Vascular Imaging Abnormalities and Cognition

Abstract

Background and Purpose The relationships between cerebrovascular lesions visible on imaging and cognition are complex. We explored the possibility that cerebral cortical volume mediated the relationship. Methods 1906 non-demented participants (59% women; 25% African-American; mean age 76.6 years) in the Atherosclerosis Risk in Communities (ARIC) study underwent cognitive assessments, risk factor assessments, and quantitative MR imaging for white matter hyperintensities (WMH) and infarcts. The Freesurfer imaging analysis pipeline was used to determine regional cerebral volumes. We examined associations of cognitive domain outcomes with cerebral volumes (hippocampus, and separate groups of posterior and frontal cortical regions of interest (ROI)) and cerebrovascular imaging features (presence of large or small cortical/subcortical infarcts and WMH volume). We performed mediation pathway analyses to assess the hypothesis that hippocampal and cortical volumes mediated associations between cerebrovascular imaging features and cognition. Results In unmediated analyses, WMH and infarcts were both associated with worse psychomotor speed/executive function (PS/EF). In mediation analyses, WMH and infarcts associations on PS/EF were significantly attenuated, but not abolished, by the inclusion of the posterior cortical ROI volume in the models, and the infarcts on PS/EF association was attenuated, but not abolished, by inclusion of the frontal cortical ROI volume. Conclusions Both WMH and infarcts were associated with cortical volume, and both lesions were also associated with cognitive performance, implying shared pathophysiological mechanisms. Although cross-sectional, our findings suggest that WMH and infarcts could be proxies for clinically covert processes that directly damage cortical regions. Microinfarcts are one candidate for such a clinically covert process.

Vascular Risk Factors and Findings on Brain MRI of Elderly Adult American Indians: The Strong Heart Study

“…Among our brain MRI findings, the strongest associations with diabetes appeared in measures of brain atrophy, including sulcal widening, ventricle enlargement, and reduced overall brain volume. Similar associations have been reported in several other studies [35][36][37][38][39][40][41], including studies of middle-aged African Americans [41,42] and Asians [43,44]. The underlying mechanism remains unclear, but in addition to microvascular disease, both hydration status and direct neurodegeneration might be involved [45,46].…”

Development of a cerebrovascular magnetic resonance imaging biomarker for cognitive aging

“…Although there have been consistent corpus callosum/vascular risk findings in the literature, the anterior part (genu) of the corpus callosum may be most susceptible to vascular disease effects due to its small diameter or thin fibers compared to the posterior part (splenium) of the corpus callosum, where the fibers are larger in diameter. In addition, frontal lobes appear to be more susceptible to cerebrovascular disease, have greater burden of WM lesions, and are also a convergence point for several brain connections,6, 32, 49 supporting the use of genu FA as the cerebrovascular biomarker.…”

“…Because the accumulation of chronic conditions (in this study, worsening vascular health) has been equated to accelerated aging, these results are as expected. There is evidence supporting the association between increased vascular risk and atrophy in regions vulnerable to AD 7, 32, 33, 34. Given that the associations of systemic vascular health and AD with sMRI are observed in the same regions, sMRI does not qualify as an independent prodromal biomarker for cerebrovascular health.…”

Age, vascular health, and Alzheimer disease biomarkers in an elderly sample

“…Several studies have shown that decline in vascular health has a significant impact on brain health and also increases the risk of AD dementia 3–9 . While it is well known that the impact of vascular health on cognitive performance is mediated via vascular brain injury 6, 8 , the direct impact of vascular health on each individual ADP process, namely amyloid, tau, and AD-associated neurodegeneration, is poorly understood and the interrelationships between ADP and vascular health are highly debated.…”