Neuropsychiatric Symptoms in Cerebral Amyloid Angiopathy: A Significant but Overlooked Association.

Abstract

Cerebral amyloid angiopathy (CAA) is an increasingly recognized cause of cognitive decline and lobar intracerebral hemorrhage in older adults. Recent research highlights that neuropsychiatric symptoms (NPSs)-including depression, anxiety, apathy, and irritability-are highly prevalent in CAA, often emerging prior to overt cognitive impairment or major vascular events. Compared to other cerebrovascular diseases, CAA presents a distinctive and multifaceted NPS profile, with symptoms closely linked to disease severity and neuroimaging biomarkers such as white matter hyperintensities and microbleeds. Critically, NPSs in CAA can complicate cognitive assessment and predict worse functional outcomes, yet remain underappreciated in clinical and research contexts. Management is complicated by pharmacologic risks-including heightened bleeding risk associated with SSRIs and novel anti-amyloid therapies-underscoring the need for individualized and multidisciplinary approaches. We highlight the urgent need for standardized NPS assessment, targeted research into mechanisms and treatment, and greater integration of neuropsychiatric evaluation into CAA care. We suggest that recognizing NPSs as core clinical features-not secondary complications-of CAA is essential to improving both patient outcomes and scientific understanding. Future studies should focus on longitudinal analyses, the development of tailored interventions, and robust comparative research to clarify the pathophysiology, clinical trajectory, and optimal management of NPSs in CAA.