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Biomedical subjects

Jean-Pierre Michel

Publications and source records attributed to Jean-Pierre Michel.

At least 19 recordsLinked to original sources

Decreased theta event-related synchronization during working memory activation is associated with progressive mild cognitive impairment.

BACKGROUND: Among the different quantitative electroencephalographic markers, theta activity is known to reflect neural resources involved in memory processes and directed attention. Previous studies suggested that synchronization likelihood analysis in theta-band frequency might be a sensitive method to identify early alterations of neuronal networks in mild cognitive impairment (MCI). METHODS: We report here a longitudinal study of 24 MCI patients with theta event-related synchronization (ERS) analysis during the n-back working memory task and neuropsychological follow-up after 1 year. Statistical analysis included analysis of variance and logistic regression to assess the relationship between cognitive decline and theta ERS. RESULTS: Upon follow-up, 13 MCI patients showed progressive MCI and 11 remained stable. In both groups, the phasic increase in theta amplitude after stimulus presentation did not depend on working memory load and electrode sites. Progressive MCI cases displayed significantly lower theta ERS power over all electrode sites compared to stable MCI cases. Theta ERS was significantly related to the cognitive outcome explaining 15.5% of its variability. In terms of MCI classification, the best combination of sensitivity and specificity was 0.87 and 0.60, respectively, with an area under the corresponding receiver operating characteristic curve reaching 76%. CONCLUSIONS: The present data indicate that a decrease in the early phasic theta ERS power during working memory activation may predict cognitive decline in MCI. This phenomenon is not related to working memory load but may reflect the presence of early deficits in directed attention-related neural circuits in MCI.

Aged↗

Pain in severe dementia: self-assessment or observational scales?

OBJECTIVES: To assess the performance of self-assessment scales in severely demented hospitalized patients and to compare it with observational data. DESIGN: Prospective clinical study. SETTING: Geriatrics hospital and a geriatric psychiatry service. PARTICIPANTS: All patients who met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria for dementia, with a Mini-Mental State Examination score less than 11 and a Clinical Dementia Rating score of 3. MEASUREMENTS: Three self-assessment tools--the verbal, horizontal visual, and faces pain scales--were administered in randomized order. A nursing team independently completed an observational pain rating scale. Main outcomes were comprehension (ability to explain scale use and correctly indicate positions for no pain and extreme pain, on two separate occasions), inter- and intrarater reliability, and comparison of pain intensities measured by the different scales. RESULTS: Sixty-one percent of 129 severely demented patients (mean age 83.7, 69% women) demonstrated comprehension of at least one scale. Comprehension rates were significantly better for the verbal and the faces pain scales. For patients who demonstrated good comprehension, the inter- and intrarater reliability of the three self-assessment scales was high (intraclass correlation coefficient=0.88-0.98). Correlation between the three self-assessment scales was moderate to strong (Spearman correlation coefficient (r)=0.45-0.94; P<.001). Observational rating correlated at least moderately with self-assessment (r=0.25-0.63), although for patients reporting pain, the observational rating scale underestimated severity compared with all three self-assessment scales. CONCLUSION: Clinicians should not apply observational scales routinely in severely demented patients, because many are capable of reliably reporting their own pain.

Aged, 80 and over↗

Cognitive consequences of thalamic, basal ganglia, and deep white matter lacunes in brain aging and dementia.

