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Objectives: Florbetapir F 18 PET can image amyloid-␤ (A␤) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting A␤ pathology using florbetapir PET in subjects at risk for progressive cognitive decline. Methods:A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (A␤ϩ) or negative (A␤Ϫ) for pathologic levels of ␤-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.

Objective:To determine the efficacy and safety of deutetrabenazine as a treatment for tardive dyskinesia (TD).Methods:One hundred seventeen patients with moderate to severe TD received deutetrabenazine or placebo in this randomized, double-blind, multicenter trial. Eligibility criteria included an Abnormal Involuntary Movement Scale (AIMS) score of ≥6 assessed by blinded central video rating, stable psychiatric illness, and stable psychoactive medication treatment. Primary endpoint was the change in AIMS score from baseline to week 12. Secondary endpoints included treatment success at week 12 on the Clinical Global Impression of Change (CGIC) and Patient Global Impression of Change.Results:For the primary endpoint, deutetrabenazine significantly reduced AIMS scores from baseline to week 12 vs placebo (least-squares mean [standard error] −3.0 [0.45] vs −1.6 [0.46], p = 0.019). Treatment success on CGIC (48.2% vs 40.4%) favored deutetrabenazine but was not significant. Deutetrabenazine and placebo groups showed low rates of psychiatric adverse events: anxiety (3.4% vs 6.8%), depressed mood/depression (1.7% vs 1.7%), and suicidal ideation (0% vs 1.7%, respectively). In addition, no worsening in parkinsonism, as measured by the Unified Parkinson's Disease Rating Scale motor subscale, was noted from baseline to week 12 in either group.Conclusions:In patients with TD, deutetrabenazine was well tolerated and significantly reduced abnormal movements.Classification of evidence:This study provides Class I evidence that in patients with TD, deutetrabenazine reduces AIMS scores.

The objective of this study was to evaluate the relationship of amyloid burden, as assessed by florbetapir F 18 (18F-AV-45) amyloid PET, and cognition in healthy older control subjects (HC). Seventy-eight HC subjects were assessed with a brief cognitive test battery and PET imaging with florbetapir F 18. A standard uptake value ratio (SUVr) was computed for mean data from six cortical regions using a whole cerebellum reference region. Scans were also visually rated as amyloid positive (Aβ+) or amyloid negative (Aβ−) by three readers. Higher SUVr correlated with lower immediate memory (r=−0.33; p=0.003) and delayed recall scores (r=−0.25; p=0.027). Performance on immediate recall was also lower in the visually rated Aβ+ compared to Aβ− HC (p=0.04), with a similar trend observed in delayed recall (p=0.06). These findings support the hypothesis that higher amyloid burden is associated with lower memory performance among clinically normal older subjects. Longitudinal follow-up is ongoing to determine whether florbetapir F 18 may also predict subsequent cognitive decline.

Background:The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) was formed by the National MS Society to develop improved measures of multiple sclerosis (MS)-related disability.Objectives:(1) To assess the current literature and available data on functional performance outcome measures (PerfOs) and (2) to determine suitability of using PerfOs to quantify MS disability in MS clinical trials.Methods:(1) Identify disability dimensions common in MS; (2) conduct a comprehensive literature review of measures for those dimensions; (3) develop an MS Clinical Data Interchange Standards Consortium (CDISC) data standard; (4) create a database of standardized, pooled clinical trial data; (5) analyze the pooled data to assess psychometric properties of candidate measures; and (6) work with regulatory agencies to use the measures as primary or secondary outcomes in MS clinical trials.Conclusion:Considerable data exist supporting measures of the functional domains ambulation, manual dexterity, vision, and cognition. A CDISC standard for MS (http://www.cdisc.org/therapeutic#MS) was published, allowing pooling of clinical trial data. MSOAC member organizations contributed clinical data from 16 trials, including 14,370 subjects. Data from placebo-arm subjects are available to qualified researchers. This integrated, standardized dataset is being analyzed to support qualification of disability endpoints by regulatory agencies.