CAIDE score, brain structure, and cognitive functions in middle-to-older aged adults: A KoGES population-based study
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Background
Although CAIDE (Cardiovascular Risk Factors, Aging, and Dementia) score estimates 20-year dementia risk, prior studies have largely focused on global or composite measures of cognitive function. Among the studies, only a few have investigated involving cognitive functions and structural neuroimaging markers, and the available structural neuroimaging evidence has largely been derived from subsamples or highly selected small cohorts rather than full population-based cohorts. We, therefore, not only investigated associations between CAIDE score and cognitive performance but also explored the mediating role of structural neuroimaging markers in middle-to-older aged population.
Methods
Of 2,864 participants who were available for structural magnetic resonance imaging (MRI) data at baseline, we excluded 230 participants who had neurological and cardiovascular disease at baseline. We also further excluded 209 participants without having exposure, covariates, and cognitive assessments data, and 2,425 participants were included for the final analysis. The CAIDE score was calculated based on midlife vascular risk factors. We categorized participants into low, moderate, and high-risk groups based on the tertile distribution of the total scores. For the original CAIDE score (without APOE4), the tertile-based cut-offs were <6, 6-to-7, and >7 points. In the sensitivity analysis incorporating APOE4 status, the cut-off points were recalculated to maintain tertile-based categorization, resulting in <7, 7-to-8, and >8 points for low, moderate, and high risk groups, respectively. The main outcomes were neuropsychological assessment battery included Story recall, Visual reproductions, Verbal fluency, Trail making, Digit symbol – coding, and Stroop tests.
Findings
Of 2,425 healthy participants (mean age of 58.5 [6.5]; men 1,189 [49.0]), higher CAIDE groups were associated with poorer cognitive performance across all cognitive domains. Compared with low-risk group, the high-risk group had significantly lower mean adjusted z-scores across all 12 cognitive assessments (all p <.001). The moderate-risk group also showed lower mean adjusted z-scores in all tests, except visual reproduction recognition and verbal fluency category tests.
Interpretation
This large-based population study showed the highest CAIDE risk group was independently associated with lower cognitive performance across all domains compared to the lowest risk group, suggesting the potential importance of managing these features for preserving neurological health in middle and older aged adults.
Research in Context
Evidence before this study
Recent studies reported the associations between CAIDE (Cardiovascular Risk Factors, Aging, and Dementia) score and cognitive functions in middle-to-older aged population. However, most studies investigated cognitive functions as composite measures or global score and the accompanying structural neuroimaging markers have not been well characterized. We therefore searched PubMed with “CAIDE risk score” [All fields] OR “dementia risk score” [All fields] OR “AD risk score” [All fields] AND “Neuroimaging” [All fields] OR “magnetic resonance imaging” [All fields] OR “brain volumetric” [All fields] AND “cognitions” [All fields] OR “cognitive functions” [All fields] AND “population-based” [All fields] between April 17 th , 2006 to April, 17 th , 2026 among CAIDE risk factors, brain volume, and cognitive functions in middle to older aged population. We identified only a few studies investigated on cognitive functions and structural neuroimaging markers, and the available structural neuroimaging evidence has largely been derived from subsamples or highly selected small cohorts rather than full population-based cohorts. We therefore examined the associations between CAIDE score and cognitive functions across all domains and further explored the potential role of structural brain measures in middle to older-aged East Asian population.
Added value of this study
Notably, this large middle-to-older aged (49 to 80 years) population study extends from prior evidence by examine the associations between CAIDE score and cognitive functions (logical memory, visual reproduction, verbal fluency, trail making test A, digit symbol – coding, and stroop tests) rather than relying solely on composite measures or global score of cognitive functions. Additionally, we further explore structural brain volumes whether underlying these associations. We further found the structural neuroimaging measures alone did not fully account for the associations between CAIDE score and cognitive functions, suggesting a more complex relationship.
Implications of all the available evidence
This large population based study highlights the importance of CAIDE risk profiles managements before onset of the cognitive impairment. Notably, our results are consistent with prior studies reporting associations between the CAIDE score and both cognitive function and structural neuroimaging measures. Importantly, we extended these findings by demonstrating that structural brain measures may partially account for the association between CAIDE score and cognitive function in this asymptomatic middle-aged population. Overall, our results suggest that the association between the CAIDE score and cognitive performance may not be fully explained by macroscopic structural brain measures only. Thus, future studies are warranted to examine additional neurobiological mechanisms beyond structural brain measures that may contribute to the associations between CAIDE risk profile and cognitive function.
