Alzheimer Disease: Legrain S

Mahieux F, Onen F, Berr C, Volteau M, Habert MO, Legrain S, Dubois B, Anonymous00017. · INSERM U610 and AP-HP Fédération de Neurologie, Hôpital de la Salpétrière, Paris, France. · J Nutr Health Aging. · Pubmed #19151903 No free full text.

Abstract: OBJECTIVES: The aim of the Pre-Al study is to evaluate and compare the predictive value of different tools for an early identification of Alzheimer's disease. DESIGN AND PARTICIPANTS: Patients coming for consultation to memory clinics without dementia were included if they had an objective memory or attention trouble assessed by a MMSE score > 25 (with at least one missing item at the words recall) and / or an Isaac set test score < 28. All were examined by a neuropsychological battery (Free and Cued Selective Reminding Test, digit ordering test, WAIS-R digit symbol, Trail making test, Benton visual retention test, verbal fluency, confrontation naming and Baddeley's double task test). A subpopulation received an MRI and SPECT assessment. RESULTS AND DISCUSSION: 251 patients were included (mean age: 72.0 years; mean education duration: 10.9 years). Validation of the predictive tests will be based on the comparison of these tests in patients developing dementia and others, after a follow-up of at least 3 years. This paper presents methodology of the study and the population description.

Robert PH, Berr C, Volteau M, Bertogliati-Fileau C, Benoit M, Guerin O, Sarazin M, Legrain S, Dubois B, Anonymous00075. · Centre Mémoire de Ressources et de Recherche, CHU de Nice, INSERM JE 2441, Nice, France. · Am J Geriatr Psychiatry. · Pubmed #18757769 No free full text.

Abstract: OBJECTIVE: Apathy is one of the most common behavioral symptoms in mild cognitive impairment (MCI). The aim of the authors' study was to examine the influence of the apathy dimensions, i.e., emotional blunting, lack of initiative, and lack of interest, on the risk of developing of Alzheimer disease (AD) in patients with MCI. DESIGN: Longitudinal study. SETTING: Fourteen French memory clinics. PARTICIPANTS: Apathy was assessed in 214 MCI patients. The main endpoint considered was the development of AD during the 3-year follow-up. MEASUREMENTS: The neuropsychiatric evaluation included the Goldberg anxiety scale and the Montgomery and Asberg Depression Rating Scale; apathy was assessed with the Apathy Inventory. RESULTS: After 3 years, 59 patients (27.2%) had developed AD. The risk of conversion to AD was significantly higher for patients with lack of interest. Using Cox analyses, controlling for age, gender and education, the difference between survival curves was significant for lack of interest. CONCLUSIONS: Lack of interest, a mild behavioral sign, could be an indicator of potential decline in MCI patients and underlines the importance of checking the cognitive status of these patients.

Sarazin M, Berr C, De Rotrou J, Fabrigoule C, Pasquier F, Legrain S, Michel B, Puel M, Volteau M, Touchon J, Verny M, Dubois B. · INSERM U 610 and Centre des Maladies Cognitives et Comportementales, Hôpital de la Salpêtrière, Paris, France. · Neurology. · Pubmed #17984454 No free full text.

Abstract: OBJECTIVE: To compare the power of tests assessing different cognitive domains for the identification of prodromal Alzheimer disease (AD) among patients with mild cognitive impairment (MCI). BACKGROUND: Given the early involvement of the medial temporal lobe, a precocious and specific pattern of memory disorders might be expected for the identification of prodromal AD. METHODS: A total of 251 patients with MCI were tested at baseline by a standardized neuropsychological battery, which included the Free and Cued Selective Recall Reminding Test (FCSRT) for verbal episodic memory; the Benton Visual Retention Test for visual memory; the Deno 100 and verbal fluency for language; a serial digit learning test and the double task of Baddeley for working memory; Wechsler Adult Intelligence Scale (WAIS) similarities for conceptual elaboration; and the Stroop test, the Trail Making test, and the WAIS digit symbol test for executive functions. The patients were followed at 6-month intervals for up to 3 years in order to identify those who converted to AD vs those who remained stable over time. Statistical analyses were based on receiver operating characteristic curve and Cox proportional hazards models. RESULTS: A total of 59 subjects converted to AD dementia. The most sensitive and specific test for diagnosis of prodromal AD was the FCSRT. Significant cutoff for the diagnosis was 17/48 for free recall, 40/48 for total recall, and below 71% for index of sensitivity of cueing (% of efficacy of semantic cues for retrieval). CONCLUSIONS: The amnestic syndrome of the medial temporal type, defined by the Free and Cued Selective Recall Reminding Test, is able to distinguish patients at an early stage of Alzheimer disease from mild cognitive impairment non-converters.

