Biomedical subjects

Bruno Dubois

Publications and source records attributed to Bruno Dubois.

11 recordsLinked to original sources

PubMed2003

A risk for early-onset Alzheimer's disease associated with the APBB1 gene (FE65) intron 13 polymorphism.

Alzheimer's disease (AD) is a genetically complex neurodegenerative disorder and the leading cause of dementia of the elderly. Recently, Hu et al. suggested that a trinucleotide deletion in intron 13 of the APBB1 gene was a factor protecting against late-onset AD. We report here the results of a case/control study aimed at replicating this association. Our study included 461 AD patients and 397 matched controls. We compared the allele and genotype frequencies of the polymorphism between the two groups but did not find any statistically significant difference (P=0.08 and P=0.09, respectively). By contrast, adjusting for age and sex, we found a slight risk associated with the deletion (odds ratio=1.47, 95% confidence interval=1.05-2.04). Stratification by age showed that the risk effect associated with the deletion concerned subjects aged less than 65 years.

Age Factors↗

PubMed2003

Subtle cognitive impairment but no dementia in patients with spastin mutations.

BACKGROUND: The most frequent form of autosomal dominant hereditary spastic paraparesis is associated with the SPG4 locus, described originally as a pure form of the disease. Mutations of the SPG4 gene have been increasingly associated with reports of cognitive impairment. OBJECTIVE: To investigate cognitive function in 10 families with hereditary spastic paraparesis due to mutations in the SPG4 gene, using intrafamilial control subjects. PATIENTS AND METHODS: Neuropsychological examinations, including the Cambridge Cognitive Evaluation, were conducted in 29 carriers with identified SPG4 mutations and 29 intrafamilial controls. RESULTS: Carriers were not demented but had a subclinical cognitive impairment primarily affecting executive functions. The dysfunction was more severe in those carriers older than 50 years, but was correlated with the progression of the disease, not with age. Disease progression and cognitive impairment appeared to be more severe in the carriers of missense mutations than in those with truncating mutations. CONCLUSION: Asymptomatic cognitive impairment mostly affecting executive functions is present in SPG4 mutation carriers and is more frequent in those with missense mutations.

Adenosine Triphosphatases↗

PubMed2003

Deficit of verb generation in nondemented patients with Parkinson's disease.

Clinical and neuroimaging studies have shown that verb processing suggests a preferential participation of a prefrontal network, which is dysfunctional in Parkinson's disease (PD). To assess a verb processing deficit in PD, we compared noun- and verb-generation tasks for 34 nondemented PD patients (according to the Dementia Rating Scale) with 34 matched normal subjects, using two intracategory tasks (noun/noun and verb/verb generation) and two intercategory tasks (noun/verb and verb/noun generation). PD patients were significantly impaired in the two tasks involving verb production, i.e., verb/verb and noun/verb generation, whereas their performance was similar to those of controls in the two tasks requiring noun production. For the two impaired tasks, we assessed 1) the influence of lexical competition that corresponds to the presence of several candidate words for a given stimulus; 2) the influence of slight cognitive dysfunction; and 3) the influence of motor deficit. Significant correlations were found between DRS scores and performance on the noun/verb task, and no significant correlations were found between lexical competition or motor deficit and performance. The specific deficit for verb production in PD patients is discussed in relation to deficits affecting either action or grammatical representations.

Antiparkinson Agents↗

PubMed2003

Metabolic correlates of behavioral and affective disturbances in frontal lobe pathologies.

OBJECTIVE: Although previous studies have shown that the human frontal cortex is involved in the experience of emotions as well as in social behavior, data regarding the exact anatomical substrates of behavioral and affective deficits in frontal lobe pathologies are still scarce. The aim of this study was to investigate the metabolic correlates of these deficits in a group of non-selected consecutive patients with frontal lobe lesions. PATIENTS AND METHODS: Clinicometabolic correlations between several emotional and social parameters and metabolic patterns in the frontal cortex and amygdala were investigated in 32 patients with frontal lobe pathologies. The behavioral disturbances were evaluated using the Lhermitte's informant questionnaire. Regional cerebral glucose metabolism was measured with [(18)F] fluorodeoxyglucose and high-resolution positron emission tomography. Statistical analysis was performed using both single variable correlation and multiple regression analyses. RESULTS: Both single variable and multivariate analyses demonstrate that decreased regional glucose metabolism in the right medial area 10 was associated with apathy. There were also significant negative relationships between metabolism in the right orbitofrontal cortex and stereotypy and indifference to rules. Impulsiveness, personality disturbances and loss of emotional control were associated with decreased metabolism in the left amygdala. CONCLUSIONS: In terms of clinicometabolic correlations, the present data support the implication of different functional anatomic systems in frontal lobe-related behavioral and affective disturbances. In particular, they imply that the classically described symptoms of impaired behavioral control may be related to right orbitofrontal cortex hypometabolism whereas impaired regulation of emotions may result from a functional damage of the left amygdala.

