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David B Arciniegas1,2, Jason R Tregellas1,3, Donald C Rojas1, Burlleen Hewitt1, C Alan Anderson1,2,41Neurobehavioral Disorders Program, Department of Psychiatry, 2Behavioral Neurology Section, University of Colorado Denver, Aurora, CO, USA; 3Research Service, 4Neurology Service, Denver Veterans Affairs Medical Denver, Denver, CO, USAAbstract: Cholinergic deficits are an early and functionally significant manifestation of Alzheimer’s disease (AD). These deficits contribute to impairment of hippocampally mediated information processing, including declarative memory impairments and abnormal auditory sensory gating. A functional imaging technique that facilitates identification of changes in cholinergically dependent hippocampal information processing would be of considerable use in the study and clinical evaluation of persons with this condition. Techniques that interrogate hippocampal function passively, ie, in a manner requiring no cognitive effort or novel task learning during the neuroimaging procedure, would also be especially useful in this cognitively impaired population. The functional magnetic resonance imaging sensory gating paradigm developed at the University of Colorado, CO, USA, is a functional neuroimaging technique that possesses both of these characteristics. We developed a demonstration project using this paradigm in which we passively interrogated hippocampal function in two subjects with probable AD of mild severity. Imaging data were quick and easy in these subjects and served usefully as an initial demonstration of the feasibility of using this neuroimaging method in this population. Preliminary analyses of the data obtained from these subjects identified abnormal blood oxygen level-dependent responses when compared with four healthy comparators, and the pattern of these responses was consistent with impaired function of the auditory sensory gating network. The strengths and limitations of this neuroimaging paradigm and the additional issues that require investigation in order to continue its development into a research and clinical technique for use in this population are discussed.Keywords: Alzheimer’s disease, hippocampus, acetylcholine, functional magnetic resonance imaging

Daniel J Abrams1, Donald C Rojas1, David B Arciniegas1,21Department of Psychiatry; 2Neurobehavioral Disorders Program, Departments of Psychiatry and Neurology, University of Colorado School of Medicine, Denver, CO, USAAbstract: Considerable debate surrounds the inclusion of schizoaffective disorder in psychiatric nosology. Schizoaffective disorder may be a variant of schizophrenia in which mood symptoms are unusually prominent but not unusual in type. This condition may instead reflect a severe form of either major depressive or bipolar disorder in which episode-related psychotic symptoms fail to remit completely between mood episodes. Alternatively, schizoaffective disorder may reflectthe co-occurrence of two relatively common psychiatric illnesses, schizophrenia and a mood disorder (major depressive or bipolar disorder). Each of these formulations of schizoaffective disorder presents nosological challenges because the signs and symptoms of this condition cross conventional categorical diagnostic boundaries between psychotic disorders and mood disorders. The study, evaluation, and treatment of persons presently diagnosed with schizoaffective may be more usefully informed by a dimensional approach. It is in this context that this article reviews and contrasts the categorical and dimensional approaches to its description, neurobiology, and treatment. Based on this review, an argument for the study and treatment of this condition using a dimensional approach is offered.Keywords: schizoaffective disorder, schizophrenia, bipolar disorder, manic-depressive disorder

Psychiatric symptoms in Guillain-Barré syndrome (GBS) can include anxiety and affective lability, which require treatment to improve functional outcomes. Three cases in which modest doses of selective serotonin reuptake inhibitors (SSRIs), alone or in combination with anticonvulsants, reduced symptoms of anxiety and affective lability during acute rehabilitation of GBS are presented. These agents were both more effective and better tolerated than benzodiazepines and appeared to facilitate engagement in rehabilitation therapies, including psychotherapy. Further investigation of the pharmacotherapy of neuropsychiatric disturbances in this population using prospective, blinded, placebo-controlled methods is recommended.

David B Arciniegas1,2,3, Gregory F Kellermeyer1,2, Nancy M Bonifer1, Kristin M Anderson-Salvi1, C Alan Anderson2,3,41Brain Injury Rehabilitation Unit, HealthONE Spalding Rehabilitation Hospital, Aurora, CO, USA; 2Neuropsychiatry Service, Department of Psychiatry, University of Colorado Health Sciences Center, Denver, CO, USA; 3Behavioral Neurology Section, Department of Neurology, University of Colorado Health Sciences Center, Denver, CO, USA; 4Neurology Service, Denver Veterans Affairs Medical Center, Denver, CO, USABackground: Progressive cognitive decline develops in a nontrivial minority of stroke survivors. Although commonly used to identify cognitive decline in older stroke survivors, the usefulness of the Mini-Mental State Examination (MMSE) as a screening tool for post-stroke cognitive decline across a wider range of ages is not well established. This study therefore investigated the usefulness of the MMSE for this purpose.Methods: Twenty-seven subjects, aged 18–82 years, with a single known remote stroke were assessed using the MMSE. The frequency of cognitive impairment was determined by comparison of MMSE scores with population-based norms. Relationships between cognitive performance, motor impairments, age, gender, handedness, stroke laterality, and time since stroke also were explored.Results: Age-adjusted MMSE scores identified mild cognitive impairment in 22.2% and moderate-to-severe cognitive impairment in 7.4% of subjects. Raw and age-adjusted MMSE scores were inversely correlated with time since stroke, but not with other patient or stroke characteristics.Conclusion: A relationship between time since single known stroke and MMSE performance was observed in this study. The proportion of subjects identified as cognitively impaired in this group by Z-transformation of MMSE scores using previously published normative data for this measure comports well with the rates of late post-stroke cognitive impairment reported by other investigators. These findings suggest that the MMSE, when normatively interpreted, may identify cognitive decline in the late period following single known stroke. Additionally, the lack of a relationship between MMSE and Fugl-Meyer scores suggests that the severity of post-stroke motor impairments is unlikely to serve as a clinically useful indicator of the need for cognitive assessment. A larger study of stroke survivors is needed to inform more fully on the usefulness of normatively interpreted MMSE scores as a method of screening for post-stroke cognitive decline.Keywords: stroke, Mini-Mental State Examination, cognitive decline, Fugl-Meyer evaluation, motor impairment&nbsp