Alzheimer Disease: Touchon J

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.

Touchon J, Portet F. · Service de neurologie, CM2R du Languedoc-Roussillon, Inserm E 361, CHU, Montpellier Cedex 05. · Presse Med. · Pubmed #17855046 No free full text.

Abstract: The concept of mild cognitive impairment (MCI) was proposed by Petersen et al. (1997, 1999) as a nosologic entity referring to elderly persons with mild cognitive deficit and without dementia. MCI is widely used in studies as an intermediate stage between cognitive normalcy and dementia. MCI now appears, however, to be a heterogeneous clinical entity. The many sources of heterogeneity that have been pointed out include: heterogeneity in etiological factors (various types of degenerative lesions, vascular risk factors, psychiatric features, concomitant non-neurological diseases), in clinical symptoms, and in clinical course (with decline, stable, or reversible cognitive impairment). New clinical criteria have thus been proposed for use in research and in clinical practice: 1) cognitive complaint from the patient, family, or both, 2) report by the subject or reporter of a decline in cognitive or functional performance, relative to previous abilities, 3) cognitive disorders evidenced by clinical evaluation: impairment in memory or another cognitive domain, 4) cognitive impairment without any repercussions on daily life, even if the subject reports difficulties concerning complex daily activities, and 5) no dementia. Those new criteria, essentially clinical, may be better adapted to both clinical research and daily clinical practice. Biological and radiological markers will provide greater and more systematic support for diagnosis in the near future, particularly for early detection of Alzheimer's disease.

Cortes F, Portet F, Touchon J, Vellas B. · F. Cortes, Alzheimer's Disease Research Centre, U 558, Toulouse, France. · J Nutr Health Aging. · Pubmed #17653493 No free full text.

Abstract: BACKGROUND: Clinical trials in Alzheimer's disease (AD) include patients benefiting from recent improvements in AD management. OBJECTIVE: To observe the progression of Alzheimer's disease (AD) after 6 and 18 months in patients treated with acetylcholinesterase inhibitors (AChEI) in order to determine the best duration of follow-up necessary to demonstrate the impact of new drugs. METHODS: Six hundred and eleven patients included in the REAL.FR cohort were treated with AChEI at baseline. We describe the cognitive, functional, behavioural, nutritional and global changes in the 509 and 364 patients who completed 6 and 18 months of follow-up, respectively, and who did not discontinue treatment. RESULTS: After 6 and 18 months, we observed a statistically significant change in the MMSE (-0.54 +/- 3.13 at 6 months and -2.90 +/- 4.10 at 18 months), ADAS-cog (1.58 +/- 5.23 and 4.02 +/- 6.83), ADL (-0.30 +/- 0.79 and -0.84 +/- 1.20), IADL (-0.31 +/- 0.95 and -0.94 +/- 1.20), CDR sum of boxes (0.75 +/- 2.03 and 2.65 +/- 3.18) and MNA scores (-0.42 +/- 2.89 and -0.95 +/- 3.57), demonstrating the progression of AD. But on examining these changes, it appears that even if they were statistically significant at 6 months, they do not appear to be clinically relevant or sufficient to allow the observation of the effect of a new drug at this time, whereas such observation would be possible after 18 months. Similar results were obtained in a subgroup of patients who answer to the inclusion criteria of disease modifying trials which confirms the need for having 18 months of follow-up. CONCLUSION: Changes in AD in patients under AChEI treatment are not sufficient to demonstrate the effect of a new treatment at 6 months. However, 18-month trials appear to have the potential to demonstrate clearly the effect of a new drug.

Touchon J, Portet F, Gauthier S. · Neurology Service, Guy de Chauliac Hospital, Montpellier, France. · Neurology. · Pubmed #17101931 No free full text.

Abstract: Finding strategies that prevent or delay the onset of dementia in Alzheimer disease (AD) will be a challenge for the years to come. Prevention trials in AD pose several unresolved questions, including methodologic, scientific, medical, regulatory, and ethical issues. A critical concern is the benefit and relative risk of giving a treatment to non-demented patients or to asymptomatic subjects. Some trials are under way and will perhaps move the field of prevention of dementia one big step forward.

