Comorbid amyloid with cerebrovascular disease in domain-specific cognitive and neuropsychiatric disturbances: a cross-sectional memory clinic study.

Dementia is a multifactorial disorder that is likely influenced by both Alzheimer's disease (AD) and vascular pathologies. We evaluated domain-specific cognitive and neuropsychiatric dysfunction using a two-neuroimaging biomarker construct (beta-amyloid [Aβ] and cerebrovascular disease [CeVD]). We analyzed data from 216 memory clinic participants (mean age = 75.9 ± 6.9; 56.5% female) with neuropsychological and neuropsychiatric assessments, 3T-MRI, and Aβ-PET imaging. Structural equation modeling showed that the largest Aβ (A+) effect was on memory (B = -1.50) and apathy (B = 0.26), whereas CeVD effects were largest on language (B = -1.62) and hyperactivity (B = 0.32). Group comparisons showed that the A+C+ group had greater memory impairment (B = -1.55), hyperactivity (B = 0.79), and apathy (B = 0.74) compared to A-C+; and greater language impairment (B = -1.26) compared to A+C-. These potentially additive effects of Aβ and CeVD burden underline the importance of early detection and treatment of Aβ alongside optimal control of vascular risk factors as a potential strategy in preventing cognitive and neurobehavioral impairment.