2016
|
I. Régner; M. Mazerolle; Béatrice ALESCIO-LAUTIER; D. Clarys; B. Michel; M. Pascalien; P. Paolino; F. Rigalleau; N. Sambuchi; P. Huguet Aging Stereotypes Must be Taken Into Account for the Diagnosis of Prodromal and Early Alzheimer Disease Article de journal Alzheimer disease and associated disorders, 30 (1), p. 77-79, 2016. Résumé | Liens | BibTeX @article{Regner2016,
title = {Aging Stereotypes Must be Taken Into Account for the Diagnosis of Prodromal and Early Alzheimer Disease},
author = {I. Régner and M. Mazerolle and Béatrice ALESCIO-LAUTIER and D. Clarys and B. Michel and M. Pascalien and P. Paolino and F. Rigalleau and N. Sambuchi and P. Huguet},
doi = {10.1097/WAD.0000000000000129},
year = {2016},
date = {2016-01-01},
journal = {Alzheimer disease and associated disorders},
volume = {30},
number = {1},
pages = {77-79},
abstract = {Because of a dramatic increase of older people worldwide, screening for prodromal state of Alzheimer disease (AD) is a major societal challenge. Many individuals diagnosed with prodromal AD, do not convert to AD, some remaining stable and others reversing back to normal. We argue that an important source of this overdiagnosis comes from negative aging stereotypes (eg, the culturally shared beliefs that aging inescapably causes severe cognitive decline and diseases). Many laboratory studies show that such stereotypes impair memory performance in healthy older adults, producing inflated age differences. Research is needed to examine how aging stereotypes implicitly permeate neuropsychological testing and contribute to false positives.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Because of a dramatic increase of older people worldwide, screening for prodromal state of Alzheimer disease (AD) is a major societal challenge. Many individuals diagnosed with prodromal AD, do not convert to AD, some remaining stable and others reversing back to normal. We argue that an important source of this overdiagnosis comes from negative aging stereotypes (eg, the culturally shared beliefs that aging inescapably causes severe cognitive decline and diseases). Many laboratory studies show that such stereotypes impair memory performance in healthy older adults, producing inflated age differences. Research is needed to examine how aging stereotypes implicitly permeate neuropsychological testing and contribute to false positives. |
2015
|
N. Sambucci; I. Muraccioli; B. Alescio-Lautier; V. Paban; R. Sambuc; E. Jouvé; Y. E. Geda; R. K. Petersen; B. F. Michel Subjective cognitive impairment and Alzheimer's disease: a two year follow up of 51 subjects during two years Article de journal Geriatr Psychol Neuropsychiatr Vieil., 13 (4), p. 462-471, 2015. Résumé | Liens | BibTeX @article{Sambucci2015z,
title = {Subjective cognitive impairment and Alzheimer's disease: a two year follow up of 51 subjects during two years},
author = {N. Sambucci and I. Muraccioli and B. Alescio-Lautier and V. Paban and R. Sambuc and E. Jouvé and Y. E. Geda and R. K. Petersen and B. F. Michel},
doi = {10.1684/pnv.2015.0575},
year = {2015},
date = {2015-12-04},
journal = {Geriatr Psychol Neuropsychiatr Vieil.},
volume = {13},
number = {4},
pages = {462-471},
abstract = {Subjective cognitive impairment (SCI) is defined by a state of subjective complaint, without objective cognitive deterioration. Amnestic mild cognitive impairment (A-MCI), which characterizes a syndrome between normal cognitive aging and early Alzheimer's disease (E-AD), is preceded by A-MCI from many years. SCI expresses a metacognitive impairment. A cohort of 51 subjects [7 normal controls (NC), 28 SCI, 12 A-MCI and 5 E-AD] was followed up during 24 months, with a neuropsychological evaluation each 6 months during 1 year (V1, V2, V3), then 1 year later (V4). Among the 28 SCI, 6 converted to A-MCI at V4 (21.42%), 1 to A-MCI-A at V3, then to E-AD at V4. These results suggest a continuum from SCI to A-MCI, and E-AD. Progressive SCI differed from non-progressive SCI on verbal episodic memory and executive functions tests at the initial examination. MRI showed anterior cingular atrophy in all SCI patients but hippocampal atrophy was only observed in 20 patients. Our results suggest that metacognition impairment is the expression of a dysfunction in the anterior pre-frontal cortex, in correlation with a syndrome of hyper-attention.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Subjective cognitive impairment (SCI) is defined by a state of subjective complaint, without objective cognitive deterioration. Amnestic mild cognitive impairment (A-MCI), which characterizes a syndrome between normal cognitive aging and early Alzheimer's disease (E-AD), is preceded by A-MCI from many years. SCI expresses a metacognitive impairment. A cohort of 51 subjects [7 normal controls (NC), 28 SCI, 12 A-MCI and 5 E-AD] was followed up during 24 months, with a neuropsychological evaluation each 6 months during 1 year (V1, V2, V3), then 1 year later (V4). Among the 28 SCI, 6 converted to A-MCI at V4 (21.42%), 1 to A-MCI-A at V3, then to E-AD at V4. These results suggest a continuum from SCI to A-MCI, and E-AD. Progressive SCI differed from non-progressive SCI on verbal episodic memory and executive functions tests at the initial examination. MRI showed anterior cingular atrophy in all SCI patients but hippocampal atrophy was only observed in 20 patients. Our results suggest that metacognition impairment is the expression of a dysfunction in the anterior pre-frontal cortex, in correlation with a syndrome of hyper-attention. |
Dubois B; Chupin M; Hampel H; Lista S; Cavedo E; Croisile B; Louis Tisserand G; Touchon J; Bonafe A; Ousset P.J; Ait Ameur A; Rouaud O; Ricolfi F; Vighetto A; Pasquier F; Delmaire C; Ceccaldi M; Girard N; Dufouil C; Lehericy S; Tonelli I; Duveau F; Colliot O; Garnero L; Sarazin M; Dormont D; Hippocampus Study Group Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal Alzheimer's disease. Article de journal Alzheimer's & Dementia, 11 (9), p. 1041-1049, 2015. Résumé | Liens | BibTeX @article{Dubois2015,
title = {Donepezil decreases annual rate of hippocampal atrophy in suspected prodromal Alzheimer's disease.},
author = {Dubois B and Chupin M and Hampel H and Lista S and Cavedo E and Croisile B and Louis Tisserand G and Touchon J and Bonafe A and Ousset P.J and Ait Ameur A and Rouaud O and Ricolfi F and Vighetto A and Pasquier F and Delmaire C and Ceccaldi M and Girard N and Dufouil C and Lehericy S and Tonelli I and Duveau F and Colliot O and Garnero L and Sarazin M and Dormont D and Hippocampus Study Group},
doi = {10.1016/j.jalz.2014.10.003},
year = {2015},
date = {2015-09-01},
journal = {Alzheimer's & Dementia},
volume = {11},
number = {9},
pages = {1041-1049},
abstract = {Introduction
The purpose of this study was to study the effect of donepezil on the rate of hippocampal atrophy in prodromal Alzheimer's disease (AD).
Methods
A double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day) in subjects with suspected prodromal AD. Subjects underwent two brain magnetic resonance imaging scans (baseline and final visit). The primary efficacy outcome was the annualized percentage change (APC) of total hippocampal volume (left + right) measured by an automated segmentation method.
Results
Two-hundred and sixteen only subjects were randomized across 28 French expert clinical sites. In the per protocol population (placebo = 92 and donepezil = 82), the donepezil group exhibited a significant reduced rate of hippocampal atrophy (APC = −1.89%) compared with the placebo group (APC = −3.47%), P < .001. There was no significant difference in neuropsychological performance between treatment groups.
Discussion
A 45% reduction of rate of hippocampal atrophy was observed in prodromal AD following 1 year of treatment with donepezil compared with placebo.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Introduction
The purpose of this study was to study the effect of donepezil on the rate of hippocampal atrophy in prodromal Alzheimer's disease (AD).
Methods
A double-blind, randomized, placebo-controlled parallel group design using donepezil (10 mg/day) in subjects with suspected prodromal AD. Subjects underwent two brain magnetic resonance imaging scans (baseline and final visit). The primary efficacy outcome was the annualized percentage change (APC) of total hippocampal volume (left + right) measured by an automated segmentation method.
Results
Two-hundred and sixteen only subjects were randomized across 28 French expert clinical sites. In the per protocol population (placebo = 92 and donepezil = 82), the donepezil group exhibited a significant reduced rate of hippocampal atrophy (APC = −1.89%) compared with the placebo group (APC = −3.47%), P < .001. There was no significant difference in neuropsychological performance between treatment groups.