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.

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Voisin T, Touchon J, Vellas B. · Department of Internal Medicine and Clinical Gerontology, Acute Unit for Alzheimer's Patients, Toulouse University, Toulouse, France. · Curr Opin Neurol. · Pubmed #15129850 No free full text.

Abstract: Mild cognitive impairment is not an established diagnosis but a concept for which different criteria have been proposed and modified over time. Mild cognitive impairment refers to the transitional zone between normal ageing and dementia. The mild cognitive impairment stage may be one of the optimum stages at which to intervene with preventive therapies. The heterogeneity of the term has been recognized. Multiple sources of heterogeneity have been described for mild cognitive impairment, including biological factors, clinical symptoms and clinical course. It is still not possible to consider mild cognitive impairment as an explicit predictor of Alzheimer's disease with the current criteria. The heterogeneity within mild cognitive impairment has been noted, and a classification has been proposed: amnestic or single memory mild cognitive impairment, multiple domains mild cognitive impairment, and single non-memory mild cognitive impairment. Future research should be focussed on redefining the criteria of the mild cognitive impairment entity. This could enable the better development of appropriate therapeutic interventions.

Touchon J, Portet F. · Unité de Neurologie Comportementale et Dégénérative, Neurologie B, CHU Gui-de-Chauliac, 34295 Montpellier Cedex 05 INSERM E 99-30, CHU de Montpellier. · Rev Neurol (Paris). · Pubmed #12529582 No free full text.

Abstract: The diagnosis of Mild Cognitive Impairment (MCI) as defined by Petersen et al. (1997), is based uniquely on clinical observations. Cerebral imaging, both morphological and functional, may in fact facilitate diagnosis, particularly with regard to the differentiation of sub-types of MCI and the identification of prodromal AD (MCI-AD). Volumetric Magnetic Resonance Imagery (MRI) examination of structures affected early in AD such as entorhinal cortex, the temporal lobe and, above all, the hippocampus, are especially useful. Hypoactivity within these regions, especially of the temporal lobe and posterior cingulate gyrus by Positon Emission Tomography, and more recently monophotonic emission tomoscintigraphy, also appears to have diagnostic utility. Studies of cholinergic system activity by functional imaging may also be of future value in MCI-AD diagnosis. MRI used in conjunction with other techniques may be of significant value, in particular the use of spectro-MRI and functional MRI. This latter technique, leading to the development of cognitive activation paradigms, is particularly promising.

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.

Torreilles F, Touchon J. · CNRS UMR 5094, Institut de Biotechnologie et Pharmacologie, UFR Pharmacie, 15 Avenue Charles Flahault, 34093 Montpellier Cedex 5, France. · Prog Neurobiol. · Pubmed #11943451 No free full text.

Abstract: Alzheimer's disease (AD) is an age-dependent dementia characterized by progressive loss of cognitive functions and by characteristic pathological changes in the brain: the formation of aggregates extracellularly by beta-amyloid (Abeta) peptide and intracellularly by tau proteins. The disease presents several major diagnostic difficulties: (1) AD develops slowly; (2) analysis of damaged brain tissues is difficult, requiring a biopsy which poses ethical problems; (3) no biochemical markers are available for the diagnosis and monitoring of the disease progression. Since the cerebrospinal fluid (CSF) is in contact with the extracellular space of the brain, many studies have tried to correlate the levels of the intrathecal peptides and amino acids and the development of dementia. The present review analyzes the main results of intrathecal content analyses in light of pathogenic theories proposed to explain the damage associated with AD and observed in the brain of patients by postmortem examination.

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.

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Blain H, Jouzeau JY, Blain A, Terlain B, Tréchot P, Touchon J, Netter P, Jeandel C. · Service de Médicine interne-Gériatrie C, Centre de Gérontologie Médicale Antonin Balmes, CHU de Montpellier. · Presse Med. · Pubmed #10701410 No free full text.

