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Biomedical subjects

Jacques Touchon

Publications and source records attributed to Jacques Touchon.

18 recordsLinked to original sources

Revised criteria for mild cognitive impairment: validation within a longitudinal population study.

BACKGROUND: Mild cognitive impairment (MCI) refers to the transitional zone between normal ageing and dementia. Current criteria perform poorly within the general population setting. Revisions have been proposed based on results obtained from clinical and epidemiological studies. OBJECTIVE: To evaluate revised diagnostic criteria for mild cognitive impairment (MCI-R) incorporating changes in activity level and non-mnesic cognitive functioning. METHOD: MCI-R subjects were recruited from a representative network of general practitioners in the south of France. A computerized neuropsychometric examination was given. At 2 years of follow-up, a diagnosis of dementia was made by a neurologist using DSM-IIIR criteria and without knowledge of the results of the cognitive testing. Rates of conversion to incident dementia were assessed by receiver operating characteristics analysis. RESULTS: The MCI-R prevalence was found to be 16.6% using revised criteria. A significantly better prediction of transition to dementia (AUC = 0.80, sensitivity: 95%, specificity: 66%) was obtained with MCI-R than with the previous MCI criteria (AUC = 0.48, sensitivity: 5%, specificity: 91%). The predictive power was found to increase when MCI subtypes were combined. CONCLUSION: Incorporating the possibility of change in activity level and alteration of non-mnesic cognitive functions have been found to ameliorate the original algorithm and better define subjects converting to dementia. This definition may be applicable to both clinical and population research.

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Utility of the Mattis dementia rating scale to assess the efficacy of rivastigmine in dementia associated with Parkinson's disease.

INTRODUCTION: The severe, cortical, cholinergic depletion accompanying Parkinson's disease (PD) is considered as a highly probable correlate of cognitive and behavioural dysfunction. Recent studies have demonstrated that cholinesterase inhibitors (notably rivastigmine) are beneficial in patients suffering from dementia associated with PD (PDD). However, the primary efficacy variables used in such work came from scales designed for Alzheimer's disease (AD), even though the cognitive symptoms in PD and AD dementia do not overlap completely. The aim of the present study (a double-blind, placebo-controlled clinical trial) was to determine the utility of the Mattis dementia rating scale - the most commonly used scale in PD patients - to assess the efficacy of a 24-week rivastigmine treatment. METHODS: Twenty-eight patients with PD, who constituted a subgroup of patients enrolled to the EXPRESS study (Emre et al, N Engl J Med 2004) participated in this study. They suffered from mild to moderately severe dementia (MMSE scores above 10 and below 24), with an onset of cognitive symptoms occurring at least two years after the diagnosis of PD. Patients were randomly assigned to treatment with rivastigmine (3 to 12 mg per day) or placebo. The Mattis dementia rating scale was administered to patients from six centres in France at the baseline and end-point visits. RESULTS: Compared with placebo, a 24-week rivastigmine treatment led to a significant improvement in the overall score on the Mattis dementia rating scale (p = 0.031), with a trend towards a significant improvement in the "Attention" subscale score (p = 0.061). Correlation analysis showed that in the rivastigmine group, performance on the Mattis "Attention" and "Initiation" subscales appeared to contribute heavily to the improvement in the overall score. Moreover, the latter was also related to an improvement in activities of daily living and a reduction in behavioural disturbances. DISCUSSION: By using the Mattis dementia rating scale (which comprises items that are sensitive to executive dysfunction), the present study confirmed that rivastigmine has a beneficial effect on cognitive function in PDD. Despite our study's small sample size, the Mattis scale was able to detect this improvement and could thus be considered as an interesting outcome measure in further work.

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Non-degenerative mild cognitive impairment in elderly people and use of anticholinergic drugs: longitudinal cohort study.

