Cerebrovascular and amyloid pathology in predementia stages: the relationship with neurodegeneration and cognitive decline

Background: Cerebrovascular disease (CVD) and amyloid-beta (A beta) often coexist, but their influence on neurodegeneration and cognition in predementia stages remains unclear. We investigated the association between CVD and A beta on neurodegenerative markers and cognition in patients without dementia. Methods: We included 271 memory clinic patients with subjective or objective cognitive deficits but without dementia from the BioBank Alzheimer Center Limburg cohort (n = 99) and the LeARN (n = 50) and DESCRIPA (n = 122) multicenter studies. CSF A beta(1-42) and white matter hyperintensities (WMH) on magnetic resonance imaging (MRI) scans were used as measures of A beta and CVD, respectively. Individuals were classified into four groups based on the presence (+) or absence (-) of A beta and WMH. We investigated differences in phosphorylated tau, total tau (t-tau), and medial temporal lobe atrophy (MTA) between groups using general linear models. We examined cognitive decline and progression to dementia using linear mixed models and Cox proportional hazards models. All analyses were adjusted for study and demographics. Results: MTA and t-tau were elevated in the A beta - WMH+, A beta + WMH-, and A beta + WMH+ groups. MTA was most severe in the A beta + WMH + group compared with the groups with a single pathology. Both WMH and A beta were associated with cognitive decline, but having both pathologies simultaneously was not associated with faster decline. Conclusions: In the present study, we found an additive association of A beta and CVD pathology with baseline MTA but not with cognitive decline. Because our findings may have implications for diagnosis and prognosis of memory clinic patients and for future scientific research, they should be validated in a larger sample with longer follow-up.