Staging and natural history of cerebrovascular pathology in dementia

Abstract

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 = 26), AD + VaD (n = 39), DLB + VaD (n = 21), AD + DLB + VaD (n = 9), AD (n = 19), and DLB (n = 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.

Figure 1. Rating templates of key cerebrovascular lesions

Figure 2. Relative frequency of the cerebrovascular lesions

The vascular group (n = 95) encompassed vascular dementia (VaD), Alzheimer disease (AD) + VaD, dementia with Lewy bodies (DLB) + VaD, and AD + DLB + VaD cases. The nonvascular group (n = 40) included AD and DLB cases. Each bar represents the proportion of cases affected by moderate to severe modifications or by the presence of infarcts.

Figure 3. Distribution of the cerebrovascular lesions, example of the frontal lobe

Cases were ordered according to the severity of cerebrovascular lesion (CVL) assessment in the frontal lobe. Gray-shaded areas represent moderate to severe modification or the presence of infarcts. The progressive increment of CVL was weighted into 7 scores from 0 to VI as defined in table 2. A similar hierarchical extent was observed in the temporal lobe and basal ganglia (not shown). AD = Alzheimer disease; DLB = dementia with Lewy bodies; VaD = vascular dementia.