9 research outputs found
Ăducation ThĂ©rapeutique du Patient (ETP) dans la maladie dâAlzheimer et les maladies apparentĂ©es en France : Ă©tat des lieux et retours dâexpĂ©rience
Introduction : LâĂducation ThĂ©rapeutique du Patient (ETP) fait partie des approches non mĂ©dicamenteuses proposĂ©es aux patients atteints de maladie dâAlzheimer et maladies apparentĂ©es (MA2). Elle est recommandĂ©e par la Haute AutoritĂ© de santĂ© et les plans Alzheimer mais reste peu dĂ©veloppĂ©e. Objectifs : Nos objectifs sont (i) exposer lâoffre dâETP sâadressant Ă ces patients en France, (ii) recueillir les retours dâexpĂ©rience des professionnels de santĂ©, patients et aidants impliquĂ©s, (iii) dĂ©crire les difficultĂ©s rencontrĂ©es et les pistes proposĂ©es. MĂ©thode : Nous avons rĂ©pertoriĂ© les programmes dâETP validĂ©s par les Agences RĂ©gionales de SantĂ© (ARS) sâadressant aux patients atteints de MA2, ayant rĂ©alisĂ© au moins un cycle dâETP. Les retours dâexpĂ©rience ont Ă©tĂ© recueillis par entretiens semi-dirigĂ©s. RĂ©sultats : Parmi les 49âprogrammes validĂ©s par les ARS, 30ârĂ©pondaient Ă nos critĂšres. Nous avons constatĂ© une grande hĂ©tĂ©rogĂ©nĂ©itĂ© territoriale, organisationnelle et clinique. Ătablir un schĂ©ma dâETP classique auprĂšs dâune population atteinte de troubles cognitifs sâavĂšre complexe, nĂ©anmoins les Ă©quipes sâadaptent. Conclusion : Notre travail souligne la dimension psycho-sociale de lâETP dans le parcours de soin des patients atteints de MA2. Son dĂ©veloppement reste un dĂ©fi et doit ĂȘtre facilitĂ© via une coordination des Ă©quipes et une harmonisation des pratiques portĂ©es entre autres par la FĂ©dĂ©ration des Centres MĂ©moire (FCM)
Characteristics and progression of patients with frontotemporal dementia in a regional memory clinic network
International audienceBackground: Due to heterogeneous clinical presentation, difficult differential diagnosis with Alzheimerâs disease (AD) and psychiatric disorders, and evolving clinical criteria, the epidemiology and natural history of frontotemporal lobar degeneration (FTD) remain elusive. In order to better characterize FTD patients, we relied on the database of a regional memory clinic network with standardized diagnostic procedures and chose AD patients as a comparator.Methods: Patients that were first referred to our network between January 2010 and December 2016 and whose last clinical diagnosis was degenerative or vascular dementia were included. Comparisons were conducted between FTD and AD as well as between the different FTD syndromes, divided into language variants (lvFTD), behavioral variant (bvFTD), and FTD with primarily motor symptoms (mFTD). Cognitive progression was estimated with the yearly decline in Mini Mental State Examination (MMSE).Results: Among the patients that were referred to our network in the 6-year time span, 690 were ultimately diagnosed with FTD and 18,831 with AD. Patients with FTD syndromes represented 2.6% of all-cause dementias. The age-standardized incidence was 2.90 per 100,000 person-year and incidence peaked between 75 and 79âyears. Compared to AD, patients with FTD syndromes had a longer referral delay and delay to diagnosis. Patients with FTD syndromes had a higher MMSE score than AD at first referral while their progression was similar. mFTD patients had the shortest survival while survival in bvFTD, lvFTD, and AD did not significantly differ. FTD patients, especially those with the behavioral variant, received more antidepressants, anxiolytics, and antipsychotics than AD patients.Conclusions: FTD syndromes differ with AD in characteristics at baseline, progression rate, and treatment. Despite a broad use of the new diagnostic criteria in an organized memory clinic network, FTD syndromes are longer to diagnose and account for a low proportion of dementia cases, suggesting persistent underdiagnosis. Congruent with recent publications, the late peak of incidence warns against considering FTD as being exclusively a young-onset dementia
Does amnesia specifically predict Alzheimer's pathology? A neuropathological study
International audienceAmnesia is a key component of Alzheimerâs disease (AD) and the most important feature of its clinical diagnosis but its specificity has recently been challenged. This study investigated the ability of amnesia to predict AD in a clinicopathological dementia series. Ninety-one patients to which free and cued verbal memory assessment was administered during early cognitive decline, were followed until autopsy. Patientsâ histological diagnoses were classified as pure-AD, mixed-AD and non-AD pathologies. Data-driven automated classification procedures explored the correspondence between memory performance and pathological diagnoses. Classifications revealed three clusters of performance reflecting different levels of amnesia. Little correspondence between these clusters and the presence of AD pathology was retrieved. A third of patients with pure/mixed AD pathology were non-amnesic at presentation and â45% of patients without AD pathology were amnesic. Data-driven prediction of AD pathology based on memory also had a poor accuracy. Free and cued memory assessments are fair tools to diagnose an amnesic syndrome but lack of accuracy to predict AD pathology
Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers
A (GGGGCC)n repeat expansion in C9orf72 gene is the major cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The relations between the repeats size and the age at disease onset (AO) or the clinical phenotype (FTD vs. ALS) were investigated in 125 FTD, ALS, and presymptomatic carriers. Positive correlations were found between repeats number and the AO (p < 10e 124) but our results suggested that the association was mainly driven by age at collection (p < 10e 124). A weaker association was observed with clinical presentation (p = 0.02), which became nonsignificant after adjustment for the age at collection in each group. Importantly, repeats number variably expanded or contracted over time in carriers with multiple blood samples, as well as through generations in parent-offspring pairs, conversely to what occurs in several expansion diseases with anticipation at the molecular level. Finally, this study establishes that measure of repeats number in lymphocytes is not a reliable biomarker predictive of the AO or disease outcome in C9orf72 long expansion carriers
Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers
International audienceA (GGGGCC)n repeat expansion in C9orf72 gene is the major cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The relations between the repeats size and the age at disease onset (AO) or the clinical phenotype (FTD vs. ALS) were investigated in 125 FTD, ALS, and presymptomatic carriers. Positive correlations were found between repeats number and the AO (p < 10e-4) but our results suggested that the association was mainly driven by age at collection (p < 10e-4). A weaker association was observed with clinical presentation (p = 0.02), which became nonsignificant after adjustment for the age at collection in each group. Importantly, repeats number variably expanded or contracted over time in carriers with multiple blood samples, as well as through generations in parent-offspring pairs, conversely to what occurs in several expansion diseases with anticipation at the molecular level. Finally, this study establishes that measure of repeats number in lymphocytes is not a reliable biomarker predictive of the AO or disease outcome in C9orf72 long expansion carriers
Plasma amyloid levels within the Alzheimer's process and correlations with central biomarkers
International audienc
Added value of 18F-florbetaben amyloid PET in the diagnostic workup of most complex patients with dementia in France: A naturalistic study
International audienceIntroductionAlthough some studies have previously addressed the clinical impact of amyloid positron emission tomography (PET), none has specifically addressed its selective and hierarchical implementation in relation to cerebrospinal fluid analysis in a naturalistic setting.MethodsThis multicenter study was performed at French tertiary memory clinics in patients presenting with most complex clinical situations (i.e., early-onset, atypical clinical profiles, suspected mixed etiological conditions, unexpected rate of progression), for whom cerebrospinal fluid analysis was indicated but either not feasible or considered as noncontributory (ClinicalTrials.gov: NCT02681172).ResultsTwo hundred five patients were enrolled with evaluable florbetaben PET scans; 64.4% of scans were amyloid positive. PET results led to changed diagnosis and improved confidence in 66.8% and 81.5% of patients, respectively, and altered management in 80.0% of cases.DiscussionHigh-level improvement of diagnostic certainty and management is provided by selective and hierarchical implementation of florbetaben PET into current standard practices for the most complex dementia cases
Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes
International audienceAbstract Background Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE -Δ4, make such estimations difficult. Methods We proposed to estimate the age-related penetrance of SORL1 -LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1- LoF variants, stratified by APOE-Δ4 , derived from the Rotterdam study ( N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1- LoF variants estimated from 27 extended pedigrees (including 307 relatives â„ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE -Δ4-stratified SORL1- LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia. Results SORL1- LoF variants penetrance curves reached 100% (95% confidence interval [99â100%]) by age 70 among APOE -Δ4Δ4 carriers only, compared with 56% [40â72%] and 37% [26â51%] in Δ4 heterozygous carriers and Δ4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1- LoF variant carriers in case-control study data. Conclusions We conclude that SORL1- LoF variants should be interpreted in light of APOE genotypes for future clinical applications