjustment for age and sex, those in cognitively stimulating jobs experienced a 23% lower risk of dementia. In the two auxiliary analyses involving plasma proteins, Kivimäki and colleagues further reported that high mental enrichment at work was associated with reduced levels of proteins that inhibit axonogenesis and synaptogenesis in the central nervous system, and that lower levels of these proteins are in turn associated with a reduced risk of dementia. Although circumstantial and not formally tested in a single mediation model, these findings provide some of the most compelling evidence to date on the role of occupational cognitive stimulation in dementia, as well as hint at the possible biological mechanisms underpinning these effects.
One consideration is the small size of the reported effect, which translates into a difference of just 2.5 incident cases of dementia per 10 000 person years of follow-up between the low and the high mental stimulation groups. While likely an underestimate, given the young mean age of participants at baseline (44 years) and the relatively low mean age of dementia onset (71 years), this observation puts into perspective the previously mixed record of interventions targeting mental stimulation as a modifiable factor against cognitive decline.10 These interventions might have been destined to fail in evaluations without large enough samples to detect such small effect sizes, and in the absence of prolonged periods of exposure afforded by decades long occupational careers.
Kivimäki and colleagues report that dementia risk reduction associated with higher education is greater (34%) than the risk reduction associated with higher mental stimulation at work (23%), and that accounting for education attenuates the point estimate for occupation by one quarter. Although this can be viewed as evidence of occupation’s limited independent contribution to dementia risk, this pattern is in many ways expected, given that education is a major determinant of occupational attainment and considering education’s multifactorial impact on dementia, that likely involves influences on health behaviours or health literacy alongside cognitive enrichment.11
While the authors also report greater risk reduction in those with high education and low work stimulation (27%) than in those with low education and high work stimulation (20%), further pointing to education and not occupation as the key driver of prevention, they clearly show that cumulative exposure to both high education and high cognitive stimulation at work is associated with the greatest risk reduction of all (37%).
An important remaining question is whether educational and occupational stimulation truly help preserve cognition in old age, or if initial differences in cognitive ability underpin both engagement in mentally enriching environments and eventual risk of dementia. While confounding by cognitive ability has been examined in a few previous studies, with initial indications that occupational engagement remains protective even after accounting for childhood cognition,1213 more large scale work is needed that, as with Kivimäki and colleagues’ study, also explores biological mechanisms.
This new work is an important reminder to all in the specialty of dementia prevention that we can only go so far with intervention studies that are short, late, small, and include only people who are heterogenous in their risk profiles to reveal any benefit of mental enrichment on dementia risk.11 Carefully designed, large, population based studies with long periods of follow-up that also aim to provide biological clues, can be an important addition to randomised controlled trials. Kivimäki and colleagues’ study is an outstanding example.
Competing interests: I have read and understood the BMJ Group policy on declaration of interests and declare the following interests: none.
Provenance and peer review: Commissioned; not externally peer reviewed.