A simple score to predict survival with dementia in the general population.

BACKGROUND/AIMS: This study was designed to develop a practical risk score for predicting 5-year survival after the diagnosis of dementia. METHODS: Using the Paquid Study (prospective, population-based, long-term cohort study), we created a prognosis score with incident cases of dementia and validated it in another prospective, population-based, long-term cohort study, the Three City Study. - RESULTS: Among the 3,777 subjects enrolled in the Paquid Study, 454 incident cases of dementia were included in this study. After a 5-year follow-up period, 319 (70.3%) were deceased. The score was constructed from three independent prognostic variables (gender, age at diagnosis and number of ADL restricted). The discriminant ability of the score was good with a c index of 0.754. Sensitivity was 64.7% and specificity 76.3%. In the validation cohort, the discriminant ability of the prognostic score with c statistics was 0.700. Sensitivity was 26.3% and specificity 95.4%. CONCLUSIONS: The prognostic factors selected in the predictive model are easily assessable, so this simple score could provide helpful information for the management of dementia, particularly to identify patients with duration of the disease greater than 5 years.

Activation of the supplementary motor area during voluntary movement in man suggests it works as a supramotor area.

Measurements of cerebral blood flow in man revealed that complex voluntary movements are associated with a blood flow increase in the supplementary motor area of the brain. This increase is additional to and similar in magnitude to the Rolandic sensorimotor area activation that occurs during all kinds of movement. When subjects counted silently there was no activation of any focal cortical area in the brain; when they counted aloud there was a marked increase in activity in the supplementary motor area. These results are consistent with the hypothesis that the supplementary motor area plays a major role in the initiation and control of at least some kinds of voluntary movement in man and is, therefore, a motor center of a higher order than the primary Rolandic areas.

Early prevention at public health issue.

Alzheimer's Disease and related disorders have recently become a priority in France and two consecutive governmental plans have been undertaken in 2001-2004 and 2004-2007. The number of prevalent cases was estimated to be 850,000 in France with an incidence of 220,000 cases. Only 50% of these cases were actually diagnosed and about 32% were treated by antidementia drugs. If the incidence and the duration of the disease do not change, the number of cases will increase to 1,200,000 in 2020 and 2,100,000 cases in 2040. In absence of curative treatment, the prevention way is necessary if one wishes to control this phenomena. The development of Memory Clinics and "Centres de Mémoires de Ressources et de Recherche" in all regions in France is one of the important measures to develop primary and secondary prevention in subjects with cognitive complaints or MCI. Several factors could be the basis of this prevention 1) Vascular risk factors (High Blood Pressure, Diabetes, Obesity, Hypercholesterolemiae, Tobacco consumption) ; 2) physical exercise ; 3) Stimulating cognitive activities ; 4) Nutrition ; 5) depressive disorders and loneliness.

[Update on vascular dementias]. / Mise au point sur les démences vasculaires.

The concept of vascular dementia greatly evolved since Hachinski's description of multi-infarct dementia. Vascular dementias are reviewed with emphasis on current diagnostic criteria, elusive natural history, neuroradiological aspects, difficult epidemiological features and intriguing links with Alzheimer's disease. The recent proposed shift from vascular dementias to a broader definition of "vascular cognitive disorders", including non demented subjects with "vascular cognitive impairment", is described, followed by a brief review of current treatments.

Atrial fibrillation is a major cause of stroke in apneic patients: a prospective study.

OBJECTIVES: Large prospective studies have established that sleep-disordered breathing (SDB) is associated with an increased incidence of cardiovascular and cerebrovascular diseases. Heterogeneous results have been published about SDB and ischaemic stroke mechanism. The aim of this study was to evaluate the relationship between poststroke apneic syndrome and stroke aetiologies according to the ASCO classification. METHODS: A total of 134 patients with acute ischaemic cerebrovascular events were prospectively included. Patients with severe or infratentorial infarctions were excluded. Stroke risk factors and clinical characteristics were recorded in all patients. An overnight polygraphy was recorded (Embletta PDS). Apneic patients were defined if the polygraphy reported an apnea-hypopnea index ≥15. A standardized diagnosis workup, including serum biological investigation, evaluation of extra and intracranial arteries and heart morphology and function, was performed. Stroke mechanism was defined using ASCO and TOAST classifications. RESULTS: A proportion of 42% (56 of 134) of the patients were diagnosed as having sleep apneas. Apneic patients were older (p < 0.001), had higher BMI (p = 0.02), and more were hypertensive (p < 0.001). Using ASCO classification, a major cardioembolic source of stroke, mainly atrial fibrillation, was more frequently observed in apneic patients (41.1% vs. 20.5%, p < 0.05), while no difference was observed when considering atherosclerosis or small-vessel disease mechanisms. Univariate analysis showed that cardioembolic stroke depends on sex, age, left atrial size and OSA; however, age remained the only significant factor in multivariate analysis. CONCLUSION: This study confirms the high prevalence of sleep apneas in stroke-affected patients and identifies atrial fibrillation as a major source of stroke in this population. The strong correlation between age and SDB seems to drive the increased frequency of stroke related to atrial fibrillation in this population.

