Bonnie Wong

A Tale of Two Methods: Chart and Interview Methods for Identifying Delirium

To compare chart‐ and interview‐based methods for identification of delirium.

Dysfunction of dendritic cells in aged C57BL/6 mice leads to failure of natural killer cell activation and of tumor eradication

Significance Immunosenescence is an important phenomenon that leads to enhanced susceptibility both to bacterial and virus infections and to tumorigenesis. The reciprocal activation of dendritic cells (DCs) and natural killer cells (NKs) is a critical point in the maturation of both the adaptive and innate immune systems. Its failure could be a key point in immunosenescence. In this article, we show that in aged C57BL/6 mice that were known to be susceptible to mousepox virus, DCs are dysfunctional and unable to activate NKs. This defect also results in failure to eliminate RMA-S lymphoma mutant tumor cells in an NK-sensitive tumor model. A more complex situation regarding DC dysfunction is also described in a small sample of the outbred human population. The reciprocal activation of dendritic cells (DCs) and natural killer cells (NKs) plays a key role in both innate and adaptive immunity. The effect of aging on this cross-talk, a critical step in virus disease control and tumor immunology, has not been reported. Splenic DCs and NKs were purified from both young and old C57BL/6 mice and cocultured in the presence of polyinosinic:polycytidylic acid (poly I:C). The resulting activation of NKs was measured as expression of CD69 and secretion of IFN-γ. However, DCs from old mice could not activate NKs from either young or old mice in vitro or in vivo. In contrast, DCs from young mice efficiently activated NKs from both young and old mice. DCs from old mice were deficient in poly I:C-stimulated secretion of IL-15, IL-18, and IFN-α. Gene expression analysis revealed many other differences between DCs of old and young mice. Young mice strongly eradicated MHC class I-negative NK-sensitive RMA-S lymphoma mutant tumor cells, but old mice did not, in concert with the previous report that mousepox kills aged, but not young, C57BL/6 mice. Furthermore, a similar dysfunction of DC and its key role in NK activation was found in 27 out of 55 healthy human donors.

Neuropsychological Profiles of an Elderly Cohort Undergoing Elective Surgery and the Relationship Between Cognitive Performance and Delirium

To examine baseline (preoperative) neuropsychological test performance in a cohort of elderly individuals undergoing elective surgery and the association between specific neuropsychological domains and postoperative delirium.

Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits

BACKGROUND Type-2 diabetes mellitus (T2DM) accelerates cognitive aging and increases risk of Alzheimers disease. Rodent models of T2DM show altered synaptic plasticity associated with reduced learning and memory. Humans with T2DM also show cognitive deficits, including reduced learning and memory, but the relationship of these impairments to the efficacy of neuroplastic mechanisms has never been assessed. OBJECTIVE Our primary objective was to compare mechanisms of cortical plasticity in humans with and without T2DM. Our secondary objective was to relate plasticity measures to standard measures of cognition. METHODS A prospective cross-sectional cohort study was conducted on 21 adults with T2DM and 15 demographically-similar non-diabetic controls. Long-term potentiation-like plasticity was assessed in primary motor cortex by comparing the amplitude of motor evoked potentials (MEPs) from single-pulse transcranial magnetic stimulation before and after intermittent theta-burst stimulation (iTBS). Plasticity measures were compared between groups and related to neuropsychological scores. RESULTS In T2DM, iTBS-induced modulation of MEPs was significantly less than controls, even after controlling for potential confounds. Furthermore, in T2DM, modulation of MEPs 10-min post-iTBS was significantly correlated with Rey Auditory Verbal Learning Task (RAVLT) performance. CONCLUSION Humans with T2DM show abnormal cortico-motor plasticity that is correlated with reduced verbal learning. Since iTBS after-effects and the RAVLT are both NMDA receptor-dependent measures, their relationship in T2DM may reflect brain-wide alterations in the efficacy of NMDA receptors. These findings offer novel mechanistic insights into the brain consequences of T2DM and provide a reliable means to monitor brain health and evaluate the efficacy of clinical interventions.

