Showing papers by "Serge Gauthier published in 1989"

Alzheimer's disease: environmental factors and etiologic hypotheses.

Abstract: A review of published reports on conventional and unconventional viruses, aluminum, neurotoxic metals and trace elements, neurotoxins of biological origin and immune systems, suggest that environmental factors, possibly multiple ones, play a significant role in the etiology of Alzheimer's disease. A complex interaction between genetic predisposition to this illness, natural aging processes, environmental factors over a life-time exposure and pathological alterations of the host immune system is proposed.

Progress report on the Canadian Multicentre Trial of tetrahydroaminoacridine with lecithin in Alzheimer's disease.

Abstract: Since the discovery of a significant depletion of acetylcholine in discrete areas of the brain of patients affected by Alzheimer's disease, attempts at symptomatic therapy have concentrated on acetylcholine supplementation, an approach that is based upon the efficacy of dopaminergic supplementation therapy for Parkinson's disease. Choline, then lecithin, used orally, failed to improve symptoms but the hypothesis that long-term choline supplementation might stabilize the course of Alzheimer's disease remains to be tested. Nerve growth factor may also offer that possibility. Bethanechol administered intracerebroventricularly did not help when a fixed dose was used but individual titration of more selective muscarinic agonists may prove more effective. In this article we report that tetrahydroaminoacridine (THA), given together with highly concentrated lecithin, appears to bring improvement in cognition and in functional autonomy using the Mini Mental State and the Rapid Disability Rating Scale-2 respectively, without change in behavior as reflected by the Behave-AD. Double-blind cross-over studies are in progress to establish its efficacy. Improvement in study design and means of assessment of cognition, functional autonomy and behavior have been made possible by these drug trials.

Canadian collaborative study of tetrahydroaminoacridine (THA) and lecithin treatment of Alzheimer's disease: effect on mood.

Abstract: Several lines of evidence have implicated acetylcholine (ACh) as one of the neurotransmitters found to be decreased in Alzheimer's disease (AD). Various methods of cholinergic augmentation have been attempted, with mixed results. Tetrahydroaminoacridine (THA), an acetylcholinesterase inhibitor, is currently being investigated at the McGill Centre for Studies in Aging. Preliminary uncontrolled data from a 10-week clinical trial of THA and lecithin, reported elsewhere, suggest a clinically modest but statistically significant beneficial effect on cognition, although problems exist with side effects, particularly gastrointestinal. Since the suggestion by Janowsky in 1972 that cholinergic neurotransmission may exert an inhibitory or depressant effect on mood, the evidence accumulated in the literature has been inconclusive. We undertook to assess several potential pretreatment correlates of depressive symptoms in AD and to monitor the course of these symptoms during the 10 week treatment period, using the Geriatric Depression Scale (GDS) of Brink and Yesavage. Pretreatment GDS scores were found to correlate with degree of overall disability and dementia as measured by the Rapid Disability Rating Scale (RDRS) and the Mini Mental State Examination (MMS), respectively. GDS scores over the treatment period did not change to a statistically significant degree. The meaning of these results is discussed, particularly with reference to the difficulty of diagnosis and measurement of depression in the setting of dementia.

Thyrotropin-releasing hormone given intrathecally to the rat increases arterial pressure and heart rate.

Abstract: In view of evidence implicating thyrotropin-releasing hormone (TRH) as a chemical mediator of synaptic transmission onto spinal sympathetic neurons, this peptide was administered intrathecally, in a dose of 6.5 nmol, at the T9 and T2 spinal levels in the anesthetized rat. At the lower thoracic level TRH increased arterial pressure and heart rate; these effects peaked at 4-7 minutes and decayed over the next 15-20 minutes. At the upper thoracic level the pressor and cardioacceleratory responses were roughly similar in time course but were smaller in magnitude. Hexamethonium (10 mg/kg i.v.) was tested on the responses from the lower thoracic level; both pressor and cardioacceleratory responses persisted after hexamethonium pretreatment. In addition, intravenous administration of 6.5 nmol of TRH failed to alter arterial pressure or heart rate, suggesting that the effects produced by the intrathecal administration of TRH were due to an action of the peptide in the spinal cord. The results also indicate that the pressor effect and the increase in heart rate may be mediated in the sympathetic ganglia at least partly via nonnicotinic transmission. Our results provide physiological support for the possibility that TRH is a chemical mediator of synaptic transmission onto sympathetic preganglionic neurons. This study indicates that the functional sympathetic pathways utilizing TRH as a chemical mediator include those regulating arterial pressure and heart rate.

Ascertainment of informative Alzheimer disease families from the IMAGE Project registry for genetic linkage analysis studies.

Abstract: Genetic linkage analysis requires the identification and documentation of large families with many affected members present, preferably in more than one generation. The IMAGE Project has been establishing a population- based Alzheimer disease (AD) registry in the Saguenay - Lac-Saint-Jean region of the Province of Quebec. The population of this region has a well-documented ancestry, with reliable genealogical records (since 1842) computerized by SORER We have recently begun to investigate the pedigrees of selected probands (definite, probable and possible) from the IMAGE registry in order to identify informative pedigrees for genetic linkage analysis. Interviews were carried out with close relatives of the probands (at least one informant per sibship) to identify secondary AD cases. The questionnaires used pertain to the accuracy of genealogical records, to family medical history and to a retrospective diagnosis of AD for people with cognitive deficits. By these means, we have documented a large extended pedigree in which a total of 15 individuals with cognitive deficits were ascertained over three generations. Of these cases, 7 are still living and there is autopsy confirmation in another one. Computer simulations using the program SIMLINK revealed that this is a potentially informative family for linkage analysis. Horizontal extension of the pedigree to second cousins of the proband is now being carried out. This will render the family IMAGE/1 even more informative in genetic linkage analysis studies.