Alzheimer Disease: Dubois B

Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, Scheltens P, Tariska P, Winblad B, Anonymous00263. · Memory Disorders Research Group, Department of Neurology, Rigshospitalet, Copenhagen University Hospital, Denmark. · Eur J Neurol. · Pubmed #17222085 No free full text.

Abstract: The aim of this international guideline on dementia was to present a peer-reviewed evidence-based statement for the guidance of practice for clinical neurologists, geriatricians, psychiatrists, and other specialist physicians responsible for the care of patients with dementia. It covers major aspects of diagnostic evaluation and treatment, with particular emphasis on the type of patient often referred to the specialist physician. The main focus is Alzheimer's disease, but many of the recommendations apply to dementia disorders in general. The task force working group considered and classified evidence from original research reports, meta-analysis, and systematic reviews, published before January 2006. The evidence was classified and consensus recommendations graded according to the EFNS guidance. Where there was a lack of evidence, but clear consensus, good practice points were provided. The recommendations for clinical diagnosis, blood tests, neuroimaging, electroencephalography (EEG), cerebrospinal fluid (CSF) analysis, genetic testing, tissue biopsy, disclosure of diagnosis, treatment of Alzheimer's disease, and counselling and support for caregivers were all revised when compared with the previous EFNS guideline. New recommendations were added for the treatment of vascular dementia, Parkinson's disease dementia, and dementia with Lewy bodies, for monitoring treatment, for treatment of behavioural and psychological symptoms in dementia, and for legal issues. The specialist physician plays an important role together with primary care physicians in the multidisciplinary dementia teams, which have been established throughout Europe. This guideline may contribute to the definition of the role of the specialist physician in providing dementia health care.

Vellas B, Gauthier S, Allain H, Andrieu S, Aquino JP, Berrut G, Berthel M, Blanchard F, Camus V, Dartigues JF, Dubois B, Forette F, Franco A, Gonthier R, Grand A, Hervy MP, Jeandel C, Joel ME, Jouanny P, Lebert F, Michot P, Montastruc JL, Nourhashemi F, Ousset PJ, Pariente J, Rigaud AS, Robert P, Ruault G, Strubel D, Touchon J, Verny M, Vetel JM, Anonymous00344. · CHU Casselardit, Toulouse. · Rev Neurol (Paris). · Pubmed #16244574 No free full text.

Abstract: Under the auspices of the French Society of Gerontology and Geriatrics, a multidisciplinary team including geriatritians, neurologists, epidemiologists, psychiatrists, pharmacologists and public health specialists developed a consensus on care for patients with severe dementia. They defined 21 recommendations for general practitioners, long-term care physicians and specialists based on knowledge available in 2005. At all stages of the disease, the objective of care is to improve as much as possible quality-of-life for the patient and his/her family, including a life project until the end of life. It is always possible to do something for these patients and their family: nutritional status, behavior disorders, and incapacities to deal with basic activities of daily life have to be taken in consideration. Resource allocation and proximity care have to be targeted. Research areas necessary to improve the care of patients with severe dementia has been selected.

McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, Cummings J, Duda JE, Lippa C, Perry EK, Aarsland D, Arai H, Ballard CG, Boeve B, Burn DJ, Costa D, Del Ser T, Dubois B, Galasko D, Gauthier S, Goetz CG, Gomez-Tortosa E, Halliday G, Hansen LA, Hardy J, Iwatsubo T, Kalaria RN, Kaufer D, Kenny RA, Korczyn A, Kosaka K, Lee VM, Lees A, Litvan I, Londos E, Lopez OL, Minoshima S, Mizuno Y, Molina JA, Mukaetova-Ladinska EB, Pasquier F, Perry RH, Schulz JB, Trojanowski JQ, Yamada M, Anonymous00346. · Institute for Ageing and Health, University of Newcastle upon Tyne, UK. · Neurology. · Pubmed #16237129 No free full text.