[Stroke-like presentation of cerebral lymphoma]. / Lymphome cérébral primitif à présentation pseudovasculaire.

INTRODUCTION: The clinical presentation of primary cerebral lymphoma can take on many forms. CASE REPORT: We report the case of a patient who experienced recurrent neurological events mimicking stroke with normal brain MRI. A late performed MRI showed a mesencephalic lesion. A biopsy was obtained and led to the diagnosis of primary B cell lymphoma. CONCLUSION: This observation illustrates the diagnostic challenge of this rare disorder with a poor prognosis.

Magnetisation transfer parameters and stroke outcome.

Our aim was to evaluate the association between magnetisation transfer imaging (MTI) parameters measured 30 to 45 days after a cerebrovascular insult and post-stroke functional outcome at the same time. MTI offers the opportunity to depict subtle microstructural changes in infarcted areas. The clinical significance of the heterogeneity of brain damage within ischaemic stroke lesions is unknown. We prospectively included 58 patients with acute middle cerebral artery stroke. Diffusion-weighted imaging was performed within 12 hours after onset and the final infarct was documented by MRI with fluid-attenuated inversion recovery (FLAIR) and MTI at 30 to 45 days follow-up. We evaluated the association between MTI histogram parameters and the clinical outcome assessed by dichotomised (threshold >2) modified rankin scale (mRS) using multivariable logistic regression models adjusted on baseline characteristics. In multivariable analyses, stroke outcome was mostly driven by initial National Institutes of Health Stroke Scale (odds ratio [OR]=1.23; 95% confidence interval [CI]=1.07-1.41; p<0.01) while after adjustment of initial stroke severity magnetisation transfer ratio peak position was the only MRI parameter associated with functional status at 30 to 45 days post-stroke (OR=0.86; 95% CI=0.75-0.98; p=0.02); lower peak position values associated with higher mRS. Conversely, stroke volume measured on FLAIR sequence was not associated with stroke prognosis (p=0.87). The intensity of microstructural changes within the infarct core measured at 30 to 45 days follow-up is independently associated with the functional status evaluated at the same time. MTI and related parameters could be used as surrogate markers of treatment response in stroke clinical trials.

Reliability of clinical criteria for the diagnosis of dementia. A longitudinal multicenter study.

The reliability of the clinical diagnosis of dementia was estimated by comparing the diagnosis made at 1-year intervals on 55 consecutive subjects with suspected cognitive impairment seen at three different centers by neurologists and gerontologists. The diagnosis was based on history and clinical examination, the criteria of the Diagnostic and Statistical Manual of Mental Disorders (revised ed 3), the Modified Ischemic Score, and a computed tomographic scan. Fifty-two of 55 subjects were given the same diagnosis a year later indicating a reliability of 95%. The study shows that a diagnosis of dementia established by simple clinical criteria comparable to the NINCDS/ADRDA criteria affords sufficient reliability to allow the comparability of groups at different centers for purposes of research, including research on the evaluation of the efficacy of pharmacologic treatment.

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.

Marital status and risk of Alzheimer's disease: a French population-based cohort study.

OBJECTIVE: To analyze the relationship between marital status and risk of AD or dementia. METHODS: This study was carried out from the Personnes Agées QUID (PAQUID) cohort, an epidemiologic study on normal and pathologic aging after age 65 years. The PAQUID cohort began in 1988. Individuals were followed up at 1, 3, and 5 years, with an active detection of dementia. Marital status was divided into four categories: widowed, never married, divorced or separated, and the reference category, married or cohabitant. The longitudinal relationship between marital status and risk of incident AD or dementia was analyzed by a Cox model with delayed entry. RESULTS: Among the 3,675 individuals initially not demented, 2,106 were married or cohabitants, 1,287 were widowers, 179 were never married, and 103 were divorced or separated. Among the 2,881 individuals reevaluated at least once for the risk of dementia during the 5-year follow-up, 190 incident cases of dementia were identified, including 140 with AD. The relative risks (RRs) of dementia (RR = 1.91, p = 0.018) and of AD (RR = 2.68, p<0.001) were increased for the never-married individuals compared with those who were married or cohabitants. This excess of risk was specifically associated with AD. Adjustment for other risk factors of dementia (education, wine consumption), or for factors reflecting social environment, leisure activities, and depression, did not modify the risk of AD for never-married individuals (RR = 2.31, p = 0.02). CONCLUSIONS: We confirmed an association between marital status and AD, with an excess risk observed among never-married individuals. This association may provide clues about the pathogenesis of AD.

