Cerebral vessel disease increases Alzheimer's dementia risk

By Lucy Piper

Cerebral vessel disease may be an under-recognised risk factor for Alzheimer's disease (AD) dementia, say researchers.

Their neuropathological study showed that cerebral atherosclerosis and arteriosclerosis were both independently associated with a higher likelihood of AD dementia and impaired performance on most cognitive domains.

"This finding suggests that the effect of cerebral vessel disease on cognition might be more widespread than anticipated", says the team, led by Zoe Arvanitakis (Rush University Medical Center, Chicago, Illinois, USA). "

Among 1143 individuals aged 65 years or older who underwent annual neuropsychological assessments as part of one of two studies of aging (The Religious Orders Study and the Rush Memory and Aging Project), cerebral vessel disease was most common among the 478 individuals with possible or probable AD dementia. Moderate-to-severe atherosclerosis was detected in 46% and arteriosclerosis in 41%, compared with a respective 34% and 31% of those without AD dementia.

The researchers report in The Lancet Neurology that with each grade increase in the severity of atherosclerosis or arteriosclerosis, the risk of AD dementia increased by a significant 33%. The association was stronger for atherosclerosis than arteriosclerosis, at risk increases of 33% and 20%, respectively.

Arvanitakis and colleagues comment that the effects of moderate atherosclerosis and severe arteriosclerosis on AD dementia risk are comparable to those of gross infarcts. However, the association was independent of gross and microscopic infarcts as well as AD pathology, vascular risk factors and apolipoprotein ε4 allele status.

Neurodegenerative pathology from autopsies suggested that the specific cognitive effects of cerebral vascular disease were not restricted to domains normally associated with vascular pathologies, namely perceptual speed. Increasing severity of either atherosclerosis or arteriosclerosis was associated with worsening global cognition and significantly impaired perceptual speed, episodic and semantic memory and, for atherosclerosis only, visuospatial abilities.

"This examination might eventually allow early detection and treatment of impairment, clinical differentiation of Alzheimer's disease from vascular pathologies, and shed further light onto the pathophysiological mechanisms by which vessel disease can lead to dementia", the researchers suggest.

In a related comment, Peter Nelson (University of Kentucky, Lexington, USA), says that the findings "emphasise three key ideas: the lack of specificity of clinically defined Alzheimer's disease, the importance and heterogeneity of cerebrovascular pathology, and the complexity of cerebral multimorbidity."

Indeed, this was also implied in another study published this week showing different factors at play in the risk of early and late dementia after intracerebral haemorrhage.

Nelson points out that the aged brain is complex and "we should resist the temptation to ration diagnoses". He says: "The cognitive deficits that occur in Alzheimer's disease, Alzheimer's disease plus atherosclerosis, and Alzheimer's disease plus arteriosclerosis might overlap extensively, but, if people, from all three diagnostic categories are included in the same clinical trial, treatment effects might be diluted.

"Furthermore, the postulated protective effects of diet and exercise (and other factors) might result from their effects on non-Alzheimer's disease processes that manifest at autopsy as cerebrovascular pathology."

Source: Lancet Neurol 2016; Advance online publication

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