Default mode network connectivity in stable vs progressive mild cognitive impairment.

OBJECTIVE: Dysfunction of the default mode network (DMN) has been identified in prior cross-sectional fMRI studies of Alzheimer disease (AD) and mild cognitive impairment (MCI); however, no studies have examined its utility in predicting future cognitive decline. METHODS: fMRI scans during a face-name memory task were acquired from a cohort of 68 subjects (25 normal control, 31 MCI, and 12 AD). Subjects with MCI were followed for 2.4 years (±0.8) to determine progression to AD. Maps of DMN connectivity were compared with a template DMN map constructed from elderly normal controls to obtain goodness-of-fit (GOF) indices of DMN expression. Indices were compared between groups and correlated with cognitive decline. RESULTS: GOF indices were highest in normal controls, intermediate in MCI, and lowest in AD (p < 0.0001). In a predictive model (that included baseline GOF indices, age, education, Mini-Mental State Examination score, and an index of DMN gray matter volume), the effect of GOF index on progression from MCI to dementia was significant. In MCI, baseline GOF indices were correlated with change from baseline in functional status (Clinical Dementia Rating-sum of boxes) (r = -0.40, p < 0.04). However, there was no additional predictive value for DMN connectivity when baseline delayed recall was included in the models. CONCLUSIONS: fMRI connectivity indices distinguish patients with MCI who undergo cognitive decline and conversion to AD from those who remain stable over a 2- to 3-year follow-up period. Our data support the notion of different functional brain connectivity endophenotypes for "early" vs "late" MCI, which are associated with different baseline memory scores and different rates of progression and conversion.

Effects of donepezil on cortical activation in mild cognitive impairment: a pilot double-blind placebo-controlled trial using functional MR imaging.

BACKGROUND AND PURPOSE: Cholinesterase-inhibitor therapy is approved for treatment of Alzheimer disease; however, application in patients with mild cognitive impairment (MCI) is still under active investigation. The purpose of this study was to determine the effect of such therapy on the neural substrates underlying memory processing in subjects with MCI by using functional MR imaging (fMRI). MATERIALS AND METHODS: Thirteen subjects with MCI (mean age, 68 +/- 6.9 years) enrolled in a multicenter double-blind placebo-controlled trial testing the clinical efficacy of the cholinesterase-inhibitor, donepezil, were studied with fMRI at baseline and following 12 or 24 weeks of therapy (single-site pilot study). The cognitive paradigm was delayed-response visual memory for novel faces. Within-group 1-sample t tests were performed on the donepezil and placebo groups at baseline and at follow-up. A repeated-measures analysis of variance design was used to look for a Treatment Group x Time interaction showing a significant donepezil- but not placebo-related change in blood oxygen level-dependent response during the course of the study. RESULTS: At baseline, both groups showed multiple areas of activation, including the bilateral dorsolateral prefrontal cortex, fusiform gyrus, and anterior cingulate cortex. On follow-up, the placebo group demonstrated a decreased extent of dorsolateral prefrontal activation, whereas the donepezil group demonstrated an increased extent of activation in the ventrolateral prefrontal cortex. Interaction demonstrated significant donepezil- but not placebo-related change in the left inferior frontal gyrus. CONCLUSIONS: Despite the limitations inherent to a pilot study of a small sample, our results point to specific cortical substrates underlying the actions of donepezil, which can be tested in future studies.

Frontal mucocele caused by an ectopic maxillary tooth.

OBJECTIVE: To present a previously unreported cause of frontal mucocele. CASE REPORT: A patient presented with a frontal mucocele and maxillary sinusitis. Computed tomography revealed an ectopic maxillary tooth as the cause of her signs and symptoms. Removal of the tooth by a Caldwell-Luc procedure facilitated resolution of the mucocele. Conventional treatment of mucoceles by endoscopic sinus surgery, and other rhinological sequelae of ectopic teeth, are considered. CONCLUSION: This is the first documented case of an ectopic tooth causing a frontal mucocele, and demonstrates how effectively the patient's symptoms resolved on removal of the tooth.

When less means more: deactivations during encoding that predict subsequent memory.

