Persistent apathy in Alzheimer's disease as an independent factor of rapid functional decline: the REAL longitudinal cohort study.

OBJECTIVE: To determine the role of persistent apathy in rapid loss of autonomy in Instrumental Activities of Daily Living (IADL) in women with Alzheimer s disease (AD), taking into account the grade of cognitive decline. METHODS: The study was conducted on 272 women from the French REAL cohort. At inclusion patients had a Mini-Mental State Examination (MMSE) score between 10-26. A rapid functional decline was defined as a yearly drop of 4 points or more on the 14-point IADL Lawton scale. Persistent apathy was defined as a frequency score equal to 3 or 4 on the Neuro-Psychiatric Inventory at the three consecutive 6-monthly assessments. RESULTS: 27.6% of women had rapid functional decline in 1 year and 22.1% of them had persistent apathy. A logistic regression analysis showed that, in addition to cognitive decline, persistent apathy plays a role in rapid functional decline in 1 year. For example, for a 3-point decline in MMSE in 1 year, the probability of a rapid loss in IADL is 0.45 for women with persistent apathy compared with 0.28 for those without persistent apathy. CONCLUSIONS: In this study, a rapid loss in IADL score was partly explained by persistent apathy.

Predictive factors of rate of loss of autonomy in Alzheimer's disease patients. A prospective study of the REAL.FR Cohort.

Alzheimer's disease is characterised by a progressive loss of autonomy in activities of daily living. Many patients lose this autonomy rapidly with dramatic consequences for the patients and their relatives, and for health and social services. The aim of this study was to determine, in a large French cohort of community-living Alzheimer patients (REAL.FR), the factors underpinning different rates of loss of autonomy. Six hundred and eighty seven patients were recruited to this French cohort. Autonomy in activities of daily living was estimated with the IADL scale (Lawton). Patients were divided into three groups according to loss of autonomy during the first one-year follow-up period. Patients with a decrease in the IADL score had worse ADAS-cog score (Alzheimer's Disease Assessment Scale, cognitive subscale), Mini-Mental State Examination (MMSE), and Clinical Dementia Rating Scale scores. Up to a point, a marked decrease in the IADL score was less frequent among patients with a better ADAS-cog score (p < 0.10, bilateral test). At one-year evaluation, patients with a marked decline in autonomy were characterised by a greater decrease in Mini-Mental State score, faster progression of behavioural disturbance, and more hospitalisations. Further prospective studies, using established models, are needed to isolate the factors associated with a high rate of loss of autonomy in activities of daily living in Alzheimer patients.

Role of behavioural disturbance in the loss of autonomy for activities of daily living in Alzheimer patients.

BACKGROUND: Cognitive impairment is associated with functional impairment in patients with Alzheimer's disease (AD). Behavioural disturbance is very common in these patients. Nevertheless, there has been very little research into the relations between behavioural disturbance and functional status in AD. The purpose of this study is to investigate the relationship between behavioural disturbance and functional status after taking account of cognitive impairment. MATERIAL AND METHODS: 579 patients were prospectively evaluated at 16 French hospitals, all referents for AD, and were diagnosed with possible or probable AD. These patients were assessed with NeuroPsychiatric Inventory (NPI), cognitive subscales of the Alzheimer's Disease Assessment Scale (ADAS-cog), Clinical Dementia Rating scale (CDR) and Instrumental Activities of Daily Living scale (IADL). RESULTS: The number of men with available data for IADL total score was too small to make any analysis. 'Group A' gathered 256 women for whom the relation between autonomy for Activities of Daily Living (ADL) and the other variables were determined. 'Group B', pooled 85 women for whom relations found were verified. Linear regression was used for the analysis. With age, cognitive impairment allows us to explain best (38%) the loss of autonomy for ADL. CONCLUSION: The role of behavioural disturbances in the loss of autonomy for ADL was not determinant in our study, whereas cognitive impairment and age were better able to determine the loss of autonomy for ADL. Further study is needed to explain the decline of functional status in AD patients.

