Higher intellectual ability and physical activity during childhood and adolescence may help protect against the development of cognitive impairment in people with multiple sclerosis (MS), an Italian study suggests.

These findings, though preliminary, suggest that intellectual enrichment and early-life physical activity may reduce the likelihood of developing cognitive deficits in these patients.

The study, “Cognitive impairment in multiple sclerosis: An exploratory analysis of environmental and lifestyle risk factors,” was published in the journal PLOS ONE.

MS is a multifactorial disease associated with both genetic and environmental risk factors. Several studies have shown that environmental and lifestyle factors such as Epstein-Barr virus (EBV) infection, smoking, low levels of vitamin D, obesity, and comorbidities — other diseases occurring simultaneously — increase the risk of developing MS, and in some cases, influence disease prognosis.

However, the potential effect of environmental and lifestyle risk factors in cognitive impairment in MS patients remain largely unclear. Cognitive impairment is estimated to affect 40% to 70% of people with MS, and is associated with a considerable negative effect in patients’ quality of life.

So, identifying environmental and lifestyle risk factors of cognitive impairment in these patients could help not only to identify those at higher risk, but also help set up preventive approaches and develop better assessment and management strategies.

Researchers in Italy set out to identify possible risk or protective factors for cognitive impairment in 150 people with MS, focusing on potentially modifiable environmental and lifestyle factors.

The team retrospectively collected participants’ demographic and clinical data, and conducted a battery of neuropsychological, cognitive, and disability tests on the patients. Researchers also conducted a semi-structured interview to investigate the patients’ previous and current exposure to hypothesized risk factors.

These risk factors included cardiovascular parameters, comorbidities, psychiatric disorders and dementia, family history of MS, history of brain trauma, hormonal therapies, body mass index, diet and lifestyle.

Diet and lifestyle factors included type of diet, vitamin D supplements, caffeine intake, smoking, alcohol consumption, cannabis and substance abuse, leisure activities, and current and childhood-adolescence physical activity.

Participants’ average age was 44.9 years, and they had a average disease duration of 11.2 years; 103 were women and most (88%) had relapsing-remitting MS.

Results showed that a total of 45 patients (30%) had cognitive dysfunction, mainly in information processing speed (46%), verbal learning (27%), executive function (26%), and visuo-spatial learning (17%) domains.

Patients with cognitive impairment were significantly older, were older at MS onset, had higher MS-associated disability, lower premorbid intelligence quotient (IQ) scores (the level of intellectual ability prior to disease onset), and progressive disease course.

Higher IQ scores are known to be associated with higher cognitive reserve, which is the mind’s resistance to damage to the brain and the ability to optimize or maximize the brain’s performance.

“Our results are in line with previous [studies] pointing to the association of [cognitive impairment] with older age at onset, aging and disability,” the researchers wrote, adding that “early and appropriate treatment of the disease with disease modifying drugs can therefore represent a key strategy to improve both the physical and cognitive outcome of the subject.”

Among potential environmental and lifestyle factors, the team also found that childhood-adolescence (but not current) physical activity, as well as hormonal therapy (estrogen-progestin) in women, were associated with a protective effect against cognitive impairment.

However, when considering multiple factors at the same time (multivariable analysis), the only significant predictors of cognitive dysfunction were older age and lower premorbid IQ. The removal of premorbid IQ from the analysis showed that cognitive impairment was significantly associated with higher MS-associated disability, and that there was still a trend to be linked with lower physical activity.

Based on the results, researchers emphasized that “higher cognitive reserve stands out as the most consistent, potentially modifiable protective factor,” and “better cognitive performance was associated with higher cognitive reserve — expressed as premorbid IQ — which confirms the findings of other studies.”

Overall, the “findings suggest that physical activity in childhood-adolescence could be a contributor to cognitive reserve building, thus representing a potential protective factors for MS-related CI [cognitive impairment] susceptible to preventive strategies.”

The team noted, however, that since “physical activity could be related to higher socio-economic status, an acknowledged proxy of cognitive reserve,” larger studies are required to confirm the protective effect of physical activity.