Abstract: POSSIBLE INFLAMMATORY MECHANISMS: Alzheimer's disease (AD) is a degenerative disease of the brain including possibly inflammatory mechanisms, as illustrated by the presence of activated microglial cells in the periphery of senile plaques and neurofibrillary tangles and the subsequent release of proinflammatory mediators with neurotoxic potency. RATIONALE FOR NSAID USE: Although not firmly demonstrated, the rationale for the prescription of non steroidal anti-inflammatory drugs (NSAIDS) as neuroprotective agents in AD lies on epidemiological data having shown a reduced risk of developing AD in patients on long-term therapy with NSAIDs (non selective cyclo-oxygenase [COX] inhibitors). RATIONALE FOR THE USE OF SELECTIVE COX-2 INHIBITORS: The rationale for the prescription of selective COX-2 inhibitors as neuroprotective drugs in AD lies on: Epidemiological data having shown a reduced risk of developing AD in patients treated with anti-inflammatory doses of classical NSAIDs (inhibition of COX-1 and COX-2) but not with antithrombotic doses of aspirin (selective inhibition of COX-1), Cellular experiments, Demonstration of a better gastro-intestinal (GI) safety profile with selective COX-2 inhibitors than with classical NSAIDs in short-term studies, allowing a possible long-term use in AD. BEFORE PRESCRIBING: COX-2 may have an ambivalent functionality in the brain since the basal production of prostaglandins through COX-2 may participate in neuronal homeostasis whereas the expression of COX-2 is associated with brain development. Classical NSAIDs are ineffective in reducing the formation of senile plaque and neurofibrillary tangles in AD, which is consistent with an ability to reduce inflammation associated with activation of microglia but illustrates their failure to suppress the degenerative process. Prophylactic use of selective COX-2 NSAIDs can be considered on the basis of their good GI safety after 6 months of marketing in United States but need to be confirmed for a longer time. CURRENT TRIALS: Clinical studies focusing on both the prevention and the slowing down of early AD are under way with two recently launched selective COX-2 inhibitors, celecoxib and rofecoxib.

Rigaud AS, André G, Vellas B, Touchon J, Pere JJ, Loria-Kanza Y. · Département de gériatrie, Service du Pr F. Forette, Hôpital Broca, Paris. · Presse Med. · Pubmed #14631268 No free full text.

Abstract: OBJECTIVE: To compare the efficacy on cognitive function of the combination of hormone replacement therapy with rivastigmine, acetylcholinesterase inhibitor, in menopausal women suffering from mild to moderately severe Alzheimer's disease. METHOD: This was a randomised double blind study of 117 women suffering from mild to moderately severe Alzheimer-like dementia (MMSE between 10 and 26). The patients were randomly assigned to continuous hormone therapy (n=59) and placebo (n=58), all receiving treatment with rivastigmine. Follow-up was of 28 weeks. ASSESSMENT CRITERIA: ADAS-Cog (Alzheimer's disease assessment scale--cognitive subscale) (primary endpoint); MMSE (mini mental state examination), GDS (global deterioration scale), CGC-Plus (clinical global change-plus), NPI (neuropsychiatric inventory), IADL (instrumental activities of daily living). Data regarding tolerance was recorded. RESULTS: No significant difference was observed in the parameters assessing efficacy (cognitive function, global assessment, functioning, neuropsychiatric symptoms) and tolerance between the two groups of treatment. CONCLUSION: Oestro-progestagen treatment did not provide further improvement when combined with rivastigmine during mild to moderately severe Alzheimer's disease.

Rigaud AS, André G, Vellas B, Touchon J, Pere JJ, Anonymous00011. · Department of Geriatrics, Broca Hospital, Paris, France. · Neurology. · Pubmed #12525745 No free full text.

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Bennys K, Rondouin G, Vergnes C, Touchon J. · Unité de neurologie comportementale et dégénérative, service de neurologie B, hôpital Gui de Chauliac, Montpellier, France. · Neurophysiol Clin. · Pubmed #11488226 No free full text.

