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Shaohua You,1,* Xiaoyan Qin,2,* Guoli Zhao,1 Zeguo Feng1 1Department of Pain Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Clinical Laboratory, Shijingshan Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing, 100049, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zeguo Feng; Guoli Zhao, Department of Pain Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Email BEIJING301@yeah.net; 2497391298@qq.comBackground: Trigeminal neuralgia (TN) is a common form of craniofacial pain, and Radiofrequency thermocoagulation (RFT) has become a commonly utilized treatment modality for TN. However, the complex anatomical configuration of the maxillofacial region and the difficulties inherent in positioning the neck in a hyperextended manner can present challenges for CT-guided punctures.Aim: The objective of this study is to assess the effectiveness and safety of 3D printed tooth-supported template(3D-PTST) guided RFT in patients who have previously undergone unsuccessful CT-guided puncture.Methods: Patients with TN undergoing RFT at the Department of Pain Medicine, PLA General Hospital, from January 2018 to January 2023, were assessed. 3D-PTST guided RFT was employed as an alternative when percutaneous puncture failed. Clinical, demographic, and follow-up data were collected. The duration of the procedure was determined by subtracting the time of anesthesia administration from the time of surgical drape removal. Pain intensity was assessed using the Numerical Rating Scale-11 scale. Treatment effects were evaluated utilizing the Barrow Neurological Institute scale. Incidences of complications related to RFA were documented.Results: Six TN patients underwent 3D-PTST guided RFT. With tooth-supported template guidance, five patients achieved therapeutic target puncture in one attempt with one CT scan. One patient required two attempts with two CT scans. Operation duration ranged from 18 to 46 mins (mean 30 mins). All completed 3D-PTST-guided RFT without difficulty, significantly improving pain symptoms. Four patients had no pain recurrence at 12, 18, 36 and 37 months follow-up, respectively. Recurrence occurred in two patients (at 1 and 13 months). No serious treatment-related complications were observed.Conclusion: 3D-PTST guided RFT is an effective, repeatable, safe, and minimally invasive treatment method for patients with TN who have failed due to difficulty in puncture.Keywords: trigeminal neuralgia, radiofrequency thermocoagulation, tooth-supported template, 3D printing technology

Shaohua You,1,* Xiaoyan Qin,2,* Li Tong,3 Zeguo Feng1 1Department of Pain Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 2Department of Clinical Laboratory, Shijingshan Teaching Hospital of Capital Medical University, Beijing Shijingshan Hospital, Beijing, 100049, People’s Republic of China; 3Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zeguo Feng, Department of Pain Medicine, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Email beijing301@yeah.net; Li Tong, Department of Anesthesiology, The First Medical Center of Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China, Email tongli301@aliyun.comBackground: Glossopharyngeal neuralgia (GPN) is a rare chronic neuropathic pain disorder that significantly impacts quality of life. Ultrasound-guided glossopharyngeal nerve blocks (UGPNB) have gained popularity due to their various advantages. However, there have been no studies reporting the long-term outcomes of UGPNB in a larger cohort of GPN patients.Aim: This study aims to evaluate the efficacy and safety of UGPNB in patients with GPN.Methods: We reviewed the electronic medical records of patients with GPN who received UGPNB at the Department of Pain Medicine of the First Medical Center, PLA General Hospital between June 1, 2011, and June 1, 2022. The effect of UGPNB was evaluated using the Barrow Neurological Institute (BNI) scale. Improvement was defined as a reduction in pain category by comparing pain categories before and after therapy. Recovery was defined as achieving BNI I after treatment. Patients who responded to treatment but then regressed to the category before therapy were considered to have experienced pain relapse.Results: A total of 43 patients with GPN who received UGPNB were included in the analysis. At discharge, 35 (81.4%) patients experienced pain improvement after treatment, and among them, 13 (30.2%) patients achieved recovery. After discharge, 13 patients (37.1%) out of the 35 effective patients experienced pain relapse at different time intervals: 0.5, 0.7, 1, 1, 3, 3, 4, 12, 15, 36, 45, 63, and 96 months. The cumulative recurrence-free survival rates were 88.85% at month 1, 82.83% at month 3, 77.04% at month 12, 70.31% at month 36, and 54.66% at month 120. Among the 13 patients who experienced relapse, four patients received a second UGPNB treatment, and pain improved in two patients (50%). No severe adverse reactions were documented.Conclusion: UGPNB is an effective, repeatable, safe, and minimally invasive treatment for patients with GPN. It may be preferable to consider UGPNB before undergoing invasive intracranial surgery or neurodestructive methods.Keywords: ultrasound-guided glossopharyngeal nerve block, glossopharyngeal neuralgia, efficacy, safety

