Autoregulation of cerebral blood flow to changes in arterial pressure in mild Alzheimer's disease.
Studies in transgenic mice overexpressing amyloid precursor protein (APP) demonstrate impaired autoregulation of cerebral blood flow (CBF) to changes in arterial pressure and suggest that cerebrovascular dysfunction may be critically important in the development of pathological Alzheimer's disease (AD). Given the relevance of such a finding for guiding hypertension treatment in the elderly, we assessed autoregulation in individuals with AD. Twenty persons aged 75±6 years with very mild or mild symptomatic AD (Clinical Dementia Rating 0.5 or 1.0) underwent (15)O-positron emission tomography (PET) CBF measurements before and after mean arterial pressure (MAP) was lowered from 107±13 to 92±9 mm Hg with intravenous nicardipine; (11)C-PIB-PET imaging and magnetic resonance imaging (MRI) were also obtained. There were no significant differences in mean CBF before and after MAP reduction in the bilateral hemispheres (-0.9±5.2 mL per 100 g per minute, P=0.4, 95% confidence interval (CI)=-3.4 to 1.5), cortical borderzones (-1.9±5.0 mL per 100 g per minute, P=0.10, 95% CI=-4.3 to 0.4), regions of T2W-MRI-defined leukoaraiosis (-0.3±4.4 mL per 100 g per minute, P=0.85, 95% CI=-3.3 to 3.9), or regions of peak (11)C-PIB uptake (-2.5±7.7 mL per 100 g per minute, P=0.30, 95% CI=-7.7 to 2.7). The absence of significant change in CBF with a 10 to 15 mm Hg reduction in MAP within the normal autoregulatory range demonstrates that there is neither a generalized nor local defect of autoregulation in AD.
Zazulia
Allyson R
AR
Department of Neurology, Washington University, St Louis, Missouri 63110, USA. zazuliaa@neuro.wustl.edu
Videen
Tom O
TO
Morris
John C
JC
Powers
William J
WJ
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000503:physiopathology*; D001794:Blood Pressure; D002560:Cerebrovascular Circulation; D005260:Female; D006706:Homeostasis; D006801:Humans; D049292:Leukoaraiosis / Q000175:diagnosis; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography; D012720:Severity of Illness Index