Adult↗

PubMed2003

Screening for Alzheimer's disease with the short cognitive evaluation battery.

Because Alzheimer's disease (AD) tends to be underdiagnosed, there is an increasing need for accurate neuropsychological screening tools that are easy to administer by general practitioners or specialists. The aim of the present study was to validate, in French, a sensitive and specific screening battery designed to improve the discrimination between patients with AD, patients with depression and healthy elderly subjects. The Short Cognitive Evaluation Battery (SCEB) consists of 4 brief tests: temporal orientation, 5-word test, clock-drawing test and a semantic verbal fluency task. The SCEB was administered to 123 ambulatory subjects (mean age 76.4+/-2.3 years): 49 patients with mild AD, 27 patients with depressive symptoms and 47 healthy elderly subjects. The mean time for administration of the test was 11.2 min in the AD group, 8.2 min in the depressive group and 7.2 min in the control group (p < 0.001). Multivariate analysis showed that, compared with controls, patients with mild AD were significantly impaired for all four tests. Response operating characteristics analysis of the SCEB showed: 93.8% sensitivity and 85% specificity for discriminating AD from control patients, and 63% sensitivity and 96% specificity for discriminating AD from depressive patients. In summary, the SCEB appears to be a highly sensitive and specific tool for discriminating between patients with mild AD and healthy elderly individuals. Furthermore, in combination with clinical evaluation, the SCEB could improve the specificity of the difficult discrimination between mild AD and depression.

Aged↗

PubMed2002

Association between the extended tau haplotype and frontotemporal dementia.

BACKGROUND: Recent studies have shown an association between an extended tau haplotype (H1) that covers the entire human tau gene and progressive supranuclear palsy or, more inconsistently, other neurodegenerative disorders, such as corticobasal degeneration, Parkinson disease, Alzheimer disease, and frontotemporal dementia (FTD). In addition, disease-causing mutations in the tau gene on chromosome 17 have been detected in some families with autosomal dominant FTD and parkinsonism. In FTD, the pathological accumulation of the microtubule-associated protein tau suggests that the tau gene may be a genetic risk factor for this disorder. OBJECTIVE: To confirm or refute the association between the H1 haplotype or the H1H1 genotype of the tau gene and FTD. DESIGN: Case-control study. SETTING: Neurology departments of 12 French university hospitals. PARTICIPANTS: One hundred unrelated patients with FTD and 79 controls. METHODS: Tau genotype (contiguous polymorphisms in exons 1, 7, and 13 and in intron 9 used to reconstruct the extended haplotypes H1 and H2). Clinical examination, psychometric testing, laboratory tests, computed tomography and magnetic resonance imaging, single-photon emission computed tomography, and electroencephalography for patients with FTD. RESULTS: The H1H1 genotype was significantly overrepresented in patients with FTD compared with controls (62% vs 46%; P=.01, 1-sided; odds ratio adjusted for age and sex, 1.95). After stratification according to apolipoprotein E (APOE) genotype, we found a significant interaction between APOE and tau genotypes (P=.03). CONCLUSIONS: This study of the largest series of patients with FTD confirms the primary role of tau in FTD and establishes that the H1 haplotype of the tau gene and the E2 allele of APOE interact by an unknown mechanism that increases the risk of FTD.

Adult↗

PubMed2002

Is the saitohin gene involved in neurodegenerative diseases?

Recently, a single nucleotide polymorphism that results in an amino acid change (Q7R) was identified in a previously undescribed gene, named saitohin, nested within the tau gene. We analyzed the distribution of this polymorphism in 499 patients with Alzheimer's disease, 91 patients with frontotemporal dementia, and 402 controls. This polymorphism was in complete disequilibrium with the well-defined extended tau haplotype. We failed to replicate the association between the RR genotype and late-onset Alzheimer's disease, but we found a trend toward an association between the QQ genotype and frontotemporal dementia. Thus, the saitohin Q allele, which is a novel determinant of the tau H1 haplotypes, might represent a causative factor involved in the determinism of several tauopathies.

Adult↗

PubMed2002

Procedural learning and striatofrontal dysfunction in Parkinson's disease.