Shengqi You,1 Tingyu Lv,1 Ruomeng Qin,2 Zheqi Hu,2 Zhihong Ke,2 Weina Yao,1 Hui Zhao,2 Feng Bai2,3 1Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, People’s Republic of China; 2Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, People’s Republic of China; 3Geriatric Medicine Center, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, People’s Republic of ChinaCorrespondence: Feng Bai, Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, 210009, Jiangsu Province, People’s Republic of China, Tel +86-25-83105960, Email baifeng515@126.comStudy Objectives: By examining spontaneous activity changes of sleep-related networks in patients with the Alzheimer’s disease (AD) spectrum with or without insomnia disorder (ID) over time via neuro-navigated repetitive transcranial magnetic stimulation (rTMS), we revealed the effect and mechanism of rTMS targeting the left-angular gyrus in improving the comorbidity symptoms of the AD spectrum with ID.Methods: A total of 34 AD spectrum patients were recruited in this study, including 18 patients with ID and the remaining 16 patients without ID. All of them were measured for cognitive function and sleep by using the cognitive and sleep subscales of the neuropsychiatric inventory. The amplitude of low-frequency fluctuation changes in sleep-related networks was revealed before and after neuro-navigated rTMS treatment between these two groups, and the behavioral significance was further explored.Results: Affective auditory processing and sensory-motor collaborative sleep-related networks with hypo-spontaneous activity were observed at baseline in the AD spectrum with ID group, while substantial increases in activity were evident at follow-up in these subjects. In addition, longitudinal affective auditory processing, sensory-motor and default mode collaborative sleep-related networks with hyper-spontaneous activity were also revealed at follow-up in the AD spectrum with ID group. In particular, longitudinal changes in sleep-related networks were associated with improvements in sleep quality and episodic memory scores in AD spectrum with ID patients.Conclusion: We speculated that left angular gyrus-navigated rTMS therapy may enhance the memory function of AD spectrum patients by regulating the spontaneous activity of sleep-related networks, and it was associated with memory consolidation in the hippocampus-cortical circuit during sleep.Clinical Trial Registration: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR2100050496, China.Keywords: Alzheimer’s disease, insomnia disorder, sleep-related functional connectivity network, neuro-navigated repetitive transcranial magnetic stimulation, spontaneous activity

Shihao You,1,* Xianghui He,2,* Mei Wang,1 Lina Mao,1 Lu Zhang3 1Department of Neurology, Qingdao Fuwai Cardiovascular Hospital, Qingdao, Shandong, People’s Republic of China; 2Department of Emergency, Qingdao Fuwai Cardiovascular Hospital, Qingdao, Shandong, People’s Republic of China; 3Department of Peripheral Vascular Diseases, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lu Zhang Email nskoiz@163.comBackground: Tanshinone IIA (TIIA) is one of the active constituents derived from the rhizome of Danshen, a traditional Chinese herbal. Recently, microRNAs (miRNAs) have been suggested to be associated with the anticancer role of TIIA. However, it remains vague of the interaction between miRNAs and TIIA in glioma, a common aggressive brain tumor in humans.Methods: Expression of miRNA (miR)-16-5p and talin-1 (TLN1) was detected using reverse transcription-quantitative polymerase chain reaction and Western blotting. Cell proliferation, migration and invasion were assessed with cell viability assay, transwell assay, Western blotting, and xenograft tumor experiment. The target binding between miR-16-5p and TLN1 was confirmed by dual-luciferase reporter assay and RNA pull-down assay.Results: TIIA treatment inhibited cell viability, migration and invasion, and decreased Cyclin D1, matrix metalloproteinase (MMP)-9 and Vimentin expression in glioma T98G and A172 cells both in vitro and in vivo. Thus, TIIA induced anti-glioma role, wherein miR-16-5p was upregulated and TLN1 was downregulated. Moreover, silencing miR-16-5p could abate TIIA-mediated suppression on glioma cell proliferation, migration and invasion in vitro and in vivo. TLN1 overexpression also exerted tumor-promoting effect in TIIA-treated T98G and A172 cells. Mechanically, miR-16-5p could regulate TLN1 expression via target binding, and depleting TLN1 could counteract the inhibitory effect of miR-16-5p knockdown on the curative effect of TIIA in T98G and A172 cells.Conclusion: TIIA exerted the anti-proliferation, anti-migration and anti-invasion role in glioma cells both in vitro and in vivo partially through regulating miR-16-5p/TLN1 axis.Keywords: tanshinone IIA, TIIA, miR-16-5p, TLN1, glioma

