title: The acetylcholine releaser linopirdine increases parietal regional cerebral blood flow in Alzheimer's disease.
abstract: Centrally acting cholinergic drugs have been reported to increase regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT) in brain regions affected by Alzheimer's disease (AD). We studied the effects of the acetylcholine releaser linopirdine (LPD) on SPECT rCBF in patients with probable AD. Twenty-four AD patients (12 M, 12 F; mean age +/- SD = 68.9 +/- 8.2 years) and 13 healthy controls (8 M, 5 F; 68.4 +/- 8.0 years) participated. AD patients were scanned with 20 mCi of Tc99m-ECD at baseline and following 4 weeks of treatment with LPD 40 mg TID (n = 15) or placebo TID (n = 9) in a double-blind trial. Healthy subjects were scanned for comparison with baseline AD scans. Cortical/cerebellar rCBF ratios were derived for nine cortical structures. The combined parietal association cortex showed a 20.6% reduction in patients relative to controls. Patients treated with LPD showed an increase in parietal rCBF of 4.1 +/- 5.8%; whereas those treated with placebo showed a decrease of -2.0 +/- 7.4% (F = 5.13; df = 1, 22; P = 0.03). These data support the conclusion that rCBF abnormalities in AD are, in part, truly "functional" and can be selectively altered with pharmacological interventions. The parietal activation seen with LPD and other cholinergic AD drug therapies suggests the importance of measuring parietal lobe neuropsychological function in the course of evaluating these drugs.
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: C H
authors.initials: CH
authors.lastname: van Dyck
authors.forename: C H
authors.initials: CH
authors.lastname: Lin
authors.forename: R
authors.initials: R
authors.lastname: Robinson
authors.forename: J
authors.initials: J
authors.lastname: Cellar
authors.forename: E O
authors.initials: EO
authors.lastname: Smith
authors.forename: J C
authors.initials: JC
authors.lastname: Nelson
authors.forename: A F
authors.initials: AF
authors.lastname: Arnsten
authors.forename: P B
authors.initials: PB
authors.lastname: Hoffer
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010296:Parietal Lobe / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000187:drug effects; D011725:Pyridines / Q000627:therapeutic use*; D012039:Regional Blood Flow; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D007211:Indoles; D011725:Pyridines; C061017:linopirdine; D000109:Acetylcholine