Objective: Most pathologic studies indicate that significant vascular changes are found in the majority of elderly persons, either alone or in association with neurodegenerative processes such as Alzheimer disease (AD) or dementia with Lewy bodies (DLB). Cumulative burden of cerebrovascular lesions can explain cognitive decline described as vascular cognitive impairment, but because there is a lack of consensus in the best way to quantify vascular pathology, the relationship between cognitive decline and cerebrovascular disease remains uncertain. We developed a rating scheme for cerebrovascular lesions using postmortem brains from patients with dementia from 2 European tertiary care memory clinics. Methods:A total of 135 brains with a neuropathologic diagnosis of vascular dementia (VaD) (n ϭ 26), AD ϩ VaD (n ϭ 39), DLB ϩ VaD (n ϭ 21), AD ϩ DLB ϩ VaD (n ϭ 9), AD (n ϭ 19), and DLB (n ϭ 21) were investigated in this study. Cerebrovascular lesions were rated on large sections from the hippocampus, the temporal lobe, the frontal lobe, and basal ganglia. Results:In patients with dementia, vessel wall modifications such as arteriolosclerosis or amyloid angiopathy are the most common and presumably the earliest changes. Modifications in perivascular spaces and myelin loss are the next most common. Lacunar or regional infarcts may occur as a consequence of an independent process or in the final phase of small vessel diseases. Conclusion:A staging system based on this conceptual model of cerebrovascular pathology could enable the neuropathologic quantification of the cerebrovascular burden in dementia. Further studies are needed to determine whether this system can be used in large-scale studies to understand clinical-cerebrovascular pathologic correlations. Neurology Vascular cognitive impairment (VCI) is regarded as the second most common cause of cognitive disorder after Alzheimer disease (AD).1 VCI is a frequent consequence of various cerebrovascular lesions (CVL) resulting from disrupted circulation or perfusion in different brain regions. Imaging and postmortem studies have shown that CVL may also be found in cognitively normal elderly subjects 2-4 and in more than 50% of cases with neurodegenerative disorders such as AD or dementia with Lewy bodies (DLB). 5Despite considerable efforts, to date there are no consensual neuropathologic criteria for vascular (VaD) and mixed dementia. The postmortem diagnosis of VCI mostly relies on the identification of significant CVL 6 in the absence of other changes that may explain the cognitive decline.7 For mixed cases, neuropathologists are compelled to identify a threshold above which CVL would be considered as significant from a strictly subjective point of view. Such quantification could only be obtained from sampled brain areas since an extensive microscopic examination of the whole brain is impractical. Attempts have been made to identify From the Institute for Ageing and Health

The aim of this study was to characterize myelin loss as one of the features of white matter abnormalities across three common dementing disorders. We evaluated post-mortem brain tissue from frontal and temporal lobes from 20 vascular dementia (VaD), 19 Alzheimer’s disease (AD) and 31 dementia with Lewy bodies (DLB) cases and 12 comparable age controls. Images of sections stained with conventional luxol fast blue were analysed to estimate myelin attenuation by optical density. Serial adjacent sections were then immunostained for degraded myelin basic protein (dMBP) and the mean percentage area containing dMBP (%dMBP) was determined as an indicator of myelin degeneration. We further assessed the relationship between dMBP and glutathione S-transferase (a marker of mature oligodendrocytes) immunoreactivities. Pathological diagnosis significantly affected the frontal but not temporal lobe myelin attenuation: myelin density was most reduced in VaD compared to AD and DLB, which still significantly exhibited lower myelin density compared to ageing controls. Consistent with this, the degree of myelin loss was correlated with greater %dMBP, with the highest %dMBP in VaD compared to the other groups. The %dMBP was inversely correlated with the mean size of oligodendrocytes in VaD, whereas it was positively correlated with their density in AD. A two-tier regression model analysis confirmed that the type of disorder (VaD or AD) determines the relationship between %dMBP and the size or density of oligodendrocytes across the cases. Our findings, attested by the use of three markers, suggest that myelin loss may evolve in parallel with shrunken oligodendrocytes in VaD but their increased density in AD, highlighting partially different mechanisms are associated with myelin degeneration, which could originate from hypoxic–ischaemic damage to oligodendrocytes in VaD whereas secondary to axonal degeneration in AD.

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