The Roles of Apathy and Depression in Predicting Alzheimer Disease: A Longitudinal Analysis in Older Adults With Mild Cognitive Impairment

Abstract

Apathy and depression have each been associated with an increased risk of conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD).These symptoms often co-occur and the contribution of each to risk of AD is not clear. National Alzheimer's Coordinating Center participants diagnosed with MCI at baseline and followed until development of AD or loss to follow-up (n = 4,932) were included. The risks of developing AD in MCI patients with neuropsychiatric symptoms (NPS) (apathy only, depression only, or both) were compared to that in those without NPS in a multivariate Cox regression survival analysis adjusting for baseline cognitive impairment, years of smoking, antidepressant use, and AD medication use. Thirty-seven percent (N = 1713) of MCI patients developed AD (median follow-up 23 months). MCI patients with both apathy and depression had the greatest risk (hazard ratio [HR] = 1.37; 95% confidence interval [CI]: 1.17-1.61; p < 0.0001; Wald χ2 = 14.70; df = 1). Those with apathy only also had a greater risk (HR = 1.24; 95% CI: 1.05-1.47; p = 0.01; Wald χ2 = 6.22; df = 1), but not those with depression only (HR = 1.08; 95% CI: 0.95-1.22; p=0.25; Wald χ2 = 1.30; df = 1). Post-hoc analyses suggested depression may exacerbate cognitive decline in MCI patients with apathy (odds ratio = 0.70; 95% CI 0.52-0.95; p = 0.02; Wald χ2 = 5.28; df = 1), compared to those without apathy. MCI patients with apathy alone or both apathy and depression are at a greater risk of developing AD compared to those with no NPS. Interventions targeting apathy and depression may reduce risk of AD.