Individuals with cognitively-stimulating jobs are at a lower risk of developing dementia than their peers with less challenging employment, new research suggests.
Results from a large, multi-cohort study also showed an association between cognitive stimulation and lower levels of certain plasma proteins, providing possible clues on a protective biological mechanism.
“These new findings support the hypothesis that mental stimulation in adulthood may postpone the onset of dementia,” Mika Kivimäki, buy cheap methotrexate no prescription au professor and director of the Whitehall II Study, Department of Epidemiology, University College London, United Kingdom, told Medscape Medical News.
The results were published online August 19 in The BMJ.
“Work Fast and Hard”
Researchers assessed the association between workplace cognitive stimulation and dementia incidence in seven cohorts that included almost 108,000 men and women (mean age, 44.6 years). All were free of dementia at baseline.
Participants included civil servants, public sector employees, forestry workers, and others from the general working population.
Investigators separated the participants into three categories of workplace cognitive stimulation: “high,” which referred to both high job demand and high job control; “low,” which referred to low demands and low control; and “medium,” which referred to all other combinations of job demand and job control.
“Highly cognitively-stimulating jobs require you to work fast and hard, learn new things, be creative, and have a high level of skill,” said Kivimäki.
Dr Mika Kivimäki
The researchers controlled for low education, hypertension, smoking, obesity, depression, physical inactivity, diabetes, low social contact, excessive alcohol consumption, and traumatic brain injury. These represent 10 of the 12 dementia risk factors named by the 2020 Lancet Commission on Dementia Prevention as having convincing evidence, Kivimäki noted.
Although the investigators had no data on the other two risk factors of hearing loss and air pollution, these are unlikely to be confounding factors, he said.
Follow-up for incident dementia varied from 13.7 to 30.1 years, depending on the cohort, and was 16.7 years in the total patient population. The mean age at dementia onset was 71.2 years.
Benefits Across the Life Course
Results showed that incident dementia per 10,000 person years was 7.3 in the low cognitive stimulation group and 4.8 in the high stimulation group, for a difference of 2.5.
“These differences were relatively small because the incidence of dementia in this relatively young population was low,” Kivimäki said.
Compared with those with low stimulation, the adjusted hazard ratio for dementia for this with high stimulation was 0.77 (95% CI, 0.65 – 0.92).
The results were similar for men and women, and for those younger and older than 60 years. However, the link between workplace cognitive stimulation appeared stronger for Alzheimer’s disease than for other dementias.
There also appeared to be additive effects of higher cognitive stimulation in both childhood, as indicated by higher educational attainment, and adulthood, based on work characteristics, said Kivimäki.
“These findings support the benefits of cognitive stimulation across the life course, with education leading to higher peak cognitive performance and cognitive stimulation at work lowering age-related cognitive decline,” he added.
The findings don’t seem to be the result of workers with cognitive impairment remaining in unchallenging jobs, he noted. Separate analyses showed lower dementia incidence even when 10 years or more separated the assessment of cognitive stimulation and the dementia diagnosis.
“This suggests that the findings are unlikely to be biased due to reverse causation,” Kivimäki said.
Findings were similar when the researchers assessed effect from job changes. “This is probably because people in highly stimulating jobs are more likely to change to another highly stimulating job than to a low-stimulating job,” said Kivimäki. “Similarly, people with less stimulating jobs are seldom able to change to a substantially more stimulating job.”
As a dementia risk factor, low workplace stimulation is comparable to high alcohol intake and physical inactivity, but is weaker than education, diabetes, smoking, hypertension, and obesity, Kivimäki noted.
When asked about individuals with less cognitively stimulating jobs who are enormously stimulated outside work, he said that “previous large-scale studies have failed to find evidence that leisure time cognitive activity would significantly reduce risk of dementia.”
To explore potential underlying mechanisms, the investigators examined almost 5000 plasma proteins in more than 2200 individuals from one cohort in the Whitehall II study. They found six proteins were significantly lower among participants with high vs low cognitive stimulation.
In another analysis that included more than 13,500 participants from the Whitehall and another cohort, higher levels of three of these plasma proteins were associated with increased dementia risk — or conversely, lower protein levels with lower dementia risk.
The findings suggest a “novel plausible explanation” for the link between workplace cognitive stimulation and dementia risk, said Kivimäki.
He noted that higher levels of certain proteins prevent brain cells from forming new connections.
“Some of the Most Compelling Evidence to Date”
In an accompanying editorial, Serhiy Dekhtyar, PhD, assistant professor (Docent), Aging Research Center, Karolinska Institute, Stockholm, Sweden, notes that the study is “an important piece of work” and “some of the most compelling evidence to date” on the role of occupational cognitive stimulation in dementia risk.
The large-scale investigation in multiple cohorts and contexts has “advanced the field” and could help “explain previously mixed findings in the literature,” Dekhtyar told Medscape Medical News.
Importantly, the researchers provide “an indication of biological mechanisms potentially connecting work mental stimulation and dementia,” he added.
However, Dekhtyar noted that the difference of 2.5 incident cases of dementia per 10,000 person years of follow-up between the low and high mental-stimulation groups “is not especially large” — although it is comparable to other established risk factors for dementia.
He suspects the effect size would have been larger had the follow-up for dementia been longer.
Dekhtyar also raised the possibility that “innate cognition” might affect both educational and occupational attainment, and the subsequent dementia risk.
“Without taking this into account, we may inadvertently conclude that education or occupational stimulation help differentially preserve cognition into late life — when in reality, it may be initial differences in cognitive ability that are preserved throughout life,” he concluded.
Funding sources for the study included Nordic Research Programme on Health and Welfare (NordForsk), Medical Research Council, Wellcome Trust, Academy of Finland, and Helsinki Institute of Life Science. Kivimäki has received support from NordForsk, the UK Medical Research Council, the Wellcome Trust, the Academy of Finland, and the Helsinki Institute of Life Science. Dekhtyar has disclosed no relevant financial relationships.
BMJ. Published online August 19, 2021. Full text, Editorial
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