Yitian Yang,1,* Xiaoyan Wang,2,* Xuan Zhang,3 Shaohua You,1 Long Feng,1 Yunliang Zhang,1 Yizheng Shi,1 Yuhai Xu,4 Hong Zhang1 1Anesthesia and Operation Center, The First Medical Center of Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100853, People’s Republic of China; 2Department of Anesthesiology, The Fourth Medical Center of Chinese PLA General Hospital, Medical School of Chinese PLA, Beijing 100037, People’s Republic of China; 3Department of Anesthesiology, Tianjin Cancer Institute & Hospital, Tianjin Medical University, Tianjin 300060, People’s Republic of China; 4Department of Anesthesiology, Air Force Medical Center, Beijing 100142, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hong Zhang; Yitian Yang Email mazuimao301@163.com; yangyitiansdu@126.comPurpose: Some patients undergoing thoracotomy may suffer from chronic post-thoracotomy pain (CPTP). Treatment of CPTP has been a clinical challenge and the underlying mechanisms of CPTP remain elusive. Recently, sonic hedgehog (Shh) signaling has been shown to be associated with various pain states but its role in the pathogenesis of CPTP is still unclear.Methods: CPTP was induced in rats by thoracotomy. Rats were divided into CPTP group and non-CPTP group based on the mechanical withdrawal threshold (MWT). Rats were administered with Shh signaling inhibitor cyclopamine and activator smoothened agonist (SAG), and then evaluated by MWT and cold allodynia testing. The expressions of Shh signaling (Shh ligand, patched and smoothened receptor, Gli transcription factors), brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase receptor B (Trk-B), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) in rat T4-5 spinal cord dorsal horn (SDH) were detected by Western blotting and immunohistochemistry.Results: The expression of Shh signaling significantly increased and the BDNF/TrkB pathway was activated in T4-5 SDH of CPTP rats. Cyclopamine attenuated hyperalgesia and down-regulated the expressions of Gil1, BDNF, p-TrkB, p-PI3K and p-Akt in CPTP rats. SAG induced hyperalgesia in non-CPTP rats and elevated the expressions of Gil1, BDNF, p-TrkB, p-PI3K and p-Akt.Conclusion: Shh signaling may contribute to CPTP via activating BDNF/TrkB signaling pathway, and inhibition of Shh signaling may effectively alleviate CPTP.Keywords: sonic hedgehog, chronic post-thoracotomy pain, brain-derived neurotrophic factor, spinal cord dorsal horn, PI3K, Akt

