title: Cortical oxygen supply during postural hypotension is further decreased in Alzheimer's disease, but unrelated to cholinesterase-inhibitor use.
abstract: Cerebrovascular function and structure of the cortical cerebral microvessels are profoundly altered in patients with Alzheimer's disease (AD). The functional hemodynamic consequences of such changes, however, remain essentially unknown. Cholinesterase inhibitors (ChEIs) potentially affect brain perfusion through either augmentation or inhibition of cerebral vasodilatation. This study investigated the cerebrovascular regulation during postural changes in AD before and after treatment with the ChEI galantamine. In 21 AD patients and 20 controls, blood pressure (BP--Finapres), frontal cortical oxygenation (near-infrared-spectroscopy), and cerebral blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasonography) were measured following a hypotensive challenge induced by postural change. In AD, measurements were repeated after 10 (SD 4) weeks of galantamine. Baseline cerebrovascular resistance was higher in AD (AD 2.83 (0.87) mmHg/cm/s, control 2.24 (1.3) mmHg/cm/s, p=0.010). 13 AD patients and 17 controls had a sufficiently large postural drop in BP (> 10 mmHg). AD patients had a larger postural decline in the frontal cortical concentration of total hemoglobin (Delta [tHb] AD=1.03 (0.70) micromol/l, control =0.30 (0.90) micromol/l, p=0.015). Moreover, the reduction in oxygenated hemoglobin was 57% larger in AD (p=0.085). Unexpectedly, the postural changes in BP were smaller in AD. Galantamine treatment affected neither orthostatic BP nor the decrease in [tHb]. In conclusion, even for moderate orthostatic hypotension during commonly occurring postural changes, cerebral cortical tissue perfusion declined more in AD, suggesting increased ischemic vulnerability of the brain. Galantamine neither improved nor impaired cerebrovascular regulation.
authors.affiliation: Radboud University Nijmegen Medical Centre, Department of Geriatric Medicine, Nijmegen, The Netherlands.
authors.forename: Arenda H E A
authors.initials: AH
authors.lastname: van Beek
authors.forename: Jaap C
authors.initials: JC
authors.lastname: Sijbesma
authors.forename: Rene W M M
authors.initials: RW
authors.lastname: Jansen
authors.forename: Marcel G M Olde
authors.initials: MG
authors.lastname: Rikkert
authors.forename: Jurgen A H R
authors.initials: JA
authors.lastname: Claassen
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage*; D005260:Female; D005702:Galantamine / Q000008:administration & dosage*; D006801:Humans; D007024:Hypotension, Orthostatic / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D020768:Middle Cerebral Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D010100:Oxygen / Q000097:blood*; D010108:Oxyhemoglobins / Q000378:metabolism; D019265:Spectroscopy, Near-Infrared; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D002800:Cholinesterase Inhibitors; D010108:Oxyhemoglobins; D005702:Galantamine; D010100:Oxygen