OBJECTIVE: To assess the potential of anticholinergic drugs as a cause of non-degenerative mild cognitive impairment in elderly people. DESIGN: Longitudinal cohort study. SETTING: 63 randomly selected general practices in the Montpellier region of southern France. PARTICIPANTS: 372 people aged > 60 years without dementia at recruitment. MAIN OUTCOME MEASURES: Anticholinergic burden from drug use, cognitive examination, and neurological assessment. RESULTS: 9.2% of subjects continuously used anticholinergic drugs during the year before cognitive assessment. Compared with non-users, they had poorer performance on reaction time, attention, delayed non-verbal memory, narrative recall, visuospatial construction, and language tasks but not on tasks of reasoning, immediate and delayed recall of wordlists, and implicit memory. Eighty per cent of the continuous users were classified as having mild cognitive impairment compared with 35% of non-users, and anticholinergic drug use was a strong predictor of mild cognitive impairment (odds ratio 5.12, P = 0.001). No difference was found between users and non-users in risk of developing dementia at follow-up after eight years. CONCLUSIONS: Elderly people taking anticholinergic drugs had significant deficits in cognitive functioning and were highly likely to be classified as mildly cognitively impaired, although not at increased risk for dementia. Doctors should assess current use of anticholinergic drugs in elderly people with mild cognitive impairment before considering administration of acetylcholinesterase inhibitors.

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Functional Vitamin E deficiency in ApoE4 patients with Alzheimer's disease.

Oxidative stress has been implicated in the development of Alzheimer's disease (AD). Consequently, antioxidant therapies including Vitamin E (VitE) supplementation for both prevention and treatment of neurodegenerative diseases currently appears to be a promising avenue of research. The aim of the present study was to examine the relationship between AD and the ApoE phenotype, lipid parameters and VitE levels in a large cohort of elderly subjects. No absolute deficit was observed in plasma VitE levels. However in AD, ApoE4 is not associated with an increase in total cholesterol (TC) and VitE levels. Moreover, our results suggest that oxidative stress-induced injury and protection by VitE in AD are related to the ApoE phenotype. Our study strongly supports the hypothesis of an impairment of lipophilic antioxidant delivery to neuronal cells in AD leading to a tissular antioxidant deficiency which could facilitate oxidative stress.

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Response to rivastigmine or donepezil in Alzheimer's patients with symptoms suggestive of concomitant Lewy body pathology.

BACKGROUND: A double-blind randomized trial evaluated the efficacy and tolerability of rivastigmine and donepezil in patients with Alzheimer's disease (AD) over 2 years. Baseline data indicated that some patients had symptoms suggestive of concomitant Lewy body disease. This retrospective analysis investigated whether AD patients with and without symptoms suggesting concomitant Lewy body pathology demonstrated different responses to therapy. METHODS: AD patients were divided by the presence/absence of symptoms suggestive of concomitant Lewy body disease. These were identified by a concomitant diagnosis of dementia with Lewy bodies and/or use of anti-parkinsonian medication at baseline. Baseline characteristics, demographics, changes on efficacy parameters and adverse event (AE) frequencies were calculated for rivastigmine- and donepezil-treated patients. Efficacy parameters were the Severe Impairment Battery (SIB), Mini-Mental State Examination (MMSE), Global Deterioration Scale (GDS), Neuropsychiatric Inventory (NPI) and AD Cooperative Study Activities of Daily Living scale (ADCS-ADL). Main efficacy analyses were based on an intent-to-treat last observation carried forward (ITT-LOCF) population. RESULTS: Both populations reached mean doses of rivastigmine and donepezil that were within therapeutic ranges. Nine hundred and ninety-four AD patients received study drug, of whom 49 (4.9%) had symptoms suggestive of concomitant Lewy body disease (25 rivastigmine, 24 donepezil). In this subpopulation, changes from baseline after 2 years of treatment with rivastigmine were significantly better than those seen with donepezil on the SIB, MMSE and ADCS-ADL (ANCOVA or Wilcoxon analyses, p < 0.05, ITT-LOCF). Statistical significance was not maintained in non-ITT-LOCF analyses, except for EP analyses on the SIB and ADCS-ADL (both p < 0.05). Rivastigmine also provided significantly better functioning than donepezil in patients without Lewy body pathology, as shown by a significant treatment difference at endpoint on the ADCS-ADL (p < 0.05, ITT-LOCF; not maintained in non-ITT-LOCF analyses). NPI changes from baseline did not differ significantly between treatment groups. AD patients with symptoms suggestive of concomitant Lewy body disease receiving rivastigmine or donepezil experienced fewer gastrointestinal side effects, leading to fewer discontinuations due to AEs, compared with patients without Lewy body pathology. CONCLUSION: In this retrospective analysis, AD patients who had symptoms suggestive of concomitant Lewy body disease appeared to show greater treatment responses to rivastigmine than to donepezil, and experienced fewer adverse events under either drug, compared with patients without Lewy body pathology.

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Effect of age on response to rivastigmine or donepezil in patients with Alzheimer's disease.

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.

Age Factors↗

[What is a mild cognitive impairment?].