Discussion
A 45% reduction of rate of hippocampal atrophy was observed in prodromal AD following 1 year of treatment with donepezil compared with placebo. |
Le Ber I.; De Septenville A.; Millecamps S.; Camuzat A.; Caroppo P.; Couratier P.; Blanc F.; Lacomblez L.; Sellal F.; Fleury M.C.; Meininger V.; Cazeneuve C.; Clot F.; Flabeau O.; LeGuern E.; Brice A.; French Clinical & Genetic Research Network on FTLD/FTLD-ALS TBK1 mutation frequencies in French fronto-temporal dementia and amyotrophic lateral sclerosis cohorts. Article de journal Neurobiology of Aging, 36 (11), p. 3116.e5–3116.e8, 2015. Résumé | Liens | BibTeX @article{LeBer2015,
title = {TBK1 mutation frequencies in French fronto-temporal dementia and amyotrophic lateral sclerosis cohorts.},
author = {Le Ber I. and De Septenville A. and Millecamps S. and Camuzat A. and Caroppo P. and Couratier P. and Blanc F. and Lacomblez L. and Sellal F. and Fleury M.C. and Meininger V. and Cazeneuve C. and Clot F. and Flabeau O. and LeGuern E. and Brice A. and French Clinical & Genetic Research Network on FTLD/FTLD-ALS},
doi = {10.1016/j.neurobiolaging.2015.08.009},
year = {2015},
date = {2015-08-08},
journal = {Neurobiology of Aging},
volume = {36},
number = {11},
pages = {3116.e5–3116.e8},
abstract = {TANK1-binding kinase 1 (TBK1) has been recently identified as a new amyotrophic lateral sclerosis (ALS) gene. Loss-of-function (LoF) mutations in TBK1 could be responsible for 0.4%–4% of ALS. Considering the strong genetic overlap existing between frontotemporal dementia (FTD) and ALS, we have evaluated the frequencies of TBK1 mutations in a cohort of French FTD and of ALS patients. We identified 5 LoF mutations, in 4 FTD-ALS and 1 ALS patients. We also identified 5 heterozygous missense variants, predicted to be deleterious, in 1 isolated FTD, 1 FTD-ALS, and 3 ALS cases. Our results demonstrate that TBK1 loss-of-function mutations are more frequent in patients with FTD-ALS (10.8%) than in isolated ALS. TBK1 should thus also be sequenced, after exclusion of C9orf72 mutation, in patients presenting FTD, particularly in cases secondarily associated with ALS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
TANK1-binding kinase 1 (TBK1) has been recently identified as a new amyotrophic lateral sclerosis (ALS) gene. Loss-of-function (LoF) mutations in TBK1 could be responsible for 0.4%–4% of ALS. Considering the strong genetic overlap existing between frontotemporal dementia (FTD) and ALS, we have evaluated the frequencies of TBK1 mutations in a cohort of French FTD and of ALS patients. We identified 5 LoF mutations, in 4 FTD-ALS and 1 ALS patients. We also identified 5 heterozygous missense variants, predicted to be deleterious, in 1 isolated FTD, 1 FTD-ALS, and 3 ALS cases. Our results demonstrate that TBK1 loss-of-function mutations are more frequent in patients with FTD-ALS (10.8%) than in isolated ALS. TBK1 should thus also be sequenced, after exclusion of C9orf72 mutation, in patients presenting FTD, particularly in cases secondarily associated with ALS. |
Di Stefano F.; Epelbaum S.; Coley N.; Cantet C.; Ousset P.J.; Hampel H.; Bakardjian H.; Lista S.; Vellas B.; Dubois B.; Andrieu S.; GuidAge study group Prediction of Alzheimer's Disease Dementia: Data from the GuidAge Prevention Trial. Article de journal Journal of Alzheimer's Disease, 48 (3), p. 793-804, 2015. Résumé | Liens | BibTeX @article{DiStefano2015,
title = {Prediction of Alzheimer's Disease Dementia: Data from the GuidAge Prevention Trial.},
author = {Di Stefano F. and Epelbaum S. and Coley N. and Cantet C. and Ousset P.J. and Hampel H. and Bakardjian H. and Lista S. and Vellas B. and Dubois B. and Andrieu S. and GuidAge study group},
doi = {10.3233/JAD-150013},
year = {2015},
date = {2015-06-30},
journal = {Journal of Alzheimer's Disease},
volume = {48},
number = {3},
pages = {793-804},
abstract = {In therapeutic trials, it is crucial to identify Alzheimer’s disease (AD) at its prodromal stage. We assessed the accuracy of the free and cued selective reminding test (FCSRT) compared to other cognitive tests to predict AD dementia in subjects with subjective cognitive decline or mild cognitive impairment. Subjects from the placebo group of the GuidAge trial over 70 years old and without clinical signs of dementia at baseline who completed the 5-year follow-up free of dementia (n = 840) or developed AD dementia (n = 73) were included in our study. Among all the tests, the sum of the 3 free recall of the FCSRT (FCSRT-FR) and the sum of free and cued recall (FCSRT-TR) yielded the best results to predict AD dementia occurrence (all p values <0.05 for comparison of FCSRT-FR ROC and MMSE, CDRsb, and CVF ROCs). FCSRT-FR had an area under the ROC curve of 0.799 (95% CI 0.738–0.85) and the optimal cut-off was 20 (se 68.06% , sp 81.43% , PPV 23.90% , NPV 96,75%). Concerning FCSRT-TR, the AUC was 0.776 and the optimal cut-off was 42 (se 62.5% , sp 82.26% , PPV 23.20% and NPV 96.24%). This study sets the framework for implementing the FCSRT in clinical and therapeutic trials for efficient subject selection.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In therapeutic trials, it is crucial to identify Alzheimer’s disease (AD) at its prodromal stage. We assessed the accuracy of the free and cued selective reminding test (FCSRT) compared to other cognitive tests to predict AD dementia in subjects with subjective cognitive decline or mild cognitive impairment. Subjects from the placebo group of the GuidAge trial over 70 years old and without clinical signs of dementia at baseline who completed the 5-year follow-up free of dementia (n = 840) or developed AD dementia (n = 73) were included in our study. Among all the tests, the sum of the 3 free recall of the FCSRT (FCSRT-FR) and the sum of free and cued recall (FCSRT-TR) yielded the best results to predict AD dementia occurrence (all p values <0.05 for comparison of FCSRT-FR ROC and MMSE, CDRsb, and CVF ROCs). FCSRT-FR had an area under the ROC curve of 0.799 (95% CI 0.738–0.85) and the optimal cut-off was 20 (se 68.06% , sp 81.43% , PPV 23.90% , NPV 96,75%). Concerning FCSRT-TR, the AUC was 0.776 and the optimal cut-off was 42 (se 62.5% , sp 82.26% , PPV 23.20% and NPV 96.24%). This study sets the framework for implementing the FCSRT in clinical and therapeutic trials for efficient subject selection. |
Krell-Roesch J.; Woodruff B. K.; Acosta J. I.; Locke D.E.; Hentz J. G.; Stonnington C. M.; Stokin G. B.; Nagle C.; Michel B. F.; Sambuchi N.; Caselli R. J.; Geda Y. E. APOE ε4 Genotype and the Risk for Subjective Cognitive Impairment in Elderly Persons Article de journal The Journal of Neuropsychiatry, 27 (4), p. 322-325, 2015. Résumé | Liens | BibTeX @article{KrellRoesch2015,
title = {APOE ε4 Genotype and the Risk for Subjective Cognitive Impairment in Elderly Persons},
author = {Krell-Roesch J. and Woodruff B. K. and Acosta J. I. and Locke D.E. and Hentz J. G. and Stonnington C. M. and Stokin G. B. and Nagle C. and Michel B. F. and Sambuchi N. and Caselli R. J. and Geda Y. E.},
doi = {10.1176/appi.neuropsych.14100268},
year = {2015},
date = {2015-01-15},
journal = {The Journal of Neuropsychiatry},
volume = {27},
number = {4},
pages = {322-325},
abstract = {The authors compared the risk for subjective cognitive impairment (SCI) between carriers of the apolipoprotein E ε4 (APOE ε4) allele (cases) and APOE ε4 noncarriers (controls). SCI was assessed by a validated self-reported questionnaire. The authors used multivariable logistic regression analyses to compute odds ratios and 95% confidence intervals adjusted for age, sex, education, and marital status. Data were available on 114 participants (83 women; 47 APOE ε4 carriers; mean age, 69 years). The risk for SCI was significantly higher among cases than controls, particularly for those 70 years of age and older. These findings should be considered preliminary until confirmed by a prospective cohort study.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The authors compared the risk for subjective cognitive impairment (SCI) between carriers of the apolipoprotein E ε4 (APOE ε4) allele (cases) and APOE ε4 noncarriers (controls). SCI was assessed by a validated self-reported questionnaire. The authors used multivariable logistic regression analyses to compute odds ratios and 95% confidence intervals adjusted for age, sex, education, and marital status. Data were available on 114 participants (83 women; 47 APOE ε4 carriers; mean age, 69 years). The risk for SCI was significantly higher among cases than controls, particularly for those 70 years of age and older. These findings should be considered preliminary until confirmed by a prospective cohort study. |
B. F. Michel; H. Becker; P. Bensa Démences avec atteinte de la substance blanche par trouble du métabolisme lipidique Book Chapter Démences, p. 473-483, 2015. BibTeX @inbook{Michel2015,
title = {Démences avec atteinte de la substance blanche par trouble du métabolisme lipidique},
author = {B. F. Michel and H. Becker and P. Bensa},
year = {2015},
date = {2015-01-01},
booktitle = {Démences},
pages = {473-483},
keywords = {},
pubstate = {published},
tppubtype = {inbook}
}
|
2014
|
Le Ber I.; Van Bortel I.; Nicolas G.; Bouya-Ahmed K.; Camuzat A.; Wallon D.; De Septenville A.; Latouche M.; Lattante S.; Kabashi E.; Jornea L.; Hannequin D.; Brice A.; French research Network on FTLD/FTLD-ALS hnRNPA2B1 and hnRNPA1 mutations are rare in patients with “multisystem proteinopathy” and frontotemporal lobar degeneration phenotypes. Article de journal Neurobiology of Aging, 35 (4), p. 934.e5–934.e6, 2014. Résumé | Liens | BibTeX @article{LeBer2014,
title = {hnRNPA2B1 and hnRNPA1 mutations are rare in patients with “multisystem proteinopathy” and frontotemporal lobar degeneration phenotypes.},
author = {Le Ber I. and Van Bortel I. and Nicolas G. and Bouya-Ahmed K. and Camuzat A. and Wallon D. and De Septenville A. and Latouche M. and Lattante S. and Kabashi E. and Jornea L. and Hannequin D. and Brice A. and French research Network on FTLD/FTLD-ALS},
doi = {10.1016/j.neurobiolaging.2013.09.016},
year = {2014},
date = {2014-04-01},
journal = {Neurobiology of Aging},
volume = {35},
number = {4},
pages = {934.e5–934.e6},
abstract = {hnRNPA2B1 and hnRNPA1 mutations have been recently identified by exome sequencing in three families presenting with multisystem proteinopathy (MSP), a rare complex phenotype associating frontotemporal lobar degeneration (FTLD), Paget disease of bone (PDB), inclusion body myopathy (IBM), and amyotrophic lateral sclerosis (ALS). No study has evaluated the exact frequency of these genes in cohorts of MSP or FTD patients so far. We sequenced both genes in 17 patients with MSP phenotypes, and in 60 patients with FTLD and FTLD-ALS to test whether mutations could be implicated in the pathogenesis of these disorders. No disease-causing mutation was identified. We conclude that hnRNPA2B1 and hnRNPA1 mutations are rare in MSP and FTLD spectrum of diseases, although further investigations in larger populations are needed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
hnRNPA2B1 and hnRNPA1 mutations have been recently identified by exome sequencing in three families presenting with multisystem proteinopathy (MSP), a rare complex phenotype associating frontotemporal lobar degeneration (FTLD), Paget disease of bone (PDB), inclusion body myopathy (IBM), and amyotrophic lateral sclerosis (ALS). No study has evaluated the exact frequency of these genes in cohorts of MSP or FTD patients so far. We sequenced both genes in 17 patients with MSP phenotypes, and in 60 patients with FTLD and FTLD-ALS to test whether mutations could be implicated in the pathogenesis of these disorders. No disease-causing mutation was identified. We conclude that hnRNPA2B1 and hnRNPA1 mutations are rare in MSP and FTLD spectrum of diseases, although further investigations in larger populations are needed. |
Clot F.; Rovelet-Lecrux A.; Lamari F.; Noël S.; Keren B.; Camuzat A.; Michon A.; Jornea L.; Laudier B.; de Septenville A.; Caroppo P.; Campion D.; Cazeneuve C.; Brice A.; LeGuern E.; Le Ber I.; French clinical & genetic research network on FTLD/FTLD-ALS Partial deletions of the GRN gene are a cause of frontotemporal lobar degeneration. Article de journal neurogenetics, 2014. Résumé | Liens | BibTeX @article{Clot2014,
title = {Partial deletions of the GRN gene are a cause of frontotemporal lobar degeneration.},
author = {Clot F. and Rovelet-Lecrux A. and Lamari F. and Noël S. and Keren B. and Camuzat A. and Michon A. and Jornea L. and Laudier B. and de Septenville A. and Caroppo P. and Campion D. and Cazeneuve C. and Brice A. and LeGuern E. and Le Ber I. and French clinical & genetic research network on FTLD/FTLD-ALS},
doi = {10.1007/s10048-014-0389-x},
year = {2014},
date = {2014-01-28},
journal = {neurogenetics},
