Cerebral blood flow in Alzheimer’s disease

Alex E Roher,1 Josef P Debbins,2 Michael Malek-Ahmadi,3 Kewei Chen,4 James G Pipe,2 Sharmeen Maze,2 Christine Belden,3 Chera L Maarouf,1 Pradeep Thiyyagura,4 Hua Mo,4 Jesse M Hunter,1 Tyler A Kokjohn,1,5 Douglas G Walker,6 Jane C Kruchowsky,6 Marek Belohlavek,7 Marwan N Sabbagh,3 Thomas G Beach81The Longtine Center for Neurodegenerative Biochemistry, Banner Sun Health Research Institute, Sun City, 2Keller Center for Imaging Innovation, Neuroimaging Research, Barrow Neurological Institute, Phoenix, 3Cleo Roberts Center for Clinical Research, Banner Sun Health Research Institute, Sun City, 4Computational Image Analysis Program, Banner Alzheimer’s Institute, Phoenix, 5Department of Microbiology, Midwestern University, Glendale, 6Laboratory of Neuroinflammation, Banner Sun Health Research Institute, Sun City, 7Division of Cardiovascular Diseases, Mayo Clinic, Scottsdale, 8Civin Laboratory for Neuropathology, Banner Sun Health Research Institute, Sun City, AZ, USABackground: 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.Keywords: Alzheimer’s disease, cerebral blood flow, brain hypoperfusion, two-dimensional phase-contrast magnetic resonance imaging, brain morphometric analyses, atherosclerosis, arteriosclerosis, cognitive impairmen