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Biomedical subjects

J M Orgogozo

Publications and source records attributed to J M Orgogozo.

At least 19 recordsLinked to original sources

Restriction in complex activities of daily living in MCI: impact on outcome.

OBJECTIVE: To describe the restriction in instrumental activities of daily living (IADL) in mild cognitive impairment (MCI) and to assess the impact of IADL restriction on the progression to dementia and on MCI reversibility. METHODS: The study sample included 1,517 participants of the PAQUID cohort, visited at 8- and 10-year follow-ups. Subjects classified as having MCI had no dementia but a cognitive deficit according to five neuropsychological tests. Four IADL (telephone, transports, medication, finances) were assessed and considered restricted if at least two of them were not performed at the highest level of performance. Cross-sectional and longitudinal analyses were conducted. RESULTS: A total of 285 subjects were classified as having MCI at baseline, and 15.2% developed dementia within 2 years. MCI subjects were more frequently IADL restricted (34.3%) than controls (5.4%) but less than those with dementia (91.1%). The IADL-restricted MCI subjects were more likely to develop dementia over 2 years (30.7%) than the nonrestricted ones (7.8%). In multivariate analyses, the odds ratio for dementia was 7.4 (CI: 3.3 to 16.5) in the IADL-restricted MCI and 2.8 (CI: 1.3 to 6.0) in the non-IADL-restricted MCI compared with the non-IADL-restricted controls. IADL restriction also lowered the chance of reversibility to normal, observed in 10.7% of the restricted MCI and 34.7% of the nonrestricted MCI. CONCLUSIONS: Inclusion of instrumental activities of daily living restriction in the criteria of mild cognitive impairment improves the prediction of dementia and the stability of this status over time. Conversely, its exclusion results in inappropriate selection of subjects with a low probability of short-term progression to dementia.

Activities of Daily Living↗

Marchiafava-Bignami disease: diffusion-weighted MRI in corpus callosum and cortical lesions.

The clinical diagnosis of Marchiafava-Bignami disease (MBD) can be difficult. Acute demyelination of the corpus callosum is characteristic of the disease. The authors report the use of MR diffusion-weighted imaging (DWI) in six cases of acute MBD. They show that apparent diffusion coefficient restriction of the corpus callosum and cortical lesions were associated with a higher mortality rate and more severe cognitive sequelae.

Adult↗

Incidence and outcome of mild cognitive impairment in a population-based prospective cohort.

OBJECTIVE: To estimate the age-specific incidence rate of mild cognitive impairment (MCI) according to sex and educational level and to explore the course of MCI, particularly its progression to AD, in a population-based cohort. METHODS: A community-based cohort of nondemented elderly people (Personnes Agées QUID [PAQUID]) was followed longitudinally for 5 years. MCI was defined as memory complaints with objective memory impairment, without dementia, impairment of general cognitive functioning, or disability in activities of daily living. Incidence rates were calculated using the person-years method. A descriptive analysis at the different follow-up times was performed to study the course of MCI. RESULTS: At baseline, there were 58 prevalent cases of MCI (2.8% of the sample). During a 5-year follow-up, 40 incident cases of MCI occurred in 1,265 subjects at risk. The global incidence rate of MCI was 9.9/1,000 person-years. MCI was a good predictor of AD with an annual conversion rate of 8.3% and a good specificity, but it was very unstable over time: Within 2 to 3 years, only 6% of the subjects continued to have MCI, whereas >40% reverted to normal. CONCLUSIONS: Conventionally defined MCI has reasonable predictive value and specificity for AD. However, MCI was very unstable across time in this study. Furthermore, the definition of MCI seems to be too restrictive and should probably be extended to other categories of individuals also at high risk of developing AD.

Activities of Daily Living↗

The effect of tirilazad mesylate on infarct volume of patients with acute ischemic stroke.

The authors investigated whether the lack of effect of tirilazad on clinical outcome in patients with acute ischemic stroke is explained by failure of tirilazad to reduce infarct volume. Overall, tirilazad had no significant effect on infarct volume. In the subgroups of male patients and of those with a cortical infarct, tirilazad significantly reduced infarct volume. These effects were reduced to nonsignificant trends after adjustment for imbalances in baseline characteristics. In conclusion, early treatment of patients with tirilazad has no effect on infarct volume.

Aged↗

Peripheral neuropathy associated with mitochondrial disorders: 8 cases and review of the literature.

