No abstract

If treatments for cognitive impairment are to be utilized successfully, clinicians must be able to determine whether they are effective and which patients should receive them. In order to develop consensus on these issues, the International Society for CNS Clinical Trials and Methodology (ISCTM) held a meeting of experts on March 20, 2014, in Washington, DC. Consensus was reached on several important issues. Cognitive impairment and functional disability were viewed as equally important treatment targets. The group supported the notion that sufficient data are not available to exclude patients from available treatments on the basis of age, severity of cognitive impairment, severity of positive symptoms, or the potential to benefit functionally from treatment. The group reached consensus that cognitive remediation is likely to provide substantial benefits in combination with procognitive medications, although a substantial minority believed that medications can be administered without nonpharmacological therapy. There was little consensus on the best methods for assessing cognitive change in clinical practice. Some participants supported the view that performance-based measures are essential for measurement of cognitive change; others pointed to their cost and time requirements as evidence of impracticality. Interview-based measures of cognitive and functional change were viewed as more practical, but lacking validity without informant involvement or frequent contact from clinicians. The lack of consensus on assessment methods was viewed as attributable to differences in experience and education among key stakeholders and significant gaps in available empirical data. Research on the reliability, validity, sensitivity, and practicality of competing methods will facilitate consensus.

At the 2008 annual meeting of the American College of Neuropsychopharmacology (ACNP), a symposium was devoted to the following question: 'what have we learned about the design of pragmatic clinical trials (PCTs) from the recent costly long-term, large-scale trials of psychiatric treatments?' in order to inform the design of future trials. In all, 10 recommendations were generated placing emphasis on (1) appropriate conduct of pragmatic trials; (2) clinical, rather than, merely statistical significance; (3) sampling from the population clinicians are called upon to treat; (4) clinical outcomes of patients, rather than, on outcome measures; (5) use of stratification, controlling, or adjusting when necessary and not otherwise; (6) appropriate consideration of site differences in multisite studies; (7) encouragement of 'post hoc' exploration to generate (not test) hypotheses; (8) precise articulation of the treatment strategy to be tested and use of the corresponding appropriate design; (9) expanded opportunity for training of researchers and reviewers in RCT principles; and (10) greater emphasis on data sharing.

Children of Alzheimer's Disease (AD) patients are at heightened risk of developing AD due to genetic influences, including the apolipoprotein E4 (ApoE4) allele. In this study, we assessed the earliest cortical changes associated with AD in 71 cognitively healthy, adult children of AD patients (AD offspring) as compared with 69 with no family history of AD (non-AD offspring). Cortical thickness measures were obtained using FreeSurfer from 1.5T magnetic resonance (MR) scans. ApoE genotyping was obtained. Primary analyses examined family history and ApoeE4 effects on cortical thickness. Secondary analyses examined age effects within groups. All comparisons were adjusted using False Discovery Rate at a significance threshold of p < 0.05. There were no statistically significant differences between family history and ApoE4 groups. Within AD offspring, increasing age was related to reduced cortical thickness (atrophy) over large areas of the precuneus, superior frontal and superior temporal gyri, starting at around age 60. Further, these patterns existed within female and maternal AD offspring, but were absent in male and paternal AD offspring. Within non-AD offspring, negative correlations existed over small regions of the superior temporal, insula and lingual cortices. These results suggest that as AD offspring age, cortical atrophy is more prominent, particularly if the parent with AD is mother or if the AD offspring is female.

Posters (Saturday) S141 Background: Short-latency afferent inhibition (SAI) is the neurophysiological transcranial magnetic stimulation (TMS) paradigm that indexes central cholinergic activity from the motor cortex (M1). Recently, we established a method to index SAI from the dorsolateral prefrontal cortex (DLPFC), an area implicated in the pathophysiology of schizophrenia (SCZ). Here, we investigated SAI in both M1 and the DLPFC in SCZ patients compared to healthy controls (HC). We hypothesized that modulation of N100 on TMS-evoked potential (TEP) by SAI paradigm from the DLPFC would be attenuated in SCZ compared to HC. Further, the modulation of N100 would be correlated with cognitive performance. Methods: Age-matched 12 SCZ and 12 HC were examined with a combined TMS-electroencephalography (EEG). SAI from the left M1 (M1-SAI) and DLPFC (DLPFC-SAI) were indexed by conditioning a single suprathreshold TMS with right median nerve stimulation at interstimulus intervals of N20+2ms (M1-SAI) and N20+4ms (DLPFC-SAI), respectively. TEPs by M1-and DLPFC-SAI were analyzed using independent component analysis individually. Results: With M1-SAI paradigm, there was no significant change in TEP N100 (t11 = −2.30, P = .822) in the SCZ group or no significant difference in N100 modulation between the HC and SCZ groups (t22 = 1.917, P = 0.068). However, with DLPFC-SAI paradigm, we observed a significant N100 attenuation at the DLPFC (t11 = −4.926, P < .0001), and modulation of N100 was significantly different between the HC and SCZ groups (t22 = 5.456, P < .0001; SCZ < HC). Furthermore, the N100 modulation by DLPFC-SAI was significantly correlated with executive function as measured with the Trail Making Test (r = −0.740, P = .006, N = 12). Conclusion: The modulation of N100 by the DLPFC-SAI may reflect the prefrontal pathophysiology of SCZ and thus could be a potential biomarker for cholinergic and executive dysfunction in SCZ.