[Clinical features of ambulatory patients over 80 years of age followed for Alzheimer's disease. French prospective multicenter study REAL.FR]. / Caractéristiques cliniques des patients ambulatoires âgés de plus de 80 ans suivis pour une maladie d'Alzheimer. Etude française multicentrique prospective REAL.FR.

PURPOSE: Twice out off three, patients with Alzheimer's disease (AD) are aged 80 and older. Very old patients are more frail, have social precariousness and have often polypathology. Few data are available about these elderly patients. The aim of our study was to analyse characteristics of AD patients aged 80 and older. MATERIAL AND METHODS: This is a prospective, multicentric French study (REAL.FR) of a cohort of ambulatory AD patients, with Mini-Mental State values between 10 and 26. Clinical and social data at inclusion of patients aged 80 and older and patients younger were compared. RESULTS: Six hundred eighty nine patients (488 women, 201 men) were included between April 2000 and June 2002. The mean age was 77.8 +/- 6.9 years. Two hundred sixty four patients (38%) were aged 80 and older. Those patients were more dependant for Activities of Daily Living (ADL) than younger patients (ADL score of Katz: 5.2 +/- 1.07 et 5.6 +/- 0.74 respectively; p < 0.001 and IADL (Instrumental Activities of Daily Living) score of Lawton: 7.3 +/- 3.57 et 9.3 +/- 1.57 respectively; p < 0.001). Duration of evolution of the disease were comparable between older and younger patients. CONCLUSION: In our cohort, AD patients aged 80 and older had a weakest autonomy for the ADL than younger patients with the same stage of the disease. Results has implications on care. Following the cohort will permit to specify evolution of data.

[Behavioral and psychologic symptoms in Alzheimer's disease: results of the REAL.FR study]. / Symptômes comportementaux et psychologiques dans la maladie d'Alzheimer: résultats de l'étude REAL.FR.

Behavioral and Psychological Signs and Symptoms of Dementia (BPSD) are important manifestations of Alzheimer's Disease (AD) and other forms of dementia, because they are associate with care-giver distress, increase the likelihood of institutionalization, and may be associated with more rapid cognitive decline In this study (REAL.FR for Réseau sur la maladie d'Alzheimer Français) we prospectively used the Neuropsychiatric Inventory NPI to examine BPSD. 255 AD patients with a Mini-Mental State Examination (MMSE) score between 11 and 20 and 244 AD patients with a MMSE between 21 and 30 were examined. Factor analysis was carried out leading to three different syndromes according to the level of cognitive impairment. BPSD were detected in 92.5% of the patients with a MMSE between 11 and 20, and in 84% of the patients with a MMSE between 21 and 30. Apathy was the most common abnormality, followed by anxiety and dysphoria. These results in a French cohort of patients with AD underline the importance of the evaluation and finally of the treatment of BPSD.

[Determination of regimen fluindione needed for anticoagulation in the elderly]. / Schéma simple d'adaptation posologique de la fluindione chez les patients âgés.

INTRODUCTION: There is no validated method to predict the daily maintenance dosage of oral anticoagulation treatment by fluindione in the elderly patients. The aim of our prospective study was to look for a relation between INR at day 2 after a fixed dosage of fluindione and the daily maintenance dosage of fluindione necessary to obtain an INR value between 2 and 3. PATIENTS AND METHODS: Ten milligrams of fluindione were administered on first and second day of treatment. INR was determined the third day. RESULTS: From this value, we were able to determine the daily dosage of fluindione (+/- 5mg) that maintained a steady state INR value between 2 and 3. CONCLUSION: In these very elderly patients, there was a relation between INR at the third day after a fixed dosage of fluindione and the daily maintenance dosage of fluindione necessary to obtain an INR value between 2 and 3.

Ideomotor apraxia test: a new test of imitation of gestures for elderly people.

