Atherosclerosis, dementia, and Alzheimer disease in the Baltimore Longitudinal Study of aging cohort

Abstract

Objective-Although it is now accepted that asymptomatic cerebral infarcts are an important cause of dementia in the elderly, the relationship between atherosclerosis per se and dementia is controversial. Specifically, it is unclear whether atherosclerosis can cause the neuritic plaques and neurofibrillary tangles that define Alzheimer neuropathology and whether atherosclerosis, a potentially reversible risk factor, can influence cognition independent of brain infarcts.Methods-We examined the relationship between systemic atherosclerosis, Alzheimer type pathology and dementia in autopsies from 200 participants in the Baltimore Longitudinal Study of Aging (BLSA), a prospective study of the effect of aging on cognition, 175 of whom had complete body autopsies.Results-Using a quantitative analysis of atherosclerosis in the aorta, heart and intracranial vessels, we found no relationship between the degree of atherosclerosis in any of these systems and the degree of Alzheimer's type brain pathology. However, we found that the presence of intracranial but not coronary or aortic atherosclerosis significantly increased the odds of dementia, independent of cerebral infarction. Given the large number of individuals with intracranial atherosclerosis in this cohort (136/200), the population attributable risk of dementia related to intracranial atherosclerosis (independent of infarction) is substantial and potentially reversible.Interpretation-Atherosclerosis of the intracranial arteries is an independent and important risk factor for dementia, suggesting potentially reversible pathways unrelated to Alzheimer's pathology and stroke through which vascular changes may influence dementia risk.

Vascular dementia: why pathology is still important

“…51 The BLSA data also raise the possibility that large diameter vessel intracranial atherosclerosis has a local effect upon the brain to produce dementia that is independent of the presence of cerebral infarction, systemic atherosclerosis (carotid disease) and AD pathology. 18 According to these authors, these data support the view of 'an association between atherosclerosis and cognition that is independent of cerebral infarction'. An explanation for this would be a common mechanism that produces both intracranial atherosclerosis and neurodegeneration (dementia), such as oxidative stress, disruption of the BBB, or dysfunction of communication between local blood flow and neuron metabolism (neurovascular unit).…”

“…The prospective Baltimore Longitudinal Study of Aging (BLSA) examined 179 brains of 579 participants 18,23 and showed that the number of macroscopic hemispheric infarcts, either obvious or clinically silent, contributed to 35% of the dementia cases in the study. It was the presence of a cerebral infarct and not any associated risk factors, such as coronary artery disease and hypertension, that determined the risk of dementia.…”

“…[17][18][19] Intracranial atherosclerosis (involving large diameter arteries) was regarded as the most likely explanation for multi-infarct dementia 20 and recently intracranial atherosclerosis has been identified as a risk factor for dementia that is independent of cerebral infarction and other risk factors, such as peripheral atherosclerosis, systemic hypertension and age. 18,[20][21][22][23] Vascular pathology, including SVD, co-existing in the same brain as individuals with only moderate AD pathology, unexpectedly increased the severity of dementia, raising the possibility of a common set of risk factors shared by VaD and AD. 5,25,26 White matter lesions detected by imaging have also been shown to have a strong influence on progression of cognitive decline and are regarded a further surrogate marker of SVD.…”

C-reactive protein levels and risk of disabling dementia with and without stroke in Japanese: The Circulatory Risk in Communities Study (CIRCS)

“…High CRP facilitates the formation of foam cells in the process of atherogenesis [25] and also impairs endothelial function by attenuating the production of nitric oxide [35]. Both processes contribute the cognitive decline in older adults [36]. In addition, increased myo-inositol signal is a neurochemical abnormality associated with cognitive decline and Alzheimer's disease [37].…”

Alzheimer’s disease and cardio-vascular pathology

“…L'étude anatomopathologique de 200 cerveaux de la Baltimore Longitudinal Study of Aging [29] montre que seule l'athérosclérose intracrânienne majore l'apparition de lésions de MA, indépendamment de la pré-sence d'infarctus cérébraux.…”