abstract = {Mutations in the progranulin gene (GRN) are an important cause of frontotemporal lobar degeneration (FTLD). Most known GRN mutations are null mutations, such as nonsense and frameshift mutations, which create a premature stop codon resulting in loss of function of the progranulin protein. Complete or near-complete genomic GRN deletions have also been found in three families, but heterozygous partial deletions that remove only one or two exons have not been reported to date. In this study, we analysed three unrelated FTLD patients with low plasma progranulin levels but no point GRN mutations by multiplex ligation-dependent probe amplification (MLPA) and quantitative multiplex polymerase chain reaction of short fluorescent fragments (QMPSF). We detected two heterozygous partial GRN deletions in two patients. One deletion removed exon 1 and part of intron 1. The second deletion was complex: it removed 1,410 bp extending from the part of intron 1 to the part of exon 3, with a small 5-bp insertion at the breakpoint junction (c.-7-1121_159delinsGATCA). Our findings illustrate the usefulness of a quantitative analysis in addition to GRN gene sequencing for a comprehensive genetic diagnosis of FTLD, particularly in patients with low plasma progranulin levels.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mutations in the progranulin gene (GRN) are an important cause of frontotemporal lobar degeneration (FTLD). Most known GRN mutations are null mutations, such as nonsense and frameshift mutations, which create a premature stop codon resulting in loss of function of the progranulin protein. Complete or near-complete genomic GRN deletions have also been found in three families, but heterozygous partial deletions that remove only one or two exons have not been reported to date. In this study, we analysed three unrelated FTLD patients with low plasma progranulin levels but no point GRN mutations by multiplex ligation-dependent probe amplification (MLPA) and quantitative multiplex polymerase chain reaction of short fluorescent fragments (QMPSF). We detected two heterozygous partial GRN deletions in two patients. One deletion removed exon 1 and part of intron 1. The second deletion was complex: it removed 1,410 bp extending from the part of intron 1 to the part of exon 3, with a small 5-bp insertion at the breakpoint junction (c.-7-1121_159delinsGATCA). Our findings illustrate the usefulness of a quantitative analysis in addition to GRN gene sequencing for a comprehensive genetic diagnosis of FTLD, particularly in patients with low plasma progranulin levels. |
POLYDOR J-P.; MICHEL B.F. Alzheimer, empathie et neurones miroirs : la représentation manipulable. Book Chapter Représentations et maladies neurodégénératives, p. 205-213, 2014. BibTeX @inbook{Polydor2014,
title = {Alzheimer, empathie et neurones miroirs : la représentation manipulable.},
author = {POLYDOR J-P. and MICHEL B.F.},
year = {2014},
date = {2014-01-17},
booktitle = {Représentations et maladies neurodégénératives},
pages = {205-213},
keywords = {},
pubstate = {published},
tppubtype = {inbook}
}
|
SAMBUCHI N.; CHEN F.; BARTOLIN A.; GALLANT C.; MURACCIOLI I.; SAINT-JEAN J-C.; ROUYER C.; BENSA P.; TAMMAM D.; GEDA Y.E.; MICHEL B.F. Représentation de soi et cognition modèles et méthodes d’évaluation. Book Chapter Représentations et maladies neurodégénératives., p. 17-40, 2014. BibTeX @inbook{Sambuchi2014,
title = {Représentation de soi et cognition modèles et méthodes d’évaluation.},
author = {SAMBUCHI N. and CHEN F. and BARTOLIN A. and GALLANT C. and MURACCIOLI I. and SAINT-JEAN J-C. and ROUYER C. and BENSA P. and TAMMAM D. and GEDA Y.E. and MICHEL B.F. },
year = {2014},
date = {2014-01-17},
booktitle = {Représentations et maladies neurodégénératives.},
pages = {17-40},
keywords = {},
pubstate = {published},
tppubtype = {inbook}
}
|
MICHEL B.F.; DEROUESNE C.; MURRAY M.; BECKER H.; BOEVE B.F. Représentation de soi et syndromes parkinsonien. Signe de la main étrangère dans la Dégénérescence Cortico-Basale. Article de journal p. 113-126, 2014. BibTeX @article{Michel2014,
title = {Représentation de soi et syndromes parkinsonien. Signe de la main étrangère dans la Dégénérescence Cortico-Basale.},
author = {MICHEL B.F. and DEROUESNE C. and MURRAY M. and BECKER H. and BOEVE B.F.},
year = {2014},
date = {2014-01-17},
booktitle = {Représentations et maladies neurodégénératives},
pages = {113-126},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
BENSA P.; SAINT-JEAN J-C.; ROUYER C.; TAMMAM D.; MURRAY M.; MICHEL B.F. Troubles de la Représentation d’Autrui dans les Dégénérescences Lobaires Fronto-Temporales. Article de journal p. 151-166, 2014. BibTeX @article{Bensa2014,
title = {Troubles de la Représentation d’Autrui dans les Dégénérescences Lobaires Fronto-Temporales.},
author = {BENSA P. and SAINT-JEAN J-C. and ROUYER C. and TAMMAM D. and MURRAY M. and MICHEL B.F.},
year = {2014},
date = {2014-01-17},
booktitle = {Représentations et maladies neurodégénératives},
pages = {151-166},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2013
|
Le Ber I.; Camuzat A.; Guerreiro R.; Bouya-Ahmed K.; Bras J.; Nicolas G.; Gabelle A.; Didic M.; De Septenville A.; Millecamps S.; Lenglet T.; Latouche M.; Kabashi E.; Campion D.; Hannequin D.; Hardy J.; Brice A.; French Clinical & Genetic Research Network on FTD/FTD-ALS French Clinical and Genetic Research Network on FTD/FTD-ALS. (2013). SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis. Article de journal JAMA Neurology, 70 (11), p. 1403-1410, 2013. Résumé | Liens | BibTeX @article{LeBer2013,
title = {French Clinical and Genetic Research Network on FTD/FTD-ALS. (2013). SQSTM1 mutations in French patients with frontotemporal dementia or frontotemporal dementia with amyotrophic lateral sclerosis.},
author = {Le Ber I. and Camuzat A. and Guerreiro R. and Bouya-Ahmed K. and Bras J. and Nicolas G. and Gabelle A. and Didic M. and De Septenville A. and Millecamps S. and Lenglet T. and Latouche M. and Kabashi E. and Campion D. and Hannequin D. and Hardy J. and Brice A. and French Clinical & Genetic Research Network on FTD/FTD-ALS},
doi = {10.1001/jamaneurol.2013.3849},
year = {2013},
date = {2013-11-01},
journal = {JAMA Neurology},
volume = {70},
number = {11},
pages = {1403-1410},
abstract = {IMPORTANCE
Mutations in the SQSTM1 gene, coding for p62, are a cause of Paget disease of bone and amyotrophic lateral sclerosis (ALS). Recently, SQSTM1 mutations were confirmed in ALS, and mutations were also identified in 3 patients with frontotemporal dementia (FTD), suggesting a role for SQSTM1 in FTD.
OBJECTIVE
To evaluate the exact contribution of SQSTM1 to FTD and FTD with ALS (FTD-ALS) in an independent cohort of patients.
DESIGN
A SQSTM1 mutation was first identified in a multiplex family with FTD by use of whole-exome sequencing. To evaluate the frequency of SQSTM1 mutations, we sequenced this gene in a cohort of patients with FTD or FTD-ALS, with no mutations in known FTD and ALS genes.
SETTING
Primary care or referral center.
PARTICIPANTS
An overall cohort of 188 French patients, including 132 probands with FTD and 56 probands with FTD-ALS.
MAIN OUTCOMES AND MEASURES:
Frequency of SQSTM1 mutations in patients with FTD or FTD-ALS; description of associated phenotypes.
RESULTS
We identified 4 heterozygous missense mutations in 4 unrelated families with FTD; only 1 family had clinical symptoms of Paget disease of bone, and only 1 family had clinical symptoms of FTD-ALS, possibly owing to the low penetrance of some of the clinical manifestations.
CONCLUSIONS AND RELEVANCE
Although the frequency of the mutations is low in our series (4 of 188 patients [2%]), our results, similar to those already reported, support a direct pathogenic role of p62 in different types of FTD.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
IMPORTANCE
Mutations in the SQSTM1 gene, coding for p62, are a cause of Paget disease of bone and amyotrophic lateral sclerosis (ALS). Recently, SQSTM1 mutations were confirmed in ALS, and mutations were also identified in 3 patients with frontotemporal dementia (FTD), suggesting a role for SQSTM1 in FTD.
OBJECTIVE
To evaluate the exact contribution of SQSTM1 to FTD and FTD with ALS (FTD-ALS) in an independent cohort of patients.
DESIGN
A SQSTM1 mutation was first identified in a multiplex family with FTD by use of whole-exome sequencing. To evaluate the frequency of SQSTM1 mutations, we sequenced this gene in a cohort of patients with FTD or FTD-ALS, with no mutations in known FTD and ALS genes.
SETTING
Primary care or referral center.
PARTICIPANTS
An overall cohort of 188 French patients, including 132 probands with FTD and 56 probands with FTD-ALS.
MAIN OUTCOMES AND MEASURES:
Frequency of SQSTM1 mutations in patients with FTD or FTD-ALS; description of associated phenotypes.
RESULTS
We identified 4 heterozygous missense mutations in 4 unrelated families with FTD; only 1 family had clinical symptoms of Paget disease of bone, and only 1 family had clinical symptoms of FTD-ALS, possibly owing to the low penetrance of some of the clinical manifestations.
CONCLUSIONS AND RELEVANCE
Although the frequency of the mutations is low in our series (4 of 188 patients [2%]), our results, similar to those already reported, support a direct pathogenic role of p62 in different types of FTD. |
Secher M.; Andrieu S.; Gillette-Guyonnet S.; Soto M.; Rolland Y.; Cantet C.; Vellas B.; Ritz P.; REAL.fr Group Weight changes in Alzheimer’s disease patients with increased aberrant motor behavior Article de journal International Journal of Geriatric Psychiatry, 28 (10), p. 998–1004, 2013. Résumé | Liens | BibTeX @article{Secher2013,
title = {Weight changes in Alzheimer’s disease patients with increased aberrant motor behavior},
author = {Secher M. and Andrieu S. and Gillette-Guyonnet S. and Soto M. and Rolland Y. and Cantet C. and Vellas B. and Ritz P. and REAL.fr Group},
doi = {10.1002/gps.3914},
year = {2013},
date = {2013-10-01},
journal = {International Journal of Geriatric Psychiatry},
volume = {28},
number = {10},
pages = {998–1004},
abstract = {OBJECTIVE
Weight loss and behavioral disturbances are frequent over the course of Alzheimer’s disease (AD) and are risk factors for poor outcome. We investigated the impact of aberrant motor behavior (AMB) on weight changes in older adults with AD. The hypothesis that patients with AMB are more likely to lose weight than patients without AMB was assessed.
METHODS
A prospective study of 686 patients with moderate AD from the REAL.FR cohort was assessed. The AMB at baseline was defined by the item 10 from the Neuropsychiatric Inventory scale (NPI-10). Patients were classified as “no or light AMB” (NPI-10 < 4), and “significant AMB” (NPI-10 ≥ 4). Weight changes were determined over the 4-year follow-up.
RESULTS
The mean weight change over the 4 years was +2.2 ± 0.9 kg in patients with “significant AMB,” whereas weight remained stable in patients with “no or light AMB” (p = 0.02).
CONCLUSION
Older adults with moderate AD and “significant AMB” do gain weight},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE
Weight loss and behavioral disturbances are frequent over the course of Alzheimer’s disease (AD) and are risk factors for poor outcome. We investigated the impact of aberrant motor behavior (AMB) on weight changes in older adults with AD. The hypothesis that patients with AMB are more likely to lose weight than patients without AMB was assessed.
METHODS
A prospective study of 686 patients with moderate AD from the REAL.FR cohort was assessed. The AMB at baseline was defined by the item 10 from the Neuropsychiatric Inventory scale (NPI-10). Patients were classified as “no or light AMB” (NPI-10 < 4), and “significant AMB” (NPI-10 ≥ 4). Weight changes were determined over the 4-year follow-up.
RESULTS
The mean weight change over the 4 years was +2.2 ± 0.9 kg in patients with “significant AMB,” whereas weight remained stable in patients with “no or light AMB” (p = 0.02).
CONCLUSION
Older adults with moderate AD and “significant AMB” do gain weight |
Secher M.; Andrieu S.; Gillette-Guyonnet S.; Soto M.; Rolland Y.; Cantet C.; Vellas B.; Ritz P.; REAL.fr Group Weight changes in Alzheimer’s disease patients with increased aberrant motor behavior. Article de journal International Journal of Geriatric Psychiatry, 28 (10), p. 998–1004, 2013. Résumé | Liens | BibTeX @article{Secher2013b,
title = { Weight changes in Alzheimer’s disease patients with increased aberrant motor behavior.},
author = {Secher M. and Andrieu S. and Gillette-Guyonnet S. and Soto M. and Rolland Y. and Cantet C. and Vellas B. and Ritz P. and REAL.fr Group},
doi = {10.1002/gps.3914},
year = {2013},
date = {2013-10-01},
journal = {International Journal of Geriatric Psychiatry},
volume = {28},
number = {10},
pages = {998–1004},
abstract = {OBJECTIVE
Weight loss and behavioral disturbances are frequent over the course of Alzheimer’s disease (AD) and are risk factors for poor outcome. We investigated the impact of aberrant motor behavior (AMB) on weight changes in older adults with AD. The hypothesis that patients with AMB are more likely to lose weight than patients without AMB was assessed.