The concept of mild cognitive impairment (MCI) has been proposed by Petersen et al. (1997, 1999) as a nosologic entity referring to elderly persons with mild cognitive deficit without dementia. MCI is being widely used in studies as an intermediate stage between cognitive normalcy and dementia. However, MCI appears to be a heterogeneous clinical entity. Multiple sources of heterogeneity have been described: heterogeneity in aetiological factors (various types of degenerative lesions, vascular risk factors, psychiatric features, association of pathological conditions), heterogeneity in clinical symptoms, and heterogeneity in clinical course with decliners and non decliners presenting stable or reversible cognitive impairment. Thus new criteria of MCI are proposed for use in research but also in clinical practice. MCI may henceforth correspond to the following: (1.) Cognitive complaint emanating from the patient and/or his/her family; (2.) the subject and/or notifying party report a decline in cognitive and/or functional performance relative to previous abilities; (3.) cognitive disorders evidenced by clinical evaluation: impairment in memory and/or another cognitive domain; (4.) cognitive impairment does not have any repercussions on daily life, the subject may report difficulties concerning complex day-to-day activities; (5.) no dementia.

Activities of Daily Living↗

Family studies in insomnia.

OBJECTIVE: Several predisposing factors to insomnia have been hypothesized, including a familial component; however, few studies have focused on this topic. The aim of this study is to evaluate the prevalence of insomnia among first-degree relatives of chronic insomniacs and to compare the symptoms between sporadic and familial insomnia. METHODS: Two hundred fifty-six consecutive chronic insomniacs completed a clinical interview, psychometric questionnaires, a questionnaire on the family history of insomnia and, when indicated, a polysomnography. A control group was performed to estimate a base-rate incidence of insomnia in their families. RESULTS: Patients with primary (n=77) and psychiatric (n=104) insomnia were definitely included. Of those with primary insomnia, 72.7% reported familial insomnia compared with 24.1% in the noninsomnia control group. Among the psychiatric insomniacs, 43.3% reported familial insomnia. The mother was the relative most frequently affected. Comparisons between the family prevalence rates of insomnia assessed by the probands and by first-degree relatives show high concordance. A tendency to a younger age at onset was observed in familial and primary insomnia. CONCLUSION: This study reports a significant increase of familial aggregation of insomnia, warranting further genetic studies in primary insomnia with early age at onset.

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Rivastigmine and donepezil treatment in moderate to moderately-severe Alzheimer's disease over a 2-year period.

OBJECTIVES: Randomised controlled trials that directly compare cholinesterase inhibitors for the treatment of Alzheimer's disease have been characterised by significant methodological limitations. As a consequence, they have failed to establish whether there are differences between agents in this class. To help address this question, a double-blind, randomised, controlled, multicentre trial was designed to evaluate the efficacy and tolerability of cholinesterase inhibitor treatment in patients with moderate to moderately-severe Alzheimer's disease over a 2-year period. METHODS: Patients were randomly assigned to rivastigmine 3-12 mg/day or donepezil 5-10 mg/day. Efficacy measures comprised assessments of cognition, activities of daily living, global functioning and behavioural symptoms. Safety and tolerability assessments included adverse events and measurement of vital signs. RESULTS: In total, 994 patients received cholinesterase inhibitor treatment (rivastigmine, n = 495; donepezil, n = 499), and 57.9% of patients completed the study. The most frequent reason for premature discontinuation in both treatment groups was adverse events, primarily gastrointestinal. Adverse events were more frequent in the rivastigmine group during the titration phase, but similar in the maintenance phase. Serious adverse events were reported by 31.7% of rivastigmine- and 32.5% of donepezil-treated patients, respectively. Rivastigmine and donepezil had similar effects on measures of cognition and behaviour, but rivastigmine showed a statistically significant advantage on measures of activities of daily living and global functioning in the ITT-LOCF population. However, this was not maintained in the non-ITT-LOCF populations. In secondary subgroup analyses, AD patients who had genotypes that encoded for full expression of the butyrylcholinesterase enzyme (BuChE wt/wt; n = 226/340), who were < 75 years of age (n = 362/994) or who had symptoms suggestive of concomitant Lewy body disease (n = 49/994) showed significantly greater benefits from rivastigmine treatment. CONCLUSIONS: Cholinesterase inhibitor treatment may offer continued therapeutic benefit for up to 2 years in patients with moderate AD. Although both drugs performed similarly on cognition and behaviour, rivastigmine may provide greater benefit in activities of daily living and global functioning.

