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

• Published in: Ageing research reviews Vol. 55; p. 100948
• Main Authors: Panza, Francesco, Lozupone, Madia, Bellomo, Antonello, Imbimbo, Bruno Pietro
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 01.11.2019
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - metabolism; Animals; Anti-Aβ drugs; Brain - drug effects; Brain - metabolism; Cognitive Dysfunction - chemically induced; Dementia; Drug side effects; Humans; Lifestyle; Neuropsychiatric symptoms; Nootropic Agents - adverse effects; Nootropic Agents - pharmacology; Nootropic Agents - therapeutic use; Suicidal Ideation; Drug side effects; Anti-Aβ drugs; Lifestyle; Suicidal ideation; Neuropsychiatric symptoms; Dementia
• ISSN: 1568-1637; 1872-9649; 1872-9649
• DOI: 10.1016/j.arr.2019.100948

•The amyloid-β (Aβ) cascade hypothesis of Alzheimer’s disease (AD) assumes that Aβ brain accumulation represents the initial pathological event.•All drugs interfering with Aβ production, clearance, and aggregation have failed clinically in AD with also accelerated cognitive decline.•Some anti-Aβ drugs were found to worsen neuropsychiatric symptoms (NPS) and triggered suicidal ideation in AD patients.•Overproduction of Aβ in AD may represent an attempt of the brain to mitigate or repair neuronal damage/insult.•Sudden reductions of brain Aβ levels, in an already precarious chemical milieu, may worsen cognition and exacerbate NPS. In the Alzheimer’s disease (AD) brain, accumulation of the amyloid-β (Aβ) 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 Aβ 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-Aβ 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 Aβ in AD may represent an attempt of the brain to mitigate or repair neuronal damage/insult. Sudden reductions of brain Aβ levels with potent anti-Aβ drugs may worsen cognition and exacerbate NPS.