Forty-three cases of peripheral neuropathy (PN) have been reported in the literature with a proven mitochondria (mt) DNA mutation, and 21 had a peripheral nerve biopsy (PNB). We studied 8 patients, 1 of whom had severe sensory PN, 3 mild PN, and 4 subclinical PN. Nerve biopsy was performed in every case; all patients showed axonal degeneration and 4 showed features of primary myelin damage. In addition, there were 2 crystalline-like inclusions in the Schwann cell cytoplasm of a patient with MERRF, and 1 in a patient with multiple deletions on the mtDNA. There are 11 cases of PNB in the literature with axonal lesions, 5 with demyelination, and 4 with mixed lesions. One PNB was not modified. A few crystalline-like inclusions were seen in 1 case of MERRF. Such inclusions were first reported in the Schwann cell cytoplasm of unmyelinated fibers in a patient with Refsum disease and were considered to be modified mitochondria. However, their mitochondrial origin remains debatable.

Adolescent↗

[Meningismus after taking kava-kava].

Neurological manifestations are uncommon after taking kava-kava. We report three cases of meningismus, two of them with focal neurological manifestations, after kava-kava absorption.

Adult↗

Tirilazad for acute ischaemic stroke.

BACKGROUND: Tirilazad mesylate is neuroprotective in experimental models of ischaemic stroke suggesting it might be of benefit clinically. OBJECTIVES: To assess whether tirilazad mesylate is safe and effective at improving outcome in patients with acute ischaemic stroke. SEARCH STRATEGY: Trials of tirilazad were identified from searches of the Cochrane Stroke Group Specialised Trials Register (last searched: May 2001) and the Cochrane Controlled Trials Register (CENTRAL/CCTR). In addition, we contacted the Pharmacia & Upjohn company, the manufacturer of tirilazad, to identify unpublished studies and further information. SELECTION CRITERIA: Truly and quasi-randomised unconfounded placebo or open controlled trials of tirilazad administered within 24 hours onset of suspected or proven acute ischaemic stroke. DATA COLLECTION AND ANALYSIS: Data relating to early and end-of-trial case fatality, disability (Barthel Index and Glasgow Outcome Scale), phlebitis, and QTc were extracted by treatment group from published data and company reports. MAIN RESULTS: Six trials (four published, two unpublished) assessing tirilazad in 1757 patients with presumed acute ischaemic stroke were identified; all were double-blind and placebo-controlled in design. Tirilazad did not alter early case fatality (odds ratio, OR 1.11, 95% confidence intervals, 95% CI 0.79 to 1.56) or end-of-trial case fatality (OR 1.12, 95% CI 0.88 to 1.44). Tirilazad increased the odds of being dead or disabled by about one fifth, though the result was only just statistically significant; the odds ratios were similar whether the expanded Barthel Index or Glasgow Outcome Scale were used to assess outcome (OR 1.23, 95% CI 1.01 to 1.51; OR 1.23, 95% CI 1.01 to 1.50 respectively). Tirilazad significantly increased the rate of infusion site phlebitis (OR 2.81, 95% CI 2.14 to 3.69). Functional outcome (EBI) was significantly worse in prespecified subgroups of patients: females (OR 1.46, 95% CI 1.08 to 1.98) and subjects receiving low dose tirilazad (OR 1.31, 95% CI 1.03 to 1.67); a non-significant worse outcome was also seen in patients with mild-moderate stroke (OR 1.40, 95% CI 0.99 to 1.98). REVIEWER'S CONCLUSIONS: Tirilazad mesylate increased the combined end-point of 'death or disability' by about one-fifth, but did not alter case fatality, when given to patients with acute ischaemic stroke. Although further trials of tirilazad are now not warranted, analysis of individual patient data from the trials may help elucidate why tirilazad appears to worsen outcome in acute ischaemic stroke.

Humans↗

Pharmacotherapy of Alzheimer's disease: is there a need to redefine treatment success?

