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Biomedical subjects

F Pasquier

Publications and source records attributed to F Pasquier.

At least 19 recordsLinked to original sources
PubMed1998

Tacrine efficacy in Lewy body dementia.

BACKGROUND: Response to tacrine varies among patients with Alzheimer's disease (AD). Lewy body dementia (LBD) could be a high responder subtype of AD. The aim of the study was to compare the effects of tacrine in LBD and AD. METHODS: Seventy-five consecutive outpatients with mild or moderate AD were screened. Tacrine was given at a dose of 40 mg/day during 6 weeks. During the next 6 weeks, the patients were treated with 80 mg/day and afterwards with 120 mg/day. Patients were assessed at baseline and treated with a dose of 120 mg/day tacrine for 2 weeks. RESULTS: Analysis was performed on 39 patients (AD, N = 20; LBD, N = 19). Eight patients were lost to follow-up, eight patients manifested with side-effects, six suffered from an intercurrent somatic disease during the study and 14 patients had poor compliance or were treated with incompatible drugs. Twenty-two patients (11 AD/11 LBD) increased their cognitive performances with tacrine. Among the 22 patients, the improvement differed between the AD and the LBD groups. In AD, conceptualization improved; in LBD, the improvements occurred in verbal initiation and digit span. CONCLUSION: This study emphasizes the importance of using appropriate tests to determine the positive effects of pharmacological treatments.

Aged↗
PubMed1998

A new polymorphism in the APOE promoter associated with risk of developing Alzheimer's disease.

The epsilon4 allele of the Apolipoprotein E gene (APOE), one of the main allele of APOE polymorphism, is a major risk factor for the development of Alzheimer's disease. However, several data suggest that genetic factors, within the APOE locus, may also modulate the risk associated with this polymorphism. We look for new mutations in the APOE promoter, susceptible to modify the risk associated with the APOE epsilon4 allele. We characterised a G-->T mutation at -186 bp of the APOE gene TATA box, named Th1/E47cs. This new polymorphism is located in a consensus sequence of a potential transcriptional (Th1/E47) factor binding site. We studied the impact of this new polymorphism with those of other markers of the APOE locus in a large case-control study and observed that Th1/E47cs modulated the influence of the APOE epsilon4 allele on the risk of Alzheimer's disease.

Aged↗
PubMed1998

Pronounced impact of Th1/E47cs mutation compared with -491 AT mutation on neural APOE gene expression and risk of developing Alzheimer's disease.

Possession of the apolipoprotein E (APOE) epsilon4 allele is the most frequently associated genetic susceptibility factor for Alzheimer's disease (AD). Recently, new polymorphisms in the regulatory region of the APOE gene have been described. We analysed the effects of three of these mutations (-491 AT, -427 CT and Th1/E47cs) on disease risk in a large case-control study, and tested their impacts on APOE allelic expression in brain tissues. The Th1/E47cs T allele was associated with an increased risk of occurrence of AD, while the -491 T allele was associated with a decreased risk, independently of the APOE epsilon2/epsilon3/epsilon4 polymorphism effect. However, the impact of the Th1/E47cs mutation was the strongest. The -427 CT polymorphism was not associated with the disease. In AD subjects heterozygous for the epsilon4 allele, analysis of allelic expression showed that the relative expression levels of the epsilon4 allele were higher than those of the corresponding controls. Consistent with epidemiological data, the relative level of expression of the epsilon4 allele was modified accordingly to the presence or absence of the two main promoter polymorphisms, indicating, in vivo, the deleterious effect of the Th1/E47cs T allele and the protective effect of the -491 T allele in population. These data indicate that in addition to the qualitative effect of the APOE epsilon2/epsilon3/epsilon4 polymorphisms on the AD occurrence, the quantitative variation of expression of these alleles due to functional APOE promoter mutations, is a key determinant of AD development.

Aged↗
PubMed1998

White matter changes on CT and MRI: an overview of visual rating scales. European Task Force on Age-Related White Matter Changes.

Since the recognition of white matter changes on CT (leukoaraiosis), rating scales for the location and severity of white matter changes have been developed, mainly for research purposes, to investigate factors such as the relation with cognition, risk factors, and pathology. The main purpose of rating scales is to provide scores that can be used in statistical analyses. The development of the NINDS-AIREN criteria for vascular dementia have introduced a new application for these rating scales in investigating and delineating the amount of white matter changes on CT/MRI sufficient to fulfill the criteria. Furthermore, in Alzheimer's disease, recognition of white matter changes may serve to delineate homogeneous groups and help to identify patients with different symptomatology. We reviewed the existing rating scales for CT and MRI and judged their properties and reliability. The ideal rating scale does not yet exist, but different rating scales may serve different purposes, for which some recommendations are made.