Ideomotor apraxia is one of the earliest disturbances in Alzheimer's disease (AD); no test of this disturbance has yet been validated for elderly people. We propose a test of meaningless gesture imitation and its relevance in elderly people is studied. The Ideomotor Apraxia Test (IAT) consists of showing 10 gestures. Each item is graded from 0 to 3. IAT was carried out on 55 patients with AD (mean age: 86.8 +/- 6.8 (71-100); mean MMS score: 14.6 +/- 6.3) and 26 elderly patients without cognitive impairment (mean age: 84.1 +/- 7.5 (70-100); mean MMS score: 27.5 +/- 1.9). The inter-rater reliability, a threshold, the apparent sensitivity and specificity and the relationship between the MMS score and the ideomotor apraxia score were determined. The mean apraxia score was 14.9 +/- 7.3 in the AD group and 28 +/- 1.6 in the normal group (P < 0.0001). Inter-rater agreement is excellent (P = 0.995). The threshold is 27. The apparent sensitivity and specificity are very good (95% and 88%, respectively). The correlation between the MMS score and ideomotor apraxia score is excellent (r = 0.83 (95% CI; 0.72-0.91). Age and educational level do not influence ideomotor apraxia score. IAT is the first test that evaluates meaningless gesture imitating capacity in an elderly population. It is an easy and quick-to-perform test, useful routinely for diagnosis of AD. It could contribute to the early diagnosis of AD and is correlated with the severity of cognitive impairment. Copyright 1998 Lippincott Williams & Wilkins

[Reference intervals and biological profile in a group of healthy elderly population in the Paris region]. / Intervalles de référence et profil biologique d'une population de sujets âgés "en bonne santé" habitant la région parisienne. (Group d'évaluation et de recherche des biologistes de l'APHP).

The superimposition of pathological processes on ageing-related metabolic changes makes the interpretation of laboratory data difficult in the elderly. Therefore, in order to establish reference values of anthropometric, hematological and biochemical variables, we have carefully selected fit, health-conscious elderly subjects on the basis of clinical and biological criteria. We observed a trend for a wider range of values than in young adults. For some variables, the values were shifted down (eg: albumin, vitamin D) or up (eg: glucose, urea, cholesterol, ferritin), as a result of slow metabolic changes or progressive functional decline of different organs. The high prevalence of hypovitaminosis D was worthy of note, particularly in women, suggesting a high risk of deficiency.

Detection of cerebrovascular disease in patients with sickle cell disease using transcranial Doppler sonography: correlation with MRI, MRA and conventional angiography.

A prospective study of 58 patients with sickle cell disease (SCD) by transcranial Doppler sonography (TCD) included both MRI and MRA in patients over 7 years of age and those with abnormal TCD. Arteriography was performed in cases where a stenosis was suspected on TCD. Middle cerebral artery (MCA) and basilar artery (BA) velocities were significantly higher in the sickle cell hemoglobin SS group than in the hemoglobin SC group. Patients with a MCA mean velocity of over 1.90 m/s had stenoses found by arteriography. Patients with unilaterally undetectable MCA flow had experienced a stroke and MCA thrombosis was confirmed at MRA and arteriography. We concluded that TCD is valuable in detecting arterial stenosis in SCD and will lead to consideration of these patients for intensive therapy, such as bone marrow transplantation (BMT) or transfusion regimes.

[The effect of human albumin in association with intensive phototherapy in the management of neonatal jaundice]. / Etude de l'action de l'albumine humaine sur l'ictère néonatal en association avec la photothérapie intensive.

