Discrepancy Between Patient and Caregiver Estimate of Apathy Predicts Dementia in Patients with Amnestic Mild Cognitive Impairment.

BACKGROUND: Apathy is a frequent behavioral symptom of Alzheimer's disease (AD). The Apathy Evaluation Scale (AES) is a tool exploring the perception of apathy by both caregivers (CG-AES) and patients (PT-AES), and the discrepancy in their ratings is a proxy of patients' disease unawareness. OBJECTIVE: To assess in a cohort study of patients with amnesic mild cognitive impairment (aMCI) whether apathy and awareness of apathy predict progression to dementia and timing. METHODS: From the global AES scores of 110 patients with aMCI and their caregivers, we obtained two principal indices for analysis: 1) 'Apathy', the mean of PT-AES and CG-AES, and 2) 'Discrepancy', obtained by subtracting CG-AES from PT-AES. Patients were followed with visits every six months for three years or until dementia. AES indices and the principal demographical/neuropsychological variables were filtered from multicollinearity. The most robust variables entered a logistic regression model and survival analyses (Cox regression, log-rank test of Kaplan-Meier curves) to estimate which predicted the risk and timing of progression, respectively. RESULTS: Sixty patients (54.5%) developed dementia (57 AD) after 6.0-36.0 months, 22 (20%) remained in an MCI stage, and 28 (25.5%) dropped out. 'Discrepancy' was a robust and accurate predictor of the risk of progression (AUC = 0.73) and, after binarization according to a computed cutoff, of timing to dementia. CONCLUSION: A structured evaluation of apathy, both self-assessed and estimated by caregivers, can provide useful information on the risk and timing of progression from aMCI to dementia. The discrepancy between the two estimates is a fairly reliable index for prediction purposes as a proxy of disease unawareness.

Accuracy of the clinical diagnosis of dementia with Lewy bodies (DLB) among the Italian Dementia Centers: a study by the Italian DLB study group (DLB-SINdem).

INTRODUCTION: Dementia with Lewy bodies (DLB) may represent a diagnostic challenge, since its clinical picture overlaps with other dementia. Two toolkits have been developed to aid the clinician to diagnose DLB: the Lewy Body Composite Risk Score (LBCRS) and the Assessment Toolkit for DLB (AT-DLB). We aim to evaluate the reliability of these two questionnaires, and their ability to enhance the interpretation of the international consensus diagnostic criteria. METHODS: LBCRS and AT-DLB were distributed to 135 Italian Neurological Centers for Cognitive Decline and Dementia (CDCDs), with the indication to administer them to all patients with dementia referred within the subsequent 3 months. We asked to subsequently apply consensus criteria for DLB diagnosis, to validate the diagnostic accuracy of the two toolkits. RESULTS: A total of 23 Centers joined the study; 1854 patients were enrolled. We found a prevalence of possible or probable DLB of 13% each (26% total), according to the consensus criteria. LBCRS toolkit showed good reliability, with a Cronbach alpha of 0.77, stable even after removing variables from the construct. AT-DLB toolkit Cronbach alpha was 0.52 and, after the subtraction of the "cognitive fluctuation" criterion, was only 0.31. Accuracy, sensitivity, and specificity were higher for LBCRS vs. AT-DLB. However, when simultaneously considered in the logistic models, AT-DLB showed a better performance (p < 0.001). Overall, the concordance between LBCRS positive and AT-DLB possible/probable was of 78.02% CONCLUSIONS: In a clinical setting, the LBCRS and AT-DLB questionnaires have good accuracy for DLB diagnosis.

Atherosclerosis in women with endometriosis.

