Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia

Alex E. Roher, Suzanne L. Tyas, Chera L. Maarouf, Ian D. Daugs, Tyler A. Kokjohn, Mark R. Emmerling, Zsolt Garami, Marek Belohlavek, Marwan N. Sabbagh, Lucia I. Sue, Thomas G. Beach

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Background: A substantial body of evidence collected from epidemiologic, correlative, and experimental studies strongly associates atherosclerotic vascular disease (AVD) with Alzheimer's disease (AD). Depending on the precise interrelationship between AVD and AD, systematic application of interventions used to maintain vascular health and function as a component of standard AD therapy offers the prospect of mitigating the presently inexorable course of dementia. To assess this hypothesis, it is vital to rigorously establish the measures of AVD that are most strongly associated with an AD diagnosis. Methods: A precise neuropathological diagnosis was established for all subjects, using a battery of genetic, clinical, and histological methods. The severity of atherosclerosis in the circle of Willis was quantified by direct digitized measurement of arterial occlusion in postmortem specimens and was compared between AD and nondemented control groups by calculating a corresponding index of occlusion. Results: Atherosclerotic occlusion of the circle of Willis arteries was more extensive in the AD group than in the nondemented control group. Statistically significant differences were also observed between control and AD groups with regard to Braak stage, total plaque score, total neurofibrillary tangle score, total white matter rarefaction score, brain weight, Mini-Mental State Examination scores, and apolipoprotein E allelic frequencies. Conclusions: Our results, combined with a consideration of the multifaceted effects of impaired cerebral circulation, suggest an immediate need for prospective clinical trials to assess the efficacy of AD prevention using antiatherosclerotic agents.

Original languageEnglish (US)
Pages (from-to)436-444
Number of pages9
JournalAlzheimer's and Dementia
Issue number4
StatePublished - Jul 2011


  • Alzheimer's disease
  • Brain hypoperfusion
  • Circle of Willis
  • Intracranial atherosclerosis
  • Vascular dementia

ASJC Scopus subject areas

  • Health Policy
  • Epidemiology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience
  • Clinical Neurology


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