METHODS
A prospective study of 686 patients with moderate AD from the REAL.FR cohort was assessed. The AMB at baseline was defined by the item 10 from the Neuropsychiatric Inventory scale (NPI-10). Patients were classified as “no or light AMB” (NPI-10 < 4), and “significant AMB” (NPI-10 ≥ 4). Weight changes were determined over the 4-year follow-up.
RESULTS
The mean weight change over the 4 years was +2.2 ± 0.9 kg in patients with “significant AMB,” whereas weight remained stable in patients with “no or light AMB” (p = 0.02).
CONCLUSION
Older adults with moderate AD and “significant AMB” do gain weight.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE
Weight loss and behavioral disturbances are frequent over the course of Alzheimer’s disease (AD) and are risk factors for poor outcome. We investigated the impact of aberrant motor behavior (AMB) on weight changes in older adults with AD. The hypothesis that patients with AMB are more likely to lose weight than patients without AMB was assessed.
METHODS
A prospective study of 686 patients with moderate AD from the REAL.FR cohort was assessed. The AMB at baseline was defined by the item 10 from the Neuropsychiatric Inventory scale (NPI-10). Patients were classified as “no or light AMB” (NPI-10 < 4), and “significant AMB” (NPI-10 ≥ 4). Weight changes were determined over the 4-year follow-up.
RESULTS
The mean weight change over the 4 years was +2.2 ± 0.9 kg in patients with “significant AMB,” whereas weight remained stable in patients with “no or light AMB” (p = 0.02).
CONCLUSION
Older adults with moderate AD and “significant AMB” do gain weight. |
Le Ber I.; Van Bortel I.; Nicolas G.; Bouya-Ahmed K.; Camuzat A.; Wallon D.; De Septenville A.; Latouche M.; Lattante S.; Kabashi E.; Jornea L.; Hannequin D.; Brice A.; French research Network on FTLD/FTLD-ALS hnRNPA2B1 and hnRNPA1 mutations are rare in patients with “multisystem proteinopathy” and frontotemporal lobar degeneration phenotypes. Article de journal Neurobiology of Aging, 35 (4), p. 934.e5–934.e6, 2013. Résumé | Liens | BibTeX @article{LeBer2013b,
title = {hnRNPA2B1 and hnRNPA1 mutations are rare in patients with “multisystem proteinopathy” and frontotemporal lobar degeneration phenotypes.},
author = {Le Ber I. and Van Bortel I. and Nicolas G. and Bouya-Ahmed K. and Camuzat A. and Wallon D. and De Septenville A. and Latouche M. and Lattante S. and Kabashi E. and Jornea L. and Hannequin D. and Brice A. and French research Network on FTLD/FTLD-ALS},
doi = {10.1016/j.neurobiolaging.2013.09.016},
year = {2013},
date = {2013-09-10},
journal = {Neurobiology of Aging},
volume = {35},
number = {4},
pages = {934.e5–934.e6},
abstract = {hnRNPA2B1 and hnRNPA1 mutations have been recently identified by exome sequencing in three families presenting with multisystem proteinopathy (MSP), a rare complex phenotype associating frontotemporal lobar degeneration (FTLD), Paget disease of bone (PDB), inclusion body myopathy (IBM), and amyotrophic lateral sclerosis (ALS). No study has evaluated the exact frequency of these genes in cohorts of MSP or FTD patients so far. We sequenced both genes in 17 patients with MSP phenotypes, and in 60 patients with FTLD and FTLD-ALS to test whether mutations could be implicated in the pathogenesis of these disorders. No disease-causing mutation was identified. We conclude that hnRNPA2B1 and hnRNPA1 mutations are rare in MSP and FTLD spectrum of diseases, although further investigations in larger populations are needed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
hnRNPA2B1 and hnRNPA1 mutations have been recently identified by exome sequencing in three families presenting with multisystem proteinopathy (MSP), a rare complex phenotype associating frontotemporal lobar degeneration (FTLD), Paget disease of bone (PDB), inclusion body myopathy (IBM), and amyotrophic lateral sclerosis (ALS). No study has evaluated the exact frequency of these genes in cohorts of MSP or FTD patients so far. We sequenced both genes in 17 patients with MSP phenotypes, and in 60 patients with FTLD and FTLD-ALS to test whether mutations could be implicated in the pathogenesis of these disorders. No disease-causing mutation was identified. We conclude that hnRNPA2B1 and hnRNPA1 mutations are rare in MSP and FTLD spectrum of diseases, although further investigations in larger populations are needed. |
Montastruc F.; Gardette V.; Cantet C.; Piau A.; Lapeyre-Mestre M.; Vellas B.; Montastruc J-L.; Andrieu S.; REAL.FR Group Potentially inappropriate medication use among patients with Alzheimer disease in the REAL.FR cohort: be aware of atropinic and benzodiazepine drugs! Article de journal European Journal of Clinical Pharmacology, 69 (8), p. 1589–1597, 2013. Résumé | Liens | BibTeX @article{Montastruc2013,
title = {Potentially inappropriate medication use among patients with Alzheimer disease in the REAL.FR cohort: be aware of atropinic and benzodiazepine drugs!},
author = {Montastruc F. and Gardette V. and Cantet C. and Piau A. and Lapeyre-Mestre M. and Vellas B. and Montastruc J-L. and Andrieu S. and REAL.FR Group},
doi = {10.1007/s00228-013-1506-8},
year = {2013},
date = {2013-08-01},
journal = {European Journal of Clinical Pharmacology},
volume = {69},
number = {8},
pages = {1589–1597},
abstract = {OBJECTIVE
Few studies have investigated potentially inappropriate medication (PIM) use in patients with Alzheimer’s disease (AD). The aim of our study was to assess the prevalence of PIM in community-dwelling patients diagnosed with mild-to-moderate AD and identify the clinical factors associated with PIM prescriptions.
METHODS
REAL.FR is a 4-year, prospective, multicenter French cohort of AD patients recruited in centers of expertise. We analyzed patient baseline data at entry into the study. PIMs were assessed using the Laroche list. A multivariate logistic regression was conducted to assess factors associated with PIMs.
RESULTS
A total of 684 AD patients were enrolled in the study [mean age 77.9 ± 6.8 years, 486 (71.0 %) females]. According to the Laroche list, 46.8 % [95 % confidence interval (CI) 43.0-50.5 %] of the patients had at least one PIM. “Cerebral vasodilators” were the most widely used class of PIM, accounting for 24.0 % (95 % CI 20.9-27.3 %) of all prescriptions, followed by atropinic drugs (17.0 %, 95 % CI 14.1-19.8 %) and long half-life benzodiazepines (8.5 %, 95 % CI 6.4-10.6 %). Atropinic drugs were associated with cholinesterase inhibitors in 16 % of patients. In the multivariate analysis, only two factors, namely, female gender [odds ratio (OR) 1.5, 95 % CI 1.1-2.2] and polypharmacy (≥5 drugs; OR 3.6, 95 % CI 2.6-4.5) were associated with prescriptions for PIMs.
CONCLUSIONS
These results reveal that approximately one out of two community-dwelling patients with mild-to-moderate AD treated by AD specialists use PIMs. They also indicate that the characteristics of the disease and the pharmacodynamic/pharmacokinetic profile of the drugs prescribed are not sufficiently taken into account by physicians when prescribing for AD patients.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE
Few studies have investigated potentially inappropriate medication (PIM) use in patients with Alzheimer’s disease (AD). The aim of our study was to assess the prevalence of PIM in community-dwelling patients diagnosed with mild-to-moderate AD and identify the clinical factors associated with PIM prescriptions.
METHODS
REAL.FR is a 4-year, prospective, multicenter French cohort of AD patients recruited in centers of expertise. We analyzed patient baseline data at entry into the study. PIMs were assessed using the Laroche list. A multivariate logistic regression was conducted to assess factors associated with PIMs.
RESULTS
A total of 684 AD patients were enrolled in the study [mean age 77.9 ± 6.8 years, 486 (71.0 %) females]. According to the Laroche list, 46.8 % [95 % confidence interval (CI) 43.0-50.5 %] of the patients had at least one PIM. “Cerebral vasodilators” were the most widely used class of PIM, accounting for 24.0 % (95 % CI 20.9-27.3 %) of all prescriptions, followed by atropinic drugs (17.0 %, 95 % CI 14.1-19.8 %) and long half-life benzodiazepines (8.5 %, 95 % CI 6.4-10.6 %). Atropinic drugs were associated with cholinesterase inhibitors in 16 % of patients. In the multivariate analysis, only two factors, namely, female gender [odds ratio (OR) 1.5, 95 % CI 1.1-2.2] and polypharmacy (≥5 drugs; OR 3.6, 95 % CI 2.6-4.5) were associated with prescriptions for PIMs.
CONCLUSIONS
These results reveal that approximately one out of two community-dwelling patients with mild-to-moderate AD treated by AD specialists use PIMs. They also indicate that the characteristics of the disease and the pharmacodynamic/pharmacokinetic profile of the drugs prescribed are not sufficiently taken into account by physicians when prescribing for AD patients. |
Gallini A.; Gardette V.; Vellas B.; Lapeyre-Mestre M.; Andrieu S.; Brefel-Courbon C.; REAL.FR/DSA group Persistent use of analgesic medications in mild-to-moderate Alzheimer’s disease. Article de journal Drugs & Aging, 30 (6), p. 439-445, 2013. Résumé | Liens | BibTeX @article{Gallini2013,
title = {Persistent use of analgesic medications in mild-to-moderate Alzheimer’s disease.},
author = {Gallini A. and Gardette V. and Vellas B. and Lapeyre-Mestre M. and Andrieu S. and Brefel-Courbon C. and REAL.FR/DSA group},
doi = {10.1007/s40266-013-0070-3},
year = {2013},
date = {2013-06-01},
journal = {Drugs & Aging},
volume = {30},
number = {6},
pages = {439-445},
abstract = {BACKGROUND AND OBJECTIVES
Previous studies have reported a lower use of analgesics in patients with Alzheimer’s disease (AD) than in non-AD elderly. To date, no study has focused on persistent analgesic use in patients with mild-to-moderate AD.
METHODS
The “Réseau sur la maladie d’Alzheimer Français” (REAL.FR) cohort study enrolled community-dwelling patients with mild-to-moderate AD. Persistent analgesic use was defined as the consumption of at least one analgesic drug during two consecutive visits (6 months). Associated factors were identified in a nested case-control study.
RESULTS
In REAL.FR, 595 patients were present during at least two consecutive visits [mean age = 77.5 ± 6.8 years, mini-mental state examination (MMSE) = 20.1 ± 4.2]. Prevalence of persistent analgesic use was 13.1 % (95 % CI = 10.4-15.9). The incidence of persistent analgesic use was 5.9/100 patient-years (95 % CI = 5.2-6.6). Women (adjusted odds ratio [OR] = 3.1, 95 % CI = 1.2-8.1), patients with musculoskeletal disorders (OR = 3.4, 95 % CI = 1.6-7.3) and patients treated with numerous medications (OR = 3.0, 95 % CI = 1.5-5.8) were more likely to use analgesics persistently. Statistically significant associations were found with disease duration and disease progression but not with AD severity at baseline.
CONCLUSIONS
Our results suggest a low use of analgesics in AD patients, which could vary with AD progression.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND AND OBJECTIVES
Previous studies have reported a lower use of analgesics in patients with Alzheimer’s disease (AD) than in non-AD elderly. To date, no study has focused on persistent analgesic use in patients with mild-to-moderate AD.
METHODS
The “Réseau sur la maladie d’Alzheimer Français” (REAL.FR) cohort study enrolled community-dwelling patients with mild-to-moderate AD. Persistent analgesic use was defined as the consumption of at least one analgesic drug during two consecutive visits (6 months). Associated factors were identified in a nested case-control study.
