Showing papers by "Serge Gauthier published in 1990"

Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats.

Abstract: There is a tendency for increased hypothalamic-pituitary-adrenal (HPA) activity with age in the rat, and the resulting elevations in circulating glucocorticoid levels have been implicated in the occurrence of hippocampal pathology and memory deficits. In the experiments reported here, we examined whether HPA dysfunction is selectively associated with cognitive impairments in a population of aged rats. Fifty-eight 23-27-month-old male Long-Evans rats were screened for spatial memory impairments using the Morris swim maze, and 2 groups of aged animals were selected; aged, cognitively impaired (AI) animals whose performance was significantly different (greater than 2 SD) from that of 6-month-old controls and aged, cognitively unimpaired (AU) animals whose performance was comparable to that of the young controls (a difference of less than 0.5 SD). Twenty-eight percent of the animals tested were designated as AI and 20% as AU. Histological analysis of a subset of these animals showed that, while both AU and AI animals showed neuron loss in the pyramidal cell fields of the hippocampus, the loss was significantly greater in the AI animals. The AI animals showed clear evidence of increased HPA activity. Thus, basal ACTH and corticosterone levels were significantly higher in the AI animals compared with both AU animals and young controls, especially during the dark phase of the cycle. The AI, AU, and young animals exhibited comparable corticosterone levels during a 20-min immobilization stress; however, following the termination of the stressor, corticosterone levels in AI animals were significantly elevated compared with both AU animals and controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Validity and reliability of the dementia behavior disturbance scale.

Abstract: Behavioral disturbance is a common and distinctive feature of Alzheimer's disease and other dementias. Existing instruments designed to quantify behavior disturbance among patients with dementia tend to be quite heterogeneous, including many items that do not refer to behavioral disturbance as such, but rather to cognitive, psychological, or somatic symptoms, or functional impairments. A 28-item Dementia Behavior Disturbance (DBD) scale was developed to avoid some of the problems encountered with the older instruments. In two samples of patients with dementia (n = 50 and n = 46), the most common symptoms were repetitive questions, losing or hiding things, lack of interest in daily activities, nocturnal wakefulness, unwarranted accusations, excessive daytime sleeping, and pacing. The coefficient of internal consistency was greater than .80 in both samples, and the correlation between scores obtained from the same subjects at a two-week interval was moderately high (Pearson's correlation coefficient = .71). There was a relatively high correlation between DBD scores and scores on Greene's Behavior and Mood Disturbance scale, and higher DBD scores were associated with increased duration and severity of disease. These preliminary results indicate that the DBD may be a useful and valid measure of one dimension of the dementia syndrome.

Tetrahydroaminoacridine-lecithin combination treatment in patients with intermediate-stage Alzheimer's disease. Results of a Canadian double-blind, crossover, multicenter study.

Abstract: We studied the efficacy and safety of oral tetrahydroaminoacridine (THA) combined with lecithin in 52 patients with Alzheimer's disease. The maximal tolerated dose of THA (up to 100 mg per day) was determined during an eight-week titration period, after which the tolerated dose of THA or placebo was given during two sequential randomized periods of treatment lasting eight weeks each. Highly purified lecithin (4.7 g per day) was administered during all phases of the study. Efficacy was expressed in terms of scores on the Mini—Mental State (MMS) test, the modified MMS test, the Hierarchic Dementia Scale, the Rapid Disability Rating Scale—ll, and the behavioral scale of Reisberg et al. Safety was assessed by careful clinical monitoring as well as serial measurements of liver aminotransferases. Forty-six patients completed the titration period, and 39 completed the double-blind period, during which only the MMS score showed a small but significant increase (P<0.05) after four weeks of treatment with ...

Assessment of Functional Changes in Alzheimer's Disease

Abstract: Functional difficulties occur in all patients with Alzheimer''s disease. Instrumental skills (shopping, handling money) are involved first, then self-care activities (toileting, dressing). Drug trials in intermediate stage Alzheimer''s disease should monitor self-care activities with structured diaries and rating scales.

Neurochemical deficits in pathological brain aging: specificity and possible relevance for treatment strategies.

