Cognitive Impairment in Cerebral Amyloid Angiopathy: A Single-Center Prospective Cohort Study

Background/Objectives: Cognitive impairment represents a core and prodromal clinical feature of cerebral amyloid angiopathy (CAA). We sought to assess specific cognitive domains which are mainly affected among patients with CAA and to investigate probable associations with neuroimaging markers and Cerebrospinal Fluid (CSF) biomarkers. Methods: Thirty-five patients fulfilling the Boston Criteria v1.5 or v2.0 for the diagnosis of probable/possible CAA were enrolled in this prospective cohort study. Brain Magnetic Resonance Imaging and CSF biomarker data were collected. Every eligible participant underwent a comprehensive neurocognitive assessment. Spearman's rank correlation tests were used to identify possible relationships between the Addenbrooke's Cognitive Examination-Revised (ACE-R) sub-scores and other neurocognitive test scores and the CSF biomarker and neuroimaging parameters among CAA patients. Moreover, linear regression analyses were used to investigate the effects of CSF biomarkers on the ACE-R total score and Mini-Mental State Examination (MMSE) score, based on the outcomes of univariate analyses. Results: Cognitive impairment was detected in 80% of patients, and 60% had a coexistent Alzheimer's disease (AD) pathology based on CSF biomarker profiles. Notable correlations were identified between increased levels of total tau (t-tau) and phosphorylated tau (p-tau) and diminished performance in terms of overall cognitive function, especially memory. In contrast, neuroimaging indicators, including lobar cerebral microbleeds and superficial siderosis, had no significant associations with cognitive scores. Among the CAA patients, those without AD had superior neurocognitive test performance, with significant differences observed in their ACE-R total scores and memory sub-scores. Conclusions: The significance of tauopathy in cognitive impairment associated with CAA may be greater than previously imagined, underscoring the necessity for additional exploration of the non-hemorrhagic facets of the disease and new neuroimaging markers.