Biomarker-based prediction of progression in MCI: Comparison of AD signature and hippocampal volume with spinal fluid amyloid-β and tau

Objective: New diagnostic criteria for mild cognitive impairment (MCI) due to Alzheimer's disease (AD) have been developed using biomarkers aiming to establish whether the clinical syndrome is likely due to underlying AD. We investigated the utility of magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers in predicting progression from amnesic MCI to dementia, testing the hypotheses that (1) markers of amyloid and neurodegeneration provide distinct and complementary prognostic information over different time intervals, and that (2) evidence of neurodegeneration in amyloid-negative MCI individuals would be useful prognostically. Methods: Data were obtained from the ADNI-1 (Alzheimer's Disease Neuroimaging Initiative Phase 1) database on all individuals with a baseline diagnosis of MCI, baseline MRI and CSF data, and at least one follow-up visit. MRI data were processed using a published set of a priori regions of interest to derive a measure known as the ``AD signature,'' as well as hippocampal volume. The CSF biomarkers amyloid-β, total tau, and phospho tau were also examined. We performed logistic regression analyses to identify the best baseline biomarker predictors of progression to dementia over 1 or 3 years, and Cox regression models to test the utility of these markers for predicting time-to-dementia. Results: For prediction of dementia in MCI, the AD signature cortical thickness biomarker performed better than hippocampal volume. Although CSF tau measures were better than CSF amyloid-β at predicting dementia within 1 year, the AD signature was better than all CSF measures at prediction over this relatively short-term interval. CSF amyloid-β was superior to tau and AD signature at predicting dementia over 3 years. When CSF amyloid-β was dichotomized using previously published cutoff values and treated as a categorical variable, a multivariate stepwise Cox regression model indicated that both the AD signature MRI marker and the categorical CSF amyloid-β marker were useful in predicting time-to-event diagnosis of AD dementia. Conclusion: In amnesic MCI, short-term (1 year) prognosis of progression to dementia relates strongly to baseline markers of neurodegeneration, with the AD signature MRI biomarker of cortical thickness performing the best among MRI and CSF markers studied here. Longer-term (3 year) prognosis in these individuals was better predicted by a marker indicative of brain amyloid. Prediction of time-to-event in a survival model was predicted by the combination of these biomarkers. These results provide further support for emerging models of the temporal relationship of pathophysiologic events in AD and demonstrate the utility of these biomarkers at the prodromal stage of the illness

Defining Success: The Politics of Evaluation in Alcohol and Drug Abuse Treatment Programs

Alcohol and drug abuse treatment programs must respond to several important stakeholders or beneficiaries of services who have an investment in how success is defined. Utilizing data from recent statewide studies of treatment outcomes of alcohol and drug abuse services, this paper concludes that a strict adherence to an abstinence-only model of success, rigidly adopted by many in the treatment industry is counterproductive. Multiple measures of success are essential to fully understand and assess a changing model of intervention in the chemical dependency field

Stability of Imipenem and Cilastatin Sodium in Total Parenteral Nutrient Solution

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141138/1/jpen0306.pd

Recognition memory in amnestic-mild cognitive impairment: insights from event-related potentials

Episodic memory loss is the hallmark cognitive dysfunction associated with Alzheimer’s disease (AD). Amnestic mild cognitive impairment (a-MCI) frequently represents a transitional stage between normal aging and early AD. A better understanding of the qualitative features of memory loss in a-MCI may have important implications for predicting those most likely to harbor AD-related pathology and for disease monitoring. Dual process models of memory argue that recognition memory is subserved by the dissociable processes of recollection and familiarity. Work studying recognition memory in a-MCI from this perspective has been controversial, particularly with regard to the integrity of familiarity. Event-related potentials (ERPs) offer an alternative means for assessing these functions without the associated assumptions of behavioral estimation methods. ERPs were recorded while a-MCI patients and cognitively normal (CN) age-matched adults performed a recognition memory task. When retrieval success was measured (hits versus correct rejections) in which performance was matched by group, a-MCI patients displayed similar neural correlates to that of the CN group, including modulation of the FN400 and the late positive complex (LPC) which are thought to index familiarity and recollection, respectively. Alternatively, when the integrity of these components was measured based on retrieval attempts (studied versus unstudied items), a-MCI patients displayed a reduced FN400 and LPC. Furthermore, modulation of the FN400 correlated with a behavioral estimate of familiarity and the LPC with a behavioral estimate of recollection obtained in a separate experiment in the same individuals, consistent with the proposed mappings of these indices. These results support a global decline of recognition memory in a-MCI, which suggests that the memory loss of prodromal AD may be qualitatively distinct from normal aging

