The objective of this paper was to assess the prevalence, incidence, persistence, and risk and mortality factors for Apathy Syndrome in Alzheimer's disease (ASAD) in a clinical sample. This was a cohort study of 491 patients with probable Alzheimer's disease (AD). The Cambridge Examination for Mental Disorders of the Elderly (CAMDEX), the Neuropsychiatric Inventory (NPI), the Rapid Disability Rating Scale (RDRS-2), and the Zarit Burden Interview (ZBI) were administered, and all patients were reevaluated after 12 months. Baseline ASAD diagnosis was made using specific diagnostic criteria. ASAD prevalence and incidence/year were 21.0% and 10.6%, respectively. After one year, ASAD persisted in 61.2% of patients. At baseline, patients with ASAD scored lower on the CAMCOG and higher on the Blessed, RDRS-2, and ZBI. Antipsychotic use was the only risk factor for ASAD (RR = 3.159; 95% CI: 1.247-8.003). ASAD was related to an increased functional disability, but no relationship with cognitive impairment or increased caregiver burden was detected. Finally, ASAD was associated with an increased risk of mortality (HR = 1.987; 95% CI: 1.145-3.450; p = 0.014). ASAD suggests a more severe AD clinical profile, with poorer functional progression and increased mortality risk. Antipsychotic use seems to be the only risk factor for ASAD.