Occupation during life and memory performance in nondemented French elderly community residents.

Using data obtained during the baseline screening of the PAQUID cohort, an epidemiologic study on brain aging conducted in the Bordeaux area of France, we studied the relationship between lifetime occupation and memory performance in visual recognition (Benton Visual Retention Test; BVRT) and verbal induced recall (Wechsler Paired Associates Test; WPAT) in 2,720 elderly community residents. Occupational category was strongly correlated with poor memory performance for both the BVRT and the WPAT. Independent of the educational level, the risk of having poor memory performance was two to three times greater for farmers, domestic service employees, and blue-collar workers than for professionals/managerials. Occupational category should be taken into account in future cross-national studies on brain aging.

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.

Vascular dementia: diagnostic criteria for research studies. Report of the NINDS-AIREN International Workshop.

Criteria for the diagnosis of vascular dementia (VaD) that are reliable, valid, and readily applicable in a variety of settings are urgently needed for both clinical and research purposes. To address this need, the Neuroepidemiology Branch of the National Institute of Neurological Disorders and Stroke (NINDS) convened an International Workshop with support from the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN), resulting in research criteria for the diagnosis of VaD. Compared with other current criteria, these guidelines emphasize (1) the heterogeneity of vascular dementia syndromes and pathologic subtypes including ischemic and hemorrhagic strokes, cerebral hypoxic-ischemic events, and senile leukoencephalopathic lesions; (2) the variability in clinical course, which may be static, remitting, or progressive; (3) specific clinical findings early in the course (eg, gait disorder, incontinence, or mood and personality changes) that support a vascular rather than a degenerative cause; (4) the need to establish a temporal relationship between stroke and dementia onset for a secure diagnosis; (5) the importance of brain imaging to support clinical findings; (6) the value of neuropsychological testing to document impairments in multiple cognitive domains; and (7) a protocol for neuropathologic evaluations and correlative studies of clinical, radiologic, and neuropsychological features. These criteria are intended as a guide for case definition in neuroepidemiologic studies, stratified by levels of certainty (definite, probable, and possible). They await testing and validation and will be revised as more information becomes available.

Identification and characterization of anti-conjugated azelaic acid antibodies in multiple sclerosis.

Human sera from patients with multiple sclerosis (MS) were tested using an enzyme-linked immunosorbent assay (ELISA) method on well plates coated with various dicarboxylic acid (C4 to C10) protein conjugates. Specific immunological binding was found with an azelaic acid (AzeA, C9) conjugate. The antibody titer was higher in the sera from the patients in acute relapse than with the progressive form, and higher than that from sera of patients with other neurological diseases and healthy subjects. Modifications of coating concentrations and of antibody dilutions, and experiments with preadsorption enabled determination of binding specificity. Competition experiments with related conjugates demonstrated that the AzeA residue was 167 times better recognized by antibodies from MS patients in acute relapse than those from controls. The suberic and sebasic acid conjugates which only differ from the AzeA conjugate by one methylene group were less well-recognized by MS sera (11 and 47 times, respectively) than the conjugate AzeA-BSA.

Tobacco consumption and cognitive impairment in elderly people. A population-based study.

We examined the relationship between tobacco consumption and Alzheimer's disease (AD), cognitive deficit, and memory performances in elderly community residents of southwestern France. Subjects were considered to have a cognitive deficit if they scored under 24 on the French version of the Mini-Mental State Examination, and poor memory performances if they scored under 8 on the Benton Visual Retention Test. Among the 3770 subjects who gave information about their smoking habits, only 356 (9.5%) were current smokers, 998 (26.5%) were past smokers, and 2416 (64%) were never smokers. Current smokers (odds ratio (OR) = 0.52, P < 0.001) and past smokers (OR = 0.54, P < 0.001) had a lower risk of cognitive deficit than did never smokers. However, this significant relationship disappeared after adjustment for potential confounding factors such as occupational category (OR = 0.91 (not significant) for current smokers and OR = 0.87 (not significant) for past smokers). Similar results were obtained for the risk of AD and of poor memory performances. The apparent protective effect of smoking habits on cognitive abilities could be due to a confounding effect of occupational category.

