Anosognosia in mild cognitive impairment: Relationship to activation of cortical midline structures involved in self-appraisal.

Awareness of cognitive dysfunction shown by individuals with Mild Cognitive Impairment (MCI), a condition conferring risk for Alzheimer's disease (AD), is variable. Anosognosia, or unawareness of loss of function, is beginning to be recognized as an important clinical symptom of MCI. However, little is known about the brain substrates underlying this symptom. We hypothesized that MCI participants' activation of cortical midline structures (CMS) during self-appraisal would covary with level of insight into cognitive difficulties (indexed by a discrepancy score between patient and informant ratings of cognitive decline in each MCI participant). To address this hypothesis, we first compared 16 MCI participants and 16 age-matched controls, examining brain regions showing conjoint or differential BOLD response during self-appraisal. Second, we used regression to investigate the relationship between awareness of deficit in MCI and BOLD activity during self-appraisal, controlling for extent of memory impairment. Between-group comparisons indicated that MCI participants show subtly attenuated CMS activity during self-appraisal. Regression analysis revealed a highly significant relationship between BOLD response during self-appraisal and self-awareness of deficit in MCI. This finding highlights the level of anosognosia in MCI as an important predictor of response to self-appraisal in cortical midline structures, brain regions vulnerable to changes in early AD.     

A Comparison of Depressive Symptoms in Stroke and Primary Care: Applying Rasch Models to Evaluate the Center for Epidemiologic Studies-Depression Scale

OBJECTIVES: Clinical trials and community-based studies often include the Center for Epidemiologic Studies-Depression scale (CES-D) as a measure of depression outcome. We compared responses to symptom-related items on the CES-D by depressed stroke and primary-care patients for several purposes: 1) to illustrate the use of Item Response Theory (IRT)-based (Rasch) models for comparing scale functioning across different patient subgroups; and 2) to inform clinicians and outcome researchers about scale functioning and depressive symptomatology in stroke- compared with primary care-based depression. METHODS: Two data sources were analyzed, including 32 depressed patients who were 3 months poststroke, and 366 depressed primary-care patients. Presence of depression was based on a CES-D score 16 or higher. Rasch models were used to assess item fit and compare item hierarchies between depressed primary-care and stroke patients. RESULTS: Item hierarchies were similar for poststroke depression and primary care-based depression. Interpersonal disruption items were the most difficult to endorse for both groups. No items misfit the scale in primary-care depression. Items relating to restless sleep, unfriendliness, and crying slightly misfit the scale in stroke patients, that is, may measure a different trait. Differential item functioning (DIF) between the groups was identified for items relating to appetite, restless sleep, crying, and feeling disliked. CONCLUSIONS: Results generally supported the use of the CES-D as measure of depression outcome, particularly in primary care-based depression. DIF may imply that slightly different clusters of depressive symptoms are reported by depressed stroke patients compared with primary care, but this is conjectural given the small stroke sample size and the same items have been previously associated with bias in studies of large nonstroke samples. This study found Rasch models to be useful tools to investigate scale performance for different clinical applications.     

Serum beta2-microglobulin and immunoglobulin levels in young hemodialysis patients

 Amyloidosis is a complication of long-term hemodialysis treatment. The major histological feature of hemodialysis-associated amyloidosis (HAA) is the deposition of amyloid fibrils in the affected lesions, due, in part, to elevated serum β₂-microglobulin (β2M) levels. In vitro studies reveal that serum immunoglobulin light and heavy chains co-deposit with β2M in tissues affected by HAA. Only one study of HAA has been performed in young dialysis patients. We therefore assessed risk factors for HAA in a group (n=30) of young (18.7±0.9 years) patients receiving chronic, uninterrupted hemodialysis using cellulose acetate membranes. All patients initiated dialysis before reaching 18 years of age. The pre-dialysis serum β2M level was 49.7±3.9 mg/l (normal 0–2.4 mg/l). Since serum albumin was normal (4.3±0.1 mg/dl) and serum protein/albumin was elevated (1.7±0.0, normal 1.2–1.5), indicating increased circulating protein, we assayed immunoglobulins in the same patients. The serum immunoglobulin levels (expressed as a percentage of the total level of serum proteins) were elevated (21.3±0.9%, normal 11.1%–21.0%). The Kt/v was 1.37±0.03, suggesting that the high levels of serum β2M and immunoglobulins were not due to inadequate dialysis in these patients. Patients with residual renal function (Kr) did display significantly lower serum levels of β2M (33.2±2.3, P=0.03). Furthermore, improved clearance of β2M correlated with higher values of Kr (r=0.914). In contrast, serum levels of immunoglobulin (22.6±3.7, P=0.5) were unaffected by Kr. In addition, there was no correlation between older age at onset of dialysis and serum levels of either β2M (r=0.107) or immunoglobulins (r=0.321). Finally, the length of time on dialysis had no effect on serum levels of either β2M (r=0.105) or immunoglobulins (r=0.092). Taken together, these results indicate that young hemodialysis patients may be at risk for HAA. Received: 13 January 1998 / Revised: 1 June 1998 / Accepted: 2 June 1998     

Exposure–response analyses of blood pressure and heart rate changes for methylphenidate in healthy adults

The aim of the study was to evaluate the exposure–response (E–R) relationships of blood pressure (BP) and heart rate (HR) changes in healthy adults taking methylphenidate (MPH). Intensive time profiles of BP and HR from healthy adults in placebo and MPH treatment arms of seven clinical trials from the FDA internal database were utilized for this analysis. The analysis model contains a circadian component for placebo effect and an E–R component to describe drug effect. Internal validation was performed using goodness-of-fit plots and visual predictive check. A meta-database based on a systemic literature search was constructed and used for external validation of the developed models. We found that circadian models could quantify the time profiles of BP/HR in placebo arms. Linear models could describe the correlations between MPH concentrations, and BP/HR changes. The BP and HR changes were highly dependent on the shapes of MPH pharmacokinetic (PK) profiles without an apparent time delay. MPH has the greatest effect on HR, followed by systolic BP, and diastolic BP. Internal validation revealed that the developed models could adequately describe the circadian rhythms of HR and BP in placebo arms and the E–R relationships of MPH. External validation showed the models had good predictive capability of the literature data. In conclusion, the developed models adequately characterized the circadian rhythm and the MPH induced effects on BP and HR. The changes in BP and HR were highly correlated with MPH blood levels with no apparent delay. The time courses of BP and HR are similar to the MPH PK profiles. As a result, the immediate-release formulation may yield larger maximum BP and HR effect than the extended-release formulation under similar dose.     

Skeletal Manifestations of Treatment of Breast Cancer

Breast cancer and osteoporosis are common diagnoses in women. Breast cancer survival has improved due to earlier detection and improved treatments. As most breast cancers are estrogen receptor positive, treatment is often aimed at altering the hormonal environment. Both pre and postmenopausal women undergoing these therapies are at risk for bone loss. The patient’s health care team ought to have an awareness of the potential for breast cancer treatments to accelerate bone loss. Women with early stage breast cancer are treated with curative intent and, therefore, maintaining bone health is important and is part of the survivorship care to ensure an optimal quality of life.