Circle of Willis Atherosclerosis Is a Risk Factor for Sporadic Alzheimer’s Disease

Abstract

Objectives-We conducted a quantitative investigation of brain arterial atherosclerotic damage and its relationship to sporadic Alzheimer's disease (AD). Methods and Results-Fifty-four consecutive autopsy cases, 32 AD and 22 nondemented control subjects, were examined to establish the degree of arterial stenosis. Vessel external and lumenal area measurements were taken from 3-mm arterial cross-sections to calculate a stenosis index. AD patient circle of Willis arteries possessed a significant degree of stenosis as a consequence of multiple and severe atherosclerotic lesions. These lesions were significantly more severe in AD cases than in age-matched controls (PϽ0.0001), and the number of stenoses and the index of occlusion (Rϭ0.67; PϽ0.00001) were positively correlated. In addition, the index of stenosis significantly correlated with the following measures of AD neuropathological lesions: total plaque score, neuritic plaque score, neurofibrillary tangle score, Braak stage score, and white matter rarefaction score. Conclusions-Our study reveals an association between severe circle of Willis atherosclerosis and sporadic AD that should be considered a risk factor for this dementia. 38 and AD subjects exhibit positive correlations between brain A␤ n-42 levels and total serum cholesterol, LDL cholesterol, and apolipoprotein (Apo) B-100 and a negative correlation with HDL cholesterol levels. 38 Elevated total and LDL cholesterol have been reported in very old patients with AD. 39 Likewise, in a meta-analysis study, patients with probable or possible early-stage AD were found to possess elevated total cholesterol values compared with a ND population. 40 In addition to the wellestablished association between vascular disease risk factors and sporadic AD, the present study provides, for the first time, a rigorous and significant neuropathological association between circle of Willis atherosclerosis and sporadic AD. See page 1951 and cover MethodsSubjects were voluntary participants in the Brain Donation Program at Sun Health Research Institute (Sun City, Ariz). Rapid autopsies (2.5-hour average postmortem delay) were performed to remove and preserve the brain. All individuals examined were Caucasian. The degree and extent of arterial stenosis was quantified in 54 consecutive autopsy cases, in which neuropathologic examination indicated presence of either AD or normal aging changes only; the latter cases were considered ND controls if the neuropsychologic profile was within normal age limits.The sample subjected to computer-based quantitative analysis contained 22 ND control cases, consisting of 14 women and 8 men with mean ages of 87.1 and 82.6 years, respectively, and 32 AD cases, 18 women and 14 men with mean ages of 84.4 and 86.4 years, respectively. History of cardiovascular disease, in particular the presence or absence of hypertension, myocardial infarction, coronary artery disease, valvular heart disease, disorders of rhythm and conduction, cardiomyopathy, cardiorespiratory failure, and peripher-

P2‐107: Intracranial Atherosclerosis as a contributing factor to Alzheimer's disease Dementia

“…The reports by ourselves and others [1][2][3][4][5] of increased intracranial AVD in AD indicate that stenosis of the arteries supplying the brain may be at least partially responsible for reduced cerebral perfusion in AD. Possible molecular mechanisms linking AD pathology and hypoperfusion include ischemia-induced alterations in Aβ precursor protein (APP) expression and APP cleavage [19], both of which increase Aβ production.…”

“…The assessment of Braak stage, total amyloid plaque score, total NFT score, total WMR score and MMSE procedure have been described elsewhere [2].…”

“…In recent years, a broad body of evidence derived from epidemiologic, correlative and experimental studies has strongly linked atherosclerotic vascular disease (AVD) with AD (reviewed in reference [1]). Postmortem studies have recently shown that individuals with AD have significantly more atherosclerotic narrowing of the intracranial arteries [1][2][3][4][5].…”

Dissimilarity-Based Classification of Anatomical Tree Structures

“…Examples of such structures and applications are: quantification of airway tree abnormalities in, e.g., chronic obstructive pulmonary disease (COPD) [1][2][3] or asthma [4], quantification of arterial stenosis in the circle of Willis in the brain [5], and quantification of retinopathy of prematurity in retinal vessels [6]. The goal is to relate the global state of the anatomical tree to the disease status based on local information in the branches of the tree.…”

“…The goal is to relate the global state of the anatomical tree to the disease status based on local information in the branches of the tree. This goal is often achieved by considering only parts of the tree and computing an average feature across the branches in those parts [1][2][3][4][5][6].…”