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Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia

Gustavo C Román1, Raj N Kalaria

  • 1University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229-3900, USA.

Neurobiology of Aging
|November 23, 2005
PubMed

Insights

Alzheimer's disease and vascular dementia share overlapping features due to cerebrovascular lesions. This review explores the cholinergic system's role in vascular dementia, similar to Alzheimer's disease.

Area of Science:

  • Neuroscience
  • Neurology
  • Pathology

Background:

  • Alzheimer's disease (AD) and vascular dementia (VaD) are leading causes of dementia.
  • Cerebrovascular lesions are common in AD, leading to overlapping clinical and pathological features with VaD.
  • Cholinergic mechanisms are established in AD pathogenesis.

Purpose of the Study:

  • To review evidence for the role of cholinergic mechanisms in vascular dementia (VaD) pathogenesis.
  • To examine the susceptibility of the basal forebrain cholinergic system to vascular insults.
  • To discuss the impact of aging and cholinergic disruption on cognition and cerebral blood flow.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Examination of the anatomy and vascularization of the basal forebrain cholinergic system.
  • Analysis of evidence for cholinergic deficits in VaD.

Main Results:

  • The basal forebrain cholinergic system is vulnerable to hypertension, hypoperfusion, and ischemic cerebrovascular disease.
  • Disruption of the cholinergic system impacts cognition and cerebral blood flow control.
  • Preclinical and clinical data support cholinergic deficits in VaD.

Conclusions:

  • Cholinergic deficits are implicated in the pathogenesis of VaD.
  • Cholinesterase inhibitors may be a viable treatment for VaD.
  • Vascular pathology may initiate cholinergic neuronal abnormalities in both VaD and AD.

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