Brain Ischemia↗
PubMed1998

White matter changes and poststroke dementia.

Stroke patients are more likely to have white matter changes than age- and sex-matched controls. White matter changes are associated with an increased risk of dementia occurring after stroke: they often indicate a higher risk of stroke recurrence and they may lead to slight cognitive impairment. Besides white matter changes, vascular lesions of the brain and associated Alzheimer pathology, the summation of 2 or 3 of these mechanisms may lead to dementia in stroke patients even when each type of lesion is not severe enough to induce dementia by its own.

Brain↗
PubMed1997

Association between the low density lipoprotein receptor-related protein (LRP) and Alzheimer's disease.

Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting elderly people. It usually occurs after 65 years old (late-onset AD). The epsilon4 allele of apolipoprotein E (APOE) gene is a risk factor which contributes about 50% of the genetic risk for this form of the disease. The low density lipoprotein receptor-related protein (LRP) is a major receptor for APOE which is found in the senile plaques of AD brains. This makes it a good candidate gene for the disease. There is a polymorphism in the region upstream of the LRP gene that has been associated with AD in an American population. We examined this polymorphism by restriction fragment length polymorphism analysis in a French population with sporadic late-onset AD. In the previous report, a significant increase of the 87 bp allele was found in the AD cases; however, in our population, we observed a significant decrease with this same allele of the LRP gene. The possible reasons for this discrepancy, linkage disequilibrium or statistical anomaly, are discussed.

Age of Onset↗
PubMed1997

Why are stroke patients prone to develop dementia?

Stroke patients are more likely to develop dementia than age- and sex-matched controls but the pathogenesis of dementia remains unresolved in most of them. The aim of this review is to determine, from the available literature, the theoretical reasons for a stroke patient to become demented. We found three distinct factors that may explain the occurrence of dementia after a stroke. Firstly, post-stroke dementia may be the direct consequence of the vascular lesions of the brain: this is the most likely cause in patients with normal cognitive functions before a strategic infarct, especially in young patients, in Icelandic-type hereditary amyloid angiopathy and in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. Secondly, post-stroke dementia may be due to an associated asymptomatic Alzheimer pathology; the reasons for such an association are that (1) some cases of dementia occurring after a stroke are progressive and Alzheimer's disease (AD) is the most frequent cause of progressive dementia; (2) age and APOE epsilon 4 genotype are risk factors for both AD and ischaemic stroke; (3) a vasculopathy is often associated with AD. Lastly, white matter changes may also contribute to dementia because they often indicate small-vessel disease and a higher risk of stroke recurrence, and may lead to slight cognitive impairment. Finally, the summation of vascular lesions of the brain, white matter changes, and Alzheimer pathology might lead to dementia, even when each type of lesion, on its own, is not severe enough to induce dementia. Therefore, in patients followed up after a stroke, the term "post-stroke dementia" is probably more appropriate than that of vascular dementia because it includes all possible causal factors.

Aged↗
PubMed1997

Medial temporal lobe atrophy in memory disorders.

Medial temporal lobe atrophy determined by temporal lobe oriented computed tomography (CT), 1 year before death, is strongly associated with histopathologically confirmed Alzheimer's disease (AD). The aim of this study was to assess the diagnostic accuracy of medial temporal lobe measurement for the diagnosis of AD in patients referred to a memory disorders clinic, especially those at an early stage of the disease. CT oriented to the temporal lobe was performed in 333 subjects aged 41-93 years consecutively recruited in a Memory Disorders Clinic: 124 had probable AD, Mini Mental State score (MMS) = 17 (8); 50 possible AD [MMS = 21 (5)]; and 119 patients had miscellaneous memory disorders [MMS = 22 (7): frontotemporal lobe dementia, subcortical dementia, cortical Lewy body disease, vascular dementia, Korsakoff syndrome, focal atrophy, etc.]. There were also 19 anxious/depressed patients [MMS = 29 (1)] with normal performance on memory tests, and 21 controls. The minimum width of the medial temporal lobe was measured. The best cut-off to distinguish AD patients from non-AD patients was 11.5 mm, in agreement with data in the literature. At this threshold, 84% of probable AD patients had a positive test and 90% of controls and anxious/depressed patients had a negative test. For the diagnosis of probable AD, sensitivity of the measurement was 0.81, specificity 0.95, predictive positive value 0.99, predictive negative value 0.45, and diagnostic accuracy 0.83. The test was positive in half the possible AD patients, and half those with miscellaneous memory disorders. It was negative in all anxious/depressed patients. Therefore, temporal lobe oriented CT might be a valuable tool for assessment of medial temporal lobe atrophy in AD routine practice.