Abstract: Normal brain aging is accompanied by the losses of certain neuronal populations and the appearance of structures such as neuronal plaques and neurofibrillary tangles. Additionally, various neurotransmitter systems are altered in the elderly, although marked variations are observed between individuals, suggesting important differences between successful and unsuccessful aging. In certain pathological conditions, only certain features of normal aging are exacerbated. For example, the densities of forebrain cholinergic neurons are markedly decreased in cortical and hippocampal (but not striatal) areas in Alzheimer's disease. We discuss here the comparative alterations of cholinergic markers in certain neurological disorders such as Alzheimer's disease, Parkinson's disease, and the combined pathology. Differential alterations of brain cholinergic profile are observed in each disorder, this most likely having functional significance. We also found that muscarinic receptors of the M2 subtype act as negative autoreceptors to decrease brain acetylcholine release, whereas nicotinic agonists induced the opposite effect. This suggests that blockade of negative M2 or stimulation of positive nicotinic autoreceptors could have beneficial effects in Alzheimer's disease. Additionally, modulation of heteroreceptor activation such as the serotonergic or interleukin-2 sites located on or in proximity to cholinergic nerve terminals could offer alternate strategies for the treatment of cholinergic deficits in pathological brain aging.

Lack of association between two restriction fragment length polymorphisms in the genes for the light and heavy neurofilament proteins and Alzheimer's disease.

Abstract: The etiology of Alzheimer disease (AD) remains unknown. The hypothesis of genetic factors playing a role in the causation of the disease, at least in its familial form, has been borne out by results showing linkage in several early-onset AD families to a locus on the proximal part of the long arm of chromosome 21. Linkage was not detected in several other families using the same markers. The metabolism of neurofilaments is perturbed in AD, as indicated by the presence of neurofilament epitopes in neurofibrillary tangles, as well as by the severe reduction of the expression of the gene for the light neurofilament subunit in AD brain. To detect a possible anomaly that might relate to the disease, we have searched for an association between the genes for the light subunit and the heavy subunit of the neurofilament triplet, and AD. Genotypes for restriction fragment length polymorphisms (RFLP) at each of the two loci were determined for an AD group and a control group. Allelic frequencies at a TaqI-defined RFLP for the gene for the light neurofilament subunit were 0.70 for the 3.7 kb allele and 0.30 for the 2.9 kb allele. HincII detected an RFLP for the heavy neurofilament subunit gene with frequencies of 0.31 for the 18.0 kb allele and 0.69 for the 6.8 kb allele. Frequencies were found to be similar in the two groups for both light and heavy neurofilament subunit loci. Although it cannot be excluded that mutations at other sites of the neurofilament genes are relevant to AD, the data reported here do not support an association between these genes and the disease.

Red cell choline in spasmodic torticollis and in a monozygotic twin pair with Tourette's syndrome

Abstract: 1. 1. Alterations in cholinergic function may play a role in the pathophysiology of idiopathic spasmodic torticollis (ST) and Gilles de la Tourette's syndrome (GTS). We measured red blood cell (RBC) choline in (i) ST (n = 24) and paired controls matched for age and gender (ii) a 20-year old pair of monozygotic twins with GTS, one of whom was moderately affected (CV) and the other virtually recovered (DV) (iii) both parents of the GTS twins, using gas chromatography — mass spectometry 2. 2. RBC choline decreased with age in control men (r = −0.76: p <0.01) but not in control women. 3. 3. RBC choline (nmol/ml) was higher in control men (18.3 ± 4.8, X ± SD) vs control women (13.1 ± 4.3) (p = 0.025). 4. 4. There was no significant difference in RBC choline (nmol/ml) between ST patients (16.6 ± 5.0) and controls (15.5 ± 5.2). 5. 5. The RBC choline values (nmol/ml) in the twins and parents were: 56.6 (CV), 58.3 (DV), 89.8 (father), 38.3 (mother) and in the controls (age 20–24) (n = 5) 18.2 ± 3.6. 6. 6. These data suggest (i) RBC choline is affected by age and gender (ii) RBC choline is unchanged In ST (iii) the regulation of RBC choline is under genetic control (iv) elevated RBC choline is not a state marker for GTS.