Intracerebroventricular bethanechol chloride infusion in Alzheimer's disease. Results of a collaborative double-blind study.

The use of intracerebroventricular bethanechol chloride infusion in patients with Alzheimer's disease was first reported in 1984. An initial trial in four patients demonstrated the feasibility of this approach for cholinergic drug delivery to the brain, but objective improvement in cognitive function was not documented. A collaborative placebo-controlled double-blind crossover study has now been carried out in 49 patients with biopsy-documented Alzheimer's disease. The results demonstrate a statistical improvement in Mini-Mental State scores and significantly slower performance on Trails A testing during drug infusion. Other neuropsychological test scores were not similarly affected. The degree of improvement was not sufficient to justify further treatment of Alzheimer's disease patients by intracerebroventricular infusion of bethanechol chloride. The drug delivery system used in the study was well tolerated, with two irreversible complications in more than 50,000 patient days.

[1]  R. Penn,et al.  Intraventricular bethanechol infusion for Alzheimer's disease , 1988, Neurology.

[2]  A. Kling,et al.  Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. , 1986, The New England journal of medicine.

[3]  M. D. O'Brien,et al.  Cerebral blood flow in dementia , 1986, Neurology.

[4]  D. Mash,et al.  Loss of M2 muscarine receptors in the cerebral cortex in Alzheimer's disease and experimental cholinergic denervation. , 1985, Science.

[5]  O. R. Blaumanis,et al.  Evidence for a ‘Paravascular’ fluid circulation in the mammalian central nervous system, provided by the rapid distribution of tracer protein throughout the brain from the subarachnoid space , 1985, Brain Research.

[6]  D. Roberts,et al.  Preliminary report: intracranial cholinergic drug infusion in patients with Alzheimer's disease. , 1984, Neurosurgery.

[7]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[8]  S. Brinkman,et al.  Measurement of cholinergic drug effects on memory in alzheimer's disease , 1983, Neurobiology of Aging.

[9]  D L Price,et al.  Alzheimer's disease: a disorder of cortical cholinergic innervation. , 1983, Science.

[10]  B. Reisberg,et al.  The Global Deterioration Scale for assessment of primary degenerative dementia. , 1982, The American journal of psychiatry.

[11]  R. Bartus,et al.  The cholinergic hypothesis of geriatric memory dysfunction. , 1982, Science.

[12]  C. Patlak,et al.  Distribution of methotrexate in the cerebrospinal fluid and brain after intraventricular administration. , 1977, Cancer treatment reports.

[13]  Elbert W. Russell,et al.  A multiple scoring method for the assessment of complex memory functions. , 1975 .

[14]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[15]  C. Patlak,et al.  Intrathecal chemotherapy: brain tissue profiles after ventriculocisternal perfusion. , 1975, The Journal of pharmacology and experimental therapeutics.

[16]  HERMAN BUSCHKE,et al.  Evaluating storage, retention, and retrieval in disordered memory and learning , 1974, Neurology.

[17]  M. Hamilton,et al.  Development of a rating scale for primary depressive illness. , 1967, The British journal of social and clinical psychology.

[18]  J. Olszewski,et al.  Penetration of radioactive bovine albumin from cerebrospinal fluid into brain tissue , 1960, Neurology.

[19]  R. Harbaugh.  Intracranial drug administration in Alzheimer's disease. , 1986, Psychopharmacology bulletin.

[20]  R. Harbaugh.  Brain biopsy in Alzheimer's disease: surgical technique and indications. , 1985, Bulletin of clinical neurosciences.

[21]  D. Rall.  Transport through the ependymal linings. , 1968, Progress in brain research.

[22]  D. Wechsler.  Manual for the Wechsler Adult Intelligence Scale. , 1955 .