Background: A number of studies have linked neuropsychiatric symptoms to increase risk of dementia.

Objective: To determine if risk of conversion to mild cognitive impairment or dementia among healthy controls varied as a function of their pattern of neuropsychiatric symptoms.

Method: We studied individuals in the National Alzheimer Coordinating Center dataset collected from 34 Alzheimer Disease Centers between 2005 and 2013. The analysis included 4,517 volunteers who were ≥60 years old, cognitively normal, and had complete Neuropsychiatric Inventory data at their baseline visit, and had at least one follow-up. We used latent class analysis to identify four classes based on patterns of NPI symptoms. We used a Cox proportional hazards model to determine if time to MCI or dementia varied by baseline latent class membership.

Results: We identified four latent classes of neuropsychiatric symptoms: irritable, depressed, complex (depression, apathy, irritability, and nighttime behaviors) and asymptomatic. 873 participants converted to MCI or dementia. Hazard ratios for conversion by class were 1.76 (95% CI: 1.34, 2.33) for the irritable class, 3.20 (95% CI: 2.24, 4.58) for the complex class, and 1.90 (95% CI: 1.49, 2.43) for the depressed class, with the asymptomatic class as the reference.

Conclusions: Membership in all three symptomatic classes was associated with greater risk of conversion to MCI or dementia; the complex class had the greatest risk. Different patterns of neuropsychiatric symptoms may represent different underlying neuropathological pathways to dementia. Further work imaging and pathology research is necessary to determine if this is the case.