Improvement In Cognitive Symptoms Research Articles

Neuropyschological Profile of Reversible Cognitive Impairment in a Patient with a Dural Arteriovenous Fistula

Objective and Importance: Patients with dural arteriovenous fistulas (dAVFs) may present with cognitive impairment secondary to venous hypertension or ischemia. Clinical Presentation: We present a patient with a dAVF supplied by the posterior meningeal artery who presented with severe encephalopathy and imaging consistent with bilateral thalamic ischemia. Results: Detailed pre-operative neuropsychological testing documented severe cognitive deficits across multiple domains, localizing diffusely in the cerebral cortex, beyond that which would be expected from purely thalamic involvement. Approximately 2 months following a combined endovascular and surgical repair, repeat neuropsychological testing documented a dramatic improvement in cognitive symptoms while MRI abnormalities in the thalami resolved. Conclusion: Detailed neuropsychological testing may be useful in patients presenting with dAVFs in order to identify cognitive impairment, which may be out of proportion to imaging findings. Recognition of dAVF-associated cognitive impairment may lead to more aggressive, timely treatment in patients with otherwise lower-risk lesions. This detailed testing can also provide a baseline in order to document cognitive recovery after fistula repair.

Science and Recovery in Schizophrenia

Mental health advocates and policy makers are increasingly attuned to the importance of the recovery concept, and psychiatrists and neuroscientists increasingly emphasize the medical model and neurobiological mechanisms in relation to schizophrenia. Studies have shown that people with schizophrenia are tremendously heterogeneous in each domain of recovery, and the various domains of recovery are themselves relatively independent from one another. Studies have also shown that current interventions are effective for specific dimensions of the illness and functions, are usually ameliorative rather than curative, and are effective only for a proportion of patients. Hence, the authors suggest defining recovery in terms of improvements in specific domains rather than globally -- for example, "recovery of cognitive functioning" or "recovery of vocational functioning" -- to signify improvements in specific areas. This definition realistically emphasizes states of relative and partial recovery that patients can achieve in response to treatment. The emphasis on a range of improvements in specific areas should allow clinicians to communicate more clearly regarding the current findings and goals of treatment. The article also examines current research on various aspects of recovery, including the effects of treatment on pathophysiology, symptoms, cognitive impairments, quality of life, and self-agency. An operational definition of recovery allows for bridging hope and recovery with important advances in the science of the brain. Future clinical and neuroscience research and service development should emphasize measures of recovery as outcomes for people with schizophrenia.

Efficacy of Rivastigmine in Alzheimer’s Disease Patients with Rapid Disease Progression: Results of a Meta-Analysis

Background: Alzheimer’s disease (AD) patients experiencing more rapid symptom progression are likely to have a poorer prognosis than those experiencing slow symptom progression. In a recent retrospective analysis, treatment effects of rivastigmine were more pronounced in AD patients with rapid cognitive decline than in those with slow cognitive decline. This warranted further investigation. Methods: Rapidly and slowly progressing patients were identified by rates of cognitive decline [≧4 points and <4 points, respectively, on the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog)] during 26 weeks of placebo treatment in four randomized controlled trials (weeks 0–26). This meta-analysis evaluated rates of cognitive decline in both subgroups during subsequent open-label rivastigmine 26-week extension studies (weeks 26–52). A longitudinal mixed effects model compared cognitive decline in rapidly and slowly progressing patients, including correction for possible regression to the mean. Results: 180 (75%) rapidly and 337 (78%) slowly progressing patients provided ADAS-cog data after 26 weeks of open-label rivastigmine treatment. Improvements in cognitive symptoms were observed during the first 12 weeks, which were more pronounced in patients with rapid progression than in those with slow progression. Rapidly progressing patients experienced significantly greater cognitive benefits than slowly progressing patients (p = 0.029), who experienced a modest decline in cognitive symptoms at the end of the study. Comment: Patients experiencing rapid symptom progression may receive greater benefit from rivastigmine than those with slow progression. In this study, cholinesterase inhibition appeared to be of particular utility in the management of AD patients whose symptoms were rapidly worsening.

Implications for Atypical Antipsychotics in the Treatment of Schizophrenia: Neurocognition Effects and a Neuroprotective Hypothesis

Cognitive impairment in schizophrenia occurs in the early phases of the disease and remains throughout its course. The basis for cognition lies in two main brain regions: the prefrontal cortex and hippocampus. Positron emission tomography, functional magnetic resonance imaging, and proton magnetic spectroscopy studies have shown that prefrontal cortex and hippocampus activity and cell density are lower in patients with schizophrenia than in healthy controls. Dopamine remains the fundamental neurotransmitter involved with schizophrenia. Catechol- O -methyltransferase accounts for about 60% of dopamine metabolism in the prefrontal cortex. Functional polymorphism for the catechol- O -methyltransferase genotypes has been identified in patients with schizophrenia. Those with the valine-valine genotype demonstrate rapid inactivation of dopamine, and performance in cognitive testing in patients is poorer with this allele than with other genotypes. N -methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate acid receptors are also strongly associated with cognitive impairment. Changes occur in apolipoproteins D and E, cholinesterase enzyme activity, neurotensin, and neural growth factors, leading to a possible neurodegenerative process and cognitive impairment in patients with schizophrenia. A fundamental link between psychosis and neurocognition probably arises from complex interactions between these systems at the intracellular secondary messenger system and with protein phosphorylation. Atypical antipsychotics evaluated in receptor models, cell cultures, and animal behavior paradigms indicate that these agents may provide neuroprotective effects. Clinical studies with atypical antipsychotics have consistently demonstrated improvement in cognitive symptoms, and such improvement appears to be correlated with improvement of negative symptoms. A neurodevelopmental model of cognitive impairment in schizophrenia aids in understanding why atypical antipsychotics improve cognitive symptoms.

Schizophrenia and diabetes

Schizophrenic patients appear to be at an increased risk for diabetes mellitus (DM) and hyperglycemia. Antipsychotic agents, particularly atypical antipsychotic agents, may further increase this risk. There is little genetic overlap with diabetes and schizophrenia. Understanding the mechanisms of glucose metabolism impairment by antipsychotic agents is critical to prevent life-threatening illnesses, such as diabetic ketoacidosis (DKA). The advantages of atypical agents, including improvement in cognitive symptoms in schizophrenia patients, must be balanced with data that suggest patients with diabetes or hyperglycemia demonstrate a cognitive decline. Recently, a great deal of attention has been given to the role of antipsychotic agents in the development of diabetes mellitus (DM) in patients with neuropsychiatric disorders, including schizophrenia. Evidence dating back to long before antipsychotic agents were developed suggests a higher rate of DM in schizophrenia patients compared to the general population. This chapter reviews the literature on schizophrenia, DM, and antipsychotic agents and discusses several implications.

Attention Deficit/Hyperactivity Disorders

Attention Deficit/Hyperactivity Disorders