Abstract: The dementia with Lewy bodies (DLB) Consortium has revised criteria for the clinical and pathologic diagnosis of DLB incorporating new information about the core clinical features and suggesting improved methods to assess them. REM sleep behavior disorder, severe neuroleptic sensitivity, and reduced striatal dopamine transporter activity on functional neuroimaging are given greater diagnostic weighting as features suggestive of a DLB diagnosis. The 1-year rule distinguishing between DLB and Parkinson disease with dementia may be difficult to apply in clinical settings and in such cases the term most appropriate to each individual patient should be used. Generic terms such as Lewy body (LB) disease are often helpful. The authors propose a new scheme for the pathologic assessment of LBs and Lewy neurites (LN) using alpha-synuclein immunohistochemistry and semiquantitative grading of lesion density, with the pattern of regional involvement being more important than total LB count. The new criteria take into account both Lewy-related and Alzheimer disease (AD)-type pathology to allocate a probability that these are associated with the clinical DLB syndrome. Finally, the authors suggest patient management guidelines including the need for accurate diagnosis, a target symptom approach, and use of appropriate outcome measures. There is limited evidence about specific interventions but available data suggest only a partial response of motor symptoms to levodopa: severe sensitivity to typical and atypical antipsychotics in approximately 50%, and improvements in attention, visual hallucinations, and sleep disorders with cholinesterase inhibitors.

Dubois B. · No affiliation provided · Rev Med Interne. · Pubmed #18222018 No free full text.

This publication has no abstract.

Laurent B, Dubois B. · No affiliation provided · Rev Neurol (Paris). · Pubmed #17028555 No free full text.

This publication has no abstract.

Dubois B. · No affiliation provided · Curr Opin Neurol. · Pubmed #10970051 No free full text.

This publication has no abstract.

de Souza LC, Sarazin M, Goetz C, Dubois B. · Research and Resource Memory Centre, INSERM UMR S-610, Université Pierre et Marie Curie-Paris 06, Pitié-Salpêtrière Hospital, Paris, France. · Front Neurol Neurosci. · Pubmed #19182457 No free full text.

Abstract: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that represents the most common form of dementia. The most prominent feature of AD is the decline in cognitive function, with an early impairment of episodic memory. The memory deficit of an AD patient is characterized by the amnestic syndrome of the medial temporal type. As the disease progresses, the condition often manifests in language disorders, visuospatial deficits and executive dysfunctions. Patients often have neuropsychiatric disturbances, as apathy and psychotic symptoms. Loss of autonomy follows cognitive impairment. The clinical diagnosis of AD is based on a complete medical examination with a neuropsychological evaluation. The FCSRT (free and cued selective reminding test) is recommended for the identification of the amnestic syndrome of the medial temporal type, which is defined by: (1) a very poor free recall and (2) a decreased total recall due to an insufficient effect of cueing. The neuropsychological tests should also assess other cognitive functions that may be perturbed in AD, such as executive functions, praxis, visuospatial capacities and language. Neuroimaging and biological exams (genetics, biomarkers) are of great utility in the evaluation. Other medical, neurological, or psychiatric disorders which could account for the impairment in memory and related symptoms must be always investigated.

Dubois B, De Souza L, Allali G, Kalafat M, Sarazin M. · Centre des Maladies Cognitives et Comportementales et Inserm U 610, Hôpital de la Salpêtrière, 47, boulevard de l'Hôpital, 75013 Paris. · Bull Acad Natl Med. · Pubmed #18819687 No free full text.

Abstract: Current treatments for Alzheimer's disease aim to compensate for biochemical deficits in the brain. They are purely symptomatic and restore the central cholinergic deficit. Acetylcholinesterase inhibitors have modest but significant efficacy on cognitive disorders, activities of daily living, and the global clinical impression. Glutaminergic receptor antagonists are used for more advanced forms. Future treatments may be curative, acting specifically on the amyloid cascade. Secretase inhibitors and immunotherapy are in the pipeline. Trials will begin within a few months and will open up new perspectives.

Small G, Dubois B. · UCLA Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA 90024-1759, USA. · Curr Med Res Opin. · Pubmed #17892635 No free full text.

