Cerebral Amyloid Angiopathy in Alzheimer Disease Continuum: Prevalence and Clinical Relevance in a Biomarker-Defined Memory Clinic Cohort

Cerebral amyloid angiopathy (CAA) frequently co-occurs with Alzheimer disease (AD), yet the prevalence and clinical significance of comorbid CAA among cognitively impaired individuals on the AD continuum remain unclear.

We aimed to determine the frequency of probable CAA (Boston criteria v2.0) in a memory-clinic cohort of symptomatic amyloid-positive individuals and to compare demographic, clinical, cognitive, and biomarker profiles between those with and without comorbid probable CAA. We conducted a retrospective cohort study at the Geneva Memory Center including amyloid-positive patients confirmed by CSF or amyloid PET.

Participants meeting the Boston criteria v2.0 for probable CAA were classified as AD-probable CAA, whereas those with possible or no CAA were classified as AD-nonprobable CAA. Group differences were assessed using standard parametric and nonparametric tests, linear mixed-effects models for cognitive trajectories, logistic regression for cerebral microbleed (CMB)-CSF biomarker associations, and voxel-wise Statistical Parametric Mapping for regional amyloid PET differences.

Among 533 participants (mean age 73.8 ± 6.7 years, 59% female), 148 (28%) met criteria for probable CAA. Demographic characteristics, baseline cognition (mini-mental state examination: rank-biserial r = -0.05, 95% CI -0.16 to 0.07, p = 0.410), and longitudinal cognitive decline (β = -0.02, 95% CI -0.05 to 0.02, p = 0.309; median follow-up 28.1 months) did not differ between groups.

Lower CSF Aβ42 was associated with lobar CMB burden (odds ratio per 1 SD decrease = 1.48, 95% CI 1.14-1.92, p = 0.004). Voxel-wise PET analyses revealed higher cortical amyloid uptake in AD-probable CAA with tracer-dependent patterns (cluster-level family-wise error p < 0.05).

More than one-quarter of amyloid-positive patients fulfilled the Boston criteria v2.0 for probable CAA.

Probable CAA was not associated with a distinct clinical presentation or trajectory of cognitive decline. Higher cortical amyloid PET uptake in probable CAA and the association of lower CSF Aβ42 with lobar CMB burden suggest more prominent cerebral amyloidosis in this population.

The binary probable CAA label may therefore reflect greater amyloid burden without necessarily delineating a clinically distinct subgroup within the AD continuum. Marker-specific approaches targeting cortical superficial siderosis and high lobar CMB burden may prove more informative.