Circle of Willis abnormalities and their clinical importance in ageing brains: A cadaveric anatomical and pathological study

Highlights

• Circle of Willis (CW) abnormalities were predominant in the ageing brains.

• >90 % of the ageing brains showed atherosclerosis of the CW at death.

• >90 % of the ageing brains had at least a single hypoplastic CW component.

• CW abnormalities did not associate with Alzheimer- related pathologies.

• Hypoplasia might contribute to white matter disease in the ageing brains.

Abstract

The circle of Willis (CW) located at the base of the brain forms an important collateral network to maintain adequate cerebral perfusion, especially in clinical situations requiring compensatory changes in blood flow. Morphopathological changes in the CW may relate to the severity of the symptoms of certain neurodegenerative and cerebrovascular disorders. The purpose of this study was to investigate the CW abnormalities and their clinical importance in ageing brains. The CW was examined macroscopically in 73 formalin-fixed samples to determine the degree of stenosis of each CW component, atherosclerosis of the CW, hypoplasia (threshold diameter < 1 mm), anatomical variations and aneurysms. Age-related neurodegenerative and cerebrovascular pathologies were screened using immunohistopathological techniques on specific neuroanatomical regions based on standard guidelines. The majority of the elderly brains −93 % (68/73) presented at least a single hypoplastic CW component at death. Anatomical variations were mostly identified in communicating arteries, followed by proximal posterior and anterior cerebral arteries. Arterial bifurcations were found to be the predominant sites for cerebral aneurysms. More than 90 % of the elderly brains presented CW atherosclerosis at death. CW abnormalities did not show any strong associations with neurodegenerative pathologies except for an “at risk” significant association observed between Braak’s neurofibrillary tangle (NFT) stages 1-VI and CW atherosclerosis grades ≥ mild (p = 0.05). However, a significant association was observed between microscopic infarcts in deep white matter and hypoplasia in communicating arteries with Fisher’s exact test (p < 0.05). Overall, CW abnormalities were predominant in the ageing brains, however their relationships to the occurrence and severity of the symptoms of neurodegenerative pathologies were found to be low.

Introduction

The circle of Willis (CW) located at the base of the brain forms an important collateral network to maintain adequate cerebral perfusion, especially in clinical situations requiring compensatory changes in blood flow. A typical CW is bilaterally symmetrical and a complete ring of arteries (Hoksbergen et al., 2003). There may be variations in this typical configuration. The CW components generally vary in caliber; often they are hypoplastic, duplicated or even absent (Hoksbergen et al., 2003). It has been reported that in more than 50 % of the healthy brains (Alpers et al., 1959; Lippert and Pabst, 1985; Macchi et al., 2005) and in more than 80 % of the dysfunctional brains (Riggs and Rupp, 1963), the CW contains at least one component that is absent or underdeveloped. Anatomical variations are probably genetically determined, develop in early embryonic stages and persist in post-natal life (Iqbal, 2013). Topological variations may affect the ability to maintain cerebral perfusion, which may increase the risk of stroke and transient ischemic attack in patients with atherosclerosis (Henderson et al., 2000). Typically, older patients who have a limited ability to compensate for acute changes in blood flow are at greater risk for developing an acute ischemia (stroke) or chronic hypoperfusion. Intracranial atherosclerosis increases the risk of stroke, and stroke is one of the main risks for vascular dementia (VaD) (Sacco et al., 1998). The significance of these problems should not be underestimated since stroke ranks second among the leading causes of death and third among the leading causes of disability in elderly populations (Feigin et al., 2017).

It is well known that subjects with cardiovascular risk factors and a history of stroke have increased risk of both VaD and Alzheimer’s disease (AD) (Hofman et al., 1997; Breteler, 2000; Snowdon et al., 1997). Vascular genetic risk factors include apolipoprotein E (ApoE), (Schachter et al., 1994; Corder et al., 1993; Mahley, 1988) angiotensin converting enzyme (ACE) (Catto et al., 1996; Cambien et al., 1992), methylenetetrahydrofolate reductase (MTHFR) (Frosst et al., 1995) and Factor V Leiden (FVL) (Bertina et al., 1994). Chapman et al. (1998) determined the ApoE, ACE, MTHFR and FVL polymorphisms in AD and VaD patients and reported that except for the association between ApoE ε4 allele and AD, genetic risk factors for vascular diseases were not associated with VaD. Our previous work on elderly Sri Lankan brains demonstrated that these were more susceptible to age-related cytoskeletal pathologies compared with those of other South Asian elderly populations and these variations might be related to their genetic, dietary and environmental factors (Wijesinghe et al., 2016a). Here, the minimum recommended brain regions for AD and Lewy body disease (LBD) neuropathologic change were sampled and evaluated to identify typical appearance in the elderly samples (Montine et al., 2012). We also demonstrated in elderly Sri Lankan brains that AD-related neuropathological stages were significantly associated with risk factors including increasing age, illiteracy and ApoE polymorphism. In addition, we have shown significant associations with coexisting cerebral small artery pathologies such as white matter hyperintensities and cerebral amyloid angiopathy (CAA) (Wijesinghe et al., 2016b).

The present study examined abnormalities of the CW in ageing brains to assess the clinical importance of these anatomical factors in age-related neurodegenerative and cerebrovascular pathologies, and to determine the associations between genetic risk factors and CW pathologies.