benztropine and Cognition-Disorders

Spatial memory is of interest in schizophrenia because of widespread impairments in adaptive functioning, including independent living skills. Short-term spatial memory is impaired in this disease, whereas spatial reference memory, a longer-term spatial memory, has not been evaluated. Animal studies have demonstrated that anticholinergics impair short-term spatial memory but not spatial reference memory. The effects of haloperidol and risperidone on these two types of spatial memory were evaluated in a double-blind randomized comparison in inpatients with schizophrenia. It was predicted that risperidone would have a greater beneficial effect on spatial working memory than haloperidol. Computerized measures of spatial working memory and spatial reference memory were developed based on animal assessment of these functions. Subjects with schizophrenia were assessed during a medication-free period and again following 4 weeks of fixed-dose treatment. Risperidone, compared to haloperidol, improved spatial working memory performance, an effect that became nonsignificant when benztropine co-treatment was controlled. There were no treatment effects on spatial reference memory performance. Consistent with animal studies, benztropine impaired spatial working memory but not spatial reference memory. The relative benefits of risperidone on spatial working memory performance were largely explained by differential benztropine treatment for the haloperidol-treated subjects.

Topics: Adult; Antipsychotic Agents; Benztropine; Cholinergic Antagonists; Cognition Disorders; Female; Humans; Male; Memory; Memory Disorders; Pattern Recognition, Visual; Psychiatric Status Rating Scales; Psychomotor Performance; Reaction Time; Risperidone; Schizophrenia; Schizophrenic Psychology; Space Perception

Topics: Acute Disease; Benztropine; Clinical Trials as Topic; Cognition Disorders; Dose-Response Relationship, Drug; Haloperidol; Humans; Milieu Therapy; Placebos; Psychiatric Status Rating Scales; Research Design; Schizophrenia; Schizophrenic Psychology; Sleep; Time Factors

Drugs used to treat attention deficit hyperactivity disorder (ADHD) improve prefrontal cortex (PFC)-dependent cognitive function. The majority of ADHD-related treatments act either as dual norepinephrine (NE) and dopamine (DA) reuptake inhibitors (psychostimulants) or selective NE reuptake inhibitors (SNRIs). Certain benztropine analogs act as highly selective DA reuptake inhibitors while lacking the reinforcing actions, and thus abuse potential, of psychostimulants. To assess the potential use of these compounds in the treatment of ADHD, we examined the effects of a well-characterized benztropine analog, AHN 2-005, on performance of rats in a PFC-dependent delayed-alternation task of spatial working memory. Similar to that seen with all drugs currently approved for ADHD, AHN 2-005 dose-dependently improved performance in this task. Clinically-relevant doses of psychostimulants and SNRIs elevate NE and DA preferentially in the PFC. Despite the selectivity of this compound for the DA transporter, additional microdialysis studies demonstrated that a cognition-enhancing dose of AHN 2-005 that lacked locomotor activating effects increased extracellular levels of both DA and NE in the PFC. AHN 2-005 produced a larger increase in extracellular DA in the nucleus accumbens, although the magnitude of this was well below that seen with motor activating doses of psychostimulants. Collectively, these observations suggest that benztropine analogs may be efficacious in the treatment of ADHD or other disorders associated with PFC dysfunction. These studies provide a strong rationale for future research focused on the neural mechanisms contributing to the cognition-enhancing actions and the potential clinical utility of AHN 2-005 and related compounds. This article is part of a Special Issue entitled 'Cognitive Enhancers'.

