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Biomedical subjects

F Pasquier

Publications and source records attributed to F Pasquier.

At least 37 records · Page 2Linked to original sources
PubMed2002

Contribution of APOE promoter polymorphisms to Alzheimer's disease risk.

OBJECTIVE: To determine whether the effects of APOE promoter polymorphisms on AD are independent of the APOE-epsilon4 allele. BACKGROUND: Recently, the -491 A-->T and -219 G-->T polymorphisms located in the APOE promoter have been suggested to be risk factors for AD. However, the effects of these polymorphisms have not always been reproduced in case-control studies, possibly because of the strong linkage disequilibrium existing at this locus or the characteristics of the populations studied. METHODS: Data collection was performed from six independent samples (1,732 patients with AD and 1,926 control subjects) genotyped for APOE exon 4 and the two APOE promoter polymorphisms. The risks associated with the APOE polymorphisms for developing AD were estimated using logistic regression procedures and calculation of odds ratios with 95% CI adjusted by age, sex, and collection center. Independence of the APOE promoter polymorphisms was tested by stratification for APOE-epsilon4 and tertile design was used for age stratification. RESULTS: The independence of the -491 AA genotype was observed in the whole sample whereas the independence of the -219 TT genotype was observed only in the oldest population. CONCLUSION: The -491 and -219 APOE promoter polymorphisms incur risk for AD in addition to risk associated with the APOE-epsilon4 allele, with age accentuating the effect of the -219 TT genotype. Because these polymorphisms appear to influence apoE levels, these results suggest that APOE expression is an important determinant of AD pathogenesis.

Aged↗
PubMed2002

[Acute rhombencephalitis with fever and bilateral hearing loss secondary to Gougerot-Sjögren's syndrome].

The usual polymorphic central nervous system involvement observed in primary Sjögren's syndrome is classified as monofocal, multifocal or diffuse involvement. We present a case of acute rhombencephalitis associated with hearing loss that could correspond to an intermediate form between diffuse and monofocal involvement. The acute onset with fever and not clinical sign of xerostomia or xerophthalmia suggest the possibility of vascular-like or infectious-like forms. We emphasize the importance of obtaining a minor salivary gland biopsy for diagnosis of Sjögren's syndrome and suggest that Sjögren's syndrome could be frequently misdiagnosed.

Abducens Nerve Diseases↗
PubMed2002

[Alzheimer's disease: a public health problem: yes, but a priority?].

Alzheimer's Disease is a major Public Health problem for many reasons. First, it is a frequent disease since, in France, the prevalence was estimated at about 400.000 cases, and the annual incidence at 100.000 cases. The frequency of the disease increases, in particular due to the ageing of the population. This disease has major consequences on the life of the patient and his/her caretaker. The cost of the disease is important, estimated at about 50 milliards of French francs. Pharmaceutical treatment and other interventions are possible in particular to delay the nursing home placement. On the other hand, this disease is often ignored, under-diagnosed, underestimated and exposed to inequality in resorting to care. In summary, Alzheimer's Disease (AD) has all the criteria required for a major public health problem. In spite of this observation, AD is not yet considered as a priority for health authorities, although attitudes are changing.

Accidents, Traffic↗
PubMed2002

[Dysfunction of the magnocellular pathway in Alzheimer's disease].

Visual disturbances are a common feature of Alhzeimer's disease. They are related primarily to visuo-spatial deficits. The pathways mediating visuo-spatial and form identification are at least partially segregated in the brain. The magnocellular pathway has characteristics which make it more suitable for detecting dynamic form, motion and depth. We assessed by means of psychophysical and electrophysiological testings the properties of the parvo and the magnocellular pathways. We found contrast sensitivity deficits for the low and middle spatial frequencies, a significant reduction of the amplitude of the steady-state pattern VEP's at 16, 20 and 24 Hz, abnormal transient pattern VEP's only for the major positivity (P100) and abnormal flash VEP's (delayed P2) as previously observed. The temporal frequency deficits and other abnormalities pointed out in this study, could be related to a dysfunction of the M-pathways in Alzheimer's disease.

Aged↗
PubMed2002

[Wernicke-Korsakoff syndrome: diagnostic contribution of magnetic resonance imaging].

