title: Cerebral blood flow in Alzheimer's disease.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, AZ 85351, USA. alex.roher@bannerhealth.com
authors.forename: Alex E
authors.initials: AE
authors.lastname: Roher
authors.forename: Josef P
authors.initials: JP
authors.lastname: Debbins
authors.forename: Michael
authors.initials: M
authors.lastname: Malek-Ahmadi
authors.forename: Kewei
authors.initials: K
authors.lastname: Chen
authors.forename: James G
authors.initials: JG
authors.lastname: Pipe
authors.forename: Sharmeen
authors.initials: S
authors.lastname: Maze
authors.forename: Christine
authors.initials: C
authors.lastname: Belden
authors.forename: Chera L
authors.initials: CL
authors.lastname: Maarouf
authors.forename: Pradeep
authors.initials: P
authors.lastname: Thiyyagura
authors.forename: Hua
authors.initials: H
authors.lastname: Mo
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Hunter
authors.forename: Tyler A
authors.initials: TA
authors.lastname: Kokjohn
authors.forename: Douglas G
authors.initials: DG
authors.lastname: Walker
authors.forename: Jane C
authors.initials: JC
authors.lastname: Kruchowsky
authors.forename: Marek
authors.initials: M
authors.lastname: Belohlavek
authors.forename: Marwan N
authors.initials: MN
authors.lastname: Sabbagh
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Beach
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000503:physiopathology* / Q000523:psychology; D053327:Apolipoprotein E4 / Q000378:metabolism; D001794:Blood Pressure / Q000502:physiology; D016022:Case-Control Studies; D002536:Cerebral Arteries / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D003071:Cognition / Q000502:physiology; D015331:Cohort Studies; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D018810:Magnetic Resonance Angiography / Q000379:methods; D008279:Magnetic Resonance Imaging; D008297:Male; D010865:Pilot Projects; D011594:Psychometrics
chemical_list: D053327:Apolipoprotein E4
keywords: Alzheimer’s disease; arteriosclerosis; atherosclerosis; brain hypoperfusion; brain morphometric analyses; cerebral blood flow; cognitive impairment; two-dimensional phase-contrast magnetic resonance imaging