Topics: Animals; Attention Deficit Disorder with Hyperactivity; Behavior, Animal; Benztropine; Cognition; Cognition Disorders; Dopamine; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Extracellular Fluid; Male; Memory, Short-Term; Neurons; Nootropic Agents; Norepinephrine; Nucleus Accumbens; Prefrontal Cortex; Random Allocation; Rats; Rats, Sprague-Dawley; Septal Nuclei; Spatial Behavior

Hereditary spastic paraplegia with thin corpus callosum is a rare degenerative disease, which is characterized by a progressive weakness of the lower limbs with a hypoplastic corpus callosum, and is often associated with other symptoms such as mental impairment, amyotrophy, sensory disturbances, dysuria, nystagmus and cataract. We describe two siblings (brother and sister) who showed a thin corpus callosum on MRI, one of whom showed the pure form of progressive spastic paraplegia, while the other showed predominant levodopa-responsive parkinsonism. The present cases are illustrative of a phenotypic heterogeneity in the same family of spastic paraplegia with a thin corpus callosum, despite the identical neuroimaging findings, and also presented another form of autosomal recessive juvenile levodopa-responsive parkinsonism.

Topics: Adolescent; Antiparkinson Agents; Benztropine; Cognition Disorders; Corpus Callosum; Electroencephalography; Female; Gait Disorders, Neurologic; Humans; Levodopa; Magnetic Resonance Imaging; Male; Muscle Weakness; Neuropsychological Tests; Parkinson Disease; Selegiline; Spastic Paraplegia, Hereditary; Tremor

A broad range of neuropsychological function was compared in samples of young adult unipolar depressed inpatients with and without psychotic features. Consistent with expectations, the psychotic depressive group demonstrated a broad range of deficit and had more impaired performances than the nonpsychotic group. Relevance of these data for hypotheses concerning psychotic depression as a unique diagnostic entity is discussed. In the context of previous research, the current findings suggest that accounting for individual differences in depression may clarify discrepancies between earlier studies of neuropsychological function in depression, and our understanding of the mechanisms by which depression influences cognition may be refined.

Topics: Adult; Attention; Benztropine; Cognition Disorders; Depressive Disorder; Dopamine; Dopamine Uptake Inhibitors; Dose-Response Relationship, Drug; Female; Humans; Male; Memory Disorders; Neuropsychological Tests; Psychotic Disorders; Severity of Illness Index; Verbal Behavior; Verbal Learning

This study evaluated the longitudinal course of neuropsychological deficits in a group of patients with new or recent onset schizophrenia. Thirty-five inpatients with DSM-III-R diagnoses of schizophrenia were administered a comprehensive battery of neuropsychological tests during their index hospitalization, and either 1 or 2 years after intake. Cognitive function remained stable in most domains, including motor speed, verbal and nonverbal memory, and verbal learning. Significant improvement in neuropsychological performance was observed on a task of complex attention (Trails B) and a set response shifting task (Stroop). These improvements were correlated with changes in clinical symptoms, but not with changes in medication dose. These findings suggest that most of the neuropsychological functioning in schizophrenia is stable over the first few years of the illness. Moreover, those neuropsychological deficits that remain unchanging appear to be independent of significant change in clinical symptoms, suggesting they may be a trait of the illness. However, a small subset of functions such as complex attention and response inhibition appear to fluctuate with time, and in particular, with clinical symptomatology, and may be considered 'state' dependent.

Topics: Adult; Antipsychotic Agents; Attention; Benztropine; Cognition Disorders; Female; Follow-Up Studies; Humans; Longitudinal Studies; Male; Mental Recall; Neurocognitive Disorders; Neuropsychological Tests; Patient Admission; Problem Solving; Prospective Studies; Reaction Time; Schizophrenia; Schizophrenic Psychology

In 3 patients who suffered oculogyric crises, mental changes accompanied upward deviation of the eyes. In 1 patient, whom we studied in detail, the mental disturbance consisted of a disorder of attention in which pathological fixation of a thought occurred. During the period of upward eye deviation, all functional types of conjugate eye movements were present in the upper field of gaze, suggesting an imbalance of the vertical gaze-holding mechanism. The eyes could be driven down only by a combined blink and downward saccade. Both the thought disorder and the ocular deviation responded promptly to anticholinergic agents. We propose that the disorders of thought and eye movement in oculogyric crisis are linked by a pharmacological imbalance common to both.

Topics: Adult; Benztropine; Cognition Disorders; Diphenhydramine; Eye Movements; Female; Humans; Male; Middle Aged; Parasympatholytics; Syndrome