Clinical trials of potential cognitive-enhancing drugs in schizophrenia: what have we learned so far?

In light of the number of studies conducted to examine the treatment of cognitive impairment associated with schizophrenia (CIAS), we critically reviewed recent CIAS trials. Trials were identified through searches of the website "www.clinicaltrials.gov" using the terms "schizophrenia AND cognition," "schizophrenia AND neurocognition," "schizophrenia AND neurocognitive tests," "schizophrenia AND MATRICS," "schizophrenia AND MCCB," "schizophrenia AND BACS," "schizophrenia AND COGSTATE," and "schizophrenia AND CANTAB" and "first-episode schizophrenia AND cognition." The cutoff date was 20 April 2011. Included trials were conducted in people with schizophrenia, the effects on cognition were either a primary or secondary outcome, and the effect of a pharmacologically active substance was examined. Drug challenge, pharmacokinetic, pharmacodynamic, or prodrome of psychosis studies were excluded. We identified 118 trials, with 62% using an add-on parallel group design. The large majority of completed trials were underpowered to detect moderate effect sizes, had ≤8 weeks duration, and were performed in samples of participants with chronic stable schizophrenia. The ongoing add-on trials are longer, have larger sample sizes (with a number of them being adequately powered to detect moderate effect sizes), and are more likely to use a widely accepted standardized cognitive battery (eg, the MATRICS Consensus Cognitive Battery) and MATRICS guidelines. Ongoing studies performed in subjects with recent onset schizophrenia may help elucidate which subjects are most likely to show an effect in cognition. New insights into the demands of CIAS trial design and methodology may help increase the probability of identifying treatments with beneficial effect on cognitive impairment in schizophrenia

Relationships between Extrapyramidal Signs and Cognitive Function in a Community-Dwelling Cohort of Patients with Parkinson's Disease and Normal Elderly Individuals

The relationship between extrapyramidal sign(DPS) severity and cognitive funcition was investigated in 184 patients with indiopathic Parkinson's disease (PD) and 301 normal elderly individuasls from a community-dwelling cohort in northern Manhattan, New York City. Fifiy-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzbeimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological rests of memory, orientation, abstract reasoning, language, construcion, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD partients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but withtout overt idiopathic PD, showed widespread cognitive changes, including imparment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia

The Frequency and Associated Risk Factors for Dementia in Patients with Parkinson's Disease

Objectives: To estimate the frequency and determine the risk factors for incident dementia in community-dwelling patients with Parkinson's disease (PD) and in control subjects. Design: Prospective cohort study. During a 3.5-year period, 140 patients with idiopathic PD without evidence of dementia and 572 nondemented control subjects were identified in the community of Washington Heights—Inwood in New York, NY. All subjects underwent neurological and neuropsychological evaluations and follow-up examinations. Results: Twenty-seven patients with PD (19.2%) became demented throughout 2 years, as compared with 87 (15.2%) of the control subjects. The relative risk (RR) for the development of dementia with PD was 1.7 (95% confidence interval [CI], 1.1 to 2.7) after adjusting for age, education, and gender. Predictive features of incident dementia were an extrapyramidal score greater than 25 (RR, 3.56; 95% CI, 1.4 to 8.9) and a Hamilton Depression Rating Scale score greater than 10 (RR, 3.55; 95% CI, 1.6 to 7.9). Conclusion: Patients with PD, especially those with severe extrapyramidal signs, have almost twice the risk for the development of dementia than do community-dwelling control subjects

Relationships between Extrapyramidal Signs and Cognitive Function in a Community-Dwelling Cohort of Patients with Parkinson's Disease and Normal Elderly Individuals