Abstract: BACKGROUND: Following prescribed medication regimens is essential for the effective treatment of any medical condition. Unfortunately, patients often fail to follow recommendations, and treatment non-compliance represents a widespread, often underestimated problem, placing tremendous burden on the healthcare system. Compliance in Alzheimer's disease (AD), a chronic neurodegenerative disease typically afflicting older adults, is especially challenging. SCOPE: To review factors contributing to poor treatment compliance in AD, considering the prominent role care givers often play in treatment management; and acknowledging strategic approaches, particularly modern transdermal patches, to improve compliance in this particularly susceptible population. Articles were identified by searching MEDLINE in November 2006 (search limits: 1987-2007) using the terms: compliance; Alzheimer's; treatment; and transdermal. Additional resources included bibliographies of identified articles. FINDINGS: Strategic approaches to improving treatment compliance include: simplifying treatment regimens, using reminder packaging, and developing more patient- or caregiver-friendly modes of administration. To date, AD therapies have been administered orally. However, recent developments in alternative modes of drug delivery, such as transdermal patches, may offer effective, well-tolerated treatment options with the potential to enhance compliance. A patch containing rivastigmine (Exelon), an established cholinesterase inhibitor, has been developed and demonstrated to have good efficacy and tolerability in patients with AD. In addition, initial caregiver experience suggests preference for the patch over oral administration. CONCLUSION: Transdermal patches may be an effective way to optimize treatment compliance for AD, as well as an increasing number of other chronic conditions that typically afflict the older population, offering the possibility of more sustained clinical benefits.

Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P, Cummings J, Delacourte A, Galasko D, Gauthier S, Jicha G, Meguro K, O'brien J, Pasquier F, Robert P, Rossor M, Salloway S, Stern Y, Visser PJ, Scheltens P. · INSERM U610, Hôpital de la Salpêtrière, Paris, France. · Lancet Neurol. · Pubmed #17616482 No free full text.

Abstract: The NINCDS-ADRDA and the DSM-IV-TR criteria for Alzheimer's disease (AD) are the prevailing diagnostic standards in research; however, they have now fallen behind the unprecedented growth of scientific knowledge. Distinctive and reliable biomarkers of AD are now available through structural MRI, molecular neuroimaging with PET, and cerebrospinal fluid analyses. This progress provides the impetus for our proposal of revised diagnostic criteria for AD. Our framework was developed to capture both the earliest stages, before full-blown dementia, as well as the full spectrum of the illness. These new criteria are centred on a clinical core of early and significant episodic memory impairment. They stipulate that there must also be at least one or more abnormal biomarkers among structural neuroimaging with MRI, molecular neuroimaging with PET, and cerebrospinal fluid analysis of amyloid beta or tau proteins. The timeliness of these criteria is highlighted by the many drugs in development that are directed at changing pathogenesis, particularly at the production and clearance of amyloid beta as well as at the hyperphosphorylation state of tau. Validation studies in existing and prospective cohorts are needed to advance these criteria and optimise their sensitivity, specificity, and accuracy.

Le Ber I, Dubois B. · Inserm U679, Neurology and Experimental Therapeutics, Paris (75). · Presse Med. · Pubmed #17555915 No free full text.

Abstract: Frontotemporal dementia usually begins before the age of 65 years. It is manifested by behavioral and language disorders. The lesions observed in frontotemporal dementia affect the frontal and temporal lobes bilaterally. One third of patients have a psychiatric diagnosis at the onset of disease. The genetic component is important: 30-50% of patients have a family history of this disease. Cholinergic effects are not associated with frontotemporal dementia and therefore anticholinesterase treatment is not indicated.

Sarazin M, Dubois B. · Centre de mémoire de ressource et de recherche d'Ile-de-France, centre de neuropsychologie et du langage et unité Inserm U 610, federation des maladies du système nerveux, groupe hospitalier La Pitié-La Salpêtrière, 75651 Paris. · Rev Prat. · Pubmed #16396228 No free full text.

Abstract: Despite the evolution of an increase of medical formation, only 50% of patients with Alzheimer's disease (AD) are diagnosed in France. It is pity, given the fact that the diagnosis of AD is relatively easy and can often be made without hospitalisation. The first stage of the medical inquiry is based on the clinical observation. It is established that the progression of the symptoms follows the progression of the brain lesions. A deficit in episodic memory is the earliest and most predominant cognitive change of AD. This is consistent with the precocious involvement of mesial temporal structures. This pattern, so-called "memory disorders of the hippocampal type," is highly suggestive of AD and markedly differs from that of other dementing illnesses. As the disease progresses and involves neocortical associative areas, patients demonstrate impairments in instrumental functions such as language, praxia, gnosia, and visuoconstructive functions. The second stage of the diagnosis is based on neuroimagery. MRI shows a bilateral atrophy of hippocampal formations even in the early stages of the disease. Standard biological parameters are normal. According to the context of occurrences of the disease or to the existence of atypical clinical or radiological changes, additional investigations can be proposed.

