Senta Frol

Monoaminergic antidepressants in Alzheimer’s disease provide only modest and inconsistent relief of depressive symptoms and are associated with increased risks of falls, hyponatremia, bleeding, mortality, and possibly faster cognitive decline. Depression in Alzheimer’s disease emerges as a neurodegenerative mood syndrome, driven by synaptic loss, neuroinflammation, cerebrovascular pathology, and network disruption, and overlaps substantially with apathy and other neuropsychiatric symptoms.

ABSTRACT Introduction Depression is one of the most frequent and disabling neuropsychiatric syndromes in Alzheimer’s disease (AD), yet antidepressant use is still largely extrapolated from late‑life depression and is poorly aligned with emerging evidence on ‘neurodegenerative depression’ and disease‑modifying therapies. This article critically re‑examines the clinical value and risks of antidepressants in AD.

1 Introduction Cerebral amyloid angiopathy (CAA), primarily affecting older adults, is characterized by the deposition of β-amyloid (Aβ) in the walls of small- and medium-sized cerebral and leptomeningeal blood vessels, often resulting in recurrent lobar intracerebral hemorrhages (ICH) [1]. Clinically, CAA is associated with ICH, cognitive decline, dementia, and transient focal neurological deficits (TFNEs) [2].