Abstract
Research on how Alzheimer's disease drugs impact neuropsychiatric symptoms is limited. Given the link between changes in cerebrospinal fluid (CSF) amyloid-β42 (Aβ42) levels and cognitive and clinical outcomes after anti-Aβ treatments, we hypothesized a similar association exists with neuropsychiatric symptoms. We conducted a meta-analysis of anti-Aβ drugs clinical trials to evaluate whether the changes in cerebrospinal Aβ42 levels are associated with neuropsychiatric symptoms, as measured by the Neuropsychiatric Inventory and if any such effect is mediated by changes in cognitive performance, as measured by the Mini-Mental State Examination. Data from 10 trials involving 10 746 Alzheimer's disease patients were included. Decreases in Aβ42 levels were associated with worsening Neuropsychiatric Inventory scores (regression coefficient: -0.68; 95% confidence interval: -1.07 to -0.29; P = 0.002), and this association persisted after adjusting for Mini-Mental State Examination. Sensitivity analyses confirmed the robustness of these findings. Changes in CSF Aβ42 levels are inversely and independently associated with the frequency and severity of neuropsychiatric symptoms in anti-Aβ trials, suggesting a potential role of Aβ42 in modulating neuropsychiatric symptoms in Alzheimer's disease.