OBJECTIVE: This study aims to determine whether women with endometriosis have greater subclinical atherosclerosis than the general population. STUDY DESIGN: This case-control study included 66 women with endometriosis and 66 controls matched for age and body mass index. All subjects were >or=35 years old. Exclusion criteria were obesity, diabetes, hypertension, hyperlipidemia, renal or metabolic diseases. Before laparoscopy, all patients underwent a measurement of intima-media thickness (IMT) and distensibility coefficient (DC) on the common carotid artery. In addition, blood samples were taken to determine the levels of lipids, fibrinogen, C-reactive protein, homocysteine, fasting glycemia, antithrombin III, plasminogen, protein C, protein S, and activated protein C resistance. RESULTS: All the biochemical parameters evaluated had similar levels in the two study groups. IMT was similar in women with endometriosis and in controls both on left (p=0.330) and right (p=0.648) carotid artery. Similarly, no significant difference was observed in the DC between women with endometriosis and controls both on left (p=0.539) and right (p=0.178) carotid artery. No significant difference was observed in IMT and DC between women with mild and severe endometriosis. CONCLUSION: Women with endometriosis do not have more subclinical atherosclerosis than the general population.

Fetal risks related to the treatment of multiple sclerosis during pregnancy and breastfeeding.

In women with multiple sclerosis, pregnancy does not have a long-term adverse effect on lifetime disability; however, there is an increased risk of relapses during the postpartum. Therapies taken during pregnancy may have adverse effects on pregnancy outcome. The small number of pregnancies included in most studies, particularly those evaluating the risks related to the administration of immunomodulating drugs, do not allow firm conclusions to be drawn with regards to their safety. Therefore, until more information regarding safety is available, glatiramer acetate, mitoxantrone and interferon-beta should be discontinued before an anticipated pregnancy. By contrast, glucocorticoids can be used to treat acute relapses during pregnancy.

Myasthenia gravis: management issues during pregnancy.

Myasthenia gravis (MG) often affects women in the second and third decades of life, overlapping with the childbearing years. The course of the disease is unpredictable during pregnancy; however, worsening of symptoms occurs more likely during the first trimester and postpartum. MG can be well managed during pregnancy with relatively safe and effective therapies. Anticholinesterase drugs are the mainstay of treatment, when MG symptoms are not satisfactorily controlled, corticosteroids, azathioprine and in some cases cyclosporin A can be used. Until information is available regarding safety, mycophenolate mofetil should be discontinued before pregnancy. Pregnancy should be avoided in women treated with methotrexate because of the risk of causing typical malformations. Plasmapheresis and intravenous immunoglobulins have been successfully used in the treatment of MG crisis during pregnancy. Caesarean section is recommended only for obstetric reasons; forceps delivery and vacuum extraction are sometimes required. Epidural anesthesia is advised to reduce physical and emotional stress. MG during pregnancy can lead to serious life-threatening conditions, including respiratory insufficiency; therefore, intensive checkups by a gynaecologist and a neurologist are necessary. Women with myasthenia gravis should not be discouraged from conceiving; however, they should discuss their plan for pregnancy with their neurologist and their gynaecologist.

Multiple sclerosis: management issues during pregnancy.

Care of pregnant women with multiple sclerosis (MS) is challenging because of the multiple physiological changes associated with pregnancy and the need to consider the impact of any intervention on the foetus. Pregnancy is associated with clinical MS stability or improvement, while the rate of relapse rises significantly during the first three months post-partum before coming back to its level prior to pregnancy. Gestational history has no influence on long-term disability and MS does not seem to influence pregnancy or the child's health. Apart from methotrexate and cyclophosphamide, most drugs used regularly to treat MS can safely be used by pregnant women. Intravenous steroids may be used with relative safety during pregnancy. Maternal use of azathioprine is not associated with an increased risk of congenital malformations, though impaired foetal immunity, intrauterine growth retardation and prematurity are occasionally observed. Cyclosporin is not teratogenic, but may be associated with growth retardation and prematurity. Pregnancy should be avoided in women treated with methotrexate because of its known abortifacient effects and risk of causing typical malformations. Cyclophosphamide is teratogenic in animals, but population studies have not conclusively demonstrated its teratogenicity in humans. Until information is available regarding safety, glatiramer acetate, mitoxantrone, interferon-beta-1a and interferon-beta-1b should be discontinued before an anticipated pregnancy. Women with MS are no more likely to experience delivery complications than are women without MS and the mode of delivery should be decided strictly on obstetrical criteria. Spinal, epidural and general anaesthesia can all be used safely in MS patients. Young women with MS who desire children can be reassured that their infants are not at increased risk of malformations, preterm delivery, low birth weight, or infant death. The progressive nature of the disease may motivate affected women to start or complete their families as soon as possible.