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Articles by Serge Gauthier
Total Records ( 9 ) for Serge Gauthier
  Serge Gauthier , Angela Garcia , Mary Sano , Philippe Robert , Vorapun Senanarong , Michael Woodward and Henry Brodaty
  Coordination and harmonization of efforts between five major research consortia on Alzheimer’s disease may increase our understanding of this condition and improve our therapeutic approaches. Specific opportunities include a registry for families with early onset dementia, a study registry, minimal data sets, validation of assessment tools and outcomes, update on ethical issues, resolution of methodological issues, new investigators training, longitudinal observation studies, prevention studies, and liaison with stakeholders such as Alzheimer Disease International.
  Serge Gauthier and Judes Poirier
  The concept of disease modification for Alzheimer's disease (AD) means different things to different people, as summarized in Table 1. For instance, an asymptomatic person at higher risk because of a family history of AD in a first-degree relative with early-onset AD will seek a delay in onset of symptoms compared with that relative. From a public-health perspective, delaying the onset of symptoms of AD in the general population by 5–10 years would significantly reduce its incidence [1]. This may be achievable by higher education, healthy lifestyles, and control of vascular risk factors, starting in midlife [2].
  Zaven S. Khachaturian , Jordi Cami , Sandrine Andrieu , Jesus Avila , Merce Boada Rovira , Monique Breteler , Lutz Froelich , Serge Gauthier , Teresa Gomez- Isla , Ara S. Khachaturian , Lewis H. Kuller , Eric B. Larson , Oscar L. Lopez , Jose Manuel Martinez- Lage , Ronald C. Petersen , Gerard D. Schellenberg , Jordi Sunyer , Bruno Vellas and Lisa J. Bain
  In recognition of the global problem posed by Alzheimer's disease and other dementias, an international think-tank meeting was convened by Biocat, the Pasqual Maragall Foundation, and the Lou Ruvo Brain Institute in February 2009. The meeting initiated the planning of a European Union-North American collaborative research enterprise to expedite the delay and ultimate prevention of dementing disorders. The key aim is to build parallel and complementary research infrastructure that will support international standardization and inter-operability among researchers in both continents. The meeting identified major challenges, opportunities for research resources and support, integration with ongoing efforts, and identification of key domains to influence the design and administration of the enterprise.
  Steven Ferris , Ralf Ihl , Philippe Robert , Bengt Winblad , Gudrun Gatz , Frank Tennigkeit and Serge Gauthier
  Background Language impairment is one of the most troublesome manifestations of Alzheimer's disease (AD). The objective of this post hoc analysis was to assess the treatment effects of Memantine on language in patients with moderate to severe AD, using the recently developed Severe Impairment Battery-Language (SIB-L) scale. Methods From a combined database including four Memantine clinical trials in moderate-to-severe AD, we analyzed 801 patients with SIB-L scores of <38 and Mini-Mental State Examination scores of <15. Patients were treated with either 20 mg Memantine per day or placebo. Mean changes in SIB-L scores from baseline were calculated. For responder analyses, a change in SIB-L score greater than or equal to the SIB-L measurement error of 3.7 points was considered a clinically relevant response. Results The mean change from baseline in SIB-L score at week 12 and weeks 24/28 (study end) significantly favored Memantine over placebo treatment (P < .0001 and P = .0182, respectively). Overall, more Memantine-treated patients than placebo-treated patients benefited from treatment. The effect was especially pronounced in patients with substantial language impairment on the SIB-L (baseline score, ≤20). At weeks 24/28, significantly more Memantine-treated patients experienced a clinically relevant improvement (25.4% vs. 10.8%, P = .0414), and significantly fewer patients experienced clinically relevant worsening (32.8% vs. 60.0%, P = .0029). Conclusions Memantine treatment of AD patients results in significant benefits for language function. Our results suggest that it is worth considering this therapeutic option, even for AD patients with marked language impairment.