BACKGROUND: The effectiveness of phototherapy in lowering serum bilirubin levels in neonates varies inversely with the rate and degree of hemolysis. Combining this therapy with albumin perfusion could enhance its effectiveness. This study examines total, unconjugated and unbound fractions of bilirubin in infants treated by phototherapy alone or by phototherapy plus albumin. PATIENTS AND METHODS: The files of 211 neonates treated from January 1990 to March 1991 for severe neonatal jaundice were analysed. Jaundice was due to ABO incompatibility in 113 cases and hereditary hemolytic anemia in 6 cases; its cause was unknown in 92 patients. Other causes of jaundice such as Rh incompatibility, premature delivery before 34 gestational weeks and neonatal infections were excluded from the study. All 211 neonates were given phototherapy from admission with similar light energy. 114 babies (group I) received only phototherapy, while the 97 others (group II) were also given human albumin, (1.5 g/kg), during the first 2 hours of phototherapy. RESULTS: The decrease in serum unconjugated and unbound bilirubin after 4 hours of phototherapy was 34% in group I and 45% in group II (p < 0.0005). There was no difference between both groups after 24 hours of phototherapy. Other factors such as the initial concentration of serum unconjugated and unbound bilirubin, age at the onset of therapy, and ethnic skin color also influenced the decrease in bilirubin after 4 and 24 hours of phototherapy, in addition to albumin perfusion. CONCLUSIONS: Albumin perfusion plus phototherapy appears to induce a rapid and early decrease in unconjugated, unbound bilirubin, the fraction that is potentially neurotoxic, while phototherapy alone acts over a longer period.

Cholesterol as risk factor for mortality in elderly women.

92 women aged 60 years and over (mean 82.2, SD 8.6) living in a nursing home and free from overt cancer were followed-up for 5 years. 53 died during this period; necropsy revealed cancer in only 1 patient. Serum total cholesterol at entry ranged from 4.0 to 8.8 mmol/l (mean 6.3, SD 1.1). Cox's proportional hazards analysis showed a J-shaped relation between serum cholesterol and mortality. Mortality was lowest at serum cholesterol 7.0 mmol/l, 5.2 times higher than the minimum at serum cholesterol 4.0 mmol/l, and only 1.8 times higher when cholesterol concentration was 8.8 mmol/l. This relation held true irrespective of age, even when blood pressure, body weight, history of myocardial infarction, creatinine clearance, and plasma proteins were taken into account. The relation between low cholesterol values and increased mortality was independent of the incidence of cancer.

Maternal-fetal transfer of fluoride in pregnant women.

Gas chromatography was used to measure the maternal and fetal plasma inorganic fluoride values at term in 91 women. They were assigned to one of four groups: group A were untreated controls; group B received a single daily dose of 1.5 mg of fluoride (as calcium fluoride) during the final trimester of pregnancy; group C was given a single dose of 1.5 mg of fluoride (as sodium fluoride) and group D was given 2 daily doses of fluoride (as sodium fluoride) totaling 1.5 mg. There was a significant difference between the cord plasma fluoride levels of the newborns in the untreated group (mean: 27.8 micrograms/l) and that of the combined supplemented groups B, C and D (mean: 58.3 micrograms/l). There was no difference between the average fluoride levels in the three supplemented groups. There was no significant effect of maternal age, infant birth weight, gestation or diet during pregnancy on the cord plasma fluoride level. These results indicate that fluoride supplementation during the final trimester of pregnancy will significantly elevate cord plasma fluoride concentrations.

[Preliminary study on transplacental transfer of fluoride. Apropos of 41 mother-infant couples]. / Etude préliminaire sur le passage transplacentaire du fluor. A propos de 41 couples mère-enfant.

Comparing the levels of ionised fluoride in the serum of maternal blood at the time of delivery and cord blood shows that there is a good correlation between the two levels (r = 0.66). This makes it possible to say that fluoride is transferred easily across the placenta. The transfer is not influenced by the parity of the age of the mother nor by epidural anaesthesia, nor by the Apgar score. It does, however, correlate with the duration of the pregnancy.

[EEG mapping during a visuo-spatial task. Averaged maps and group statistics]. / Cartographie EEG au cours d'une tache visuo-spatiale. Cartes moyennes et statistiques de groupes.