BACKGROUND AND PURPOSE: Most previous studies addressed the cognitive impact of lacunar infarcts using radiologic correlations that are known to correlate poorly with neuropathological data. Moreover, absence of systematic bilateral assessment of vascular lesions and masking effects of Alzheimer disease pathology and macrovascular lesions may explain discrepancies among previous reports. To define the relative contribution of silent lacunes to cognitive decline, we performed a detailed analysis of lacunar and microvascular pathology in both cortical and subcortical areas of 72 elderly individuals without significant neurofibrillary tangle pathology or macrovascular lesions. METHODS: Cognitive status was assessed prospectively using the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included Abeta-protein deposition staging and bilateral assessment of microvascular ischemic pathology and lacunes; statistical analysis included multivariate models controlling for age, amyloid deposits, and microvascular pathology. RESULTS: Thalamic and basal ganglia lacunes were negatively associated with CDR scores; cortical microinfarcts, periventricular and diffuse white matter demyelination also significantly affected cognition. In a multivariate model, cortical microinfarcts and thalamic and basal ganglia lacunes explained 22% of CDR variability; amyloid deposits and microvascular pathology explained 12%, and the assessment of thalamic and basal ganglia lacunes added an extra 17%. Deep white matter lacunes were not related to cognitive status in univariate and multivariate models. CONCLUSIONS: In agreement with the recently proposed concept of subcortical ischemic vascular dementia, our autopsy series provides important evidence that gray matter lacunes are independent predictors of cognitive decline in elderly individuals without concomitant dementing processes such as Alzheimer disease.

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[The economical impact of dementia].

An epidemiology closely linked with the increase in life span. In most countries, the prevalence of dementia varies between 6 and 8% for individuals aged 65 years or more. It then dramatically increases with each subsequent decade, reaching around 30% of the population aged over 85. The costs associated with dementia are correlated with the increase in age and are of increasing concern for politicians, healthcare professionals and family members of demented patients. Current estimations are approximate, but dementia appears to be the most costly disease for society after the age of 65 years in France, the Netherlands, Sweden, or the United States. Detailed cost analyses have distinguished the direct medical,direct non-medical and intangible costs. The most important contribution in costs for society is the long-term care by health care professionals (institutionalization corresponding to 2/3 of the total costs for society!), but the care provided by the helpers and the families is even greater, even though difficult to quantify. The current question is to know whether present and future medical treatments will be able to reduce the tremendous financial costs of this chronic disease.

Activities of Daily Living↗

Upper extremity fractures in the elderly: consequences on utilization of rehabilitation care.

BACKGROUND AND AIMS: While hip fractures represent the most dramatic consequence of osteoporosis, fractures of the humerus, forearm and wrist account for one-third of the total incidence of fractures due to osteoporosis in the older population. The aim of this retrospective cohort study was to evaluate rehabilitation care utilization and associated factors in elderly individuals with upper limb fracture. METHODS: Over two years, 667 patients 65 years of age or older were studied, who presented to the emergency department either from their private homes or nursing homes with an upper extremity fracture. The following outcome variables were collected: gender; age; residence; location of fracture; treatment; discharge destination; length of hospitalization; length of stay in a rehabilitation facility; and ultimate place of habitation after the event. RESULTS: The most frequent sites of fracture were distal radius (37.2%) and proximal humerus (29.1%). Two-thirds of the patients were treated non-operatively. Inpatient rehabilitation care was necessary for 248 patients (37.2%; length of stay, 46 days). Factors associated with increased care included older age (> or = 80 years), coming from private home, sustaining two fractures, fractures of the humerus, and operative treatment. Six percent of the patients required permanent nursing home care. CONCLUSIONS: Upper extremity fractures in older people often require prolonged hospitalization and therefore account for considerable health care costs. Reasons are more related to advanced age and living conditions than to particular injury or treatment.

Accidental Falls↗

Association between social relationships and survival of Swiss octogenarians. A five-year prospective, population-based study.