Cognitive and Physical Demands of Activities of Daily Living in Older Adults: Validation of Expert Panel Ratings

Difficulties with performance of functional activities may result from cognitive and/or physical impairments. To date, there has not been a clear delineation of the physical and cognitive demands of activities of daily living.

The SAGES telephone neuropsychological battery: correlation with in-person measures.

Neuropsychological test batteries are administered in person to assess cognitive function in both clinical and research settings. However, in‐person administration holds a number of logistical challenges that makes it difficult to use in large or remote populations or for multiple serial assessments over time. The purpose of this descriptive study was to determine whether a telephone‐administered neuropsychological test battery correlated well with in‐person testing.

The interplay of neuroscience and cryptography: technical perspective

级人机接口 (BCI) 的发展扫清障碍。 有一部分甚至已向游戏玩家提供。 此类接口或许能免去用户在响应刺 激时键入操作的必要,也能加快以 内隐记忆为基础的用户身份验证。 未来某一天,更加先进的技术可能 会提供精细的大脑实时功能图,可 直接通过神经方式执行问答式身份 验证协议,而无需用户的有意识行 为。事实上,有证据表明,以刺激 神经可塑性(即大脑适应性)为目 标的技术可以增强许多形式的学习 和记忆,其中或许也包含密码。经 颅直流电刺激 (tDCS) 就是这样的一 种技术,现在已应用于让游戏玩家 感知“刺激”的低成本头戴式装置 中。奥巴马政府近期宣布了雄心勃 勃的“通过推动创新型神经技术开 展大脑研究 (BRAIN)”计划,该计划 有望能促进此类工具的发明。 有关神经科学与计算机安全的 相互作用还有许多未解答的问题。 可否利用大脑的自然计算能力实现 与智能卡或硬件身份验证令牌相当 的效用?现有的内隐记忆可否通过 精心制作的刺激而诱出?或许通过 人机接口来实现?最后,可否直接 从大脑读取用户的意图来检测和预 防恶意活动?人机接口对于隐私意 味着什么? 现在,请阅读一篇可激发此类 问题的精彩论文,文中当然也提供 了对一些问题的回答。

HARMONIZING TOGETHER: SPEECH AND MUSIC THERAPY AND SUPPORT FOR PATIENTS AND PARTNERS WITH PPA

The Frontotemporal Disorders Unit at Massachusetts General Hospital, Boston, Massachusetts, USA, facilitated an eight-week interdisciplinary therapeutic support group targeted at early stage PPA patients and their care partners. Group goals included providing patients and their care partners with functional communication strategies, decreasing patient isolation, support for caregiver resilience and music therapy to promote utilization of language, social engagement and emotional connections between patients and care partners.

NONLINEAR N-SCORE ESTIMATION FOR ESTABLISHING COGNITIVE NORMS FROM THE NATIONAL ALZHEIMER’S COORDINATING CENTER (NACC) DATASET

Background: The cerebrospinal fluid (CSF) Ab42/Ab40 ratio has been proposed a better biomarker for cerebral b-amyloidosis than CSFAb42 alone. Since 2014, the test has been available in our clinical laboratory practice upon request. Here, we evaluated the distribution of the CSF Ab42/Ab40 ratio, as well as its diagnostic accuracy in relation amyloid PET. Methods:The CSF Ab42/Ab40 ratio was measured on a weekly basis in clinical laboratory practice on consecutive samples from 3647 patients (1853 men, 1794 women, mean age 6 standard deviation, 71.5 6 8.2 years) over 3 years using the MSD Abeta Triplex assay according the manufacturer’s instructions (Meso Scale Discovery, Rockville, MD). Longitudinal stability in the measurements was maintained using an elaborate QC system. One thousand nineteen of the patients were from the specialized memory clinic at Sk ane University Hospital. One hundred and forty three of these had undergone amyloid ([18]F-flutemetamol) PET. Optimal cut-points to discriminate bimodally distributed groups were determined by mixture modelling. The optimal cut-point for differentiating Ab-positive from -negative patients according to amyloid PET was determined as the one that generated the highest Youden index. Results: The CSF Ab42/Ab40 ratio (all data) showed a bimodal normal distribution. The mixture modelling-derived optimal cut-point for differentiating the two groups was 0.076. More patients (56%) were found in the low (Ab-positive) group. When examining patients from the specialized memory clinic separately, a similar bimodal distribution was seen; the optimal cut-point for distinguishing the two groups was 0.080 and 49% of the patients had ratios below this limit. In patients who had undergone amyloid PET, the optimal mixture modelling-derived cut-point was 0.077, which was a little lower than the Youden index-derived cut-point (0.083) that best discriminated Ab-positive from -negative cases (diagnostic accuracy 97%). Conclusions: The CSF Ab42/Ab40 ratio is a bimodal biomarker. The striking lack of individuals with grey zone CSF Ab42/Ab40 ratios suggests that people change Ab status according to the ratio quite rapidly. It is not a gradual increase of Ab plaque pathology over years that slowly changes the ratio; rather, the ratio appears to reflect a switch-like shift in Ab homeostasis in the CSF.

