Apathy as a Predictor of Conversion from Mild Cognitive Impairment to Alzheimer’s Disease: A Texas Alzheimer’s Research and Care Consortium (TARCC) Cohort-Based Analysis

Background: Apathy is among the neuropsychiatric symptoms frequently observed in people with cognitive impairment. It has been postulated to be a potential predictor of conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Objective: To detect conversion rates from MCI to AD, and to determine the effect of apathy on the progression to AD in patients with MCI enrolled in the Texas Alzheimer’s Research and Care Consortium (TARCC) cohort. Methods: Apathy was determined by a positive response to the respective item in the Neuropsychiatric Inventory – Questionnaire (NPI-Q) completed by family members or caregivers. The final dataset included 2,897 observations from 1,092 individuals with MCI at the baseline. Kaplan-Meier survival curves were estimated to provide indices of the probability of conversion to AD over time across all individuals as well as between those with and without apathy. Cox proportional hazards regression measured the hazard associated with apathy and several other predictors of interest. Results: Over a period of 8.21 years, 17.3% of individuals had conversion from MCI to AD (n = 190 of 1,092 total individuals) across observations. The median time-to-conversion across all participants was 6.41 years. Comparing individuals with apathy (n = 158) versus without apathy (n = 934), 36.1% and 14.2% had conversion to AD, respectively. The median time-to-conversion was 3.79 years for individuals with apathy and 6.83 years for individuals without apathy. Cox proportional hazards regression found significant effects of several predictors, including apathy, on time-to-conversion. Age and cognitive performance were found to moderate the relationship between apathy and time-to-conversion. Conclusions: Apathy is associated with progression from MCI to AD, suggesting that it might improve risk prediction and aid targeted intervention delivery.