BACKGROUND AND AIMS: Data from the literature reveal the contrasting influences of family members and friends on the survival of old adults. On one hand, numerous studies have reported a positive association between social relationships and survival. On the other, ties with children may be associated with an increased risk of disability, whereas ties with friends or other relatives tend to improve survival. A five-year prospective, population-based study of 295 Swiss octogenarians tested the hypothesis that having a spouse, siblings or close friends, and regular contacts with relatives or friends are associated with longer survival, even at a very old age. METHODS: Data were collected through individual interviews, and a Cox regression model was applied to assess the effects of kinship and friendship networks on survival, after adjusting for socio-demographic and health-related variables. RESULTS: Our analyses indicate that the presence of a spouse in the household is not significantly related to survival, whereas the presence of siblings at baseline improves the oldest old's chances of surviving five years later. Moreover, the existence of close friends is a central component in the patterns of social relationships of oldest adults, and one which is significantly associated with survival. Overall, the protective effect of social relationships on survival is more related to the quality of those relationships (close friends) than to the frequency of relationships (regular contacts). CONCLUSIONS: We hypothesize that the existence of siblings or close friends may beneficially affect survival, due to the potential influence on the attitudes of octogenarians regarding health practices and adaptive strategies.

Aged, 80 and over↗

Expression of mRNA for ROS-generating NADPH oxidases in the aging stomach.

Oxidative damage is thought to play a key role in the aging of various organ systems. In this study, we have therefore analyzed mRNA expression of ROS-generating NADPH oxidases in the aging stomach. Gastric biopsies of hospitalized geriatric patients were analyzed for histology (Sidney classification), and real-time PCR was used to quantify mRNA expression of the superoxide-generating NADPH oxidases NOX1, NOX2, and NOX5. We found that stomach biopsies of elderly patients expressed NOX5 and NOX2 mRNA, but not NOX1. The mRNA expression of NOX5 (a lymphocyte NADPH oxidase) neither depended on age nor on the results of the stomach histology. In contrast, mRNA expression of NOX2 (phagocyte NADPH oxidase) was a function of two variables. Increased NOX2 mRNA levels were observed in biopsies with signs of chronic inflammation (p=0.01). Interestingly, however, there was also an age-dependent increase in NOX2 mRNA levels (p=0.01). We conclude that in elderly patients the gastric mRNA expression of the ROS-generating enzyme NOX2 increases as a function of age, possibly contributing to stomach aging and gastric vulnerability of the elderly.

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Feasibility and reliability of four pain self-assessment scales and correlation with an observational rating scale in hospitalized elderly demented patients.

BACKGROUND: Acute and chronic pain is common in hospitalized demented elderly people, yet there are limited data about the performance of pain assessment tools in this population. The aim of this study was to evaluate the feasibility and reliability of four pain self-assessment scales in this population and compare their performance to an observational pain rating scale. METHODS: Our prospective clinical study was conducted in an acute-care and intermediate-care geriatric hospital on 160 consecutive inpatient referrals to the dementia consultation who met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for dementia. Exclusion criteria were delirium, terminal care, and severe sensory impairment. Four unidimensional self-assessment tools--the verbal, horizontal visual, vertical visual, and faces pain scales--were administered in randomized order to mild, moderate, and severely demented patients. An observational pain rating scale was independently completed by the nursing team. RESULTS: Only 12% of the 160 patients (mean age 85 years, 71% women) understood no scale. Respectively, 97%, 90%, and 40% of patients with mild, moderate, and severe dementia understood at least one scale (p <.05). There was a nonsignificant trend toward poorer comprehension of the faces scale. Test-retest reliability was high for all four self-assessment scales, and the correlation between these scales was very strong (Spearman's r(s) = 0.81-0.95; p <.001). Observational rating correlated moderately with self-assessment and tended to underestimate pain intensity (r(s) = 0.31-0.40; p <.05). CONCLUSIONS: Self-assessment pain scales can be used reliably in the vast majority of older hospitalized patients with mild to moderate dementia and in nearly half of those with severe dementia. Observational pain rating scales correlate only moderately with self-assessment and should be reserved for those few patients who have demonstrated that they cannot complete a self-assessment.

Aged↗

Early event-related potential changes during working memory activation predict rapid decline in mild cognitive impairment.

