Cerebral blood flow in Alzheimer's disease

Alex E. Roher, Josef P. Debbins, Michael Malek-Ahmadi, Kewei Chen, James G. Pipe, Sharmeen Maze, Christine Belden, Chera L. Maarouf, Pradeep Thiyyagura, Hua Mo, Jesse M. Hunter, Tyler A. Kokjohn, Douglas G. Walker, Jane C. Kruchowsky, Marek Belohlavek, Marwan N. Sabbagh, Thomas G. Beach

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


Background: Alzheimer's disease (AD) dementia is a consequence of heterogeneous and complex interactions of age-related neurodegeneration and vascular-associated pathologies. Evidence has accumulated that there is increased atherosclerosis/arteriosclerosis of the intracranial arteries in AD and that this may be additive or synergistic with respect to the generation of hypoxia/ischemia and cognitive dysfunction. The effectiveness of pharmacologic therapies and lifestyle modification in reducing cardiovascular disease has prompted a reconsideration of the roles that cardiovascular disease and cerebrovascular function play in the pathogenesis of dementia. Methods: Using two-dimensional phase-contrast magnetic resonance imaging, we quantified cerebral blood flow within the internal carotid, basilar, and middle cerebral arteries in a group of individuals with mild to moderate AD (n = 8) and compared the results with those from a group of age-matched nondemented control (NDC) subjects (n = 9). Clinical and psychometric testing was performed on all individuals, as well as obtaining their magnetic resonance imaging-based hippocampal volumes. Results: Our experiments reveal that total cerebral blood flow was 20% lower in the AD group than in the NDC group, and that these values were directly correlated with pulse pressure and cognitive measures. The AD group had a significantly lower pulse pressure (mean AD 48, mean NDC 71; P = 0.0004). A significant group difference was also observed in their hippocampal volumes. Composite z-scores for clinical, psychometric, hippocampal volume, and hemodynamic data differed between the AD and NDC subjects, with values in the former being significantly lower (t = 12.00, df = 1, P = 0.001) than in the latter. Conclusion: These results indicate an association between brain hypoperfusion and the dementia of AD. Cardiovascular disease combined with brain hypoperfusion may participate in the pathogenesis/pathophysiology of neurodegenerative diseases. Future longitudinal and larger-scale confirmatory investigations measuring multidomain parameters are warranted.

Original languageEnglish (US)
Pages (from-to)596-611
Number of pages16
JournalVascular health and risk management
Issue number1
StatePublished - 2012


  • Alzheimer's disease
  • Arteriosclerosis
  • Atherosclerosis
  • Brain hypoperfusion
  • Brain morphometric analyses
  • Cerebral blood flow
  • Cognitive impairment
  • Two-dimensional phase-contrast magnetic resonance imaging

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Hematology
  • Public Health, Environmental and Occupational Health
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)


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