Manufactured Clinical Risk: Why Better Decisions Matter More Than Faster Investigations.

Cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterized by the deposition of β-amyloid in the walls of cerebral vessels. In a community-based autopsy study, CAA was linked to an increased risk of dementia and cognitive impairment, along with antemortem impairments in global cognition, perceptual speed, episodic memory, and semantic memory. Similarly, participants with CAA have been found to perform worse than age-adjusted norms on tests of episodic memory, executive function, and processing speed. CAA can be clinically diagnosed using established MRI markers. Characteristic neuroimaging biomarkers of CAA, such as white matter lesions, have been linked to impaired cognitive performance. Other CAA-related markers, including white matter hyperintensities (WMH), disseminated cortical superficial siderosis (cSS), and higher small vessel disease (SVD) scores, are similarly associated with an increased risk of developing dementia following an intracerebral hemorrhage (ICH). Together, these disease-related MRI features highlight the impact of CAA-related vascular injury on cognitive outcomes. Beyond cognitive and structural consequences, CAA has also been linked to depression. In a study conducted by our research group exploring the neuropsychiatric profiles of participants with CAA, depression/dysphoria was the most frequently reported symptom on the Neuropsychiatric Inventory Questionnaire. In addition, survivors of CAA-related ICH are more likely to experience depression, both before and after hemorrhage, compared with those with ICH because of hypertensive arteriopathy. Studies examining depression in CAA have primarily used informant reports or have focused on certain populations of participants with CAA, such as survivors of ICH or specific CAA subtypes. Kaushik et al. used the self-reported Centre for Epidemiologic Studies Depression Scale and identified that 25% of participants with CAA had symptoms of depression or anxiety, highlighting the need to further explore depressive symptoms across the broader CAA population to inform appropriate screening and interventions.