1. Few studies assessed collinearity or interactions between neuropathologies. Deramecourt et al. 31 assessed the distribution and frequency of individual cerebrovascularlesions and reported vessel wall modifications as the most common pathology. They postulated a staging system for CVD and suggested that initial vessel wall modification (arteriolosclerosis, CAA, or both) could lead to perivascular space changes and parenchymal damage, which manifest as either white matter changes or microinfarcts. The weighting of the constituent neuropathologies was then based on the frequency and presumed order of these lesions. Several SVD studies 33 – 35 used a semiquantitative scale to reflect the presumed progression of microvascular disease, often with visual aids. The majority of studies included pathologic markers based on a priori knowledge without an explicit description of weighting of individual pathologies. Two studies examined the univariate associations of lesions with cognitive impairment to help construct an index. Skrobot et al. 11 found that 7 of their 14 agreed-upon neuropathologies were associated with cognitive impairment. These were then entered into a multivariable regression model to identify which combination of pathologies was most strongly associated with cognitive impairment and they reported that a single pathology predicted cognitive impairment with 60%–65% accuracy, but using the best 3 predictors increased this to 78%. Further, having 1, 2, or 3 of these pathologies predicted cognitive impairment with 38%, 75%, and 95% accuracy, respectively. Strozyk et al. 32 reported that all their macrovascular lesions were associated with VaD: large infarcts, lacunar infarcts, and leukoencephalopathy. However, when considered together, only the presence of large infarcts remained significant.
2. Cerebral small vessel disease: from pathogenesis and clinical characteristics to therapeutic challenges
3. The overlap between vascular disease and Alzheimer’s disease - lessons from pathology
4. Pathophysiologic relationship between Alzheimer's disease, cerebrovascular disease, and cardiovascular risk: a review and synthesis;Santos;Alzheimers Dement,2017
5. Potential for primary prevention of Alzheimer's disease: an analysis of population-based data