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