RESULTS
In REAL.FR, 595 patients were present during at least two consecutive visits [mean age = 77.5 ± 6.8 years, mini-mental state examination (MMSE) = 20.1 ± 4.2]. Prevalence of persistent analgesic use was 13.1 % (95 % CI = 10.4-15.9). The incidence of persistent analgesic use was 5.9/100 patient-years (95 % CI = 5.2-6.6). Women (adjusted odds ratio [OR] = 3.1, 95 % CI = 1.2-8.1), patients with musculoskeletal disorders (OR = 3.4, 95 % CI = 1.6-7.3) and patients treated with numerous medications (OR = 3.0, 95 % CI = 1.5-5.8) were more likely to use analgesics persistently. Statistically significant associations were found with disease duration and disease progression but not with AD severity at baseline.
CONCLUSIONS
Our results suggest a low use of analgesics in AD patients, which could vary with AD progression. |
2012
|
Le Ber I.; Camuzat A.; Guillot-Noel L.; Hannequin D.; Lacomblez L.; Golfier V.; Puel M.; Martinaud O.; Deramecourt V.; Rivaud-Pechoux S.; Millecamps S.; Vercelletto M.; Couratier P.; Sellal F.; Pasquier F.; Salachas F.; Thomas-Antérion C.; Didic M.; Pariente J.; Seilhean D.; Ruberg M.; Wargon I.; Blanc F.; Camu W.; Michel B.F.; Berger E.; Sauvée M.; Thauvin-Robinet C.; Mondon K.; Tournier-Lasserve E.; Goizet C.; Fleury M.; Viennet G.; Verpillat P.; Meininger V.; Duyckaerts C.; Dubois B.; Brice A. C9ORF72 repeat expansions in the fronto-temporal dementias spectrum of diseases: a flow-chart for genetic testing. Article de journal Journal of Alzheimer's Disease, 34 (2), p. 485-499, 2012. Résumé | Liens | BibTeX @article{LeBer2013b,
title = { C9ORF72 repeat expansions in the fronto-temporal dementias spectrum of diseases: a flow-chart for genetic testing.},
author = {Le Ber I. and Camuzat A. and Guillot-Noel L. and Hannequin D. and Lacomblez L. and Golfier V. and Puel M. and Martinaud O. and Deramecourt V. and Rivaud-Pechoux S. and Millecamps S. and Vercelletto M. and Couratier P. and Sellal F. and Pasquier F. and Salachas F. and Thomas-Antérion C. and Didic M. and Pariente J. and Seilhean D. and Ruberg M. and Wargon I. and Blanc F. and Camu W. and Michel B.F. and Berger E. and Sauvée M. and Thauvin-Robinet C. and Mondon K. and Tournier-Lasserve E. and Goizet C. and Fleury M. and Viennet G. and Verpillat P. and Meininger V. and Duyckaerts C. and Dubois B. and Brice A.},
doi = {10.3233/JAD-121456},
year = {2012},
date = {2012-11-13},
journal = {Journal of Alzheimer's Disease},
volume = {34},
number = {2},
pages = {485-499},
abstract = {Frontotemporal dementia (FTD) refers to a disease spectrum including the behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy/corticobasal degeneration syndrome (PSP/CBDS), and FTD with amyotrophic lateral sclerosis (FTD-ALS). A GGGGCC expansion in C9ORF72 is a major cause of FTD and ALS. C9ORF72 was analyzed in 833 bvFTD, FTD-ALS, PPA, and PSP/CBDS probands; 202 patients from 151 families carried an expansion. C9ORF72 expansions were much more frequent in the large subgroup of patients with familial FTD-ALS (65.9%) than in those with pure FTD (12.8%); they were even more frequent than in familial pure ALS, according to estimated frequencies in the literature (23-50%). The frequency of carriers in non-familial FTD-ALS (12.7%) indicates that C9ORF72 should be analyzed even when family history is negative. Mutations were detected in 6.8% of PPA patients, and in 3.2% of patients with a clinical phenotype of PSP, thus enlarging the phenotype spectrum of C9ORF72. Onset was later in C9ORF72 (57.4 years, 95%CI: 55.9-56.1) than in MAPT patients (46.8, 95%CI: 43.0-50.6; p = 0.00001) and the same as in PGRN patients (59.6 years; 95%CI: 57.6-61.7; p = 0.4). ALS was more frequent in C9ORF72 than in MAPT and PGRN patients; onset before age 50 and parkinsonism were indicative of MAPT mutations, whereas hallucinations were indicative of PGRN mutations; prioritization of genetic testing is thus possible. Penetrance was age- and gender-dependent: by age 50, 78% of male carriers were symptomatic, but only 52% of females. This can also guide genetic testing and counseling. A flowchart for genetic testing is thus proposed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Frontotemporal dementia (FTD) refers to a disease spectrum including the behavioral variant FTD (bvFTD), primary progressive aphasia (PPA), progressive supranuclear palsy/corticobasal degeneration syndrome (PSP/CBDS), and FTD with amyotrophic lateral sclerosis (FTD-ALS). A GGGGCC expansion in C9ORF72 is a major cause of FTD and ALS. C9ORF72 was analyzed in 833 bvFTD, FTD-ALS, PPA, and PSP/CBDS probands; 202 patients from 151 families carried an expansion. C9ORF72 expansions were much more frequent in the large subgroup of patients with familial FTD-ALS (65.9%) than in those with pure FTD (12.8%); they were even more frequent than in familial pure ALS, according to estimated frequencies in the literature (23-50%). The frequency of carriers in non-familial FTD-ALS (12.7%) indicates that C9ORF72 should be analyzed even when family history is negative. Mutations were detected in 6.8% of PPA patients, and in 3.2% of patients with a clinical phenotype of PSP, thus enlarging the phenotype spectrum of C9ORF72. Onset was later in C9ORF72 (57.4 years, 95%CI: 55.9-56.1) than in MAPT patients (46.8, 95%CI: 43.0-50.6; p = 0.00001) and the same as in PGRN patients (59.6 years; 95%CI: 57.6-61.7; p = 0.4). ALS was more frequent in C9ORF72 than in MAPT and PGRN patients; onset before age 50 and parkinsonism were indicative of MAPT mutations, whereas hallucinations were indicative of PGRN mutations; prioritization of genetic testing is thus possible. Penetrance was age- and gender-dependent: by age 50, 78% of male carriers were symptomatic, but only 52% of females. This can also guide genetic testing and counseling. A flowchart for genetic testing is thus proposed. |
Vellas B.; Coley N.; Ousset P.J.; Berrut G.; Dartigues J.F.; Dubois B.; Grandjean H.; Pasquier F.; Piette F.; Robert P.; Touchon J.; Garnier P.; Mathiex-Fortunet H.; Andrieu S.; GuidAge Study Group Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer’s disease (GuidAge): a randomised placebo-controlled trial. Article de journal The Lancet Neurology, 11 (10), p. 851–859, 2012. Résumé | Liens | BibTeX @article{Vellas2012,
title = {Long-term use of standardised Ginkgo biloba extract for the prevention of Alzheimer’s disease (GuidAge): a randomised placebo-controlled trial.},
author = {Vellas B. and Coley N. and Ousset P.J. and Berrut G. and Dartigues J.F. and Dubois B. and Grandjean H. and Pasquier F. and Piette F. and Robert P. and Touchon J. and Garnier P. and Mathiex-Fortunet H. and Andrieu S. and GuidAge Study Group},
doi = {10.1016/S1474-4422(12)70206-5},
year = {2012},
date = {2012-10-01},
journal = {The Lancet Neurology},
volume = {11},
number = {10},
pages = {851–859},
abstract = {BACKGROUND
Prevention strategies are urgently needed to tackle the growing burden of Alzheimer’s disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract for the reduction of incidence of Alzheimer’s disease in elderly adults with memory complaints.
METHODS
In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer’s disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov, number NCT00276510.
FINDINGS
Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer’s disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio [HR] 0·84, 95% CI 0·60-1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69-1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77-1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups.
INTERPRETATION
Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer’s disease compared with placebo.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND
Prevention strategies are urgently needed to tackle the growing burden of Alzheimer’s disease. We aimed to assess efficacy of long-term use of standardised ginkgo biloba extract for the reduction of incidence of Alzheimer’s disease in elderly adults with memory complaints.
METHODS
In the randomised, parallel-group, double-blind, placebo-controlled GuidAge clinical trial, we enrolled adults aged 70 years or older who spontaneously reported memory complaints to their primary-care physician in France. We randomly allocated participants in a 1:1 ratio according to a computer-generated sequence to a twice per day dose of 120 mg standardised ginkgo biloba extract (EGb761) or matched placebo. Participants and study investigators and personnel were masked to study group assignment. Participants were followed-up for 5 years by primary-care physicians and in expert memory centres. The primary outcome was conversion to probable Alzheimer’s disease in participants who received at least one dose of study drug or placebo, compared by use of the log-rank test. This study is registered with ClinicalTrials.gov, number NCT00276510.
FINDINGS
Between March, 2002, and November, 2004, we enrolled and randomly allocated 2854 participants, of whom 1406 received at least one dose of ginkgo biloba extract and 1414 received at least one dose of placebo. By 5 years, 61 participants in the ginkgo group had been diagnosed with probable Alzheimer’s disease (1·2 cases per 100 person-years) compared with 73 participants in the placebo group (1·4 cases per 100 person-years; hazard ratio [HR] 0·84, 95% CI 0·60-1·18; p=0·306), but the risk was not proportional over time. Incidence of adverse events was much the same between groups. 76 participants in the ginkgo group died compared with 82 participants in the placebo group (0·94, 0·69-1·28; p=0·68). 65 participants in the ginkgo group had a stroke compared with 60 participants in the placebo group (risk ratio 1·12, 95% CI 0·77-1·63; p=0·57). Incidence of other haemorrhagic or cardiovascular events also did not differ between groups.
INTERPRETATION
Long-term use of standardised ginkgo biloba extract in this trial did not reduce the risk of progression to Alzheimer’s disease compared with placebo. |
Majounie E.; Renton A.E.; Mok K.; Dopper E.G.; Waite A.; Rollinson S.; Chiò A.; Restagno G.; Nicolaou N.; Simon-Sanchez J.; van Swieten J.C.; Abramzon Y.; Johnson J.O.; Sendtner M.; Pamphlett R.; Orrell R.W.; Mead S.; Sidle K.C.; Houlden H.; Rohrer J.D.; Morrison K.E.; Pall H.; Talbot K.; Ansorge O.; Chromosome 9-ALS/FTD Consortium; French research network on FTLD/FTLD/ALS; ITALSGEN Consortium; Hernandez D.G.; Arepalli S.; Sabatelli M.; Mora G.; Corbo M.; Giannini F.; Calvo A.; Englund E.; Borghero G.; Floris G.L.; Remes A.M.; Laaksovirta H.; McCluskey L.; Trojanowski J.Q.; Van Deerlin V.M.; Schellenberg G.D.; Nalls M.A.; Drory V.E.; Lu C.S.; Yeh T.H.; Ishiura H.; Takahashi Y.; Tsuji S.; Le Ber I.; Brice A.; Drepper C.; Williams N.; Kirby J.; Shaw P.; Hardy J.; Tienari P.J.; Heutink P.; Morris H.R.; Pickering-Brown S.; Traynor B.J. Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study. Article de journal The Lancet Neurology, 11 (4), p. 323-330, 2012. Résumé | Liens | BibTeX @article{Majounie2012,
title = { Frequency of the C9orf72 hexanucleotide repeat expansion in patients with amyotrophic lateral sclerosis and frontotemporal dementia: a cross-sectional study.},
author = {Majounie E. and Renton A.E. and Mok K. and Dopper E.G. and Waite A. and Rollinson S. and Chiò A. and Restagno G. and Nicolaou N. and Simon-Sanchez J. and van Swieten J.C. and Abramzon Y. and Johnson J.O. and Sendtner M. and Pamphlett R. and Orrell R.W. and Mead S. and Sidle K.C. and Houlden H. and Rohrer J.D. and Morrison K.E. and Pall H. and Talbot K. and Ansorge O. and Chromosome 9-ALS/FTD Consortium and French research network on FTLD/FTLD/ALS and ITALSGEN Consortium and Hernandez D.G. and Arepalli S. and Sabatelli M. and Mora G. and Corbo M. and Giannini F. and Calvo A. and Englund E. and Borghero G. and Floris G.L. and Remes A.M. and Laaksovirta H. and McCluskey L. and Trojanowski J.Q. and Van Deerlin V.M. and Schellenberg G.D. and Nalls M.A. and Drory V.E. and Lu C.S. and Yeh T.H. and Ishiura H. and Takahashi Y. and Tsuji S. and Le Ber I. and Brice A. and Drepper C. and Williams N. and Kirby J. and Shaw P. and Hardy J. and Tienari P.J. and Heutink P. and Morris H.R. and Pickering-Brown S. and Traynor B.J.},
doi = {10.1016/S1474-4422(12)70043-1},
year = {2012},
date = {2012-04-01},
journal = {The Lancet Neurology},
volume = {11},
number = {4},
pages = {323-330},
abstract = {BACKGROUND
We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
METHODS
We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion.