Vellas B, Gauthier S, Allain H, Andrieu S, Aquino JP, Berrut G, Berthel M, Blanchard F, Camus V, Dartigues JF, Dubois B, Forette F, Franco A, Gonthier R, Grand A, Hervy MP, Jeandel C, Joel ME, Jouanny P, Lebert F, Michot P, Montastruc JL, Nourhashemi F, Ousset PJ, Pariente J, Rigaud AS, Robert P, Ruault G, Strubel D, Touchon J, Verny M, Vetel JM. · No affiliation provided · J Nutr Health Aging. · Pubmed #16222399 No free full text.

This publication has no abstract.

McKeith I, Mintzer J, Aarsland D, Burn D, Chiu H, Cohen-Mansfield J, Dickson D, Dubois B, Duda JE, Feldman H, Gauthier S, Halliday G, Lawlor B, Lippa C, Lopez OL, Carlos Machado J, O'Brien J, Playfer J, Reid W, Anonymous00116. · Institute for Ageing and Health, University of Newcastle, Newcastle upon Tyne, UK. · Lancet Neurol. · Pubmed #14693108 No free full text.

Abstract: Dementia with Lewy bodies (DLB) is the second commonest cause of neurodegenerative dementia in older people. It is part of the range of clinical presentations that share a neuritic pathology based on abnormal aggregation of the synaptic protein alpha-synuclein. DLB has many of the clinical and pathological characteristics of the dementia that occurs during the course of Parkinson's disease. Here we review the current state of scientific knowledge on DLB. Accurate identification of patients is important because they have specific symptoms, impairments, and functional disabilities that differ from those of other common types of dementia. Severe neuroleptic sensitivity reactions are associated with significantly increased morbidity and mortality. Treatment with cholinesterase inhibitors is well tolerated by most patients and substantially improves cognitive and neuropsychiatric symptoms. Clear guidance on the management of DLB is urgently needed. Virtually unrecognised 20 years ago, DLB could within this decade be one of the most treatable neurodegenerative disorders of late life.

Sarazin M, Dubois B. · Inserm EPI 007 et Hôpital Bretonneau, Paris. · Rev Neurol (Paris). · Pubmed #12529583 No free full text.

Abstract: The concept of Mild Cognitive Impairment (MCI) is proposed to define a state of cognition where the deficiency is greater than expected for a subject's age and socio-cultural background, but not sufficiently severe to satisfy the criteria of nosographic classifications of dementia. The concept of MCI cannot provide an etiological diagnosis but can be useful for recognizing and following patients with mild impairment. It raises the question of early diagnosis of Alzheimer's disease. The risk of progression to dementia is greater in patients with MCI, particularly those whose memory is the only domain involved - "amnesic MCI". Patients with amnesic MCI can be distinguished from those with MCI with multiple domains slightly impaired or non-amnesic MCI where only one domain (language, visual-spatial.) other than memory is involved. Depending on the type of deficiency, amnesic MCI may progress to different types of disease states. At the early stage of pure memory impairment, a distinction should be made between Alzheimer-related memory disorders and those related to another neurological conditions or the brain aging process. The question is whether the diagnosis of Alzheimer's disease can be made at this stage. Biological markers and brain imaging provide useful information, but these diagnostic tools remain imprecise and have not been validated for routine use. The process of diagnosis must therefore focus on an analysis of the cognitive impairment. The predementia phase of Alzheimer's disease is characterized by a progressive "hippocampal" decline in memory, sometimes associated with impaired execution. A careful analysis of the cognitive impairment helps identify "hippocampal amnesia syndrome" suggestive of the diagnosis of Alzheimer's disease.

Dartigues JF, Helmer C, Dubois B, Duyckaerts C, Laurent B, Pasquier F, Touchon J. · Unité INSERM 330, Université de Bordeaux II, Bordeaux. · Rev Neurol (Paris). · Pubmed #11976590 No free full text.