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Successful management of cataplexy with intravenous immunoglobulins at narcolepsy onset.

Hypocretin/orexin deficiency appears to be a consistent feature of narcolepsy with a putative autoimmune mechanism involved. We treated four hypocretin/orexin-deficient narcolepsy patients with intravenous immunoglobulins and assessed the efficacy by repeated polysomnographies and questionnaires. Three patients received the treatment within a few months after acute onset of narcolepsy. A clear improvement in the frequency and severity of cataplexy was obtained with a benefic effect up to 7 months without any anticataplectics drugs at follow-up. Our findings point to the importance of early diagnosis of narcolepsy, which once treated quickly may modify its long-term outlook.

Adult↗

Effect of cognitive behavioural therapy for insomnia on sleep architecture and sleep EEG power spectra in psychophysiological insomnia.

There is now an overwhelming preponderance of evidence that cognitive behavioural therapy for insomnia (CBT-I) is effective, as effective as sedative hypnotics during acute treatment (4-8 weeks), and is more effective in long term (following treatment). Although the efficacy of CBT-I in the treatment of chronic insomnia is well known, however there is little objective data on the effects of CBT-I on sleep architecture and sleep EEG power densities. The present study evaluated, first, subjective change in sleep quality and quantity, and secondly the modifications occurring in polysomnography and EEG power densities during sleep after 8 weeks of CBT-I. Nine free drug patients with psychophysiological insomnia, aged 33-62 years (mean age 47 +/- 9.7 years), seven female and two male participated in the study. Self-report questionnaires were administered 1 week before and 1 week after CBT-I, a sleep diary was completed each day 1 week before CBT-I, during CBT-I and 1 week after CBT-I. Subjects underwent two consecutive polysomnographic nights before and after CBT-I. Spectral analysis was performed the second night following 16 h of controlled wakefulness. After CBT-I, only scales assessing insomnia were significantly decreased, stages 2, REM sleep and SWS durations were significantly increased. Slow wave activity (SWA) was increased and the SWA decay shortened, beta and sigma activity were reduced. In conclusion CBT-I improves both subjective and objective sleep quality of sleep. CBT-I may enhance sleep pressure and improve homeostatic sleep regulation.

Adult↗

[Oestro-progestagen treatment combined with rivastigmine in menopausal women suffering from Alzheimer's disease. The results of a 28-weeks controlled study].

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.

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Mild cognitive impairment: a nosological entity?

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.

Alzheimer Disease↗

Mild extrapyramidal signs and functional impairment in ageing.

BACKGROUND: Little is known about the clinical significance of mild extrapyramidal signs (EPS) in elderly individuals. We investigated whether EPS are associated with functional impairment in older people with cognitive decline. METHODS: A sub-group of 105 participants from the EUGERIA Study of Cognitive Ageing without Parkinson's disease or dementia, but with informant evidence of cognitive decline, were followed across three years and underwent neurological examination and assessment of mental health, cognition and functional capacity. RESULTS: 28.6% had at least one EPS (resting tremor, muscular rigidity or akinesia, of which rigidity was the most frequent). EPS presence was significantly associated with functional impairment after controlling for age and cognitive impairment (AAMI), although the association was reduced to borderline significance after further adjustment for depression and psychotropic medication use. There was evidence of colinearity between EPS and depression, possibly suggesting similar underlying mechanisms. CONCLUSIONS: There is an association between mild EPS and functional impairment in older persons with evidence of cognitive decline, but free of dementia or Parkinson's disease.

Activities of Daily Living↗

Pathogenic theories and intrathecal analysis of the sporadic form of Alzheimer's disease.

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.

Alzheimer Disease↗

Text structure and content modulate the recall of patients with dementia of the Alzheimer's type.

Two descriptive and two narrative texts were constructed. The basic forms of each type of text comprised 27 micropropositions, while the detailed forms incorporated an additional 24 micropropositions. Forty DAT patients and 14 control subjects were asked to read and recall the 4 texts and the total number of micropropositions recalled was recorded. Recall performance among DATs was always inferior to that of controls. For both groups, the narrative texts yielded superior recall than the descriptive texts, while the detailed text forms elicited inferior recall than the basic forms. However, the addition of details to the narrative text increased the recall of the basic propositions of DATs, bringing it to similar levels as controls. Results are discussed with reference to the influence of text structure and the situation model on text recall.

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