Kory Schuh

Comparison of neuroimaging modalities for the prediction of conversion from mild cognitive impairment to Alzheimer's dementia.

In this study we compared Pittsburgh compound-B (PIB) positron emission tomography (PET) amyloid imaging, fluorodeoxyglucose PET for metabolism, and magnetic resonance imaging (MRI) for structure to predict conversion from amnestic mild cognitive impairment (MCI) to Alzheimers dementia using data from the Alzheimers Disease Neuroimaging Initiative cohort. Numeric neuroimaging variables generated by the Alzheimers Disease Neuroimaging Initiative-funded laboratories for each neuroimaging modality along with apolipoprotein-E genotype (n = 29) were analyzed. Performance of these biomarkers for predicting conversion from MCI to Alzheimers dementia at 2 years was evaluated in 50 late amnestic MCI subjects, 20 of whom converted. Multivariate modeling found that among individual modalities, MRI had the highest predictive accuracy (67%) which increased by 9% to 76% when combined with PIB-PET, producing the highest accuracy among any biomarker combination. Individually, PIB-PET generated the best sensitivity, and fluorodeoxyglucose PET had the lowest. Among individual brain regions, the temporal cortex was found to be most predictive for MRI and PIB-PET.

Validation of the Adult ADHD Investigator Symptom Rating Scale (AISRS)

Objective: Validation of the Adult ADHD Investigator Symptom Rating Scale (AISRS) that measures aspects of ADHD in adults. Method: Psychometric properties of the AISRS total and AISRS subscales are analyzed and compared to the Conners’ Adult Attention-Deficit/Hyperactivity Disorder Rating Scale-Investigator Rated: Screening Version (CAARS-Inv:SV) and the Clinical Global Impression-ADHD-Severity Scale using data from a placebo-controlled 6-month clinical trial of once-daily atomoxetine. Results: The AISRS has high internal consistency, good convergent, and discriminant validities; modest divergent validity; and small ceiling and floor effects (≤1%). It correlates highly with the CAARS-Inv:SV. Factor analysis confirms 2 AISRS subscales, hyperactivity-impulsive scale and inattention. The AISRS total and AISRS subscales perform stably. All scales demonstrate responsiveness to change with medication. Conclusion: The AISRS and its subscales are robust, valid efficacy measures of ADHD symptoms in adult patients. Its anchored items and semistructured interview are advancements over existing scales. (J. of Att. Dis. 2010; 14(1) 57-68)

Neurobiology of Alzheimer’s Disease: Integrated Molecular, Physiological, Anatomical, Biomarker, and Cognitive Dimensions

Background: Alzheimer’s disease (AD), the most common form of dementia, is a progressive neurodegenerative disorder with interrelated molecular, physiological, anatomical, biomarker, and cognitive dimensions. Methods: This article reviews the biological changes (genetic, molecular, and cellular) underlying AD and their correlation with the clinical syndrome. Results: Dementia associated with AD is related to the aberrant production, processing, and clearance of beta-amyloid and tau. Beta-amyloid deposition in brain follows a distinct spatial progression starting in the basal neocortex, spreading throughout the hippocampus, and eventually spreading to the rest of the cortex. The spread of tau pathology through neural networks leads to a distinct and consistent spatial progression of neurofibrillary tangles, beginning in the transentorhinal and hippocampal region and spreading superolaterally to the primary areas of the neocortex. Synaptic dysfunction and cell death is shown by progressive loss of cerebral metabolic rate for glucose and progressive brain atrophy. Decreases in synapse number in the dentate gyrus of the hippocampus correlate with declining cognitive function. Amyloid changes are detectable in cerebrospinal fluid and with amyloid imaging up to 20 years prior to the onset of symptoms. Structural atrophy may be detectable via magnetic resonance imaging up to 10 years before clinical signs appear. Conclusion: This review highlights the progression of biological changes underlying AD and their association with the clinical syndrome. Many changes occur before overt symptoms are evident and biomarkers provide a means to detect AD pathology even in patients without symptoms.