Adult↗
PubMed1997

Resistance to Bacillus sphaericus involves different mechanisms in Culex pipiens (Diptera:Culicidae) larvae.

Field Culex pipiens pipiens (L.) mosquitoes that were collected after a control failure with Spherimos in southern France developed high resistance (> 10,000-fold) to Bacillus sphaericus crystal toxin after < 8 generations of laboratory selection. We show that this resistance is encoded by a single major recessive gene on linkage group I at 22.1 recombination units from the sex locus, and that it is not associated with any loss of binding affinity between brush border membrane fractions and the B. sphaericus radiolabeled toxin. Thus, in Southern France, resistance differs from the high B. sphaericus resistance developed after laboratory selection of Californian C. p. quinquefasciatus. This demonstrates that at least 2 different mechanisms may confer high levels of resistance to B. sphaericus crystal toxin in mosquitoes of the C. pipiens complex. These results have important implications for mosquito control strategies.

Animals↗
PubMed1997

No effect of the alpha1-antichymotrypsin A allele in Alzheimer's disease.

The apolipoprotein E (ApoE)-epsilon4 allele is associated in a dose dependent manner to an increased risk for Alzheimer's disease. However, the ApoE-epsilon4 allele effect does not account for all patients with Alzheimer's disease, and the existence of other genetic risk factors has been postulated. Kamboh et al reported an association between Alzheimer's disease and the A allele of alpha1-antichymotrypsin (Aact) gene, which was not confirmed in a larger series more recently analysed. The ApoE and Aact genotypes were analysed in 314 patients with Alzheimer's disease and 173 healthy controls, confirming the dose dependent effect of the ApoE-epsilon4 allele. Nevertheless, even using odds ratios adjusted for age and sex, there was no significant effect of the Aact genotype on Alzheimer's disease or on the ApoE-epsilon4 allele associated risk for Alzheimer's disease.

Alleles↗
PubMed1997

Association between medial temporal lobe atrophy on CT and parietotemporal uptake decrease on SPECT in Alzheimer's disease.

OBJECTIVES: Alzheimer's disease is the most frequent cause of degenerative dementia. Despite the available diagnostic criteria, improvement of diagnosic accuracy is still required. The aim of this prospective study was to assess in a large population of patients referred to a memory clinic the diagnostic value of the combination of medial temporal lobe atrophy on temporal oriented CT and decreased temporoparietal uptake on HMPAO single photon emission tomography (SPECT). METHODS: The study was conducted in 125 patients aged 51-93: 64 with probable Alzheimer's disease (Mean (SD) mini mental state examination (MMSE)=18.34 (6.93)), duration of disease=6.48 (2.93) years, 13 possible Alzheimer's disease (MMSE=21.58 (5.48), duration of disease=6.08 (2.56)), 48 patients with miscellaneous memory disorders (MMSE=21.98 (6.10), duration the disease = 6.85 (3.91)). RESULTS: For the diagnosis of probable Alzheimer's disease, the sensitivity of this association was 0.56, the specificity 0.93, the positive predictive value 0.95, and the negative predictive value 0.45. The diagnosic accuracy was 0.68. Both medial temporal atrophy and parietotemporal decrease in uptake were present in four of 13 patients with possible Alzheimer's disease and 11 of 48 with miscellaneous memory disorders. The association was absent in 27 of 29 patients with frontotemporal dementia. In mild stages (MMSE>18; n = 32), the sensitivity of the association was 0.34, the specificity 0.93, the positive predictive value 0.85, and the negative predictive value 0.57. The diagnosic accuracy was 0.53. CONCLUSION: This association, although not sensitive, helps to select patients with high probability of Alzheimer's disease at an early stage which can be of interest for clinical and research purposes.

Aged↗
PubMed1997

Frontotemporal dementia: its rediscovery.

Frontotemporal dementia (FTD) is the second most frequent degenerative cause of dementia. Although described for more than a century, it remains often misdiagnosed, mistaken for Alzheimer's disease or psychiatric disorders, which is prejudicial to care and research. It is a clinical syndrome corresponding to at least three histological entities: (1) Pick's disease, (2) non-specific frontotemporal degeneration, (6 times more frequent), and (3) frontal lobe abnormalities associated with motor neurone disease. It never corresponds to Alzheimer pathology. It must be suspected in patients with behavioural dyscontrol predating memory impairment, without spatial disorientation and normal EEG.

Alzheimer Disease↗
PubMed1997

Qualitative assessment of cerebral atrophy on MRI: inter- and intra-observer reproducibility in dementia and normal aging.