BACKGROUND: The conversion of mild cognitive impairment (MCI) to Alzheimer's disease is associated with substantial compromise of neocortical circuits subserving rapid cognitive functions such as working memory. Event-related potential (ERP) analysis is a powerful tool to identify early impairment of these circuits, yet research for an electrophysiological marker of cognitive deterioration in MCI is scarce. Using a "2-back" activation paradigm, we recently described an electrophysiological correlate of working memory activation (positive-negative working memory [PN(wm)] component) over parietal electrodes. METHODS: Ours was a longitudinal study of 24 MCI patients with ERP analysis at inclusion and neuropsychological follow-up after 1 year. We used ERP waveform subtraction analysis between the n-back and control tasks. Analysis of variance (ANOVA) was used to compare electroencephalograph latencies between progressive MCI (PMCI) and stable MCI (SMCI), and univariate regression was used to assess the relationship between neuropsychological measures at baseline and clinical outcome. RESULTS: Thirteen (54%) MCI patients showed PMCI, and 11 (46%) remained stable (SMCI). In SMCI, a PN(wm) component with significantly larger density compared to baseline was identified when subtracting the detection task for both the 1- and 2-back tasks. In contrast, in PMCI, the PN(wm) component was absent in both 1-back and 2-back conditions. Neuropsychological variables and n-back test performance at inclusion did not predict cognitive deterioration 1 year later. CONCLUSIONS: In conjunction with recent functional imaging data, the present results support the notion of an early dysfunction of neural generators within the parietal cortex in MCI. They also reveal that the absence of the PN(wm) component may provide an easily applicable qualitative predictive marker of rapid cognitive deterioration in MCI.

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Procalcitonin and infection in elderly patients.

OBJECTIVES: To compare the usefulness of procalcitonin (PCT) in detecting infection in elderly patients with that of other clinical and biological markers. DESIGN: Prospective observational study to compare PCT levels in infected and uninfected patients. SETTING: Geriatric teaching hospital in Switzerland. PARTICIPANTS: Two hundred eighteen elderly patients aged 75 and older admitted to an acute geriatric care unit. MEASUREMENTS: Demographic characteristics, comorbidities, Charlson index, general signs (respiratory rate, temperature, pulse rate, confusion, falls, shivering), presence of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock, functional score (Functional Independence Measurement (FIM)) biological parameters (PCT, C-reactive protein (CRP), leukocytes, albumin), and definite diagnosis at admission were collected prospectively for each patient. RESULTS: Long-term corticotherapy, chronic immune diseases, fever of 38 degrees C or higher, white blood cell count, pulse rate, FIM, SIRS, sepsis, CRP of 3 mg/mL or higher, and PCT of 0.5 ng/mL or higher were associated with an infection at admission. In multivariate analysis, only sepsis and CRP of 3 mg/mL or higher were still associated with an infection; PCT levels do not show any significant association in the multivariate analysis. In addition, when PCT had good specificity (94%), it had low sensitivity (24%). False-negative PCT was related to lower severity of infection (lower inflammatory reaction and lower acute renal failure) than true-positive PCT. This finding may also be related to aging per se. CONCLUSION: PCT may be useful to identify severely ill elderly patients admitted to an acute geriatric ward but not to discriminate patients with infection from those without.

Aged↗

Cortical microinfarcts and demyelination significantly affect cognition in brain aging.