Twenty young volunteers (10 men, 10 women), righthanded, students, have been recorded in EEG cartography in different situations. We have compared the quantified EEGs when the subjects were resting, eyes closed and later, eyes opened, looking at a cartoon. The EEGs were quantified by spectral Fourier analysis and submitted to data reduction. Ten spectral parameters were computed, yielding 51 variables allowing computations and drawings of 90 EEG maps. Mean parameters, mean variables, averaged EEG maps have been computed for the entire group, between sub-groups, between hemispheres. Non-parametric permutation Fisher tests have been applied for statistical comparisons and statistical validations of the EEG maps computed between subjects. The activation of EEG tracings produced by the opening of the eyes were caracterized topographically by: mean alpha frequencies increased over temporal and rolandic areas; mean alpha amplitudes in microV divided by a factor 3 for occipital areas but unchanged in topography; mean relative amplitudes divided by a factor 2 but with a topography being more parietal than occipital for the alpha rhythm; a resonance coefficient greater over the left parietal than the right (alpha more regular), whereas it was greater over the right occipital than the left during the resting condition. Statistically for the whole group, the left hemisphere, recorded after the right, is more 'activated' in the eyes closed situation. During visual attention, the left hemisphere is less activated than the right.

Electroencephalographic cartography. II. By means of statistical group studies-activation by visual attention.

10 male volunteers, right-handers, mean age 30.4 years, were recorded in four successive sequences: under 'eyes closed' conditions, right and then left hemisphere, followed by an 'eyes open' situation with visual attention fixed on a cartoon, right and then left hemisphere recordings. Each EEG recording was made simultaneously over 16 EEG channels for each hemisphere, according to a protocol previously described as well as Fourier analysis and EEG mapping on a minicomputer (HP 5451 C, HP 1000). Each EEG recording was stored on a cartography data base, and 90 maps could be drawn from 10 spectral parameters applied to the raw EEG and 5 frequency bands. Permutation paired Fisher tests were applied to three main EEG parameters: mean centroid frequencies, RMS amplitudes in microvolts and relative (%) amplitudes. Activation of EEG in the 'eyes open' situation during visual fixation was found compared to the 'eyes closed' situation: decreasing dominant EEG frequency and low delta and theta mean frequencies, no change in a mean alpha frequency; increasing fast mean beta frequencies, together with a major decrease in theta, alpha, beta 1 amplitudes, and a concomitant increase in raw EEG, delta and beta 2 amplitudes. Finally, the percent alpha amplitude was decreased when other percent amplitudes were increased in delta, theta, beta 1 and beta 2 frequency bands. A symmetry between hemispheres was observed in the 'eyes closed' situation. Averaged EEG maps between subjects illustrate these findings, especially relative (%) alpha amplitude maps and also maps of coefficients of resonance of the alpha rhythm.

Computerized topo-EEG spectral maps: difficulties and perspectives.

An electric potential measurement tells us only about the difference between two electrode locations. When prior experiments or present measurements prove that an electrode's location is inactive (especially in 'mono-polar' or scalp-to-reference technique), then EEG records and EEG maps can be interpreted regionally near each electrode location. Topographical mapping requires spatial interpolation which is one factor involved in spatial resolution. The interpolation algorithm has been studied by changing the power exponent n of the interelectrode distance d. When n is close to zero, interpolated values are all equal to the average of the four electric potential measurement Vs bounding the quadrilateral in which the interpolated points of the EEG map are located. When n is very high (n = 20 or higher), the values are essentially equal to the V which is at the minimum distance d. For n = 1, the map seems unlikely to represent the true scalp field. The choice between n = 2 and n = 3 is difficult, but n = 3 EEG mapping looks better (more plausible) and is our regular choice. The choice of recording/reporting method has also been studied. If the quantitative EEG map is linearly calculated from observations, the interpretation of record activity resulting from charge separation near the non-reference electrode attached to a particular channel is only possible when inactivity can be assured. This is completely different when the quantity mapped is not linearly calculated from observations (like power values or rms amplitudes in microvolts).(ABSTRACT TRUNCATED AT 250 WORDS)