Identifying Factors That Influence the Risk for Mild Cognitive Impairment

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Researchers sought to investigate the predictors of incident MCI and subsequent course of MCI over follow-up and assessed the rates of sustained MCI diagnoses, cognitive normal individuals, and dementia progression.

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

Identifying risk factors for MCI, a prodromal phase of dementia, can help aid prevention and intervention strategies of dementia, according to the researchers. However, MCI will not always subsequently progress to dementia. In the current study, the researchers investigated the demographic factors, socioeconomic factors, medical and genetic factors, and depressive symptoms and antidepressant use related to incident MCI and subsequent course of MCI over follow-up. They also assessed the rates of sustained MCI diagnoses, cognitively normal individuals, and dementia progression.

The study included 2903 participants within a community-based cohort who were considered cognitively normal at baseline. In the overall cohort, a total of 752 participants (mean age, 76.1 years) developed MCI after a mean of 6.3 years, corresponding to an incidence rate of 56 out of 1000 person-years. A total of 301 participants (mean age, 79.5 years) developed incident dementia. Incident MCI risk was increased in individuals with apolipoprotein E (APOE) ε4 (full Cox regression model: hazard ratio [HR], 1.18; 95% CI, 1.02-1.36; P =.025) and higher medical burden (full Cox regression model: HR, 1.05; 95% CI, 1.00-1.09; P =.048).

In contrast, the risk of incident MCI was decreased in individuals with a greater number of years of education (sensitivity analysis: HR, 0.96; 95% CI, 0.95-0.98; P <.001), greater participants in leisure activities (HR, 0.95; 95% CI, 0.93-0.98; P <.001), and higher income (HR, 0.79; 95% CI, 0.63-0.99; P =.044).

Among the cases of incident MCI, approximately 12.9% progressed to dementia and 9.6% declined in functioning but did not meet criteria for MCI or dementia over a mean of 2.4 years of follow-up. Over this follow-up period, another 29.6% of patients with incident MCI had sustained MCI, while 47.9% of participants no longer met criteria for MCI.

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

Study limitations included a relatively small sample size as well as the short follow-up duration. The researchers noted that additional studies “should investigate the course of MCI across multiple follow-up visits across a longer period of time to further dissect which factors are most informatively related to development of neurodegenerative disease.”

The researchers concluded that their “findings can refine expectations for cognitive and functional course of those presenting with MCI.”


Angevaare MJ, Vonk JMJ, Bertola L, et al. Predictors of incident mild cognitive impairment and its course in a diverse community-based population. Neurology. Published online December 1, 2021. doi:10.1212/WNL.0000000000013017