In event-related functional MRI (fMRI) studies, greater activity for items that are subsequently remembered (R-items) than for items that are subsequently forgotten (F-items), or Dm effect (Difference in memory), has been attributed to successful encoding operations. In contrast, regions showing a reverse DM effect (revDM = F-items > R-items) have been linked to detrimental processes leading to forgetting. Yet, revDMs may reflect not only activations for F-items (aFs) but also deactivations for R-items (dRs), and the latter alternative is more likely to reflect beneficial rather than detrimental encoding processes. To investigate this issue, we used a paradigm that included a fixation baseline and could distinguish between the two types of revDMs (aF vs. dR). Participants were scanned while encoding semantic associations between words or perceptual associations between words and fonts, and their memory was measured with associative recognition tests. For both semantic and perceptual encoding, dR effects were found in dorsolateral prefrontal, temporoparietal, and posterior midline regions. In contrast with a prior study that attributed revDMs in these regions to detrimental processes, the present results suggest that these effects reflect beneficial processes, that is, the efficient reallocation of neurocognitive resources. At the same time, aF effects were found in other regions, such as the insula, and these are more consistent with an interpretation in terms of detrimental processes. Whereas most fMRI studies of encoding have focused on activation increases, the present study indicates that activation decreases are also critical for successful learning of new information.

Integrative behavioral couple therapy: an acceptance-based, promising new treatment for couple discord.

Although traditional behavioral couple therapy (TBCT) has garnered the most empirical support of any marital treatment, concerns have been raised about both its durability and clinical significance. Integrative behavioral couple therapy (IBCT) was designed to address some of these limitations by combining strategies for fostering emotional acceptance with the change-oriented strategies of TBCT. Results of a preliminary clinical trial, in which 21 couples were randomly assigned to TBCT or IBCT, indicated that therapists could keep the 2 treatments distinct, that both husbands and wives receiving IBCT evidenced greater increases in marital satisfaction than couples receiving TBCT, and that IBCT resulted in a greater percentage of couples who either improved or recovered on the basis of clinical significance data. Although preliminary, these findings suggest that IBCT is a promising new treatment for couple discord.

Klebsiella pneumoniae pneumonia.

Klebsiella pneumoniae is an uncommon cause of community-acquired pneumonia except in alcoholics. Klebsiella may mimic pulmonary reactivation tuberculosis because it presents with hemoptysis and cavitating lesions. Klebsiella pneumoniae is a difficult infection to treat because of the organism's thick capsule. Klebsiella is best treated with third- and fourth-generation cephalosporins, quinolones, or carbapenems. Monotherapy is just as effective as a combination treatment in Klebsiella pneumoniae because newer agents are used. In the past, older agents with less anti-Klebsiella activity were needed for effective treatment. The patient we present was initially thought to have pulmonary tuberculosis, and when found to have Klebsiella pneumoniae, the suggested treatment was monotherapy with ceftriaxone. The patient was treated parenterally initially, and then was treated for 3 weeks with oral ofloxacin.

Postpericardiotomy syndrome.

Fever after a cardiac operation is commonly caused by myocardial infarction, postpericardiotomy syndrome, post-myocardial infarction syndrome (Dressler's syndrome), or postperfusion syndrome resulting from cytomegalovirus infection. Postpericardiotomy syndrome and post-myocardial infarction syndrome are autoimmune disorders characterized by eosinophilia, pleuritic chest pain, and pleural effusions. In contrast, the diagnosis of postperfusion syndrome caused by cytomegalovirus is suggested if the patient has a mild sore throat, no pleural component or chest pain, no eosinophilia, and atypical lymphocytosis. The syndromes of injury after cardiac surgical procedures are diagnoses of exclusion, but the diagnosis of postperfusion syndrome ("40-day postoperative fever") may be made on the basis of elevated cytomegalovirus IgM titers.

A component analysis of cognitive-behavioral treatment for depression.

The purpose of this study was to provide an experimental test of the theory of change put forth by A. T. Beck, A. J. Rush, B. F. Shaw, and G. Emery (1979) to explain the efficacy of cognitive-behavioral therapy (CT) for depression. The comparison involved randomly assigning 150 outpatients with major depression to a treatment focused exclusively on the behavioral activation (BA) component of CT, a treatment that included both BA and the teaching of skills to modify automatic thoughts (AT), but excluding the components of CT focused on core schema, or the full CT treatment. Four experienced cognitive therapists conducted all treatments. Despite excellent adherence to treatment protocols by the therapists, a clear bias favoring CT, and the competent performance of CT, there was no evidence that the complete treatment produced better outcomes, at either the termination of acute treatment or the 6-month follow-up, than either component treatment. Furthermore, both BA and AT treatments were just as effective as CT at altering negative thinking as well as dysfunctional attributional styles. Finally, attributional style was highly predictive of both short- and long-term outcomes in the BA condition, but not in the CT condition.