CHARACTERISTICS AND PROGRESS ON THE INITIAL 209 SUBJECTS IN THE LONGITUDINAL EVALUATION OF FAMILIAL FRONTOTEMPORAL DEMENTIA SUBJECTS (LEFFTDS) PROTOCOL

O2-14-01 CHARACTERISTICS AND PROGRESS OF 320 SUBJECTS IN THE LONGITUDINAL EVALUATION OF FAMILIAL FRONTOTEMPORAL DEMENTIA SUBJECTS (LEFFTDS) PROTOCOL LeahK. Forsberg, Bradley F. Boeve, Howard J. Rosen, AdamL. Boxer, Jessica Bove, Danielle Brushaber, Giovanni Coppola, Christina Dheel, Brad C. Dickerson, Susan Dickinson, Kelley Faber, Julie A. Fields, Jamie Fong, Tatiana M. Foroud, Ralitza H. Gavrilova, Debra Gearhart, Nupur Ghoshal, Jill Goldman, Jonathan Graff-Radford, Neill R. GraffRadford, Murray Grossman, Dana Haley, Hilary W. Heuer, John Hsiao, Ging-Yuek Robin Hsiung, Edward D. Huey, David J. Irwin, David T. Jones, Lynne Jones, Kejal Kantarci, Anna M. Karydas, David S. Knopman, John Kornak, Joel H. Kramer, Walter K. Kremers, Walter A. Kukull, Maria I. Lapid, Diane Lucente, Ian R. Mackenzie, Masood Manoochehri, Scott M. McGinnis, Bruce L. Miller, Rodney Pearlman, Leonard Petrucelli, Madeline Potter, Rosa Rademakers, Katherine Rankin, Katya Rascovsky, Pheth Sengdy, Leslie M. Shaw, Marg Sutherland, Jeremy Syrjanen, Nadine Tatton, Joanne Taylor, Arthur W. Toga, John Q. Trojanowski, Sandra Weintraub, Bonnie Wong, Zbigniew Wszolek, Mayo Clinic, Rochester, MN, USA; University of California San Francisco, San Francisco, CA, USA; Penn Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, PA, USA; University of California, Los Angeles School of Medicine, Los Angeles, CA, USA; Massachusetts General Hospital, Boston, MA, USA; Association of Frontotemporal Degeneration, Radnor, PA, USA; Indiana University School of Medicine, Indianapolis, IN, USA; Washington University, Saint Louis,MO, USA; ColumbiaUniversity, New York, NY, USA; MayoClinic, Jacksonville, FL, USA; National Institutes of Health, Bethesda, MD, USA; University of British Columbia, Vancouver, BC, Canada; National Alzheimer’s Coordinating Center, University of Washington, Seattle, WA, USA; The Harvard Clinical and Translational Science Center, Boston, MA, USA; Brigham and Women’s Hospital, Boston, MA, USA; The Bluefield Project, San Francisco, CA, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Northwestern University, Chicago, IL, USA. Contact e-mail: Forsberg.Leah@mayo.edu