Neuropsychiatric Symptoms and Risk of Progression to Alzheimer's Disease Among Mild Cognitive Impairment Subjects

Background: Neuropsychiatric symptoms (NPS) are prevalent in mild cognitive impairment (MCI), but we do not know much about their role in progression to dementia. Objective: To investigate NPS and the risk of progression to probable Alzheimer's disease dementia (AD) among subjects with MCI. Methods: 96 MCI participants were followed for 4 years. Progression to probable AD was defined by the change of CDR total score from 0.5 to >= 1, reviewed by an expert consensus panel. NPS were determined using the Neuropsychiatric Inventory (NPI) 12-items. This study analyzed prognostic value of each NPI item and 5 sub-syndromes of NPS (apathy, psychosis, affective, hyperactivity, and vegetative) for prediction of progression to probable AD. A Cox proportional hazard model was used; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with time dependent variable to compare the incidence of progression considering presence/absence of any NPS or sub-syndromes throughout the study. Results: The presence of symptoms agitation/aggression, delusions, and aberrant motor behavior significantly increased the risk of probable AD (HR = 3.9; 95%CI = 1.9-8.2; HR = 13.9; 95%CI = 4.1-48.9; HR = 4.3; 95%CI = 1.7-10.3, respectively). The presence of sub-syndromes psychosis and hyperactivity were also predictors of progression (HR = 14.0; 95%CI = 4.4-44.5; HR = 2.0; 95%CI= 1.1-3.7, respectively). These results did not change after adjusting by potential confounders. Conclusion: Presence of delusions, agitation/aggression, and aberrant motor behavior is predictor of progression to probable AD.