The neural basis of procedural learning remains controversial. We further analyzed procedural learning in nondemented patients with Parkinson's disease (PD) according to the specific demands of the tasks and the severity of striatal and frontal lobe dysfunction. In the first experiment, the performance of 20 nondemented PD patients and matched normal control subjects was studied in two procedural learning tasks, rotor pursuit and mirror reading, that differ in terms of motor and cognitive involvement. A second experiment further assessed the relationship between learning in mirror reading and executive functions in a new group of 15 nondemented PD patients. In rotor pursuit, PD patients significantly progressed across the first sessions, although their asymptotic performance was inferior to that of controls. In mirror reading, both experiments showed substantial learning in PD patients considered as a group. However, subsequent analyses allowed us to distinguish PD patients without executive dysfunction, whose learning was normal, from PD patients with executive dysfunction, whose learning was severely impaired. These results confirm the involvement of striatofrontal circuits in procedural learning and indicate that the intervention of the frontal network may depend on the characteristics of the task.

Aged↗

PubMed2002

Relationship between attentional performance and corpus callosum morphometry in patients with Alzheimer's disease.

There has been considerable interest in cognitive deficits associated with Alzheimer's disease (AD) and relationships between these impairments and specific cortical atrophies. Two previous studies [Neuropsychologia 28 (1990) 1197; Dementia 3 (1992) 350] have found that AD patients exhibit significant impairments in the attentional ID/ED set-shifting tasks of the CANTAB battery which involved attentional shifting abilities. But, at present, no study has examined the neural bases of these abilities in AD patients. In the present study, the relationship between performances on this attentional test and morphometry of the anterior and posterior corpus callosum is examined in AD patients in the mild to moderate stages of the disease (n=30, mean age=74.1+/-4.9 years, mean MMSE score=23.9+/-2.6). A control group is constituted (n=20, mean age=73.15+/-5.5 years) for comparison of cerebral measurements. The stepwise multiple regression analysis indicates that the relative contribution for the total callosal and the anterior CC areas of the simple discrimination subtest is significantly positive whereas for the posterior callosal areas the relative contribution of the more complex subtest is significantly positive. AD patients from the subgroup "low", who failed to do the nine subtests of the attentional set-shifting tasks, exhibit smaller callosal areas than control subjects. There is no significant difference for all callosal measurements between AD patients from the subgroup "high", who completely succeeded the test, and control subjects. Our findings suggest that the anterior corpus callosum would be related to attentional shifting abilities in AD patients. Moreover, these patients with probable AD seem heterogeneous for performances in the attentional test of the CANTAB and for callosal atrophies.

Aged↗

PubMed2002

[An anatomofunctional brain database].

This study proposes a closer look at the neuropsychological method defined as the study of the neural bases of the behavioural and cognitive functions using an organisation-representation model for current data and knowledge of the brain, and the application of an anatomofunctional database. A Centre of Cognitive Anatomy (CAC) was set up for the collection and processing of neuronatomical, neuropsychological, and psycho-behavioural data for patients presenting sequels of focal brain damage. Such a system would allow concurrent treatment of anatomical and functional data. We would expect the results from such a model to produce stable 'anatomofunctional laws' that would be independent of all inter-individual variations in the functioning of the brain and could be checked against the entire database of information. A direct application would be the improvement of cognitive and/or behavioural rehabilitation of patients with brain damage.

Brain↗

PubMed2002

Apolipoprotein E gene in frontotemporal dementia: an association study and meta-analysis.

No definite genetic risk factor of non-monogenic frontotemporal dementia (FTD) has yet been identified. Several groups have examined the potential association of FTD with the apolipoprotein E (APOE) gene, but the results are inconsistent. Our objective was to determine whether APOE is a risk factor of FTD, using the largest series of patients with FTD and controls analysed so far (94 unrelated patients and 392 age and sex-matched controls), and a meta-analysis. Homozygosity for the E2E2 genotype was significantly associated with FTD (odds ratio (OR)=11.3; P=0.033, exact test). After stratification on familial history (FH) for FTD, the OR for E2E2 was still found significant when analysing only patients with a positive FH (OR=23.8; P=0.019). The meta-analysis, using 10 case-control studies with available genotype or allele information, comprising a total of 364 FTD patients and 2671 controls, including the patients of the present study, did not reach statistical significance even if the E2E2 genotype was more frequent in patients than in controls (0.018 vs 0.006, respectively). Because of studies heterogeneity (Mantel-Haenszel statistics: P=0.004), we analysed on one hand the neuropathologically-confirmed studies, and on the other hand the clinical-based studies. In the neuropathologically-confirmed studies (Mantel-Haenszel statistics: P=ns), we found a significant increase of the E2 allele frequency in FTD patients (OR[E2 vs E3]=2.01; 95% CI=1.02-3.98; P=0.04). The same result was found in the clinical-based studies, but studies heterogeneity remained. No result was significant with the E4 allele. The E2 allele seems so to be a risk factor of FTD whereas this allele is associated with the lowest risk in Alzheimer's disease. If this finding was confirmed, it could provide new insights into the mechanisms of differential risk related to APOE in neurodegenerative diseases.

Adult↗