Anti-acetylcholine antibodies and the pathogenesis of myasthenia gravis.

Using an ELISA system, antibodies recognizing conjugated acetylcholine (ACh) were detected in sera of patients suffering from myasthenia gravis. The mean antibody level was three times higher in sera from myasthenic than from control patients. No correlation was found between anti-ACh antibody levels and anti-ACh receptor (AChR) titer. Also, the anti-ACh antibody titers were independent of sex and age of patients. Competition experiments demonstrated that the most immunoreactive compounds were choline-glutaryl-bovine serum albumin (BSA) and choline-succinyl-BSA. Antibodies present in the sera of myasthenic patients recognized an antigenic determinant mimicking conjugated ACh. The antibody affinity and specificity were sufficiently high for the detection of ACh in locust brain.

Detection of anti-acetylcholine antibodies in myasthenic patients.

Antibodies, directed against an acetylcholine (ACh) conjugate, were found in the sera of myasthenic patients by using a modified enzyme-linked immunosorbent assay method. Binding of sera from control patients to the conjugate was extremely low. From competition experiments, done with compounds close to ACh, a good antibody specificity for the ACh conjugate was demonstrated in the sera of myasthenic patients. Laboratory tests will be done to help a more precise diagnostic of the disease to be given. These results may also be of value in further understanding of the process of the disease itself.

Natural seric anti-fatty acid antibodies in multiple sclerosis.

Naturally occurring anti-oleic acid conjugate antibodies were detected in human sera using an adapted direct immunoenzymatic assay. They were present to a higher level in the sera of patients with multiple sclerosis in acute relapse compared to patients with other neurological diseases or healthy subjects and even patients with multiple sclerosis in progressive form.

Effects of galantamine in patients with mild Alzheimer's disease.

BACKGROUND: Galantamine is an acetylcholinesterase inhibitor that modulates nicotinic receptors. It is effective in mild to moderate Alzheimer's disease (AD) but no trial has focused exclusively on mild AD. We performed a post-hoc sub-set analysis using data from four randomised trials to explore the efficacy of galantamine versus placebo in mild AD. METHODS: Participants in all studies met NINCDS-ADRDA criteria for probable AD. We examined data from patients with baseline Mini Mental State Examination (MMSE) 21-24 who received galantamine 24 mg/day (GAL) or placebo (PLAC). Scores for the Alzheimer's Disease Assessment Scale-cognitive subset (ADAS-cog), Clinician's Interview-Based Impression of Change (CIBIC), Disability Assessment for Dementia (DAD), and ACDS-ADL scales were compared. RESULTS: Of the 694 patients (362 GAL, 332 PLAC, mean baseline MMSE 22.4 +/- 1.1, mean age 74 +/- 7.9 years), 65% completed 6 months treatment (223 GAL, 229 PLAC). Mean change in ADAS-cog at 6 months was -1.5 (95% confidence interval -2.2, -0.8, p < 0.001) for GAL and +0.2 (-0.6, 0.9, p = 0.72) for PLAC. This difference was statistically significant (p = 0.001). Significantly more patients receiving galantamine were classified as 'improved' using the CIBIC (26.9% GAL vs 14.3% PLAC, p < 0.001). Galantamine was generally well tolerated; most common adverse events were nausea, vomiting and diarrhoea. CONCLUSIONS: Pooled data from four randomised trials of patients with mild AD indicate that patients who received galantamine 24 mg/day for 6 months improved cognition more often than those who received placebo and that a higher proportion receiving galantamine were globally improved. This suggests that patients with mild AD benefit from galantamine treatment.

Clinical consequences of corticectomies involving the supplementary motor area in man.

Three patients with well-mapped, circumscribed ablations of the medial part of the frontal lobe are reported. A specific clinical evolution in 3 stages was observed: (1) post-operatively there was global akinesia, more prominent contralaterally, with an arrest of speech; (2) recovery occurred suddenly but even then there was severe reduction of spontaneous motor activity contralaterally, an emotional type facial palsy and a reduction of spontaneous speech; (3) long after the operation the only sequela was disturbance of the alternating movements of the hands. The anatomical basis of these disorders appears to be a lesion of the supplementary motor area (SMA). Three main points have been discussed, namely: (1) the nature of the motor disorder which may be a disturbance of the function of the SMA in initiating and sustaining spontaneous and automatic motor activity; (2) the nature of the arrest of speech which appears not to be aphasic; the studies reported in the present paper do not support a left cerebral dominance for the SMA as suggested by previous studies; (3) the method of clinical examination appears to be important in distinguishing between spontaneous and voluntary motor and speech performance. Differences in method may account for differences between our findings and those reported in previous studies.