Possible mechanism
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 Dr. 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 with high alcohol intake and physical inactivity, but is weaker than education, diabetes, smoking, hypertension, and obesity, Dr. 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 5,000 plasma proteins in more than 2,200 individuals from one cohort in the Whitehall II study. They found six proteins were significantly lower among participants with high versus 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 Dr. 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, noted 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 said in an interview.
Importantly, the researchers provide “an indication of biological mechanisms potentially connecting work mental stimulation and dementia,” he added.
However, Dr. 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 with other established risk factors for dementia.
He suspects the effect size would have been larger had the follow-up for dementia been longer.
Dr. 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. Dr. 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. Dr. Dekhtyar disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.