Abstract: The aim of this study was to determine the performance of several spectral indices of the EEG (ratios between fast and slow EEG activities) as descriptors of the EEG changes occurring at the onset and during the evolution of Alzheimer's disease (AD). These indices were calculated from quantitative analysis of EEGs recorded in AD patients and from a matched non-demented group of control subjects. One advantage of such indices is to be independent of the absolute value of power spectral densities, which may vary from subject to subject, another being to take into account fast EEG activities. Conventional statistic tests and Receiver Operating Curves (ROC) analysis were performed upon these data to determine the accuracy of the power ratios to discriminate a) between controls and patients (i.e., to detect dementia) and b) between subgroups of patients defined according to the Global Deterioration Scale of Reisberg (GDS). The defined ratios provided a good classification of AD patients for all cerebral regions except the frontal areas, because of eye movement artefacts; the results confirm the increase in slow activities and the concomitant decrease in fast activities early in AD patients. Moreover, our results demonstrate that these indices are adapted tools to perform a good discrimination between demented and non-demented patients in routine clinical practice. We therefore propose the use of these EEG power ratios to discriminate between different stages of Alzheimer's disease, and to perform long-term monitoring of AD patients.

Gillette-Guyonnet S, Andrieu S, Dantoine T, Dartigues JF, Touchon J, Vellas B, Anonymous00037. · Gérontopôle de Toulouse, Department of Geriatrics, CHU Toulouse, Purpan University Hospital, Toulouse, France. · Alzheimers Dement. · Pubmed #19328438 No free full text.

Abstract: BACKGROUND: Because no effective curative approaches are available, preventive approaches in the field of Alzheimer's disease (AD) are needed. We present the design of the ongoing Multidomain Alzheimer Preventive Trial (MAPT) Study. Several previous studies suggested that many factors may be involved in the occurrence of AD at late ages. Because of the probable multifactorial nature of AD, it seems logical to initiate multidomain interventions to examine their potential synergistic effects. The MAPT Study aims to evaluate the efficacy of a multidomain intervention (nutritional, physical, and cognitive training) and omega 3 treatment in the prevention of cognitive decline in frail elderly persons aged 70 years or over. The study also collects imaging and biological data that could be used in future AD prevention and treatment trials. METHODS: The MAPT Study is a 3-year, randomized, controlled trial conducted by university hospital practitioners specializing in memory disorders in four French cities (Bordeaux, Limoges, Montpellier, and Toulouse). The study plans to enroll 1200 frail elderly subjects on the basis of at least one of the following criteria: subjective memory complaint spontaneously expressed to a general practitioner, limitation in one instrumental activity of daily living (IADL), and slow walking speed. To demonstrate the protective effect of interventions, subjects are randomized into one of the following four groups: omega 3 alone, multidomain intervention alone, omega 3 plus multidomain intervention, or placebo (n = 300 each). The principal outcome measure is a change in cognitive function at 3 years, as determined by the Grober and Buschke Test. CONCLUSIONS: The MAPT Study is the first preventive trial involving multidomain interventions. Final results should be available in 2013.

Guetin S, Portet F, Picot MC, Defez C, Pose C, Blayac JP, Touchon J. · Equipe Inserm U888, service de neurologie, centre mémoire de ressources et de recherches, CHU de Montpellier, 34295 Montpellier, France. · Encephale. · Pubmed #19250995 No free full text.