The relationship between extrapyramidal sign(DPS) severity and cognitive funcition was investigated in 184 patients with indiopathic Parkinson's disease (PD) and 301 normal elderly individuasls from a community-dwelling cohort in northern Manhattan, New York City. Fifiy-six of the patients with PD met criteria for dementia of the Diagnostic and Statistical Manual of Mental Disorders third edition, revised, and of the National Institute of Neurological and Communicative Disorders and Stroke-Alzbeimer's Disease and Related Disorders Association. EPS were rated according to the Unified Parkinson's Disease Rating Scale. Cognitive function was assessed by neuropsychological rests of memory, orientation, abstract reasoning, language, construcion, and psychomotor speed. Significant associations were found between EPS and neuropsychological performance in PD partients without dementia. Yet EPS severity was unable to account for the pronounced cognitive impairment in PD dementia. Individuals in the normal group with subtle EPS, but withtout overt idiopathic PD, showed widespread cognitive changes, including imparment in most of the tests that differentiated PD patients from normal subjects. Prospective follow-up of these individuals will determine whether this represents a preclinical stage of PD or constitutes an early manifestation of dementia

Smoking and Parkinson's Disease

Smoking was examined in relation to Parkinson's disease (PD) in a population-based study in northern Manhattan (New York City) because of its putative “protective effect.” Using a case-control design, information on smoking and associated behaviors was obtained in structured interviews after standard diagnostic evaluations in both cases and controls. The overall prevalence of smoking in the population was 43.7%, decreasing to 37% after age 85. Smoking was most frequent in men, Blacks, and in both cases and controls using alcohol once per week or more. Cases had quit smoking more often than controls (87 vs. 64%), and had smoked for significantly fewer years (31 vs. 41 yrs; p < 0.05 for both). The age-at-onset for smokers with PD was similar to age-at-onset for nonsmokers with PD. The odds ratio (OR) for a history of smoking associated with PD was 1.1 (95% CI 0.7–1.8). No protective gradient was associated with heavier smoking patterns. However, the odds that patients with PD were still smoking at the time of the interview were significantly less than those for controls (OR = 0.2; 95% CI 0.1–0.5). These results do not support the hypothesis that smoking protects against PD; rather they strongly imply the converse, that PD reduces smoking

MRI Low Signal Prominence at the Anteroinferior Glenohumeral Joint Recess: Frequency, Associated MRI Findings, and Arthroscopic Correlation

Shoulder MRI occasionally shows a low signal prominence at the anteroinferior glenohumeral joint (GHJ) recess resembling thickened capsular tissue which has an uncertain clinical significance.Objectives are to examine the frequency of this finding on MR and if it is visualized on arthroscopy, and to correlate with other common shoulderpathologies seen on MR

Serum Neopterin Level Predicts HIV-Related Mortality but Not Progression to Aids or Development of Neurological Disease in Gay Men and Parenteral Drug Users

Objective: To investigate the ability of elevated serum neopterin levels to predict independently mortality, progression to acquired immunodeficiency syndrome, and development of neurological disease. Design: Cross-sectional and longitudinal study of gay and/or bisexual men and parenteral drug users. Setting and Patients: Patients included human immunodeficiency virus (HIV)—negative and —positive gay and/or bisexual men and parenteral drug—using men and women who volunteered for an outpatient study of the natural history of HIV infection. Results: Serum neopterin levels were significantly elevated in HIV-positive patients (mean, 18.0 nmol/L; SD, 19.2 nmol/L), compared with those in HIV-negative patients (mean, 7.5 nmol/L; SD, 5.5 nmol/L) (P<.001). No differences in the serum neopterin levels could be detected between gay men and parenteral drug users. In HIV-positive patients, women had a higher serum neopterin level than did men (P=.03). The elevated serum neopterin levels were associated with an advanced clinical stage of HIV infection. After adjusting for the CD4 lymphocyte count and other potential confounders, the serum neopterin level was a significant independent predictor of mortality. The elevated serum neopterin levels did not predict progression to acquired immunodeficiency syndrome or development of clinically significant neurological disease. Conclusion: An elevated serum neopterin level predicts mortality, but it does not predict progression to acquired immunodeficiency syndrome or development of neurological disease among HIV-infected individuals

Interrater Reliability of Extrapyramidal Signs in a Group Assessed for Dementia

Extrapyramidal signs were rated by three neurologists in 20 patients who had either been diagnosed as having probable Alzheimer's disease or who were being evaluated for dementia. In general, good inter-rater reliability was found for the presence or absence of extrapyramidal signs, although agreement over the presence of some signs was reduced when distinctions between normality and slight departures from normality were required