Do anti-amyloid-β drugs affect neuropsychiatric status in Alzheimer's disease patients?

In the Alzheimer's disease (AD) brain, accumulation of the amyloid-beta (A beta) peptide starts 15-20 years before clinical symptoms become apparent and is believed to be the initial event of the pathological process. Unfortunately, candidate drugs targeting production, clearance and deposition of A beta have failed to show clinical benefit in patients with established or prodromal disease, or in cognitively normal subjects with high risk of developing AD. Surprisingly, several potent anti-A beta drugs accelerated cognitive decline of AD and, in some cases, worsened neuropsychiatric symptoms (NPS) and triggered suicidal ideation. Clarifying the relationships between the AD-related pathology and NPS of AD patients may be useful for elucidating the underlying pathophysiological process. We believe that steady overproduction of A beta in AD may represent an attempt of the brain to mitigate or repair neuronal damage/insult. Sudden reductions of brain A beta levels with potent anti-A beta drugs may worsen cognition and exacerbate NPS.