Patterns of Neuropsychiatric Symptoms in Mild Cognitive Impairment and Risk of Dementia

Objective: To identify clusters of patients with incident mild cognitive impairment (MCI) based on their neuropsychiatric symptoms (NPS) and to examine the risk of progression to dementia based on these clusters. Methods: In this cohort study with a median of 2 years of follow-up from the National Alzheimer's Coordinating Center, 540 patients with MCI at least 60 years old with complete data and follow-up were studied. Latent class analysis was used to identify clusters of patients based on their NPS, and Cox proportional hazards models were used to examine risk of progression to dementia based on clusters. Incident MCI was defined as a participant having MCI at a current visit but having been cognitively normal at his or her previous (yearly) visit. The Neuropsychiatric Inventory Questionnaire assessed the presence of 12 neuropsychiatric behavioral domains. Results: Three clusters were identified: a severe cluster (agitation, anxiety, apathy, nighttime behaviors, inhibition), an affective cluster (depression, anxiety, irritability, nighttime behaviors), and an asymptomatic cluster. The prevalence of each class was 56% for the asymptomatic class followed by the affective class (37%) and finally the severe class (7%). Compared with the asymptomatic class, the severe class had more than twice the hazard of progression to dementia (2.69; 95% CI: 1.12-2.70) and the affective class had over 1.5 times the hazard of progression to dementia (1.79; 95% CI: 1.12-2.70). Conclusion: Among persons with incident MCI, patterns of NPS may increase the likelihood of progression to dementia. Implications for early detection and treatment are discussed.