Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia

Gustavo C. Román, Raj N. Kalaria

Research output: Contribution to journalReview articlepeer-review

164 Scopus citations


Alzheimer's disease (AD) and vascular dementia (VaD) are widely accepted as the most common forms of dementia. Cerebrovascular lesions frequently coexist with AD, creating an overlap in the clinical and pathological features of VaD and AD. This review assembles evidence for a role for cholinergic mechanisms in the pathogenesis of VaD, as has been established for AD. We first consider the anatomy and vascularization of the basal forebrain cholinergic neuronal system, emphasizing its susceptibility to the effects of arterial hypertension, sustained hypoperfusion, and ischemic cerebrovascular disease. The impact of aging and consequences of disruption of the cholinergic system in cognition and in control of cerebral blood flow are further discussed. We also summarize preclinical and clinical evidence supporting cholinergic deficits and the use of cholinesterase inhibitors in patients with VaD. We postulate that vascular pathology likely plays a common role in initiating cholinergic neuronal abnormalities in VaD and AD.

Original languageEnglish (US)
Pages (from-to)1769-1785
Number of pages17
JournalNeurobiology of Aging
Issue number12
StatePublished - Dec 2006


  • Alzheimer's disease
  • Cerebrovascular disease
  • Cholinesterase inhibitors
  • Hypertension
  • Vascular dementia

ASJC Scopus subject areas

  • Clinical Neurology
  • Biological Psychiatry
  • Developmental Neuroscience
  • Neurology
  • Psychology(all)


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