Increased CAIDE dementia risk, cognition, CSF biomarkers and vascular burden in healthy adults

Objective: To investigate the cognitive profile of healthy individuals with increased CAIDE dementia risk score, and to explore whether this association is related to vascular burden and CSF biomarkers of amyloidosis and neurodegeneration.
Method: Cognitively normal participants (mean age = 57.6 years) from the Gipuzkoa Alzheimer Project study were classified as having high risk (HR, n = 82) or low risk (LR, n = 293) for dementia according to a CAIDE score cut off of 9. Cognitive composites were compared between groups. We explored the role of APOE genotype, MRI white matter hyperintensities (WMH) and CSF (n = 218) levels of amyloid-β1-42 (Aβ1-42), total tau (t-tau) and phosphorylated tau (p-tau) in the association between CAIDE and cognition conducting generalized linear models.
Results: HR participants obtained lower scores on executive function (EF) (p = .001) and visual perception and construction (VPC) (p < .001) composites. EFc was associated with CAIDEp-tau (p = .001), CAIDEt-tau (p = .001) and WMH (p = .003). VPCc was associated with APOE (p = .001), Aβ1-42 (p = .004), the interaction APOEAβ1-42 (p = .003), and WMH (p = .004). Performance on global memory was associated with Aβ1-42 (p = .006), APOE (p = .008), and their interaction (p = .006). Analyses were adjusted for age, education, sex, premorbid intelligence and stress.
Conclusion: Healthy participants at increased dementia risk, based on CAIDE scores, show lower performance in executive function and visual perception and construction. This difference is related to APOE, WMH and Alzheimer’s biomarkers.