Vantelon C, Gilbert S, Kerneis S, Wolmark Y, Legrain S, Kergoat MJ. · Service de médecine gériatrique, centre hospitalo-universitaire Bichat-Claude-Bernard, 48, rue Henri-Huchard, 75877 Paris, France. · Rev Med Interne. · Pubmed #16806591 No free full text.

Abstract: PURPOSE: Cholinesterase Inhibitors (ChEIs) have proven efficacy in outpatients with mild to moderate Alzheimer's Disease (AD). The benefits of maintaining this treatment once patients are institutionalised remain controversial. The aim of this study was to present current therapeutic strategies regarding ChEIs use in long-term care settings (LTC). METHODS: A multicentric, retrospective, observational study was conducted on currently available ChEIs (donezepil, rivastigmine, galantamine) prescribed in LTC. Data were obtained from medical records. Judgement was based on three criteria: ChEIs indication, follow-up, and justification for maintenance of treatment. RESULTS: Among the 1,373 patients evaluated, 6% (N=81) were receiving ChEIs. They represented various stages of the disease, with cognitive and functional decline ranging from severe (18%) to very mild (10%). Among patients receiving ChEIs, 29% met neither the indication for which these drugs were approved, nor professional guidelines. Patient evaluation at entry was of high quality, with 90% of records including cognitive, functional and behavioural evaluation. Follow-up evaluations were weaker, with at least one assessment domain missing in 40% of the medical records. ChEIs treatment was maintained, although almost half of patients experienced a worsening of their clinical state. CONCLUSION: This study shows that follow-up of institutionalised patients receiving ChEIs could be improved. While treatment maintenance seems to be the rule, it should be questioned on ethical, efficacy, and economic grounds. The rationale for use and discontinuation of these therapeutic strategies in institutional settings requires urgent review.

Robert PH, Berr C, Volteau M, Bertogliati C, Benoit M, Sarazin M, Legrain S, Dubois B, Anonymous00781. · Centre Mémoire de Ressources et de Recherche, CHU de Nice, INSERM JE 2441, France. · Clin Neurol Neurosurg. · Pubmed #16567037 No free full text.

Abstract: OBJECTIVE: To evaluate the relation between apathy and development of dementia in patients with amnestic mild cognitive impairment (MCI). METHODS: Two hundred and fifty-one French-speaking outpatients fulfilling the criteria of amnestic MCI were enrolled. Apathy was assessed with the Apathy Inventory (IA). Neuropsychiatric evaluation also included the Goldberg anxiety scale and the Montgomery and Asberg Depressive Rating Scale (MADRS). The main end point considered after a 1-year follow-up was the development of dementia of Alzheimer type (DAT). RESULTS: At baseline there were 86 (39.8%) subjects presenting at least one symptom of apathy among the 216 included in analysis. After a 1-year follow-up, 22 patients developed DAT. Of the patients with apathy at baseline 13 (15.1%) developed DAT in comparison with 9 (6.9%) of the non-apathetic patients. At the 1-year follow-up, patients developing DAT had a significantly higher frequency of apathetic symptoms (91.7%) than patients without DAT (26.9%). CONCLUSION: Taking into account that apathy is one of the most frequently observed neuropsychiatric symptoms in MCI and in DAT the present study suggests that patients with MCI and apathy should be more closely observed.

Lambert JC, Chartier-Harlin MC, Cottel D, Richard F, Neuman E, Guez D, Legrain S, Berr C, Amouyel P, Helbecque N. · Service d'Epidémiologie et de Santé Publique - INSERM U.508, Institut Pasteur de Lille, 1 rue Calmette, F-59019 Lille Cedex, France. · Neurogenetics. · Pubmed #10369887 No free full text.

Abstract: LDL-related protein receptor (LRP) is the main receptor in the brain for apolipoprotein E. Moreover, the LRP gene is located on chromosome 12, the site of a potential Alzheimer's disease (AD) locus. We explored the association between the LRP gene and AD in 600 French Caucasian patients (37.8% men, mean age 72.0+/-8.0 years, mean age at onset 68.7+/-8.1 years) and age-matched controls (n=646, 37.0% men, mean age 72.5+/-8.2 years) and observed an association between a (TTTC) repeat at the 3' end of an Alu sequence in the LRP gene and the risk of developing AD. Three alleles were detected in this population [corresponding to 83, 87, and 91 base pairs (bp)], the 91-bp allele being associated with an increased risk of developing AD [all patients: odds ratio (OR) 1.6, P<0.01; late-onset AD: OR 1.8, P<0.01]. This suggests an association between the LRP locus and AD. However, in the light of studies related to the exon 3 LRP polymorphism and given the low strength of the association reported here, a biologically active variant may exist on chromosome 12, either in the LRP gene itself or in another gene in the vicinity.