Characterization of neuropsychiatric symptoms in patients with early-stage Alzheimer's disease in a specialized outpatient clinic.

OBJECTIVE: To describe the frequency and temporal onset of neuropsychiatric symptoms (NPS) around the diagnosis of Alzheimer's disease (AD) and to explore their associations with clinical and paraclinical variables. METHODS: We conducted a retrospective observational study of patients diagnosed with AD between 2020 and 2024, including NPS emerging from six years before to four years after diagnosis. Symptoms were classified by temporal onset as preNPS or postNPS and categorized into affective, psychotic, and behavioral domains. Clinical and demographic data, cerebrospinal fluid (CSF) biomarkers, and FDG-PET imaging findings were collected. RESULTS: Among 184 patients (mean age 76.7 ± 9.0 years; 68% female), preNPS occurred in 78.2% and postNPS in 53.8%. Psychotic preNPS were associated with older age (81.4 ± 8.6 vs. 76.3 ± 8.9 years; p = 0.049), lower Mini-Mental State Examination scores (19.9 ± 3.7 vs. 22.1 ± 4.1; p = 0.033), and use of benzodiazepines (38.5% vs. 14.0%; p = 0.036) and antipsychotics (61.5% vs. 7.0%; p < 0.001). Affective preNPS were more common in women (71.9% vs. 55.4%; p = 0.029) and were associated with antidepressant use (p < 0.001) and lower alcohol intake (p = 0.018). Behavioral preNPS predominated in men (57.1% vs. 30.1%; p = 0.013) and were associated with a greater preservation of temporal lobe metabolism in FDG-PET imaging (28.0% vs. 76.2%; p = 0.04). PostNPS correlated with disease duration (r = 0.19; p = 0.01) and higher CSF total tau levels (386.9 ± 112.8 vs. 347.1 ± 148.9; p = 0.04). CONCLUSION: NPS are frequent in early-stage AD, with psychotic preNPS linked to older age and greater cognitive decline, and postNPS correlating with disease duration and CSF tau, indicating an association with neurodegeneration.