The roles of apathy and depression in predicting Alzheimer's disease: a longitudinal analysis in older adults with mild cognitive impairment.

ABSTRACT Objective 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. Methods 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. Results 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 2  = 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 χ 2  = 6.22; df = 1), but not those with depression only (HR = 1.08; 95% CI: 0.95–1.22; p=0.25; Wald χ 2  = 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 χ 2  = 5.28; df = 1), compared to those without apathy. Conclusion 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.