To assess the reproducibility of a qualitative rating scale of cerebral atrophy on MRI in an aged population of demented and non-demented individuals, 4 raters independently judged cerebral atrophy (CA) in 13 regions on a 0-3 scale on 75 MRI scans, on two occasions. The level of agreement was expressed by kappa statistics as well as by analysis of variance for interexaminer reproducibility studies. The mean CA scores ranged from 13.3 to 21.2, indicating moderately high prevalence of cerebral atrophy in this sample. Complete agreement among observers was reached in 49.7% of the ratings during the first assessment and in 44.1% in the second assessment. The inter-observer agreement was poor in both sessions (mean overall kappas 0.34 and 0.24). The intra-observer agreement was moderate to good for all raters (mean overall kappa: 0.58). The average standard deviation of the differences between CA scores of the 4 raters was 5.12 in the first and 5.13 in the second session. The average standard deviation for the differences within raters was 2.4. We conclude that the assessment of cerebral atrophy using this rating scale on MRI in an aged population has a poor reproducibility among raters. However, it provides regional atrophy measurements and is quite reliable when performed by a single rater.

Aged↗
PubMed1997

Preexisting dementia in stroke patients. Baseline frequency, associated factors, and outcome.

BACKGROUND AND PURPOSE: The link between stroke and degenerative dementia, especially Alzheimer's disease, is closer than expected by chance. Dementia after stroke may be due to the cumulative effect of vascular and degenerative changes. The prevalence of dementia just before stroke onset remains unsettled. The aim of this study was to determine the frequency of preexisting dementia in stroke patients, associated factors, and consequences on outcome. METHODS: We evaluated the cognitive functioning prior to stroke in 202 consecutive patients with ischemic or hemorrhagic stroke by means of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). We classified in the dementia group patients with IQCODE scores of 104 or more. Six months after stroke onset, survivors underwent a battery of neuropsychological tests. RESULTS: Thirty-three patients were demented before stroke (16.3%; 95% confidence interval, 11.2 to 21.4). There was no diagnosis of dementia in 32 of these 33 patients. We determined by logistic regression analysis that female sex, family dementia, leukoaraiosis, and cerebral atrophy are independently associated with prestroke dementia. All survivors who had IQCODE scores of 104 or more at the acute stage met criteria for dementia 6 months later. CONCLUSIONS: Our study showed that one sixth of stroke patients have preexisting dementia. Therefore, some patients with so-called "poststroke dementia" probably had unrecognized preexisting dementia.

Adult↗
PubMed1997

Apolipoprotein E and Alzheimer disease: genotype-specific risks by age and sex.

The distribution of apolipoprotein E (APOE) genotypes as a function of age and sex has been examined in a French population of 417 Alzheimer disease (AD) patients and 1,030 control subjects. When compared to the APOE epsilon3 allele, an increased risk associated with the APOE epsilon4 allele (odds ratio [OR] [epsilon4] = 2.7 with 95% confidence interval [CI] = 2.0-3.6; P < .001) and a protective effect of the APOE epsilon2 allele (OR[epsilon2] = 0.5 with 95% CI = 0.3-0.98; P = .012) were retrieved. An effect of the epsilon4 allele dosage on susceptibility was confirmed (OR[epsilon4/epsilon4] vs. the epsilon3/epsilon3 genotype = 11.2 [95% CI = 4.0-31.6]; OR[epsilon3/epsilon4] vs. the epsilon3/epsilon3 genotype = 2.2 [95% CI = 1.5-3.5]). The frequency of the epsilon4 allele was lower in male cases than in female cases, but, since a similar difference was found in controls, this does not lead to a difference in OR between sex. ORs for the epsilon4 allele versus the epsilon3 allele, OR(epsilon4), were not equal in all age classes: OR(epsilon4) in the extreme groups with onset at < 60 years or > 79 years were significantly lower than those from the age groups 60-79 years. In epsilon3/epsilon4 individuals, sex-specific lifetime risk estimates by age 85 years (i.e., sex-specific penetrances by age 85 years) were 0.14 (95% CI 0.04-0.30) for men and 0.17 (95% CI 0.09-0.28) for women.

Age of Onset↗
PubMed1997

[Mitochondrial anomalies in oculopharyngeal muscular dystrophy].

Oculopharyngeal muscular dystrophy (OPMD) was described by Taylor in 1915. This autosomal dominant inheritance affection begins at the age of 40-50 years associating bilateral ptosis and dysphagia. In 1980, Tome and Fardeau described rimmed vacuoles and typical intranuclear tubulo-filamentous inclusions in the muscle biopsy. We report two cases (brother and sister) of clinical and histological OPMD with mitochondrial abnormalities (Ragged red fibers) associated with classical OPMD lesions. Those observation remind the question already vised since a long time by some authors, of the signification of mitochondrial abnormalities in OPMD.

Female↗