FINDINGS
In patients with sporadic ALS, we identified the repeat expansion in 236 (7·0%) of 3377 white individuals from the USA, Europe, and Australia, two (4·1%) of 49 black individuals from the USA, and six (8·3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39·3%) of 552 white individuals with familial ALS from Europe and the USA. 59 (6·0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24·8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic ALS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years.
INTERPRETATION
A common Mendelian genetic lesion in C9orf72 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND
We aimed to accurately estimate the frequency of a hexanucleotide repeat expansion in C9orf72 that has been associated with a large proportion of cases of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).
METHODS
We screened 4448 patients diagnosed with ALS (El Escorial criteria) and 1425 patients with FTD (Lund-Manchester criteria) from 17 regions worldwide for the GGGGCC hexanucleotide expansion using a repeat-primed PCR assay. We assessed familial disease status on the basis of self-reported family history of similar neurodegenerative diseases at the time of sample collection. We compared haplotype data for 262 patients carrying the expansion with the known Finnish founder risk haplotype across the chromosomal locus. We calculated age-related penetrance using the Kaplan-Meier method with data for 603 individuals with the expansion.
FINDINGS
In patients with sporadic ALS, we identified the repeat expansion in 236 (7·0%) of 3377 white individuals from the USA, Europe, and Australia, two (4·1%) of 49 black individuals from the USA, and six (8·3%) of 72 Hispanic individuals from the USA. The mutation was present in 217 (39·3%) of 552 white individuals with familial ALS from Europe and the USA. 59 (6·0%) of 981 white Europeans with sporadic FTD had the mutation, as did 99 (24·8%) of 400 white Europeans with familial FTD. Data for other ethnic groups were sparse, but we identified one Asian patient with familial ALS (from 20 assessed) and two with familial FTD (from three assessed) who carried the mutation. The mutation was not carried by the three Native Americans or 360 patients from Asia or the Pacific Islands with sporadic ALS who were tested, or by 41 Asian patients with sporadic FTD. All patients with the repeat expansion had (partly or fully) the founder haplotype, suggesting a one-off expansion occurring about 1500 years ago. The pathogenic expansion was non-penetrant in individuals younger than 35 years, 50% penetrant by 58 years, and almost fully penetrant by 80 years.
INTERPRETATION
A common Mendelian genetic lesion in C9orf72 is implicated in many cases of sporadic and familial ALS and FTD. Testing for this pathogenic expansion should be considered in the management and genetic counselling of patients with these fatal neurodegenerative diseases. |
C. Herrera; Caroline CHAMBON; B. F. Michel; Veronique PABAN; Béatrice ALESCIO-LAUTIER Positive effects of computer-based cognitive training in adults with mild cognitive impairment Article de journal Neuropsychologia, 50 (8), p. 1871–1881, 2012, ISSN: 1873-3514. Résumé | BibTeX @article{herrera_positive_2012,
title = {Positive effects of computer-based cognitive training in adults with mild cognitive impairment},
author = { C. Herrera and Caroline CHAMBON and B. F. Michel and Veronique PABAN and Béatrice ALESCIO-LAUTIER},
issn = {1873-3514},
year = {2012},
date = {2012-01-01},
journal = {Neuropsychologia},
volume = {50},
number = {8},
pages = {1871--1881},
abstract = {Considering the high risk for individuals with amnestic Mild Cognitive Impairment (A-MCI) to progress towards Alzheimer's disease (AD), we investigated the efficacy of a non-pharmacological intervention, that is, cognitive training that could reduce cognitive difficulties and delay the cognitive decline. For this, we evaluated the efficacy of a 12-week computer-based memory-attention training program based on recognition in subjects with A-MCI and compared their performances with those of A-MCI controls trained in cognitively stimulating activities. The effect of training was assessed by comparing outcome measures in pre- and post-tests 15 days before and after training. To evaluate the duration of training benefits, a follow-up test session was performed 6 months after memory and attention training or cognitively stimulating activities. Outcome measures showed that the trained group, compared to control group, improved episodic recall and recognition. Six months after training, scores remained at the level of the post-test. Since the training program was exclusively based on recognition, our results showed a generalization from recognition to recall processes, which are memory components that represent part of the core cognitive impairments in individuals at risk of converting to AD. Thus, cognitive training based on recognition holds promise as a preventive therapeutic method and could be proposed as a non-pharmacological early-intervention strategy. Future investigations need to focus on methodological constraints and delineating possible neuroplastic mechanisms of action.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Considering the high risk for individuals with amnestic Mild Cognitive Impairment (A-MCI) to progress towards Alzheimer's disease (AD), we investigated the efficacy of a non-pharmacological intervention, that is, cognitive training that could reduce cognitive difficulties and delay the cognitive decline. For this, we evaluated the efficacy of a 12-week computer-based memory-attention training program based on recognition in subjects with A-MCI and compared their performances with those of A-MCI controls trained in cognitively stimulating activities. The effect of training was assessed by comparing outcome measures in pre- and post-tests 15 days before and after training. To evaluate the duration of training benefits, a follow-up test session was performed 6 months after memory and attention training or cognitively stimulating activities. Outcome measures showed that the trained group, compared to control group, improved episodic recall and recognition. Six months after training, scores remained at the level of the post-test. Since the training program was exclusively based on recognition, our results showed a generalization from recognition to recall processes, which are memory components that represent part of the core cognitive impairments in individuals at risk of converting to AD. Thus, cognitive training based on recognition holds promise as a preventive therapeutic method and could be proposed as a non-pharmacological early-intervention strategy. Future investigations need to focus on methodological constraints and delineating possible neuroplastic mechanisms of action. |
2011
|
Gillette-Guyonnet S.; Andrieu S.; Nourhashemi F.; Gardette V.; Coley N.; Cantet C.; Gauthier S.; Ousset P.J.; Vellas B.; REAL.FR study group Long-term progression of Alzheimer’s disease in patients under antidementia drugs. Article de journal Alzheimer's & Dementia, 7 (6), p. 579–592, 2011. Résumé | Liens | BibTeX @article{Gillette-Guyonnet2011,
title = {Long-term progression of Alzheimer’s disease in patients under antidementia drugs.},
author = {Gillette-Guyonnet S. and Andrieu S. and Nourhashemi F. and Gardette V. and Coley N. and Cantet C. and Gauthier S. and Ousset P.J. and Vellas B. and REAL.FR study group},
doi = {10.1016/j.jalz.2011.02.009},
year = {2011},
date = {2011-11-01},
journal = {Alzheimer's & Dementia},
volume = {7},
number = {6},
pages = {579–592},
abstract = {BACKGROUND
Patients with Alzheimer’s disease (AD), even in the presence of symptomatic relief from medical intervention, face a persistent worsening of cognitive decline and performance in activities of daily living. Data regarding the long-term disease progression outside of therapeutic trials are lacking. We examined the effects of standard of care for AD patients on the prognosis of the disease in a real-life study over a 4-year period.
METHODS
A total of 686 patients with mild-moderate AD were enrolled in 16 memory clinics (REseau sur la maladie d’ Alzheimer FRançais [REAL.FR] cohort) and followed up twice annually with tools used in therapeutic trials (Mini-Mental Status Examination, Alzheimer Disease Assessment Scale-cognitive subscale [ADAS-cog]: cognitive function, Clinical Dementia Rating: dementia severity, Activity of Daily Living [ADL]: incapacities, NeuroPsychiatric Inventory: neuropsychiatric symptom).
RESULTS
More than 90% of the patients used AD-specific medication over 4 years. Patients lost on average 2.4 points per year on the Mini-Mental Status Examination and gained 4.5 points on the ADAS-cog. ADL and NeuroPsychiatric Inventory scores became significantly worse over time. Incidence of incapacities for ADL and worsening of neuropsychiatric symptoms were 52.5 (95% confidence interval [CI]: 47.7-57.4) and 51.1 (95% CI: 46.2-56.1), respectively. Rates of mortality and institutionalization were 7.4 (95% CI: 6.2-8.5) and 13.4 (95% CI: 11.7-15.1). In all, 17% of patients in mild stage at baseline (Clinical Dementia Rating = 0.5) did not experience a major event (functional disabilities, neuropsychiatric symptoms, or death) over a 4-year period.
CONCLUSIONS
As compared with previous surveys, the current study shows slower rates of decline in AD patients. The present data also underline the high level of variability of disease progression among AD patients. Outcome measures commonly used in clinical trials will need to take into account the recent changes in the prognosis of the disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND
Patients with Alzheimer’s disease (AD), even in the presence of symptomatic relief from medical intervention, face a persistent worsening of cognitive decline and performance in activities of daily living. Data regarding the long-term disease progression outside of therapeutic trials are lacking. We examined the effects of standard of care for AD patients on the prognosis of the disease in a real-life study over a 4-year period.
METHODS
A total of 686 patients with mild-moderate AD were enrolled in 16 memory clinics (REseau sur la maladie d’ Alzheimer FRançais [REAL.FR] cohort) and followed up twice annually with tools used in therapeutic trials (Mini-Mental Status Examination, Alzheimer Disease Assessment Scale-cognitive subscale [ADAS-cog]: cognitive function, Clinical Dementia Rating: dementia severity, Activity of Daily Living [ADL]: incapacities, NeuroPsychiatric Inventory: neuropsychiatric symptom).
RESULTS
More than 90% of the patients used AD-specific medication over 4 years. Patients lost on average 2.4 points per year on the Mini-Mental Status Examination and gained 4.5 points on the ADAS-cog. ADL and NeuroPsychiatric Inventory scores became significantly worse over time. Incidence of incapacities for ADL and worsening of neuropsychiatric symptoms were 52.5 (95% confidence interval [CI]: 47.7-57.4) and 51.1 (95% CI: 46.2-56.1), respectively. Rates of mortality and institutionalization were 7.4 (95% CI: 6.2-8.5) and 13.4 (95% CI: 11.7-15.1). In all, 17% of patients in mild stage at baseline (Clinical Dementia Rating = 0.5) did not experience a major event (functional disabilities, neuropsychiatric symptoms, or death) over a 4-year period.
