Showing papers by "Serge Gauthier published in 1994"

Predictive value of apolipoprotein E genotyping in Alzheimer's disease: Results of an autopsy series and an analysis of several combined studies

Abstract: Apoliprotein E (apoE) is associated with Alzheimer's neurofibrillary tangles and beta-amyloid protein in senile plaques. Recent studies have shown an increased frequency of the epsilon 4 allele of the apoE gene in familial and sporadic cases of Alzheimer's disease (AD). In the present case control study, we have determined the apoE genotype by allele-specific extension of 113 postmortem cases of sporadic AD and 77 control brains shown to be free of AD neuropathological features and then calculated the frequency of the various allelic forms of apoE (epsilon 2, epsilon 3, epsilon 4). The odds ratio associating epsilon 4 with AD was 15.5 (95% confidence interval [CI] 6.2-38.5), and the population attributable risk was 0.53. We have also combined the results of our study and several others to calculate these same parameters in a larger population (570 controls and 961 AD subjects); the odds ratio for this larger group was 6.2 (95% CI 4.9-7.8) and the population attributable risk was 0.57. These results further substantiate and strengthen the association between the epsilon 4 allele of apoE gene and AD. We have also used these results to investigate the usefulness of the determination of epsilon 4 carrier status in the diagnosis of AD.

Health of Family Members Caring for Elderly Persons with Dementia: A Longitudinal Study

Abstract: Objective: To estimate the change in depression and physical symptoms during a 1-year period in a group of caregivers for elderly persons with dementia and in a group of comparison participants. De...

Cross–national interrater agreement on the clinical diagnostic criteria for dementia

Abstract: We assessed the interobserver agreement on the clinical diagnosis of dementia syndrome and dementia subtypes as part of a cross-national project on the prevalence of dementia. Fourteen clinicians from the participating countries (Canada, Chile, Malta, Nigeria, Spain, and the United States) independently assessed the diagnosis of 51 patients whose clinical information was in standard records written in English. We used the DSM-III-R and ICD-10 criteria for dementia syndrome, the NINCDS-ADRDA criteria for Alzheimer9s disease (AD), and the ICD-10 criteria for other dementing diseases, and measured interobserver agreement. We found comparable levels of agreement on the diagnosis of dementia using the DSM-III-R (K = 0.67) as well as the ICD-10 criteria (K = 0.69). Cognitive impairment without dementia was a major source of disagreement (K = 0.10). The kappa values were 0.58 for probable AD, 0.12 for possible AD, and rose to 0.72 when the two categories were merged. The interrater reproducibility of the diagnosis of vascular dementia was 0.66 in terms of kappa index; the diagnoses of other dementing disorders as a whole reached a kappa value of 0.40. This study suggests that clinicians from different cultures and medical traditions can use the DSM-III-R and the ICD-10 criteria for dementia effectively and thus reliably identify dementia cases in cross-national research. The interrater agreement on the diagnosis of dementia might be improved if clear-cut guidelines in the definition of cognitive impairment are provided. To improve the reliability of AD diagnosis in epidemiologic studies, we suggest that the NINCDS-ADRDA “probable” and “possible” categories be merged.

Multiple cholinergic markers are unexpectedly not altered in the rat dentate gyrus following entorhinal cortex lesions

Abstract: Since major cholinergic deficits are observed in Alzheimer's disease, the development of models to study possible cholinergic plasticity has generated great interest. In this regard, it has been shown that lesions of the entorhinal cortex, which sends glutamatergic projections to the hippocampus, promote the sprouting and plasticity of presumptive cholinergic septohippocampal fibers in the dentate gyrus, as revealed by AChE histochemistry. This sprouting was reported to be evident at 8 d and up to 30 d postlesion (DPL) and is now widely used as a model of cholinergic neuronal plasticity. In the present study, unilateral lesions of the entorhinal cortex were made in adult rats, and the status of various putative pre- and postsynaptic cholinergic markers was assessed after 2, 4, 8, 14, and 30 DPL. As expected, AChE was increased in the outer molecular layer of the ipsilateral dentate gyrus from 8 to 30 DPL. In contrast, the activity of ChAT, the enzyme responsible for the synthesis of ACh, and the densities of specific binding sites for 3H-AH5 183/vesamicol (blocker of the ACh vesicular transport sites), 3H-hemicholinium-3 (blocker of the high-affinity choline uptake sites), muscarinic-M2 (3H-AF-DX 384 and 3H-ACh), muscarinic-M1 (3H-pirenzepine), and nicotinic (3H-N- methylcarbamylcholine) cholinergic receptors were not increased on the ipsilateral molecular layer of the dentate gyrus, as compared to their contralateral controls. We conclude that the increase in AChE staining in the molecular layer of the dentate gyrus following entorhinal cortex lesions may be due to changes in noncholinergic neurons.

Apolipoprotein E4 and Cholinergic Dysfunction in Alzheimer’s Disease

Abstract: Apolipoprotein E (apoE) is a well-characterized lipophilic protein associated with plasma and CSF lipoproteins. Apolipoprotein E is synthesized primarily by the liver, but also at other sites including brain, macrophages and adrenals (Elshourbagy et al., 1985). Furthermore, apoE is unique among apolipoproteins in that it has a special relevance to the central and peripheral nervous systems. It is a key determinant in the cellular recognition and internalization of cholesterol-and phospholipid-rich lipoproteins in the developing brain and in the response to neuronal injury (Boyles et al., 1989; Poirier et al., 1991a,b, 1993a). It was shown to play a fundamental role in the CNS during hippocampal synaptic plasticity induced by entorhinal cortex lesions in the rat (Poirier et al., 1991a,b, 1993).