Incidence and predictive factors of depressive symptoms in Alzheimer's disease: the REAL.FR study

Many patients develop psychiatric and behavioral disturbances in the course of Alzheimer's disease (AD). Among these disturbances, depressive symptoms are frequent and affect nearly 40% of patients. The natural history and course of such symptoms in AD, and in particular the predictive factors, are little known. We studied the incidence and risk factors for the development of the first depressive symptoms in AD.

Multicenter prospective study.

Three hundred twelve AD patients from the French Network on AD (REAL.FR) without depression and without antidepressant treatment at baseline were followed up and assessed every 6 months for 4 years. During follow-up, all events occurring between two visits were carefully recorded.

We used the Neuropsychiatric Inventory (NPI) for comprehensive evaluation of behavioral and psychological symptoms and depressive symptoms in particular. A multivariate analysis was performed using a backward stepwise Cox proportional hazards model.

The incidence of depressive symptoms was 17.45% person/years, 95%CI (13.88-21.02). Among non-time dependent variables, duration of disease (RR=0.51; 95%CI: 0.30-0.85, p=0.0102) and the number of comorbid conditions (RR=0.45; 95%CI: 0.24-0.83, p=0.0115) were protective factors against the development of depressive symptoms. Agitation/aggression (RR=1.96; 95%CI: 1.19-3.23, p=0.0078) and sleep disturbances (RR=2.65; 95%CI: 1.40-5.00, p=0.0026) were time-dependent variables predictive of depressive symptoms.

Better knowledge of predictive factors of mood disturbances in AD will enable clinicians to set up appropriate management of their patients. As published longitudinal studies are few, further works should be carried out to improve knowledge of the pattern and course of depression and depressive symptoms in AD.