Abstract: Alzheimer's Disease is a major Public Health problem for many reasons. First, it is a frequent disease since, in France, the prevalence was estimated at about 400.000 cases, and the annual incidence at 100.000 cases. The frequency of the disease increases, in particular due to the ageing of the population. This disease has major consequences on the life of the patient and his/her caretaker. The cost of the disease is important, estimated at about 50 milliards of French francs. Pharmaceutical treatment and other interventions are possible in particular to delay the nursing home placement. On the other hand, this disease is often ignored, under-diagnosed, underestimated and exposed to inequality in resorting to care. In summary, Alzheimer's Disease (AD) has all the criteria required for a major public health problem. In spite of this observation, AD is not yet considered as a priority for health authorities, although attitudes are changing.

Petit H, Albarède JL, Bakchine S, Boulliat J, Cogneau J, Darcourt G, Dubois B, Forette F, Franco A, Héres J, Hinault P, Laurent B, Léger JM, Marin La Meslée R, Montagne B, Poncet M, Robert P, Sorbé G, Touchon J, Velas B, Vetel JM. · Neurologue (Clinique Neurologique, CHRU Roger Salengro 59037 Lille Cedex, France. · Rev Neurol (Paris). · Pubmed #10844378 No free full text.

This publication has no abstract.

Waldemar G, Dubois B, Emre M, Scheltens P, Tariska P, Rossor M. · Department of Neurology, Copenhagen University Hospital, Copenhagen, Denmark. · Eur J Neurol. · Pubmed #10809933 No free full text.

Abstract: In 1998 a task force to develop guidelines for diagnostic evaluation and treatment of dementia was initiated by the European Federation of Neurological Societies (EFNS) scientist panel on dementia. The aims of the task force were to provide evidence-based recommendations and to highlight the role of the neurologist in the management of patients with Alzheimer's disease and other disorders associated with dementia. We based our recommendations on a review of available evidence-based guidelines supplemented with further literature reviews. The recommendations were derived from consensus meetings and relate to individual patient management, as there are inadequate data on the cost-effectiveness of different diagnostic evaluations and treatments for dementia. Their specific applications will depend upon available resources. The particular contributions of the neurologist include: early identification and differential diagnosis of rare and common brain disorders causing cognitive and behavioural symptoms, referral for and interpretation of ancillary investigations, and identification and treatment of vascular and other concurrent diseases. A review of the management of dementia in Europe revealed considerable variation. In some countries neurologists have taken the lead in the management of patients with dementia, while in other countries the neurologist is rarely involved. We recommend that neurologists should have a clear role in the management of dementia in the whole of Europe. They should be involved in the diagnostic evaluation of dementia and facilitate the development of multidisciplinary teams for evaluation and management of patients with cognitive disturbances. The increasing role of neurology in the management of patients with dementia has important implications for training and education.

Lôo H, Rigaud AS, Dubois B, Gallarda T, Aurenche S. · No affiliation provided · Encephale. · Pubmed #17115480 No free full text.

This publication has no abstract.

Orgogozo JM, Gilman S, Dartigues JF, Laurent B, Puel M, Kirby LC, Jouanny P, Dubois B, Eisner L, Flitman S, Michel BF, Boada M, Frank A, Hock C. · Federation of Neurology, CHU Pellegrin, Bordeaux, France. · Neurology. · Pubmed #12847155 No free full text.