  Steven Ferris , Ralf Ihl , Philippe Robert , Bengt Winblad , Gudrun Gatz , Frank Tennigkeit and Serge Gauthier
  Background Communication problems are common in Alzheimer's disease (AD) patients, but instruments to assess these symptoms are limited. Our objective was to create a new scale, based on the language subscale of the Severe Impairment Battery (SIB), as a sensitive and reliable measurement of treatment effects on language performance. Methods All 24 items of the SIB language subscale were chosen for analysis. Baseline scores of 1320 moderate-to-severe patients (Mini-Mental State Examination [MMSE] score, <15), from a combined AD database of four Memantine clinical trials (Study Codes: IE-2101, MEM-MD-01, MEM-MD-02, and MRZ-9605), were used for item reduction according to a standard principal components factor analysis. All items with loadings >0.5 on the identified factors were selected for inclusion in the new language scale. Correlations with existing AD scales were examined. Results The analysis indicated six factors, with 21 of 24 items showing loadings >0.5. The resulting 21-item SIB Language (SIB-L) scale exhibited high internal consistency (Cronbach's α = 0.809). The maximal SIB-L score was 41 points, with a measurement error of 3.7 points. The stratification of baseline SIB-L scores (mean, 31.7; SD, 8.4) by MMSE scores (mean, 9.7; SD, 3.3) showed a high variance in SIB-L scores. This confirms that patients with a low MMSE score can possess preserved language abilities. The SIB-L scale did not exhibit substantial floor-and-ceiling effects. Conclusions The new SIB-L is a fast (<15 minutes) and easily administered scale with favorable psychometric characteristics for assessing language impairment and treatment effects on the language performance of patients with moderate to severe AD.
  Serge Gauthier and Philip Scheltens
  The past 30 years have seen multiple attempts at demonstrating the safety and efficacy of drugs for Alzheimer's disease (AD), predominantly to improve symptoms. Only five drugs (tacrine, donepezil, rivastigmine, galantamine, memantine) have obtained regulatory approval in most countries. Their cost-effectiveness from a societal perspective has not been universally recognized, and anybody who thinks these drugs are useful for individual patients will have to agree that the improvement above the starting point of treatment is moderate. Most of the benefit has been in slowing down progression of symptoms rather than a readily detectable improvement above baseline. There have also been attempts at arresting progression of AD, but all have failed until now. Should we change our approach to developing new drugs for AD so as to move forward? This review will highlight some options to consider in the development of future drugs for AD, with emphasis on strategies to prevent AD or arrest its progression.
  Serge Gauthier , Christopher Patterson , Michael Gordon , Jean-Paul Soucy , François Schubert and Antoine Leuzy
  The criteria for mild cognitive impairment due to Alzheimer's disease (AD) and preclinical AD, while offering great hope of fostering research on primary and secondary prevention for AD, are currently unsuitable for use in general clinical practice and must be used with great caution in specialized memory clinics.
  Sophie Gillette- Guyonnet , Sandrine Andrieu , Fati Nourhashemi , Virginie Gardette , Nicola Coley , Christelle Cantet , Serge Gauthier , Pierre-Jean Ousset and Bruno Vellas
  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 FRancais [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.
  Serge Gauthier and Jose L. Molinuevo
  Background Clinical studies and post hoc analyses have investigated the use of combination therapy for the treatment of Alzheimer's disease (AD). We review the evidence for the short- and long-term efficacy of combination therapy in AD. Methods The review is based on a search of the PubMed database to identify relevant articles concerning combination treatment with memantine and cholinesterase inhibitors (ChEIs). Results In patients with moderate–to–severe AD, combination treatment with the N-methyl–d–aspartate receptor antagonist memantine and the ChEI donepezil has produced significant benefits in cognition, function, behavior, global outcome, and care dependency, compared with donepezil treatment alone. Data from long–term observational studies support these findings. Compared with ChEI monotherapy, combination treatment slowed cognitive and functional decline (a 4–year sustained effect that appeared to increase over time) and reduced the risk of nursing home admission. Preclinically, the combination of N–methyl–d–aspartate receptor modulation and acetylcholinesterase inhibition has been shown to act synergistically, which may explain the observed clinical effects of combination treatment. Conclusion Treatment with memantine/ChEI combination therapy in moderate–to–severe AD produces consistent benefits that appear to increase over time, and that are beyond those of ChEI treatment alone.
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