Abstract: INTRODUCTION: The impact of music therapy on dementia care for patients with Alzheimer's disease (AD) is well-recognized. Music alters the different components of the disease through sensory, cognitive, emotional, behavioral and social impacts. The academic aspect of music therapy in this area was based on the fact that music can alter the various components of the overall evolution of this disease. We found around 10 case studies presenting various results from receptive music therapy sessions on patients with Alzheimer's disease. The results of these studies point out the interest of music therapy in the multidisciplinary care of Alzheimer's disease and its related syndromes. It has been deemed useful for significantly reducing the medication given to AD patients. A music therapy protocol, specifically tailored to the patient's needs has been shown to significantly reduce anxiety, depression and aggressiveness in patients suffering from Alzheimer's disease. This technique has also demonstrated its impact on helping AD patients recall their previous life experience. OBJECTIVE: To demonstrate the feasibility and to evaluate the impact of music therapy on anxiety and depression at the early to moderate stage of Alzheimer's disease and on the main caregiver burden. METHOD: Five outpatients suffering from early stage of Alzheimer's disease (MMS: 18-26) were prospectively included. They were living in Montpellier with a reliable caregiver. A weekly receptive music therapy session was delivered to patients over a 10-week period, according to the U method standardized protocol. This technique was based on the recommendations made by Gardner and Good relating to the importance given to an individualized choice of music. Instrumental tracks were selected from various music styles (classic, jazz, world music...) and were tailored to the patient's requirements. This individual session was always followed by an interview with the music therapist in order to allow the patient to express the emotions felt during the session and to stimulate the patient's cognitive functions by recalling memories and images from his past life experience. The main evaluation criterion was regular session attendance at the hospital. Secondary criteria were: anxiety score (Hamilton scale), depression score (Cornell scale) and the burden score felt by the main caregiver (Zarit scale). Evaluations took place at W1, W4 and W10. The score evolution on the Hamilton, Cornell and Zarit scales were tested using the Wilcoxon test on paired data. The significance threshold has conventionally been set at 5% for all tests used. The statistical analysis was done using the SAS software (8th version) (SAS Institute, Cary, N.C.; proc npar1way, proc univariate, proc freq). Alzheimer's disease is a recognized indication for music therapy. A simple oral consent was collected prior to the study inclusion. RESULTS: Five patients were included for a total of 44 sessions. The patients' regular attendance at the music therapy sessions showed its feasibility. Thanks to oral feedback, we were able to see that music therapy was very well-accepted both by patients and caregivers. After the sessions, all patients expressed a sensation of well-being and pleasure, such as: "Music made me feel better, I feel more relaxed", "I feel better", "I didn't know that music could have such an impact on me"... Other verbal comments were collected regarding the patients' previous life experience: "This music reminds me of my childhood", "I imagined myself dancing just like I used to in the old days", "This reminds me of my trip to Italy with my children"... The level of anxiety (Hamilton scale) dropped significantly from 9.4 (+/-2.2) to 3.4 (+/-2.6) between the first session and the fourth session (P<0.004). The differences observed between W4-W10 and W1-W10 were close to the threshold of significance due to a major drop in the anxiety level starting at W4 (P=NS). On the Cornell scale, the depression level dropped significantly from 10.8 (+/-5.3) to 2.2 (+/-1.9) between the first session and the fourth session (P<0.01). The differences observed between W4-W10 and W1-W10 were not significant (P=NS). The weight of the physical and emotional burden experienced by the main caregiver (Zarit scale) fell significantly from 30.2 (+/-11.7) to 15.6 (+/-10.4) between W1-W4 (P<0.002). The differences observed between W4-W10 and W1-W10 were not significant (P=NS). DISCUSSION/CONCLUSION: This preliminary study demonstrates the feasibility as well as the initial efficacy of music therapy in terms of its impact on the overall care for patients suffering from Alzheimer's disease. This easily applicable technique can be useful in treating anxiety and depression in a patient with Alzheimer's disease and also in relieving the emotional and physical burden experienced by the main caregiver.

Nobili F, Frisoni GB, Portet F, Verhey F, Rodriguez G, Caroli A, Touchon J, Calvini P, Morbelli S, De Carli F, Guerra UP, Van de Pol LA, Visser PJ. · Clinical Neurophysiology Unit, Dept. of Endocrinological and Medical Sciences, University of Genoa, Viale Benedetto XV, 6, 16132, Genoa, Italy. · J Neurol. · Pubmed #18958573 No free full text.

