Dementia with Lewy bodies: Impact of co-pathologies and implications for clinical trial design.

Dementia with Lewy bodies (DLB) is clinically defined by the presence of visual hallucinations, fluctuations, rapid eye movement (REM) sleep behavioral disorder, and parkinsonism. Neuropathologically, it is characterized by the presence of Lewy pathology. However, neuropathological studies have demonstrated the high prevalence of coexistent Alzheimer's disease, TAR DNA-binding protein 43 (TDP-43), and cerebrovascular pathologic cases. Due to their high prevalence and clinical impact on DLB individuals, clinical trials should account for these co-pathologies in their design and selection and the interpretation of biomarkers values and outcomes. Here we discuss the frequency of the different co-pathologies in DLB and their cross-sectional and longitudinal clinical impact. We then evaluate the utility and possible applications of disease-specific and disease-nonspecific biomarkers and how co-pathologies can impact these biomarkers. We propose a framework for integrating multi-modal biomarker fingerprints and step-wise selection and assessment of DLB individuals for clinical trials, monitoring target engagement, and interpreting outcomes in the setting of co-pathologies.

The Diagnosis of Delirium Superimposed on Dementia: An Emerging Challenge.

Delirium occurring in patients with dementia is referred to as delirium superimposed on dementia (DSD). People who are older with dementia and who are institutionalized are at increased risk of developing delirium when hospitalized. In addition, their prior cognitive impairment makes detecting their delirium a challenge. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision are considered the standard reference for the diagnosis of delirium and include criteria of impairments in cognitive processes such as attention, additional cognitive disturbances, or altered level of arousal. The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and the International Statistical Classification of Diseases and Related Health Problems, 10th Revision does not provide guidance regarding specific tests for assessment of the cognitive process impaired in delirium. Importantly, the assessment or inclusion of preexisting cognitive impairment is also not addressed by these standards. The challenge of DSD gets more complex as types of dementia, particularly dementia with Lewy bodies, which has features of both delirium and dementia, are considered. The objective of this article is to critically review key elements for the diagnosis of DSD, including the challenge of neuropsychological assessment in patients with dementia and the influence of particular tests used to diagnose DSD. To address the challenges of DSD diagnosis, we present a framework for guiding the focus of future research efforts to develop a reliable reference standard to diagnose DSD. A key feature of a reliable reference standard will improve the ability to clinically diagnose DSD in facility-based patients and research studies.

Covariance 99mTc-exametazime SPECT patterns in Alzheimer's disease and dementia with Lewy bodies: utility in differential diagnosis.

(99m)Tc-exametazime single photon emission computed tomography (SPECT) scans of 36 patients with Alzheimer's disease (AD) and 30 with dementia with Lewy bodies (DLB) underwent region of interest (ROI) and principal component analysis (PCA). Principal component analysis was performed on the entire ROI data set. Principal components (PCs) were obtained, representing common intercorrelated regions in AD and DLB. Topographic expression that signified the extent to which a participant expressed the topographic covariance pattern was derived and used as a discriminatory variable. Principal components were identified, accounting for 77% of total data variance. Significant (PC x group) interaction was observed (P < .001). Topographic expression was significantly higher in DLB than AD (F(1,64) = 21.6, P < .001), and differentiated DLB from AD with sensitivity 73% specificity 72%. Calculating the topographic expression in an independent data set of 48 patients with AD and 23 with DLB gave sensitivity = 70%, specificity = 67%. Principal component analysis captures additional sources of variance and if perfusion SPECT is the only scan available, this procedure may offer extra information.

False recognition following study of semantically related lists presented in jumbled word form.

Three experiments explored a jumbled word effect in false recognition. Lists of theme-related items were presented in word or nonword form. Results indicated that critical lures semantically related to studied items were falsely recognised regardless of whether they were presented as words or nonwords. High false recognition rates to either SLEEP or SELEP following study of an appropriate theme list of items in nonword form should only occur if nonwords are recoded at study. With study conditions conducive to recoding, jumbled words induced false recognitions based on semantic associations among their respective base words. Disrupting a recoding process by creating "difficult" letter rearrangements for jumbled words (Experiment 2) appeared to eliminate the false recognition effect. In Experiment 3, presentation durations ranged from 110 ms to 880 ms. Although there was little evidence of a semantic false recognition effect at the fastest presentation rate, the brief durations appeared to be effective in eliminating the effect when items were studied in nonword form. These results appear to be consistent with an encoding activation/retrieval monitoring model.

Repetitive transcranial magnetic stimulation for negative symptoms of schizophrenia: a randomized controlled pilot study.

BACKGROUND: Negative symptoms in schizophrenia are associated with deficits in executive function and frequently prove highly resistant to neuroleptic medication. Using repetitive transcranial magnetic stimulation (rTMS) to activate the prefrontal cortex has been suggested as a treatment for negative symptoms. METHODS: We performed a double-blind randomized controlled pilot study of real versus sham rTMS for negative symptoms in schizophrenia. 17 right-handed patients with prominent negative symptoms (PANSS negative subscore >or=20) were randomized to a 10 day course of real (n=8) or sham rTMS (n=9) applied to the left dorsolateral prefrontal cortex (20 trains per day, 10 s treatment at 10 Hz, 50 s inter-train interval, 110% of motor threshold). The primary outcome measure was PANSS negative symptom score. Secondary outcomes included mood, cognitive function and side-effects. Patients were followed-up two weeks afterwards. The main effect of treatment arm was evaluated across end of treatment and two-week follow-up time points using ANCOVA. RESULTS: All subjects completed the treatment course. There was no significant difference between the two groups on PANSS negative symptom scores at either time point. At the end of treatment, no subjects in either group met the criterion for response (i.e. a 20% reduction in baseline PANSS negative symptom score). The real rTMS group had better delayed recall on a test of verbal learning than the sham group at 2 week follow-up. CONCLUSIONS: Real rTMS was not found to be better than sham rTMS in alleviating negative symptoms of schizophrenia although it was associated with some improvement in aspects of cognitive function at follow-up.

Control of Tamarix in the Western United States: implications for water salvage, wildlife use, and riparian restoration.

Non-native shrub species in the genus Tamarix (saltcedar, tamarisk) have colonized hundreds of thousands of hectares of floodplains, reservoir margins, and other wetlands in western North America. Many resource managers seek to reduce saltcedar abundance and control its spread to increase the flow of water in streams that might otherwise be lost to evapotranspiration, to restore native riparian (streamside) vegetation, and to improve wildlife habitat. However, increased water yield might not always occur and has been substantially lower than expected in water salvage experiments, the potential for successful revegetation is variable, and not all wildlife taxa clearly prefer native plant habitats over saltcedar. As a result, there is considerable debate surrounding saltcedar control efforts. We review the literature on saltcedar control, water use, wildlife use, and riparian restoration to provide resource managers, researchers, and policy-makers with a balanced summary of the state of the science. To best ensure that the desired outcomes of removal programs are met, scientists and resource managers should use existing information and methodologies to carefully select and prioritize sites for removal, apply the most appropriate and cost-effective control methods, and then rigorously monitor control efficacy, revegetation success, water yield changes, and wildlife use.