Abstract: BACKGROUND: AD is characterized by cerebral deposition of beta-amyloid plaques with amyloid beta-peptide (Abeta) 42 as the major peptide constituent, along with neurofibrillary tangles and neuronal loss. In transgenic mice, active immunization against Abeta42 removes these plaques and improves cognitive function. A Phase I study in AD patients demonstrated good safety and tolerability of multiple injections of aggregated Abeta42 (AN1792) with QS-21 as adjuvant. METHODS: Three hundred seventy-two patients with mild to moderate AD were randomized to receive IM injections of AN1792 or placebo (4:1) at baseline and at months 1, 3, 6, 9, and 12 in a multicenter Phase II safety, tolerability, and pilot efficacy study. Dosing was terminated after four early reports of meningoencephalitis, but follow-up continued. The study remains blinded, and further results will be reported after its termination. RESULTS: Symptoms and laboratory findings consistent with meningoencephalitis occurred in 18 of 298 (6%) patients treated with AN1792 compared with 0 of 74 on placebo (p = 0.020). Sixteen of the 18 had received two doses, one had received one dose, and one had received three doses of the study drug before symptoms occurred. The median latency from the first and last injections to symptoms was 75 and 40 days. No case occurred later than 6 months after the first immunization. Anti-Abeta42 antibody titers were not correlated with the occurrence or severity of symptoms or relapses. Twelve patients recovered to or close to baseline within weeks, whereas six remain with disabling cognitive or neurologic sequelae. All 18 patients remain alive to date (December 31, 2002), 6 months to >1 year after symptom onset. CONCLUSIONS: Postvaccination meningoencephalitis occurred without clear relation to serum anti-Abeta42 antibody titers. Potential mechanisms such as T-cell and microglial activation may be responsible and are under consideration to develop a safer anti-Abeta immunotherapy for AD.

Shikiar R, Shakespeare A, Sagnier PP, Wilkinson D, McKeith I, Dartigues JF, Dubois B. · MEDTAP International, Seattle, Washington, USA. · J Am Geriatr Soc. · Pubmed #10733052 No free full text.

Abstract: OBJECTIVE: To assess the impact on burden reported by caregivers of patients with mild to moderate Alzheimer's disease (AD) who were treated with metrifonate during a randomized double blind clinical trial. DESIGN: Randomized clinical trial, with a 2-week screening period and a 26-week double blind, placebo controlled, treatment phase. Caregivers were assessed at baseline, at 12 weeks, and at end of trial. SETTING: Caregivers were interviewed at clinics as part of the assessment of the patients. PARTICIPANTS: Six hundred and three caregivers of AD patients who were enrolled in the MALT trial; 591 (98%) provided data suitable for analysis at baseline, and 546 (91%) provided data allowing for inclusion in the analysis of change scores. MEASUREMENTS: The Caregiver Burden Assessment consisted of the Screen for Caregiver Burden, including both subjective (SCB-subj) and objective (SCB-obj) scores; the cognitive subscale of Poulshock and Deimling (PD); an abridged version of the Relatives Stress Scale (aRSS); assessments of time spent in providing care, including the Caregiver Activity Time Scale (CATS); and demographic and background variables on both the patient and caregiver. RESULTS: Treatment of mild to moderate AD patients with metrifonate for a duration of 26 weeks significantly reduced the psychological burden of care to the caregivers, as measured by the SCB-subj, the PD, and the aRSS. There were no statistically significant differences on the measures assessing the time spent in caregiving, except for the caregiver's subjective impression of the change in time spent providing care during the trial. When comparing individual dose groups, most of the measures of burden showed the largest benefits in burden for the 60/80 mg group, followed by the 40/50 mg group, and then the placebo group. However, there was no statistically significant dose effect. CONCLUSIONS: This study provides the first evidence from a randomized clinical trial of any acetylcholinesterase inhibitor used in the treatment of AD demonstrating a positive impact on the patient's caregiver as well as benefits to the patient. These results were shown consistently across several measurement scales and were observed after six months of treatment. These findings reinforce the clinical significance of research that has shown that metrifonate has beneficial impacts on the cognitive, behavioral, and functional abilities of AD patients. Because caregiver burden is a leading factor in the decision for institutional care placement, the ability to favorably impact that burden through pharmacological treatment of the patient is important.

Dubois B, McKeith I, Orgogozo JM, Collins O, Meulien D. · Hôpital de la Pitié-Salpêtrière, Paris, France. · Int J Geriatr Psychiatry. · Pubmed #10556869 No free full text.