Abstract: The Development of Screening Guidelines and Clinical Criteria of Predementia Alzheimer's Disease (DESCRIPA) multicenter study enrolled patients with MCI or subjective cognitive complaints (SUBJ), a part of whom underwent optional brain perfusion SPECT. These patients were classified as SUBJ (n = 23), nonamnestic MCI (naMCI; n = 17) and amnestic MCI (aMCI; n = 40) based on neuropsychology. Twenty healthy subjects formed the control (CTR) group. Volumetric regions of interest (VROI) analysis was performed in six associative cortical areas in each hemisphere. ANOVA for repeated measures, corrected for age and center, showed significant differences between groups (p = 0.01) and VROI (p < 0.0001) with a significant group-region interaction (p = 0.029). In the post hoc comparison, SUBJ did not differ from CTR. aMCI disclosed reduced uptake in the left hippocampus and bilateral temporal cortex (compared with CTR) or in the left hippocampus and bilateral parietal cortex (compared with SUBJ). In the naMCI group, reduced VROI values were found in the bilateral temporal cortex and right frontal cortex. In the comparison between aMCI and naMCI, the former had lower values in the left parietal cortex and precuneus. Discriminant analysis between SUBJ/CTR versus all MCI patients allowed correct allocations in 73 % of cases. Mean VROI values were highly correlated (p < 0.0001) with the learning measure of a verbal memory test, especially in the bilateral precunei and parietal cortex and in the left hippocampus. In a subset of 70 patients, mean VROI values showed a significant correlation (p < 0.05) with the white matter hyperintensities score on MRI. In conclusion, MCI subtypes have different perfusion patterns. The aMCI group exhibited a pattern that is typical of early Alzheimer's disease, while the naMCI group showed a more anterior pattern of hypoperfusion. Instead, a homogeneous group effect was lacking in SUBJ.

Gillette Guyonnet S, Abellan Van Kan G, Andrieu S, Aquino JP, Arbus C, Becq JP, Berr C, Bismuth S, Chamontin B, Dantoine T, Dartigues JF, Dubois B, Fraysse B, Hergueta T, Hanaire H, Jeandel C, Lagleyre S, Lala F, Nourhashemi F, Ousset PJ, Portet F, Ritz P, Robert P, Rolland Y, Sanz C, Soto M, Touchon J, Vellas B. · Gerontopole, Pole Geriatrie Gerontologie, Hopital La Grave-Casselardit, Toulouse. · J Nutr Health Aging. · Pubmed #18810298 No free full text.

Abstract: Alzheimer's disease (AD) is the most frequent form of dementia and according to the most recent estimation it affects nearly 27 million people in the world. The onset of the disease is generally insidious. It is becoming increasingly evident that the underlying pathophysiological mechanisms are active long before the appearance of the clinical symptoms of the disease. In the current context, it is important to develop strategies to delay the onset of cognitive decline. Delaying the onset by 5 years would reduce the prevalence by half at term, and a delay of 10 years would reduce it by three-quarters. The effectiveness of currently suggested preventive approaches remains to be confirmed, but certain strategies could be applied straight away to at-risk subjects. We propose that a health-promoting memory consultation should be set up for elderly persons who have attended a specialized memory consultation and in whom the diagnosis of dementia and of AD in particular, has not been established by standardized tools. Through this consultation, they would be offered full multidimensional investigation of all aspects of their health status, follow-up could be organized, general practitioners in private practice could be made more conscious of this population and the elderly could be made more aware of the risk factors to which they are exposed. The development of an information policy for the elderly would meet a present need. In our reflection, we must take into account the question of how to give this preventive consultation its due place in the healthcare pathway of the elderly person in order to ensure coordinated follow-up with all the other health professionals involved. The principle of the health-promoting memory consultation is undergoing validation in a large French multicentre preventive trial in 1200 frail elderly persons aged 70 years followed for three years, the Multidomain Alzheimer Preventive Trial (MAPT).

Visser PJ, Verhey FR, Boada M, Bullock R, De Deyn PP, Frisoni GB, Frolich L, Hampel H, Jolles J, Jones R, Minthon L, Nobili F, Olde Rikkert M, Ousset PJ, Rigaud AS, Scheltens P, Soininen H, Spiru L, Touchon J, Tsolaki M, Vellas B, Wahlund LO, Wilcock G, Winblad B. · Department of Psychiatry and Neuropsychology, University of Maastricht, Maastricht, The Netherlands. · Neuroepidemiology. · Pubmed #18515975 No free full text.

