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September 2006

Stroke and Memory Decline: A Question of Degenerative or Vascular Origin

Arch Neurol. 2006;63(9):1348. doi:10.1001/archneur.63.9.1348

In reply

We appreciate the comments by Dr Panza and colleagues regarding our article demonstrating a relation between stroke and memory decline.1 Several studies have shown an association between dementia and cognitive decline and cerebrovascular disease, defined either by history of a clinical stroke2 or identified by brain imaging.3 Cerebrovascular disease is a precursor to vascular dementia, but it is unclear what role cerebrovascular disease or its antecedents have in AD, which is characterized by the deposition of amyloid β.4 It is possible that cerebrovascular disease causes an amnestic syndrome that mimics AD through strategic infarcts, hippocampal sclerosis, or other mechanisms. Alternatively, vascular disease may be a more direct cause of AD or act as a comorbid condition accompanying diabetes, hypercholesterolemia, or other vascular risk factors, reducing the threshold at which symptoms develop. Our study could not address any of these mechanisms and simply underlines the importance of stroke in what until recently were thought to be nonvascular cognitive syndromes. The coexistence of pathological features of cerebrovascular disease and AD at autopsy does not help clarify these issues either because one cannot discern the sequence of events and thus separate cause and effect. A study of more than 1000 autopsied brains showed that large vessel atherosclerotic disease, but not cerebral infarcts or small vessel cerebrovascular disease, was related to increased frequency of neuritic plaques,5 suggesting that ischemia or atherosclerosis risk factors, but not stroke itself, may cause AD pathology. Thus, studies are needed to clarify the full range of mechanisms linking cerebrovascular disease to AD and amnestic syndromes. In the meantime, it seems sensible to recommend the prevention and treatment of cerebrovascular disease and its risk factors for the prevention or delay of all forms of cognitive impairment associated with aging.