Abstract: BACKGROUND: Metrifonate is a long-lasting acetylcholinesterase inhibitor being developed for the symptomatic treatment of Alzheimer's disease (AD).OBJECTIVES: This study compared the efficacy, tolerability and safety of two doses of metrifonate in patients with mild-to-moderate AD, over a 26-week treatment period. METHODS: Six hundred and five patients were randomized to placebo (n=208), a 40/50 mg dose (40 or 50 mg by weight; n=200) or a 60/80 mg dose (60 or 80 mg by weight; n=197) metrifonate. Patients randomized to receive metrifonate were administered a once-daily loading dose of 80 or 120 mg based on weight for 2 weeks, followed by the relevant maintenance dose for 24 weeks. Four main clinical domains of AD were assessed: cognition (ADAS-cog and MMSE), psychiatric and behavioural symptoms (ADAS-noncog and NPI), instrumental and basic activities of daily living (DAD) and global functioning (CIBIC-plus, CIBIS-plus and GDS).RESULTS: ADAS-cog performance was significantly improved in the 60/80 mg and 40/50 mg dose groups, compared with placebo, in the intention-to-treat (ITT) population. In addition, statistically significant treatment differences were demonstrated between the 60/80 mg dose group and placebo on MMSE, ADAS-noncog, the NPI subitems of hallucinations and apathy, DAD, CIBIC-plus, CIBIS-plus and the GDS. The performance of the 40/50 mg dose group was also significantly superior to placebo on the CIBIS-plus and the NPI subitem aberrant motor behaviour. CONCLUSIONS: Metrifonate significantly improved a wide range of symptoms across all four clinical domains of AD in a dose-dependent manner, and was safe and well tolerated at both doses studied.

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.

Magnin B, Mesrob L, Kinkingnéhun S, Pélégrini-Issac M, Colliot O, Sarazin M, Dubois B, Lehéricy S, Benali H. · UMR-S 678, Inserm, Paris, France. · Neuroradiology. · Pubmed #18846369 No free full text.

Abstract: PURPOSE: We present and evaluate a new automated method based on support vector machine (SVM) classification of whole-brain anatomical magnetic resonance imaging to discriminate between patients with Alzheimer's disease (AD) and elderly control subjects. MATERIALS AND METHODS: We studied 16 patients with AD [mean age +/- standard deviation (SD) = 74.1 +/- 5.2 years, mini-mental score examination (MMSE) = 23.1 +/- 2.9] and 22 elderly controls (72.3 +/- 5.0 years, MMSE = 28.5 +/- 1.3). Three-dimensional T1-weighted MR images of each subject were automatically parcellated into regions of interest (ROIs). Based upon the characteristics of gray matter extracted from each ROI, we used an SVM algorithm to classify the subjects and statistical procedures based on bootstrap resampling to ensure the robustness of the results. RESULTS: We obtained 94.5% mean correct classification for AD and control subjects (mean specificity, 96.6%; mean sensitivity, 91.5%). CONCLUSIONS: Our method has the potential in distinguishing patients with AD from elderly controls and therefore may help in the early diagnosis of AD.

Attali E, De Anna F, Dubois B, Dalla Barba G. · INSERM Unit 610, Pavillon Claude Bernard, Hôpital de la Salpêtrière, 47, bd de l'Hôpital, Paris, France. · Brain. · Pubmed #18829697 No free full text.

Abstract: Patients who confabulate retrieve personal habits, repeated events or over-learned information and mistake them for actually experienced, specific unique events. Although some hypotheses favour a disruption of frontal/executive functions operating at retrieval, the respective involvement of encoding and retrieval processes in confabulation is still controversial. The present study sought to investigate experimentally the involvement of encoding and retrieval processes and the interference of over-learned information in the confabulation of Alzheimer's disease patients. Twenty Alzheimer's disease patients and 20 normal controls encoded and retrieved unknown stories, well-known fairy tales (e.g. Snow White) and modified well-known fairy tales (e.g. Little Red Riding Hood is not eaten by the wolf) under three experimental conditions: (i) full attention at encoding and at retrieval; (ii) divided attention at encoding (i.e. performing an attention demanding secondary task) and full attention at retrieval; (iii) full attention at encoding and divided attention at retrieval. We found that confabulations in Alzheimer's disease patients were more frequent for the modified well-known fairy tales and when encoding was weakened by a concurrent secondary task (61%), compared with the other types of stories and experimental conditions. Confabulations in the modified fairy tales always consisted of elements of the original version of the fairy tale (e.g. Little Red Riding Hood is eaten by the wolf). This is the first experimental evidence showing that poor encoding and over-learned information are involved in confabulation in Alzheimer's disease.