Abstract: BACKGROUND: There is an urgent need to identify subjects with Alzheimer's disease (AD) in the predementia phase, but validated diagnostic approaches are currently lacking. In this paper, we present the background, design and methods of a study, which aims to develop clinical criteria for predementia AD. We also present baseline characteristics of the subjects included. The study was part of the multicentre DESCRIPA project, which is being conducted within the network of the European Alzheimer's Disease Consortium. METHODS: Clinical criteria will be based on a prospective cohort study of non-demented subjects older than 55 years and referred to a memory clinic. At baseline, a number of markers and risk factors for AD were collected, including demographic variables, measures of performance in activities of daily living, cognitive, neuroimaging and genetic markers, and serum and cerebrospinal fluid markers. Subjects will be reassessed annually for 2-3 years, and we will evaluate which combination of variables best predicts AD-type dementia at follow-up. RESULTS: Between 2003 and 2005, 881 subjects were included from 20 memory clinics. Subjects were on average 70.3 years old, and had 10.4 years of education. The average score on the Mini-Mental State Examination was 27.4.

Canolle M, Messaoudi M, Ayoub B, Descours I, Bocquet P, Gely-Nargeot MC, Touchon J. · Hôpital Corentin Celton, Issy-les-Moulineaux, France. · Psychol Neuropsychiatr Vieil. · Pubmed #18364298 No free full text.

Abstract: Semantic intrusions are inappropriate responses frequently observed in patients with Alzheimer's disease. They belong to the same category as the words to be remembered, but their prototypic value remains largely unexplored. The prototype is the most representative word in a particular lexical category. The prototypic value is measured according to different criteria: written and oral lexical frequency, frequency of use, degree of typicality, degree of familiarity and rank of quotation. The objective of the study was to evaluate the prototypic value of intrusions produced by 17 Alzheimer's patients with mild to severe dementia, during the cued recall of the Grober & Buschke procedure (RL/RI 16 items). The prototypic value was compared to the categorial norms provided by 1) 17 control subjects and 2) the lexical database "Lexique 3". The results show that intrusions had a significantly higher prototypic value than targeted items. The prototypic value increased with the progression of the disease, and according to the evaluation criteria used. Thus with the criteria "frequency of use", "degree of typicality" and "degree of familiarity," the prototypic value increased exponentially with the severity of dementia. In contrast, in spite of the development of the pathology, the prototypic value decreased when assessed by the criteria of "rank of quotation", and "lexical frequency" (oral and written). In conclusion, the qualitative analysis of the prototypic value of intrusion errors in Alzheimers opens up new clinical and methodological considerations.

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.

Bennys K, Portet F, Touchon J, Rondouin G. · Department of Neurology, University Hospital of Montpellier, France. · J Clin Neurophysiol. · Pubmed #17912065 No free full text.

Abstract: Event-related potentials (ERPs) have a large application in the evaluation of cognitive processes, particularly in Alzheimer's disease (AD). The aim of the present study was to evaluate the clinical relevance of event-related evoked potentials (N2 and P3 subcomponents) in early diagnosis of AD and mild cognitive impairment (MCI). We prospectively studied 60 subjects. They all underwent the following investigations: neurologic and neuropsychological examination; functional evaluation, i.e., ERPs; cerebral imagery (morphologic and functional). Subjects were classified into 3 groups: group 1: 30 dementia of Alzheimer type (NINCDS-ADRDA, DSM-IV criteria); group 2: 20 MCI; and group 3: 10 control subjects. ERPs were significantly different between the groups (AD, MCI, control subjects), with a marked increase of P3 latencies, particularly when compared with N2 latencies (P < 0.0001). Furthermore, sensitivity was 87% to 95% for the differentiation of AD patients from MCI and control subjects, using prolonged P3 latencies (specificity, 90% to 95%), whereas using N2 prolonged latencies, sensitivity was 70% to 75% (specificity, 70% to 90%). Moreover, in the MCI group, N2 latencies strongly discriminated MCI from control subjects, with 90% sensitivity and 70% specificity and correctly categorized 80% of MCI subjects against 73% for P3. The abnormalities of N2 and P3 components may be linked, in AD and MCI, to an alteration of automatic and controlled attention processing.

Ollat H, Laurent B, Bakchine S, Michel BF, Touchon J, Dubois B. · Association pour la Neuro Psycho Pharmacologie, 25 rue de la Plaine, 75020 Paris. · Encephale. · Pubmed #17675917 No free full text.

