CAIDE dementia risk score relates to severity and progression of cerebral small vessel disease in healthy midlife adults: the PREVENT-Dementia study

Abstract

BackgroundMarkers of cerebrovascular disease are common in dementia, and may be present before dementia onset. However, their clinical relevance in midlife adults at risk of future dementia remains unclear. We investigated whether the Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score was associated with markers of cerebral small vessel disease (SVD), and if it predicted future progression of SVD. We also determined its relationship to systemic inflammation, which has been additionally implicated in dementia and SVD.MethodsCognitively healthy midlife participants were assessed at baseline (n=185) and 2-year follow-up (n=158). To assess SVD, we quantified white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), microbleeds and lacunes. We derived composite scores of SVD burden, and subtypes of hypertensive arteriopathy and cerebral amyloid angiopathy. Inflammation was quantified using serum C-reactive protein (CRP) and fibrinogen.ResultsAt baseline, higher CAIDE scores were associated with all markers of SVD and inflammation. Longitudinally, CAIDE scores predicted greater total (p<0.001), periventricular (p<0.001) and deep (p=0.012) WMH progression, and increased CRP (p=0.017). Assessment of individual CAIDE components suggested that markers were driven by different risk factors (WMH/EPVS: age/hypertension, lacunes/deep microbleeds: hypertension/obesity). Interaction analyses demonstrated that higher CAIDE scores amplified the effect of age on SVD, and the effect of WMH on poorer memory.ConclusionHigher CAIDE scores, indicating greater risk of dementia, predicts future progression of both WMH and systemic inflammation. Findings highlight the CAIDE score’s potential as both a prognostic and predictive marker in the context of cerebrovascular disease, identifying at-risk individuals who might benefit most from managing modifiable risk.

Inflammatory biomarkers and motoric cognitive risk syndrome: Multicohort survey

“…Inflammation has been linked to risk of ischemic strokes [41] and white matter disease on neuroimaging [ 42 , 43 ], which in turn has been linked to MCR [44] . The relationship of vascular risk factors and inflammation is bidirectional with higher vascular risk predicting progression of inflammation as well as white matter hyperintensities on neuroimaging [45] . However, Eastern and Western general populations have different anatomical distributions of small vessel disease [46] ; suggesting population specific factors that may determine pathogenesis of MCR regionally.…”

Emotion Recognition in a Health Continuum: Comparison of Healthy Adults of Advancing Age, Community Dwelling Adults Bearing Vascular Risk Factors and People Diagnosed with Mild Cognitive Impairment

“…For the emotion of positive surprise, the recognition of which is also included in the Total Emotion Recognition score, it has also been found that regions involved in uncertain event recognition and processing, amygdala and insula as well as the parahippocampal, fusiform, and postcentral gyri [ 67 ], are directly affected in MCI pathology. Given that most people in the MCI group were aMCI, it must be noted that according to recent research aMCI subtypes with medial temporal lobe dysfunction perform worse in emotion recognition compared to other MCI subtypes; moreover, it has even been argued that emotion recognition is a sensitive and reliable indicator of their differential diagnosis [ 42 ].…”

“…Beyond SVD, inflammation has recently been proposed as a possible pathogenic mechanism mediating the effect of vascular risk factors on the small cerebral arteries [ 79 ] implicated in neurodegeneration [ 80 ]. A recent study [ 42 ] has shown that lower education was the main predictor of increasing levels of systemic inflammation. Furthermore, an association between age, hypertension and inflammation has already been shown [ 81 ].…”

“…In a health continuum from ‘absolute health’ to ‘death’, before MCI, a ‘stage’ of experiencing vascular aging and subtle cognitive impairment could be proposed, and, in this vein, recent research has shown that non-diagnosed vascular pathology and vascular pathology related to vascular risk factors is indeed linked to cognitive impairment [ 40 , 41 , 42 ]. In other words, it has already been argued that subclinical diseases, such as hypertension or diabetes that are common among community dwelling older adults, are linked to impaired cognition.…”

“…Indeed, recent studies have shown that cerebral small vessel disease (SVD) is recognized as a major contributor in the pathogenesis of neurodegeneration, including AD, and is closely associated with modifiable vascular risk factors, such as hypertension. Hence, SVD affecting perforating vessels in the brain, may function as a main dynamic underlying brain pathology that links the stage of experiencing vascular risk factors to the next stages of developing AD pathology [ 42 , 43 , 44 , 45 ].…”