The traditional aim of Alzheimer's disease treatment in clinical trials has been to improve cognitive abilities. It has become increasingly clear, however, that other aspects are important in assessing treatment responses. A group of 10 physicians recently gathered to review the current criteria for assessing treatment success in Alzheimer's disease. While cognition has been previously viewed as the primary measure of efficacy, areas such as functional abilities, behaviour, caregiver burden, quality of life and resource utilization all need to be comprehensively assessed to fully evaluate treatment effects in patients with Alzheimer's disease, as well as their impacts on caregivers and society. Postponing or slowing decline in any of these areas may represent an important benefit and should be considered as an outcome measure in clinical trials, clinical practice and decision-making about healthcare budgets. Accepted instruments are available for assessing outcomes in each aspect of Alzheimer's disease, but they need to be selected carefully to provide valid, meaningful data. Some of the most frequently used outcome measures in Alzheimer's disease are reviewed. Using expanded criteria for treatment success and clinically relevant outcome measures, data from currently available studies show that cholinesterase inhibitors produce clinically meaningful long-term benefits in multiple domains in patients with Alzheimer's disease.

Activities of Daily Living↗

Occupation during life and risk of dementia in French elderly community residents.

OBJECTIVE: To determine whether principal occupation during life is a risk factor for incident Alzheimer's disease, vascular dementia, or dementia with parkinsonism. METHODS: This study was carried out from the PAQUID (Personnes Agées QUID) cohort, an epidemiological study on normal and pathological aging after 65 years in the south west of France. At baseline, 2950 non-demented people living at home were identified and re-examined 1, 3, 5, 8, and 10 years later with identical standardised neurological and neuropsychological measures. Cox proportional hazards models with delayed entry were used, taking age as the time scale and adjusting for sex, education, tobacco, and wine consumption to estimate the risk ratio (RR) of incident dementia, Alzheimer's disease, vascular dementia, and dementia with parkinsonism associated with occupational category. RESULTS: Of the 2950 subjects, 393 became demented, of whom 251 had Alzheimer's disease, 112 had vascular dementia, and 27 had dementia with parkinsonism. The risk of Alzheimer's disease was not related to a given occupation. However the risk of dementia with parkinsonism seemed to be increased in farmers in comparison with professionals and managerials, particularly among women (RR 7.47; 95%CI, 1.80-31.07). CONCLUSION: The data suggest that occupation does not change the risk of Alzheimer's disease, which seems to be more influenced by cognitive abilities in childhood and adolescence than by occupation in adult life. However, being a farmer may increase the risk of dementia with parkinsonism among women; occupation could act by the way of differences in health behaviour or in exposure to environmental factors.

Age Distribution↗

Nutritional factors in cerebral aging and dementia: epidemiological arguments for a role of oxidative stress.

There is increasing evidence that oxidative stress is involved in cerebral aging and dementia. The objective of this review is to give a progress report on the more recent results of the various epidemiologic cohorts studied for the association between nutrition of older people, the evolution of cognitive performances and the risk of later occurrence of dementia or stroke. The oxidative theory of pathological brain ageing is supported by animal laboratory experiments. Furthermore, experimental research has consistently suggested that diet-related factors play an important role in cognitive functions in ageing. In humans, a number of epidemiological case-control and prospective studies analyzed the association between nutrition, particularly fatty acids and antioxidant molecules (vitamins A, E, C, beta-carotene and polyphenols) and cognition. In the context of evidence already available, further studies are needed to identify the specific role of various nutrients, their interactions and the influence of genetic factors and living habits on cerebral aging and dementia. Vascular dementia and Alzheimer's disease, that share several risk factors, might be targets for primary prevention through nutritional recommendations and/or supplementation.

Aged↗

Alzheimer disease: diagnosis, costs, and dimensions of treatment.

Alzheimer disease (AD) is the most frequent cause of dementia in developed Western countries. Over time, affected patients invariably develop cognitive and functional decline, and most develop early or later behavioral disturbances. Declining cognitive and functional abilities contribute to loss of independent living and feelings of denial, confusion, fear and guilt until, finally, the patient loses most abilities to think, move, speak, or perceive. As patients' dependency on assistance increases, the level of caregiver strain rises. The caregiver may develop feelings of anger, grief, loneliness and resentment, and the health and well-being of most caregivers are often affected. Approximately 3-4 million people currently have AD in the USA, at an annual cost of up to US$100 billion, and the disease is expected to reach epidemic proportions by 2020. To achieve a clinically relevant, long-term outcome, pharmacotherapy must have sustained favorable effects on cognitive, functional and behavioral symptoms of AD. Slowing the development of these features of the disease will mean a long-term improvement in quality of life for patients and caregivers. Postponing the emergence of behavioral symptoms would bring about direct beneficial effects on patients with AD and their families, help delay long-term care placement and lower costs.

Activities of Daily Living↗