CONCLUSIONS
As compared with previous surveys, the current study shows slower rates of decline in AD patients. The present data also underline the high level of variability of disease progression among AD patients. Outcome measures commonly used in clinical trials will need to take into account the recent changes in the prognosis of the disease. |
De Paula A.M.; Michel B.F.; Dickson D.W.; Wszolek Z.K.; Pellissier J-F. Sporadic diffuse leucoencephalopathy with axonal spheroids: report of a profuse and rapid cortical-spinal degeneration. Article de journal Neurological Sciences, 33 (4), p. 905-909, 2011. Résumé | Liens | BibTeX @article{DePaula2011,
title = {Sporadic diffuse leucoencephalopathy with axonal spheroids: report of a profuse and rapid cortical-spinal degeneration.},
author = {De Paula A.M. and Michel B.F. and Dickson D.W. and Wszolek Z.K. and Pellissier J-F.},
doi = {10.1007/s10072-011-0817-8},
year = {2011},
date = {2011-10-18},
journal = {Neurological Sciences},
volume = {33},
number = {4},
pages = {905-909},
abstract = {Diffuse leucoencephalopathy with axonal spheroids (DLS) is a rare disease affecting the white matter leading to dementia and progressive motor impairment. The neuropathological hallmark includes axonal swelling and spheroids as well as myelin loss. We report a case of a 46-year-old man with memory deficit and behavioral changes followed by a rapid cognitive decline and pyramidal syndrome. Head magnetic resonance imaging showed cortical atrophy of the brain and symmetric corticospinal tract involvement. He died 4 years after the first symptoms. Autopsy was performed and the brain revealed cortical and corpus callosum atrophy, a grayish granular appearance of the white matter and ventricular enlargement. Myelin stains showed a significant demyelination of the centrum ovale and corticospinal tract. Such degeneration was accompanied by axonal loss, axonal swelling, and numerous spheroids. There was no pigment overload or inflammation. We discuss this new DLS case with bilateral, severe, and rapid cortical-spinal involvement.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Diffuse leucoencephalopathy with axonal spheroids (DLS) is a rare disease affecting the white matter leading to dementia and progressive motor impairment. The neuropathological hallmark includes axonal swelling and spheroids as well as myelin loss. We report a case of a 46-year-old man with memory deficit and behavioral changes followed by a rapid cognitive decline and pyramidal syndrome. Head magnetic resonance imaging showed cortical atrophy of the brain and symmetric corticospinal tract involvement. He died 4 years after the first symptoms. Autopsy was performed and the brain revealed cortical and corpus callosum atrophy, a grayish granular appearance of the white matter and ventricular enlargement. Myelin stains showed a significant demyelination of the centrum ovale and corticospinal tract. Such degeneration was accompanied by axonal loss, axonal swelling, and numerous spheroids. There was no pigment overload or inflammation. We discuss this new DLS case with bilateral, severe, and rapid cortical-spinal involvement. |
Abraham J.D.; Calvayrac-Pawlowski S.; Cobo S.; Salvetat N.; Vicat G.; Molina L.; Touchon J.; Michel B.F.; Molina F.; Verdier J-M.; Fareh J.; Mourton-Gilles C. Combined measurement of PEDF, haptoglobin and tau in cerebrospinal fluid improves the diagnostic discrimination between Alzheimer’s disease and other dementias. Article de journal Biomarkers, 16 (2), p. 161-171, 2011. Résumé | Liens | BibTeX @article{Abraham2011,
title = { Combined measurement of PEDF, haptoglobin and tau in cerebrospinal fluid improves the diagnostic discrimination between Alzheimer’s disease and other dementias.},
author = {Abraham J.D. and Calvayrac-Pawlowski S. and Cobo S. and Salvetat N. and Vicat G. and Molina L. and Touchon J. and Michel B.F. and Molina F. and Verdier J-M. and Fareh J. and Mourton-Gilles C.},
doi = {10.3109/1354750X.2010.536995},
year = {2011},
date = {2011-02-17},
journal = {Biomarkers},
volume = {16},
number = {2},
pages = {161-171},
abstract = {Using proteomic approach in cerebrospinal fluid (CSF) we identified pigment epithelium-derived factor (PEDF) and Haptoglobin (Hp) as putative markers that could discriminate between AD and other dementias. ELISA assays were developed to measure the levels of PEDF and Hp in CSF from patients with AD (AD, n=27), non-AD (NAD, n=30) and in non-demented patients (ND, n=27). The combined assessment of PEDF, Hp and Tau levels, using Iterative Marginal Optimization, improved the differential diagnosis of AD, especially in patients with moderate to severe dementia (p<0.002). This pilot study highlights the probable different contribution of oxidative mechanisms in dementia.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Using proteomic approach in cerebrospinal fluid (CSF) we identified pigment epithelium-derived factor (PEDF) and Haptoglobin (Hp) as putative markers that could discriminate between AD and other dementias. ELISA assays were developed to measure the levels of PEDF and Hp in CSF from patients with AD (AD, n=27), non-AD (NAD, n=30) and in non-demented patients (ND, n=27). The combined assessment of PEDF, Hp and Tau levels, using Iterative Marginal Optimization, improved the differential diagnosis of AD, especially in patients with moderate to severe dementia (p<0.002). This pilot study highlights the probable different contribution of oxidative mechanisms in dementia. |
2010
|
Ghanim M; Guillot-Noel L; Pasquier F; Jornea L; Deramecourt V; Dubois B; Le Ber I; Brice A; French Research Network on FTD/FTD-MND CHMP2B mutations are rare in French families with frontotemporal lobar degeneration. Article de journal Journal of Neurology, 257 (12), p. 2032-2036, 2010. Liens | BibTeX @article{Ghanim2010,
title = {CHMP2B mutations are rare in French families with frontotemporal lobar degeneration.},
author = {Ghanim M and Guillot-Noel L and Pasquier F and Jornea L and Deramecourt V and Dubois B and Le Ber I and Brice A and French Research Network on FTD/FTD-MND},
doi = {10.1007/s00415-010-5655-8},
year = {2010},
date = {2010-12-01},
journal = {Journal of Neurology},
volume = {257},
number = {12},
pages = {2032-2036},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Vercelletto M; Boutoleau-Bretonnière C; Volteau C; Puel M; Auriacombe S; Sarazin M; Michel B.F; Couratier P; Thomas-Antérion C; Verpillat P; Gabelle A; Golfier V; Cerato E; Lacomblez L; French research network on Frontotemporal dementia Memantine in behavioral variant frontotemporal dementia: negative results. Article de journal Journal of Alzheimer's Disease, 23 (4), p. 749-759, 2010. Résumé | Liens | BibTeX @article{Vercelletto2011,
title = { Memantine in behavioral variant frontotemporal dementia: negative results.},
author = {Vercelletto M and Boutoleau-Bretonnière C and Volteau C and Puel M and Auriacombe S and Sarazin M and Michel B.F and Couratier P and Thomas-Antérion C and Verpillat P and Gabelle A and Golfier V and Cerato E and Lacomblez L and French research network on Frontotemporal dementia},
doi = {10.3233/JAD-2010-101632},
year = {2010},
date = {2010-11-01},
journal = {Journal of Alzheimer's Disease},
volume = {23},
number = {4},
pages = {749-759},
abstract = {We tested the efficacy and tolerability of one-year treatment with memantine (10 mg bid) in behavioral variant frontotemporal dementia (bvFTD). BvFTD patients aged 45 to 75 years, with a Mini-Mental Status Examination (MMSE) score ≥19, were enrolled in a national, randomized, double-blind, placebo-controlled (DBPC), Phase II trial. The primary endpoint was the CIBIC-Plus (Clinician’s Interview-Based Impression of Change Plus Caregiver Input). The secondary endpoints included: Neuropsychiatric Inventory (NPI), Frontal Behavioral Inventory (FBI), Mattis Dementia Rating Scale (MDRS), MMSE, Disability Assessment for Dementia (DAD), and the Zarit Burden Inventory (ZBI). Forty-nine patients were analyzed. At baseline, mean age was 65.6 years and mean MMSE was 25.0 (range: 19-30). On the CIBIC-Plus, 52 weeks after baseline, there were no significant differences between the memantine group (n = 23) and the placebo group (n = 26); p = 0.4458; however, 10 patients had worsened in the memantine group versus 17 in the placebo group. For the secondary endpoints there were no differences in the evolution of score between the memantine group and the placebo group (MMSE, p = 0.63); (MDRS, p = 0.95); (NPI, p = 0.25); (ZBI, p = 0.43); (DAD, p = 0.10) except for the FBI score, which was lower in the memantine group (p = 0.0417). Memantine was well-tolerated. This is the first DBPC trial in a large group of bvFTD patients involving neuroprotective treatment. A multinational study with a larger number of patients is now needed in order to verify the results of our study. The trial is registered with ClinicalTrials.gov; number NCT 00200538.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We tested the efficacy and tolerability of one-year treatment with memantine (10 mg bid) in behavioral variant frontotemporal dementia (bvFTD). BvFTD patients aged 45 to 75 years, with a Mini-Mental Status Examination (MMSE) score ≥19, were enrolled in a national, randomized, double-blind, placebo-controlled (DBPC), Phase II trial. The primary endpoint was the CIBIC-Plus (Clinician’s Interview-Based Impression of Change Plus Caregiver Input). The secondary endpoints included: Neuropsychiatric Inventory (NPI), Frontal Behavioral Inventory (FBI), Mattis Dementia Rating Scale (MDRS), MMSE, Disability Assessment for Dementia (DAD), and the Zarit Burden Inventory (ZBI). Forty-nine patients were analyzed. At baseline, mean age was 65.6 years and mean MMSE was 25.0 (range: 19-30). On the CIBIC-Plus, 52 weeks after baseline, there were no significant differences between the memantine group (n = 23) and the placebo group (n = 26); p = 0.4458; however, 10 patients had worsened in the memantine group versus 17 in the placebo group. For the secondary endpoints there were no differences in the evolution of score between the memantine group and the placebo group (MMSE, p = 0.63); (MDRS, p = 0.95); (NPI, p = 0.25); (ZBI, p = 0.43); (DAD, p = 0.10) except for the FBI score, which was lower in the memantine group (p = 0.0417). Memantine was well-tolerated. This is the first DBPC trial in a large group of bvFTD patients involving neuroprotective treatment. A multinational study with a larger number of patients is now needed in order to verify the results of our study. The trial is registered with ClinicalTrials.gov; number NCT 00200538. |
Abdel Rassoul R; Alves S; Pantesco V; De Vos J; Michel B; Perret M; Mestre-Francés N; Verdier J.M; Devau G Distinct transcriptome expression of the temporal cortex of the primate Microcebus murinus during brain aging versus Alzheimer's disease-like pathology. Article de journal PLoS One, 5 (9), 2010. Liens | BibTeX @article{Rassoul2010,
title = {Distinct transcriptome expression of the temporal cortex of the primate Microcebus murinus during brain aging versus Alzheimer's disease-like pathology.},
author = {Abdel Rassoul R and Alves S and Pantesco V and De Vos J and Michel B and Perret M and Mestre-Francés N and Verdier J.M and Devau G},
doi = {10.1371/journal.pone.0012770},
year = {2010},
date = {2010-09-16},
journal = {PLoS One},
volume = {5},
number = {9},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
B. F. Michel; V. Luciani; Y. E. Geda; N. Sambuchi; Véronique Paban; J.-M. Azorin [In Alzheimer's disease, the clinical expression of behavioral and psychological signs and symptoms is early and specific of neuropathological stages] Article de journal L'Encéphale, 36 (4), p. 314–325, 2010, ISSN: 0013-7006. Résumé | BibTeX @article{michel_[alzheimers_2010,
title = {[In Alzheimer's disease, the clinical expression of behavioral and psychological signs and symptoms is early and specific of neuropathological stages]},
author = { B. F. Michel and V. Luciani and Y. E. Geda and N. Sambuchi and Véronique Paban and J.-M. Azorin},
issn = {0013-7006},
year = {2010},
date = {2010-09-01},
journal = {L'Encéphale},
volume = {36},
number = {4},
pages = {314--325},
