Identifying factors that influence the risk of mild cognitive impairment

According to a study in Neurology, sociodemographic factors, including years of education and income, are associated with a lower risk of MCI, while taking antidepressants may be associated with an increased risk of progression from mild cognitive impairment to dementia. In the study, the researchers also found that nearly 50% of patients with new-onset MCI diagnoses do not meet MCI criteria after 2 years of follow-up and are instead classified as cognitively normal.

According to the researchers, identifying risk factors for MCI, a prodromal phase of dementia, can help support strategies for prevention and intervention in dementia. However, MCI will not always later progress to dementia. In the current study, researchers examined the demographic, socioeconomic, medical, and genetic factors, as well as depressive symptoms and antidepressant use associated with incidents of MCI and the subsequent course of MCI over the course of follow-up. They also assessed the rates of persistent MCI diagnoses, cognitively normal individuals, and dementia progression.

The study included 2,903 participants in a community-based cohort who were considered cognitively normal at baseline. In the total cohort, a total of 752 participants (mean age 76.1 years) developed an MCI after a mean of 6.3 years, which corresponds to an incidence rate of 56 out of 1000 person-years. A total of 301 participants (mean age 79.5 years) developed incident dementia. MCI event risk was increased in individuals with apolipoprotein E (APOE) ε4 (Cox full regression model: hazard ratio [HR], 1.18; 95% CI, 1.02-1.36; P=0.025) and higher medical burden (full Cox regression model: HR, 1.05; 95% CI, 1.00-1.09; P=0.048).

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In contrast, the risk of an MCI event was greater in individuals with a greater number of years of education (sensitivity analysis: HR, 0.96; 95% CI, 0.95-0.98; p<0.001), more participants in leisure activities ( HR, 0.95; 95% CI, 0.93-0.98; p<0.001) and higher income (HR, 0.79; 95% CI, 0.63-0.99; p=0.044).

Among the cases of MCI events, approximately 12.9% progressed to dementia and 9.6% worsened in functioning but did not meet criteria for MCI or dementia over a mean follow-up of 2.4 years. During this follow-up period, an additional 29.6% of patients with new-onset MCI had developed MCI, while 47.9% of participants no longer met criteria for MCI.

Variables associated with an increased risk of MCI progression to dementia included multidomain MCI, presence of APOE ε4, depressive symptoms, and antidepressant use.

The limitations of the study included a relatively small sample size and the short follow-up period. Researchers noted that additional studies “should examine the course of MCI across multiple follow-up visits over time to further analyze which factors are most informatively associated with the development of neurodegenerative disease.”

The researchers concluded that their “results may refine expectations for the cognitive and functional outcomes of patients with MCI.”


Angevaare MJ, Vonk JMJ, Bertola L, et al. Predictors of the occurrence and course of mild cognitive impairment in a diverse community-based population. Neurology. Published online December 1, 2021. doi:10.1212/WNL.00000000000013017

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