BACKGROUND AND PURPOSE: Microvascular lesions are common in brain aging, but their clinical impact is debated. Methodological problems such as the masking effect of concomitant pathologies may explain discrepancies among previous studies. To evaluate the cognitive consequences of such lesions, we prospectively investigated elderly individuals with various degrees of cognitive impairment but without significant neurofibrillary tangle pathology or macrovascular lesions. METHODS: This was a clinicopathological study of 45 elderly individuals. Cognitive status was assessed prospectively with the Clinical Dementia Rating (CDR) scale; neuropathological evaluation included Abeta-protein deposition staging and bilateral semiquantitative assessment of cortical microinfarcts, focal cortical and white matter glioses, and diffuse white matter and periventricular demyelination. RESULTS: In a univariate logistic regression model, cortical microinfarcts explained 36.1% of the variability in CDR; periventricular demyelination, 10.6%; and diffuse white matter demyelination, 4.6%. After controlling for age and Abeta-protein deposition, cortical microinfarcts were the best predictor of cognitive status (19.9% of CDR variability), whereas periventricular and diffuse white matter demyelination accounted for 9.7% and 5.4% of CDR variability, respectively. Altogether, these 3 types of microvascular lesions explained 27.9% of the clinical variability. Focal cortical and white matter glioses were not related to clinical outcome. CONCLUSIONS: Our data imply that cortical microinfarcts and both periventricular and deep white matter demyelination contribute significantly to the progression of cognitive deficits in brain aging. In contrast, the neuropathological evaluation of focal cortical and white matter gliosis has no clinical validity.

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Looking forward to a general theory on population aging.

The main theories on population aging based on recent data on human longevity, life expectancy, morbidity changes, disability trends, and mortality decrease are presented and discussed within their own geographic, cultural, socioeconomic, and medical contexts. The complex interactions between all these components do not facilitate trend forecasting of aging population (healthy aging versus disability pandemic). In the context of population aging, four elements were introduced with their implications: 1) an increase in the survival rates of sick persons, which would explain the expansion of morbidity, 2) a control of the progression of chronic diseases, which would explain a subtle equilibrium between the decrease in mortality and the increase in disability, 3) an improvement of the health status and health behaviors of new cohorts of elderly people, which would explain the compression of morbidity, and eventually 4) an emergence of very old and frail populations, which would explain a new expansion of morbidity. Obviously, all these elements coexist today, and future trend scenarios-expansion or compression of disability-depend on their respective weights leading to the need of elaborating "a general theory on population aging." This theory has to be based on a world harmonization of functional decline measurements and a periodic "International Aging Survey" to monitor global aging through a sample of carefully selected countries.

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Effect of a comprehensive, multidisciplinary, educational program on the use of antibiotics in a geriatric university hospital.

OBJECTIVES: To assess the effect of a comprehensive, educational antibiotic management program designed to improve antibiotic use and reduce treatment costs in elderly patients with suspected urinary or respiratory tract infection. DESIGN: Interventional cohort study with 12 cross-sectional drug utilization reviews of antibiotic use before, during, and after the multifaceted intervention. SETTING: A 304-bed university hospital for geriatric patients. PARTICIPANTS: A total of 3,383 elderly patients. INTERVENTIONS: An educational program including distribution of guidelines on the diagnosis and treatment of urinary and respiratory tract infections; lectures on geriatric infectious diseases; weekly ward rounds for patients with suspected infection; and targeted, individual counseling on diagnosis and antibiotic treatment of infections. MEASUREMENTS: Antibiotic utilization data were collected from the patients' records. Antimicrobial costs were calculated using 1998 hospital wholesale prices. RESULTS: Of 3,383 screened patients, 680 (20%) received at least one antibiotic. During the study period, the mean number of prescribed drugs per patient increased from 5.9 to 7.6 (29%; P<.001). In contrast, a reduction of 15% was observed in the proportion of patients exposed to antibiotic agents (P=.08) and a drop of 26% in the number of antibiotics administered (P<.001). This resulted in a 54% decrease in cumulative daily antibiotic costs. In 83 (75%) of 110 surveyed patients, the guidelines were correctly implemented. The intervention had no measurable negative clinical effect. CONCLUSION: A comprehensive, multifaceted educational program for treating urinary and respiratory tract infections in the elderly was a safe and practical method to change physicians' antibiotic prescribing practice and significantly reduce the consumption and costs of antibiotics in a geriatric hospital.

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