Data regarding the magnetic resonance imaging (MRI) features in Wernicke-Korsakoff syndrome (WKS) are scarce. WKS usually combines a cerebellar syndrome, oculomotor disorder and confusion. The aim of this study was to determine more precisely the clinical presentation of WKS and the frequency and topography of MRI abnormalities. Furthermore, we try to assess the prognostic value of both clinical signs and MRI abnormalities. We retrospectively studied 25 patients with WKS in which an MRI was available. We assessed the initial clinical presentation and the outcome. We also analyzed the frequency and the location of MRI lesions. We then correlated clinical and MRI data with the clinical outcome. Eleven patients (44 p. 100) had the full WKS. Fourteen of the 25 patients (56 p. 100) had a poor evolution. The occurrence of full WKS was correlated with a poor outcome (p < 0.02). Signal abnormalities on T2-weighted images were found in the periacqueducal region, in the thalami or in the mamillar bodies in 16 cases (64 p. 100). There was a correlation between an hypersignal in at least one region and a poor clinical outcome (p < 0.02). Our study demonstrates the high frequency of brain MRI lesions in WKS and the correlation of both initial clinical signs and MRI abnormalities with a poor clinical outcome.

Adult↗
PubMed2001

Poststroke dementia: incidence and relationship to prestroke cognitive decline.

OBJECTIVE: To evaluate the 3-year incidence of poststroke dementia (PSD) and the influence of prestroke cognitive decline. METHODS: The authors evaluated prestroke cognitive functions in 202 consecutive stroke patients > or =40 years old using the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE), with a cut-off of 104 for the diagnosis of dementia. Six months and then annually after stroke, dementia was reassessed. The diagnosis of dementia was based on the International Classification of Diseases, 10th revision criteria in survivors who underwent a visit with a neurologist, or on the IQCODE score obtained by telephone contact with the family in survivors who did not. Statistics were performed using life-table methods. RESULTS: Thirty-three patients were excluded because of prestroke dementia. In the 169 remaining patients, the cumulative proportion of patients with dementia was 28.5% at the end of the follow-up period, with most of PSD occurring during the first 6 months. Using multivariate analysis, independent predictors of PSD were aging, preexisting cognitive decline, severity of deficit at admission, diabetes mellitus, and silent infarcts. Leukoaraiosis was an independent predictor of PSD when prestroke cognitive decline was not taken into account. The presumed etiology of dementia was vascular dementia (VaD) in two-thirds of patients and AD in one-third. CONCLUSIONS: The risk of PSD is high, and increased in patients with prestroke cognitive decline, with about one-third of patients meeting the criteria for AD and two-thirds meeting the criteria for VaD. These results confirm that, in stroke patients, an underlying degenerative pathology may play a role in the development of PSD.

Adult↗
PubMed2001

Silent infarcts in stroke patients: patient characteristics and effect on 2-year outcome.

Although silent infarcts (SIs) are frequent in stroke patients, their clinical significance remains controversial, and their effect on stroke outcome remains unclear. This study evaluated the prevalence of SI on computed tomography, associated factors, and the effect on outcome in stroke patients. We studied 202 consecutive patients admitted for acute ischaemic or haemorrhagic stroke with clinical deficits lasting more than 24 h. Survivors were followed up for 24 months; no patient was lost to follow-up. Patients with Rankin scores of 2 or lower were considered separately. New vascular events were also recorded. Computed tomography showed that one-fourth of patients (52/202) had at least one SI; these were located in deep hemispheric areas in 46 patients, superficial hemispheric areas in 5, and the posterior fossa in 7. Logistic regression analysis showed the factors independently associated with SI to be severe leukoaraiosis (OR 1.71, 95% CI 1.26-2.31) and small-vessel occlusion as presumed cause of the index stroke (OR 2.66, 95% CI 1.22-5.79). SI did not affect vital or functional outcome or the occurrence of new vascular events within 2 years after stroke. Whether they affect cognitive outcome remains under evaluation over a longer follow-up period.

Adult↗
PubMed2001

The nature of semantic memory deficits in Alzheimer's disease: new insights from hyperpriming effects.

While semantic memory deficits are a common landmark of Alzheimer's disease, the nature of these impairments remains to be clarified. Implicit tasks which assess semantic priming effects are often used to understand semantic deficits in Alzheimer's disease, but they have led to unclear conclusions because of methodological problems such as intervention of attentional mechanisms. To explore the effects of semantic priming in Alzheimer's disease and their relationship with semantic memory deficits, we used two tasks, one implicit and the other explicit. The implicit task was a lexical decision task to assess semantic priming, and in which pairs of words had coordinate (tiger-lion) or attribute relationships (zebra-stripe). The explicit task was a semantic knowledge task composed of namings and questions involving superordinate categories and attribute knowledge of concepts. The two tasks systematically assessed the integrity of the same concepts. This protocol was given to 53 Alzheimer's disease patients with mild to moderate dementia and to 20 controls. The Alzheimer's disease group as a whole obtained significantly greater priming effects (hyperpriming) than controls in the coordinate condition, and equivalent priming in the attribute condition. In the coordinate condition, a subgroup of 26 patients, with attribute knowledge deficits, had larger priming effects than both a subgroup without semantic deficits and the control group. These results show that in Alzheimer's disease the semantic priming effects vary according to the degree of attribute loss, and the presence of hyperpriming would reflect semantic memory deficits. This study unravels the fine-grained structure of semantic memory disturbances in Alzheimer's disease with mild to moderate dementia, affecting initially the attributes of concepts within a hierarchical network in which superordinate concepts remain preserved.