Abstract: The efficacy of the inhibitors of acetylcholinesterase in Alzheimer's Disease (AD) is moderated and some patients do not respond to these treatments. Sulbutiamine potentializes cholinergic and glutamatergic transmissions, mainly in hippocampus and prefrontal cortex. This multicentric, randomized and double-blind trial evaluates the effects of the association of sulbutiamine to an anticholinesterasic drug in cognitive functions in patients with AD at an early stage (episodic memory, working memory, executive functions, attention). Patients had first donepezil (D) or sulbutiamine (S) during three months. During this period, only attention improved in both groups. During the three following months, a placebo (P) in patients D and donepezil in patients S were added. Compared to entry results, episodic memory decreased in group D + P but improved in group S + D. At the same time the improvement of attention persisted in both groups. Daylife activities only improved in group S + D. In conclusion sulbutiamine can be an adjuvant to treatment in early stage and moderate AD by anticholinesterasic drugs.

Ancelin ML, Artero S, Beluche I, Besset A, Boulenger JP, Carrière I, Chaudieu I, Courtet P, Dupuy AM, Jaussent I, Malafosse A, Norton J, De Roquefeuil G, Ryan J, Scali J, Touchon J, Ritchie K. · INSERM, E361, Montpellier, F-34093 France, Univ Montpellier 1, Montpellier, F-34000 France. · Encephale. · Pubmed #17099584 No free full text.

This publication has no abstract.

Bullock R, Bergman H, Touchon J, Gambina G, He Y, Nagel J, Lane R. · Kingshill Research Centre, Swindon, UK. · Curr Med Res Opin. · Pubmed #16574032 No free full text.

Abstract: BACKGROUND: Younger Alzheimer's disease (AD) patients appear to differ genetically and neuropathologically from older AD patients, and may experience a more aggressive disease course compared with older patients. A randomised trial investigated the efficacy and tolerability of rivastigmine, an inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), and donepezil, an AChE-selective inhibitor, in patients with AD over a 2-year period. This retrospective analysis investigated whether younger and older patients showed differential tolerability and efficacy responses to cholinesterase inhibitor treatment. METHODS: For the current analysis, patients were divided according to age at baseline: those aged < 75 years and those aged >or= 75 years. Efficacy measures were the Severe Impairment Battery (SIB), Neuropsychiatric Inventory (NPI), Global Deterioration Scale (GDS), Mini-Mental State Examination (MMSE) and the AD Cooperative Study Activities of Daily Living scale (ADCS-ADL). Changes in efficacy parameters and adverse event frequencies were calculated for rivastigmine and donepezil-treated patients in both age groups. Exploratory analyses were also conducted on SIB, ADCS-ADL and NPI in patients who consented to pharmacogenetic testing at baseline. Genotyping of the apolipoprotein E (APOE) epsilon4 allele and the BuChE K-variant was conducted using the TaqMan assay. Main efficacy analyses were based on an intent-to-treat last observation carried forward (ITT-LOCF) population. RESULTS: Of the 994 patients who received the study drug, 362 (36.4%) were younger than 75 years and 632 (63.6%) were aged 75 years or over. Rivastigmine provided significant benefits in younger patients compared with donepezil on the NPI-10, NPI-12, NPI-D, GDS and ADCS-ADL (all p < 0.05, ITT-LOCF). With the exception of the NPI-D in favour of donepezil (p < 0.05, ITT-LOCF), no significant treatment differences were observed in older patients. Younger patients with two wild-type BuChE alleles had a significantly greater response to rivastigmine than donepezil on the ADCS-ADL (p < 0.01, ITT-LOCF) and SIB (p < 0.05, ITT-LOCF). The most common adverse events were nausea and vomiting and these were more frequent in rivastigmine-treated patients. CONCLUSION: In this sub group analysis, patients younger than 75 years of age showed greater treatment responses to rivastigmine than donepezil. Analysis of response by BuChE genotype suggests that this differential effect may be due to the inhibition of BuChE, in addition to AChE, by rivastigmine.