The Evolution of Psychiatric Symptoms in Alzheimer's Disease: A Natural History Study

OBJECTIVE: To characterize the natural history of Alzheimer's Disease (AD); in particular, to determine the prevalence and time of onset of psychiatric symptoms. DESIGN: Retrospective medical records review. SETTING: Regional brain bank operated by a university hospital. PARTICIPANTS: One hundred randomly selected autopsy-confirmed AD patients. MEASUREMENTS: The presence of psychiatric symptoms (e.g., anxiety, wandering, agitation) was documented, and the time of onset relative to diagnosis was measured. RESULTS: Irritability, agitation, and aggression were documented in 81 patients (81%) an average of 10 months after diagnosis. A total of 72% of patients experienced depression, changes in mood, social withdrawal, and suicidal ideation more than 2 years before diagnosis (26.4 months). Hallucinations, paranoia, accusatory behavior, and delusions were documented around the time of diagnosis (0.1 months after diagnosis) in 45% of patients. Patients with early-onset disease, more years of formal education, and male gender experienced psychiatric symptoms later, relative to diagnosis, than their counterparts. CONCLUSIONS: Psychiatric manifestations of depression may herald a diagnosis of AD, as such behaviors occurred more than 2 years before diagnosis, on average, in this cohort. Psychotic symptoms manifested around the time of diagnosis, perhaps even prompting diagnosis, whereas agitative symptoms occurred in the first year after diagnosis. The evolution of psychiatric symptoms in this cohort differed according to age at onset of disease, years of formal education, and gender.