Aged↗
PubMed2001

Memory impairment differs in frontotemporal dementia and Alzheimer's disease.

The aim of this study was to assess short-term and long-term explicit memory and implicit memory in frontotemporal dementia (FTD; frontal variant) and to compare FTD and Alzheimer's disease (AD) patients with similar severity of dementia. Fifteen FTD patients [mean age: 68 years; Mini-Mental State (MMS): 24], 30 probable AD patients (mean age: 72 years; MMS: 23) and 12 healthy subjects participated in the study. The three groups were comparable in terms of gender and educational level. Short-term memory was assessed with the digit span and Corsi block-tapping tests. Explicit verbal memory was assessed with the Grober and Buschke test, and implicit memory with a verbal priming task and a fragmented picture test. FTD patients demonstrated a genuine memory deficit with impaired digit span, encoding deficit and retrieval strategy difficulties, but preserved implicit verbal and visual priming. Memory patterns differed in AD and FTD: short-term memory and free recall were similarly decreased in FTD and AD but cues provided more benefit to FTD than to AD; encoding was more impaired and the forgetting rate was faster in AD than in FTD; priming was lower in AD than in FTD. AD patients with clinical and imaging frontal lobe dysfunction tended to have lower memory performance and to differ even more from FTD patients than AD patients without frontal lobe dysfunction.

Aged↗
PubMed2001

A new rating scale for age-related white matter changes applicable to MRI and CT.

BACKGROUND AND PURPOSE: MRI is more sensitive than CT for detection of age-related white matter changes (ARWMC). Most rating scales estimate the degree and distribution of ARWMC either on CT or on MRI, and they differ in many aspects. This makes it difficult to compare CT and MRI studies. To be able to study the evolution and possible effect of drug treatment on ARWMC in large patient samples, it is necessary to have a rating scale constructed for both MRI and CT. We have developed and evaluated a new scale and studied ARWMC in a large number of patients examined with both MRI and CT. METHODS: Seventy-seven patients with ARWMC on either CT or MRI were recruited and a complementary examination (MRI or CT) performed. The patients came from 4 centers in Europe, and the scans were rated by 4 raters on 1 occasion with the new ARWMC rating scale. The interrater reliability was evaluated by using kappa statistics. The degree and distribution of ARWMC in CT and MRI scans were compared in different brain areas. RESULTS: Interrater reliability was good for MRI (kappa=0.67) and moderate for CT (kappa=0.48). MRI was superior in detection of small ARWMC, whereas larger lesions were detected equally well with both CT and MRI. In the parieto-occipital and infratentorial areas, MRI detected significantly more ARWMC than did CT. In the frontal area and basal ganglia, no differences between modalities were found. When a fluid-attenuated inversion recovery sequence was used, MRI detected significantly more lesions than CT in frontal and parieto-occipital areas. No differences were found in basal ganglia and infratentorial areas. CONCLUSIONS: We present a new ARWMC scale applicable to both CT and MRI that has almost equal sensitivity, except for certain regions. The interrater reliability was slightly better for MRI, as was the detectability of small lesions.

Aging↗
PubMed2000

A FE65 polymorphism associated with risk of developing sporadic late-onset alzheimer's disease but not with Abeta loading in brains.

The FE65 protein was previously described interacting with amyloid protein precursor (APP) and mediating its internalization. Hu et al. (Hum. Genet., 103 (1998) 295) recently reported that a deletion polymorphism in intron 13 of the FE65 gene may be protective for sporadic Alzheimer's disease (AD) forms and suggested that this deletion may modify splicing between exon 13 and 14 (the two exons encoding the interaction domain of FE65 with APP). We tested the impact of this polymorphism in 646 controls and 639 sporadic AD cases. We were only able to detect a protective effect of the deletion in the population over 75 years (odds ratio = 0.53, 95% confidence interval (0.35-0.82), P= 0.002). Furthermore, no association of this polymorphism with Abeta40, Abeta42(43) and total Abeta loads were detected in 74 AD brains, although, we could expect that this deletion was associated with modifications of the APP metabolism. In conclusion, the FE65 gene may be a minor genetic determinant only for sporadic late-onset AD forms, although, we cannot conclude that this impact is mediated by a modulation of the APP process and/or Abeta peptide deposition.

Age of Onset↗
PubMed2000

The transcriptional factor LBP-1c/CP2/LSF gene on chromosome 12 is a genetic determinant of Alzheimer's disease.

