Association of amyloid and cardiovascular risk with cognition: Findings from KBASE

Abstract

Background: Limited research has explored the effect of cardiovascular risk and amyloid interplay on cognitive decline in East Asians.

Methods: Vascular burden was quantified using Framingham's General Cardiovascular Risk Score (FRS) in 526 Korean Brain Aging Study (KBASE) participants. Cognitive differences in groups stratified by FRS and amyloid positivity were assessed at baseline and longitudinally.

Results: Baseline analyses revealed that amyloid-negative (Aβ-) cognitively normal (CN) individuals with high FRS had lower cognition compared to Aβ- CN individuals with low FRS (p < 0.0001). Longitudinally, amyloid pathology predominantly drove cognitive decline, while FRS alone had negligible effects on cognition in CN and mild cognitive impairment (MCI) groups.

Conclusion: Our findings indicate that managing vascular risk may be crucial in preserving cognition in Aβ- individuals early on and before the clinical manifestation of dementia. Within the CN and MCI groups, irrespective of FRS status, amyloid-positive individuals had worse cognitive performance than Aβ- individuals.

Highlights: Vascular risk significantly affects cognition in amyloid-negative older Koreans. Amyloid-negative CN older adults with high vascular risk had lower baseline cognition. Amyloid pathology drives cognitive decline in CN and MCI, regardless of vascular risk. The study underscores the impact of vascular health on the AD disease spectrum.

Keywords: Alzheimer's disease; CN; Framingham Risk Score; Korean older adults; MCI; amyloid; cognition; longitudinal; vascular risk factors.

FIGURE 1

Overall study design. Vascular burden was quantified using the Framingham General Cardiovascular Risk Score (FRS), and participants were categorized into four groups based on combinations of FRS (FRS high or FRS low with a median split) and amyloid status (Aβ+ or Aβ– based on a cutoff of 1.2373). Cognitive function was evaluated using standardized neuropsychological tests processed with structural equation models to produce domain scores for memory, executive functioning, language, and visuospatial. Analysis of variance was employed at baseline to analyze cognitive differences among these groups and within each clinical diagnosis. Longitudinal mixed‐effects models spanning 4 years from the initial visit captured cognitive changes within these groups. Aβ, amyloid beta; ANOVA, analysis of variance; EXF, composite score for executive functioning; FRS, Framingham General Cardiovascular Risk Score; KBASE, Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease; LAN, composite score for language; MEM, composite score for memory, VSP, composite score for visuospatial functioning.

FIGURE 2

Analysis of covariance (ANCOVA) results for baseline cognitive differences in memory and executive function domains stratified by amyloid status and cardiovascular risk in each diagnosis group. (A) Baseline memory. Within each diagnosis, pairwise differences in baseline memory scores were assessed for the four groups stratified by amyloid status (Aβ–, Aβ+) and the Framingham General Cardiovascular Risk Score (FRS low, FRS high). Lower memory scores in FRS high Aβ– compared to FRS low Aβ– (p < 0.001) and FRS low Aβ+ individuals (p < 0.01) were found in the cognitively normal (CN) group. (B) Baseline executive function. Within each diagnosis, pairwise differences in baseline executive function were assessed for the four groups stratified by amyloid status (Aβ–, Aβ+) and FRS low versus FRS high. FRS high Aβ– individuals had lower executive function scores compared to FRS low Aβ– (p < 0.001) and FRS low Aβ+ individuals (p < 0.01) only in the CN group. AD, Alzheimer's disease; MCI, mild cognitive impairment. *p < 0.05, **p < 0.01, ***p< 0.001, ****p < 0.0001.

FIGURE 3

Longitudinal changes in (A) memory and (B) executive function stratified by amyloid status and cardiovascular risk groups within the clinical diagnosis groups of CN, MCI, and AD. These plots show the longitudinal changes in memory performance and executive functioning over a 4‐year follow‐up period. The participants in each diagnosis group were categorized into four groups based on their amyloid status (Aβ– or Aβ+) and the Framingham General Cardiovascular Risk Score (FRS low or FRS high). Distinct longitudinal patterns of cognitive decline for each clinical diagnosis group indicate that the impact of amyloid status and cardiovascular risk on memory and executive function differ depending on the clinical condition of the individuals. AD, Alzheimer's disease; CN, cognitively normal; MCI, mild cognitive impairment. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.