Improved Proper Name Recall in Aging after Electrical Stimulation of the Anterior Temporal Lobes

Evidence from neuroimaging and neuropsychology suggests that portions of the anterior temporal lobes (ATLs) play a critical role in proper name retrieval. We previously found that anodal transcranial direct current stimulation (tDCS) to the ATLs improved retrieval of proper names in young adults (Ross et al., 2010). Here we extend that finding to older adults who tend to experience greater proper-naming deficits than young adults. The task was to look at pictures of famous faces or landmarks and verbally recall the associated proper name. Our results show a numerical improvement in face naming after left or right ATL stimulation, but a statistically significant effect only after left-lateralized stimulation. The magnitude of the enhancing effect was similar in older and younger adults but the lateralization of the effect differed depending on age. The implications of these findings for the use of tDCS as tool for rehabilitation of age-related loss of name recall are discussed

Stable Coronal X-Ray Emission Over Twenty Years of XZ Tau

XZ Tau AB is a frequently observed binary YSO in the Taurus Molecular Cloud; XZ Tau B has been classified as an EXOr object. We present new Chandra/HETG-ACIS-S observations of XZ Tau AB, complemented with variability monitoring of the system with XMM-Newton, to constrain the variability of this system and identify high-resolution line diagnostics to better understand the underlying mechanisms that produce the X-rays. We observe two flares with XMM-Newton, but find that outside of these flares the coronal X-ray spectrum of XZ Tau AB is consistent over twenty years of observations. We compare the ensemble of XZ Tau X-ray observations over time with the scatter across stars observed in point-in-time observations of the Orion Nebula Cluster and find that both overlap in terms of plasma properties, i.e., some of the scatter observed in the X-ray properties of stellar ensembles stems from intrinsic source variability.Comment: Accepted for publication in the Astronomical Journal. 19 pages, 11 figure

Orbiting clouds of material at the Keplerian co-rotation radius of rapidly rotating low mass WTTs in Upper Sco

Using K2 data, we have identified 23 very low mass members of the ρ Oph and Upper Scorpius star-forming region as having periodic photometric variability not easily explained by well-established physical mechanisms such as star spots, eclipsing binaries, or pulsation. All of these unusual stars are mid-to-late M dwarfs without evidence of active accretion, and with photometric periods generally <1 day. Often the unusual light curve signature takes the form of narrow flux dips; when we also have rotation periods from star spots, the two periods agree, suggesting that the flux dips are due to material orbiting the star at the Keplerian co-rotation radius. We sometimes see “state-changes” in the phased light curve morphologies where ∼25% of the waveform changes shape on timescales less than a day; often, the “state-change” takes place immediately after a strong flare. For the group of stars with these sudden light curve morphology shifts, we attribute their flux dips as most probably arising from eclipses of warm coronal gas clouds, analagous to the sling-shot prominences postulated to explain transient Hα absorption features in AB Doradus itself and other rapidly rotating late type stars. For another group of stars with somewhat longer periods, we find the short duration flux dips to be highly variable on both short and long timescales, with generally asymmetric flux dip profiles. We believe that these flux dips are due to particulate clouds possibly associated with a close-in planet or resulting from a recent collisional event.PostprintPeer reviewe