Although the varepsilon4 allele of the apolipoprotein E gene appears as an important biological marker for Alzheimer's disease (AD) susceptibility, other genetic determinants are clearly implicated in the AD process. Here, we propose that a genetic variation in the transcriptional factor LBP-1c/CP2/LSF gene, located close to the LRP locus, is a genetic susceptibility factor for AD. We report an association between a non-coding polymorphism (G-->A) in the 3'-untranslated region of this gene and sporadic AD in French and British populations and a similar trend in a North American population. The combined analysis of these three independent populations provides evidence of a protective effect of the A allele (OR = 0.58, 95% CI 0.44-0.75). We describe a potential biologically relevant role for the A allele whereby it reduces binding to nuclear protein(s). The absence of the A allele was associated with a lower LBP-1c/CP2/LSF gene expression in lymphocytes from AD cases compared with controls. Our data suggest that polymorphic variation in the implication of the LBP-1c/CP2/LSF gene may be important for the pathogenesis of AD, particularly since LBP-1c/CP2/LSF interacts with proteins such as GSKbeta, Fe65 and certain factors involved in the inflammatory response.

3' Untranslated Regions↗
PubMed2000

How can cerebral infarcts and hemorrhages lead to dementia?

The incidence of new onset dementias is increased after stroke. The objective of this review is to investigate how cerebral infarcts and hemorrhages can lead to dementia. Stroke subtypes, total volume of cerebral lesion and functional tissue loss, and location of the lesions are the major determinant of dementia in stroke patients. The causal relationship between stroke and dementia is clear: (1) in young patients who are unlikely to have associated Alzheimer pathology; (2) when the cognitive functioning was normal before stroke, impaired immediately after, and does not worsen over time; (3) when the lesions are located in strategic areas; and (4) when a well-defined vasculopathy known to be associated with dementia is proven. However, white matter changes and associated Alzheimer pathology may also contribute to the dementia syndrome in stroke patients.

Brain↗
PubMed2000

Relevance of white matter changes to pre- and poststroke dementia.

White matter changes are often associated with stroke, risk factors for stroke, and dementia. From a theoretical point of view, they may be associated with an increased risk of pre- or poststroke dementia because (i) they are linked with subtle cognitive decline, which may add to the consequences of the stroke lesions and of associated Alzheimer pathology; and (ii) they indicate an increased risk of stroke recurrence. The aim of this study was to evaluate the contribution of white matter changes to pre- and poststroke dementia. The relationship between preexisting dementia and white matter changes was evaluated in the Lille stroke-dementia cohort. We assessed 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. White matter changes were rated on CT with the Blennow's rating scale. Thirty-three of 202 patients were demented before stroke (16.3%; 95% confidence interval: 11.2-21.4); the logistic regression analysis found that female sex, family dementia, white matter changes, and cerebral atrophy were independently associated with prestroke dementia. White matter changes were also associated with an increased risk of poststroke dementia, 2 years after stroke onset. Thus, white matter changes contribute to dementia occurring in stroke patients.

Adult↗
PubMed2000

Alzheimer's disease and frontotemporal dementia are differentiated by discriminant analysis applied to (99m)Tc HmPAO SPECT data.

OBJECTIVE: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the most frequent neurodegenerative cognitive disorders. However, FTD remains poorly recognised clinically. The use of (99m)HmPAO-single photon emission computed tomography (SPECT) has been demonstrated in the differentiation of AD and FTD. Nethertheless, there are very few comparative studies designed to assess its precise value in this differential diagnosis. The aim was to determine a simple decision rule, deduced from statistical analysis, which, if applied to regions of interest (ROIs) and mini mental state examination (MMSE), could improve the predictive value of SPECT in differential diagnosis between AD and FTD. METHODS: Forty patients, 20 with probable AD and 20 with probable FTD were included. All patients underwent brain SPECT imaging, after an intravenous injection of (99m)Tc HmPAO-(555mBq). For each patient, 20 ROIs were determined on the Fleishig's slice and their activity was normalised to the mean cerebellar activity. Bivariate analysis (Wilcoxon rank tests) and multivariate analysis (stepwise discriminant analysis) were performed to determine the subgroup of variables able to give the highest predictive value for this differential diagnosis. A simple decision rule was built from a predictive score derived by factorial discriminant analysis. RESULTS: As previously described, the fixation defect was found in frontal regions of interest (ROIs) in FTD and in the left temporoparietal-occipital ROIs in AD. Among the 21 variables, five were finally selected: right median frontal, left lateral frontal, left tempoparietal, left temporoparietal-occipital areas, and MMSE. One hundred per cent of patients with FTD were correctly classified by the decision rule (20/20 patients) and 90% of patients with AD (18/20). CONCLUSION: AD and FTD are differentiated by SPECT. Automatic classification based on a decision rule deduced from factorial discriminant analysis could enhance its performance.

Alzheimer Disease↗