abstract = {INTRODUCTION: The early diagnosis of Alzheimer's disease is a new challenge. This study concerns 50 patients, 34 females (68 %) and 16 males (32 %) with Alzheimer (AD), according to NINCDS-ADRDA diagnostic criteria. OBJECTIVES: To systematically evaluate in all patients behavioral and psychological signs and symptoms of dementia (BPSSD), according to the stage of AD, with the patients of our population separated into two MMS groups. METHODS: The first group was composed of patients with an MMS score from 10 to 20 (eight males and 19 females). Patients of the second group had an MMS score between 21 and 28 (eight males and 19 females). The Neuro-Psychiatric Inventory (NPI) was used to collect information on the presence of BPSSD in AD patients. NPI scores were correlated to the cognitive part of the Alzheimer's Disease Assessment Scale (ADAS-Cog) that permits evaluation of the severity of cognitive impairment in AD patients. Before starting the study, all patients gave their informed consent to participate in the study of BPSSD in AD. Statistical treatment of data was performed using STATVIEW. RESULTS: Our study demonstrates that BPSSD are present not only in early but also in moderate stages of AD. As cognitive impairment, BPSSD are an integrate part of the clinical picture. With a frequency of 74 % for the whole population, "anxiety" represented the more predominant BPSSD for all our patients at all stages of AD. At the very early stages of AD, BPSSD appeared to precede cognitive disorders. CONCLUSION: The symptomatic association of "depression", "agitation", and "irritability of mood" may remain in a steady state for a few months before the appearance of verbal episodic memory impairment, which is characteristic of hippocampus involvement. "Irritability" seems to specifically characterise the initial phase of AD. On the other hand, two BPSSD are characteristic of the late stages of AD: "sleep disorder" and "hallucinations".},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: The early diagnosis of Alzheimer's disease is a new challenge. This study concerns 50 patients, 34 females (68 %) and 16 males (32 %) with Alzheimer (AD), according to NINCDS-ADRDA diagnostic criteria. OBJECTIVES: To systematically evaluate in all patients behavioral and psychological signs and symptoms of dementia (BPSSD), according to the stage of AD, with the patients of our population separated into two MMS groups. METHODS: The first group was composed of patients with an MMS score from 10 to 20 (eight males and 19 females). Patients of the second group had an MMS score between 21 and 28 (eight males and 19 females). The Neuro-Psychiatric Inventory (NPI) was used to collect information on the presence of BPSSD in AD patients. NPI scores were correlated to the cognitive part of the Alzheimer's Disease Assessment Scale (ADAS-Cog) that permits evaluation of the severity of cognitive impairment in AD patients. Before starting the study, all patients gave their informed consent to participate in the study of BPSSD in AD. Statistical treatment of data was performed using STATVIEW. RESULTS: Our study demonstrates that BPSSD are present not only in early but also in moderate stages of AD. As cognitive impairment, BPSSD are an integrate part of the clinical picture. With a frequency of 74 % for the whole population, "anxiety" represented the more predominant BPSSD for all our patients at all stages of AD. At the very early stages of AD, BPSSD appeared to precede cognitive disorders. CONCLUSION: The symptomatic association of "depression", "agitation", and "irritability of mood" may remain in a steady state for a few months before the appearance of verbal episodic memory impairment, which is characteristic of hippocampus involvement. "Irritability" seems to specifically characterise the initial phase of AD. On the other hand, two BPSSD are characteristic of the late stages of AD: "sleep disorder" and "hallucinations". |
Nourhashemi F. and Andrieu S. and Gillette-Guyonnet S. and Giraudeau B. and Cantet C. and Coley N. and Vellas B.; PLASA Group
Effectiveness of a specific care plan in patients with Alzheimer's disease: cluster randomised trial (PLASA study). Article de journal British Medical Journal, 2010. Liens | BibTeX @article{Nourhashemi2010,
title = {Effectiveness of a specific care plan in patients with Alzheimer's disease: cluster randomised trial (PLASA study).},
author = {Nourhashemi F. and Andrieu S. and Gillette-Guyonnet S. and Giraudeau B. and Cantet C. and Coley N. and Vellas B. and PLASA Group
},
doi = {10.1136/bmj.c2466},
year = {2010},
date = {2010-06-03},
journal = {British Medical Journal},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Voisin T; Andrieu S; Cantet C; Vellas B; REAL.FR Group Predictive factors of hospitalizations in Alzheimer's disease: a two-year prospective study in 686 patients of the REAL.FR study. Article de journal The journal of nutrition, health & aging, 14 (4), p. 288-291, 2010. BibTeX @article{Voisin2010,
title = {Predictive factors of hospitalizations in Alzheimer's disease: a two-year prospective study in 686 patients of the REAL.FR study.},
author = {Voisin T and Andrieu S and Cantet C and Vellas B and REAL.FR Group},
year = {2010},
date = {2010-04-01},
journal = {The journal of nutrition, health & aging},
volume = {14},
number = {4},
pages = {288-291},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Arbus C.; Gardette V.; Bui E.; Cantet C.; Andrieu S.; Nourhashémi F.; Schmitt L.; Vellas B.; REAL.FR Group Antidepressant use in Alzheimer’s disease patients: results of the REAL.FR cohort. Article de journal International Psychogeriatrics, 22 (1), p. 120-128, 2010. Résumé | Liens | BibTeX @article{Arbus2010,
title = { Antidepressant use in Alzheimer’s disease patients: results of the REAL.FR cohort.},
author = {Arbus C. and Gardette V. and Bui E. and Cantet C. and Andrieu S. and Nourhashémi F. and Schmitt L. and Vellas B. and REAL.FR Group},
doi = {10.1017/S1041610209990780},
year = {2010},
date = {2010-02-01},
journal = {International Psychogeriatrics},
volume = {22},
number = {1},
pages = {120-128},
abstract = {BACKGROUND
Psychotropic medication is widely prescribed in clinical practice for the management of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). However, there have been few pharmaco-epidemiological studies or studies conducted in a natural setting on the real use of antidepressants in AD. The aim of this survey was to assess the prevalence of antidepressant use in AD and to identify the clinical factors associated with antidepressant prescription.
METHODS
REAL.FR is a four-year, prospective, multi-center study. Baseline data including demographic characteristics, clinical variables and drug intake were obtained. Depressive symptoms were determined using the Neuropsychiatric Inventory (NPI).
RESULTS
A total of 686 AD patients were included. Antidepressant treatment was prescribed for 34.8% of patients. Clinically significant depressive symptoms (NPI >or= 4) were observed in 20.5% of the total population. Although depressed subjects were significantly more likely to be treated with antidepressants than non-depressed subjects (p<0.0001), only 60% of depressed subjects overall were prescribed an antidepressant. In multivariate analysis, clinically significant depressive symptoms were associated with antidepressant prescription although this result was only observed in subjects without a previous history of depression.
CONCLUSIONS
The available data on antidepressant efficacy in BPSD other than depression (in particular, agitation, aggression and, occasionally, psychotic symptoms) do not influence prescription choices. Depressive symptoms may be taken more seriously in the absence of a previous history of depression, leading to increased antidepressant prescription rates in individuals presenting with depression for the first time.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND
Psychotropic medication is widely prescribed in clinical practice for the management of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). However, there have been few pharmaco-epidemiological studies or studies conducted in a natural setting on the real use of antidepressants in AD. The aim of this survey was to assess the prevalence of antidepressant use in AD and to identify the clinical factors associated with antidepressant prescription.
METHODS
REAL.FR is a four-year, prospective, multi-center study. Baseline data including demographic characteristics, clinical variables and drug intake were obtained. Depressive symptoms were determined using the Neuropsychiatric Inventory (NPI).
RESULTS
A total of 686 AD patients were included. Antidepressant treatment was prescribed for 34.8% of patients. Clinically significant depressive symptoms (NPI >or= 4) were observed in 20.5% of the total population. Although depressed subjects were significantly more likely to be treated with antidepressants than non-depressed subjects (p<0.0001), only 60% of depressed subjects overall were prescribed an antidepressant. In multivariate analysis, clinically significant depressive symptoms were associated with antidepressant prescription although this result was only observed in subjects without a previous history of depression.
CONCLUSIONS
The available data on antidepressant efficacy in BPSD other than depression (in particular, agitation, aggression and, occasionally, psychotic symptoms) do not influence prescription choices. Depressive symptoms may be taken more seriously in the absence of a previous history of depression, leading to increased antidepressant prescription rates in individuals presenting with depression for the first time. |
Lechowski L; Van Pradelles S; Le Crane M; d’Arailh L; Tortrat D; Teillet L; Vellas B; REAL Group Patterns of loss of basic activities of daily living in Alzheimer patients: A cross-sectional study of the French REAL cohort. Article de journal Dementia and Geriatric Cognitive Disorders, 29 (1), p. 46-54, 2010. Résumé | Liens | BibTeX @article{Lechowski2010,
title = {Patterns of loss of basic activities of daily living in Alzheimer patients: A cross-sectional study of the French REAL cohort.},
author = {Lechowski L and Van Pradelles S and Le Crane M and d’Arailh L and Tortrat D and Teillet L and Vellas B and REAL Group},
doi = {10.1159/000264632},
year = {2010},
date = {2010-02-01},
journal = {Dementia and Geriatric Cognitive Disorders},
volume = {29},
number = {1},
pages = {46-54},
abstract = {BACKGROUND/AIMS
To characterize loss of basic activities of daily living (BADL) in 687 Alzheimer’s disease (AD) community-dwelling patients included in the French REAL cohort.
METHODS
Patients had mild to moderately severe AD, and the mean age was 77.8 years. Patterns of loss of the 6 BADL were described at inclusion using the Lawton scale.
RESULTS
With 6 binary BADL scores, each patient presented at inclusion a set of losses. For 53% of women, the sets of losses were included within each other or were identical, adding losses in physical ambulation, grooming, bathing, dressing, toilet and feeding, respectively. For 47% of men, a similar sequence was identified, with loss of dressing occurring secondly. A global cohesion of sets of losses was found for 87% of women and 86% of men. The Lawton scale is very useful for the assessment of AD patients},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND/AIMS
To characterize loss of basic activities of daily living (BADL) in 687 Alzheimer’s disease (AD) community-dwelling patients included in the French REAL cohort.
METHODS
Patients had mild to moderately severe AD, and the mean age was 77.8 years. Patterns of loss of the 6 BADL were described at inclusion using the Lawton scale.
RESULTS
With 6 binary BADL scores, each patient presented at inclusion a set of losses. For 53% of women, the sets of losses were included within each other or were identical, adding losses in physical ambulation, grooming, bathing, dressing, toilet and feeding, respectively. For 47% of men, a similar sequence was identified, with loss of dressing occurring secondly. A global cohesion of sets of losses was found for 87% of women and 86% of men. The Lawton scale is very useful for the assessment of AD patients |
Michel B.F; Luciani V; Geda Y.E; Sambuchi N; Paban V; Azorin J.M [In Alzheimer's disease, the clinical expression of behavioral and psychological signs and symptoms isearly and specific of neuropathological stages]. Article de journal Encephale, 36 (4), p. 314-325, 2010. Liens | BibTeX @article{Michel2010,
title = {[In Alzheimer's disease, the clinical expression of behavioral and psychological signs and symptoms isearly and specific of neuropathological stages].},
author = {Michel B.F and Luciani V and Geda Y.E and Sambuchi N and Paban V and Azorin J.M},
doi = {10.1016/j.encep.2009.10.012},
year = {2010},
date = {2010-01-01},
journal = {Encephale},
volume = {36},
number = {4},
pages = {314-325},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Broustal O; Camuzat A; Guillot-Noël L; Guy N; Millecamps S; Deffond D; Lacomblez L; Golfier V; Hannequin D; Salachas F; Camu W; Didic M; Dubois B; Meininger V; Le Ber I; Brice A; French clinical & genetic research network on FTD/FTD-MND FUS mutations in frontotemporal lobar degeneration with amyotrophic lateral sclerosis. Article de journal Journal of Alzheimer's Disease, 22 (3), p. 765-769, 2010. BibTeX @article{Broustal2010,
title = {FUS mutations in frontotemporal lobar degeneration with amyotrophic lateral sclerosis.},
author = {Broustal O and Camuzat A and Guillot-Noël L and Guy N and Millecamps S and Deffond D and Lacomblez L and Golfier V and Hannequin D and Salachas F and Camu W and Didic M and Dubois B and Meininger V and Le Ber I and Brice A and French clinical & genetic research network on FTD/FTD-MND},
year = {2010},
date = {2010-01-01},
journal = {Journal of Alzheimer's Disease},
volume = {22},
number = {3},
pages = {765-769},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
MICHEL Bernard François