Trajectories of neuropsychiatric symptoms over time in healthy volunteers and risk of MCI and dementia

Objectives: To identify subtypes of neuropsychiatric symptom (NPS) course among cognitively normal individuals and to assess the association between these subtypes and hazard of later mild cognitive impairment (MCI) or dementia diagnosis. Methods: We modeled neuropsychiatric inventory questionnaire (NPI-Q) scores from 4184 volunteers over approximately 4 years using growth mixture models, generating latent classes of trajectory. We then fit Cox proportional hazard models to determine if membership in trajectory classes was associated with increased hazard of diagnosis of MCI or dementia. Results: We identified four trajectory classes: the majority of the sample (65%) would be expected to belong to a class with consistently low or zero NPS. The next most prevalent class, (16%) showed a decrease over time in NPI-Q total score but, compared with the majority class had an almost threefold increase in hazard of MCI or dementia (HR: 2.92; 95% CI: 1.82-4.68). Another class (14%) showed an increase in NPS over time and was also associated with greater hazard of MCI or dementia (HR: 3.96; CI: 2.61-6.03). The smallest class (5%) had high and fluctuating NPI-Q total scores and had the greatest hazard (HR: 4.57; CI: 2.72-7.63). Conclusion: We have demonstrated that it is possible to identify meaningful groups of NPS trajectories and that trajectory of NPS can convey information beyond a single cross-sectional measure. While even those whose NPS improved were at increased hazard of MCI or dementia, hazard increased as a function of the severity of the NPS trajectory.