Once-Daily Atomoxetine for Treating Pediatric Attention-Deficit/Hyperactivity Disorder: Comparison of Morning and Evening Dosing

In this 3-arm, randomized, double-blind trial, once-daily morning-dosed atomoxetine, evening-dosed atomoxetine, and placebo were compared for treating pediatric attention-deficit/hyperactivity disorder (ADHD). Patients received morning atomoxetine/evening placebo (n = 102), morning placebo/evening atomoxetine (n = 93), or morning placebo/evening placebo (n = 93) for about 6 weeks. Core symptom efficacy was measured at weeks 0, 1, 3, and 6. Parent assessments of the child’s home behaviors in the evening and early morning were collected daily during the first 2 weeks of treatment. Morning-dosed and evening-dosed atomoxetine significantly decreased core ADHD symptoms relative to placebo and produced symptom improvements that were measured up to 24 hours later. Morning dosing was superior to evening dosing on some efficacy measures. Evening dosing showed greater tolerability with significantly more patients receiving morning atomoxetine reporting at least 1 adverse event than those receiving evening atomoxetine.

Effect of Atomoxetine on Executive Function Impairments in Adults with ADHD.

Objective: To assess the effect of atomoxetine on ADHD-related executive functions over a 6-month period using the Brown Attention-Deficit Disorder Scale (BADDS) for Adults, a normed, 40-item, self-report scale in a randomized, double-blind, placebo-controlled clinical trial. Method: In a randomized, double-blind clinical trial, adults with ADHD received either atomoxetine 25 to 100 mg/day or placebo for 6 months. Patients completed the BADDS to report their current daily functioning in 5 clusters of ADHD-related impairments of executive functioning: (1) Organizing and Activating to Work; (2) Focusing for Tasks; (3) Regulating Alertness and Effort; (4) Modulating Emotions; and (5) Utilizing Working Memory. Results: Mean scores were significantly more improved in the atomoxetine group compared to the placebo group: total score, -27.0 versus -19.0 (p < .001); all 5 cluster scores, p < .01. Conclusions: Once-daily atomoxetine can improve executive function impairments in adults with ADHD as assessed by the BADDS. (J. of Att. Dis. 2011; 15(2) 130-138)

Decline in hospitalization risk and health care cost after initiation of depot antipsychotics in the treatment of schizophrenia

Purpose: To assess change in hospitalization and cost of care from 6 months pre- to 6 months post-initiation on any depot antipsychotic among schizophrenia patients. Patients and methods: Using a large United States commercial claims and encounters database, patients younger than 65 years diagnosed with schizophrenia were identified. Patients initiated on a depot antipsychotic were studied in a mirror-image design to assess change in hospitalization rates, mean duration hospitalized, and hospitalization cost. McNemar’s test and paired t-tests compared the proportions of patients hospitalized and the mean duration. Paired t-test and bootstrapping methods compared costs. Results: In these patients (n = 147), psychiatric hospitalizations declined from 49.7% pre-initiation to 22.4% post-initiation (P < 0.001), and the mean hospitalized duration for psychiatric purposes numerically declined from 7.3 to 4.7 days (P = 0.05). Total health care costs declined from

Reasons for discontinuation and continuation of antipsychotics in the treatment of schizophrenia from patient and clinician perspectives.

11,111 to

Atomoxetine Treatment for ADHD: Younger Adults Compared with Older Adults

7884 (P < 0.05) driven by reduction in costs for psychiatric hospitalizations from

Atomoxetine treatment in adolescents with attention-deficit/hyperactivity disorder.

5384 to

The Life Participation Scale for Attention-Deficit/Hyperactivity Disorder–Child Version: Psychometric Properties of an Adaptive Change Instrument

2538 (P < 0.05). Conclusion: Initiation of depot antipsychotic therapy appeared to be associated with a decline in hospitalization rates and costs. Current findings suggest that treatment with depot antipsychotics may be a cost-effective option for a subgroup of patients with schizophrenia who are at high risk of nonadherence with their oral antipsychotic medication regimen.