Yue Zhao,1,2,* Ya-qi Yu,1,* Song You,3 Chang-mao Zhang,4 Liang Wu,5 Wenxiu Zhao,1 Xiao-min Wang1 1Department of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen, Fujian 361004, People’s Republic of China; 2Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich 81377, Germany; 3Mengchao Hepatobiliary Hospital of Fujian Medical University, The Liver Center of Fujian Province, Fujian Medical University, Fuzhou 350025, People’s Republic of China; 4Faculty of Clinical Medicine, Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 5Department of Nephrology, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian 361003, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-min WangDepartment of Hepatobiliary Surgery, Zhongshan Hospital, Xiamen University, Fujian Provincial Key Laboratory of Chronic Liver Disease and Hepatocellular Carcinoma, Xiamen, Fujian 361004, People’s Republic of ChinaEmail wxm2203@xmu.edu.cnPurpose: Accumulating studies have explored the potential diagnostic value of lncRNA MALAT1 in various cancers. However, there are still inconsistent results in diagnostic accuracy and reliability in individual studies. The aim of this pooled study was to summarize the overall diagnostic capacity of lncRNA MALAT1 in cancer detection and diagnosis.Methods: Eligible studies satisfying the inclusion criteria were screened and selected from the online database. All statistical analyses were performed using Stata 14.0.Results: A total of 17 eligible studies were included in this pooled analysis, with 1777 cases and 1478 controls. The overall results were shown as follows: sensitivity, 0.74 (95% CI=0.65– 0.81), specificity, 0.79 (95% CI=0.73– 0.84), positive likelihood ratio (PLR), 3.48 (95% CI=2.79– 4.32), negative likelihood, 0.33 (95% CI=0.25– 0.44), diagnostic score, 2.34 (95% CI=1.99– 2.69), diagnostic odds ratio, 10.41 (95% CI=7.33– 14.78) and area under the curve, 0.83 (95% CI=0.80– 0.86). Deeks’ funnel plot asymmetry test (p = 0.66) suggested no potential publication bias.Conclusion: All these results indicate that lncRNA MALAT1 achieves a relatively moderate accuracy in cancer detection and diagnosis, and could serve as a diagnostic biomarker for cancers.Keywords: lncRNA, MALAT1, cancer, pooled analysis, detection, diagnosis

Sunghwa You, 1, 2 Woojae Han, 1–3 Saea Kim, 1, 2 Sanga Maeng, 4 Young Joon Seo 4 1Laboratory of Hearing and Technology; 2Division of Speech Pathology and Audiology; 3Research Institute of Audiology and Speech Pathology, College of Natural Sciences, Hallym University, Chuncheon, Korea; 4Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, Wonju, KoreaCorrespondence: Woojae Han #8603 Natural Sciences Bd., 1 Hallymdaehak-Gil, Chuncheon 24252, Republic of KoreaTel +82-33-248-2216Fax +82-33-256-3420Email woojaehan@hallym.ac.krObjective: The present study aimed to identify the reliability and validity of a screening tool for the elderly who wish to check their level of hearing loss by themselves.Design: A total of 170 older adults with different hearing levels participated. The Self-Assessment for Hearing Screening of the Elderly-Revised (SHSE-R) consisted of 20 questions measured on a 5-point scale and developed in terms of characteristics of age-related hearing loss. For reliability, the subjects responded to SHSE-R twice with a three-week interval. They also took various subjective and objective hearing tests and a working memory test and filled out two other questionnaires for validation.Results: SHSE-R showed a high internal consistency and a high reliability when comparing test–retest scores. Its content validity was as high as 0.88– 1. Convergent validity supported SHSE-R and its subcategories while showing either a positive or negative correlation with pure-tone average, word recognition scores, and otoacoustic emission tests. Construct validity was proved by a moderate negative correlation with the tests of speech in noise, speech with fast speed, and working memory. In criterion validity, a strong positive correlation existed between SHSE-R and the other questionnaires, except for a group with severe hearing loss. The factor analysis showed similar results to the original version of SHSE having three factors, although some items were interchanged.Conclusion: We confirmed that SHSE-R was well developed with both excellent internal consistency and test–retest reliability and valuable convergent, construct, and criterion validities, consequently making SHSE-R useful for self-checking hearing loss in the elderly.Keywords: hearing screening, self-assessment, questionnaire, age-related hearing loss, older adults

Zhongping Duan,1,* Shaojie Xin,2,* Jing Zhang,1 Shaoli You,2 Yu Chen,1 Hongling Liu,2 Sujun Zheng,1 Zheng Li,3 Robert Ashley,3 Michael Millis4 1Artificial Liver Center, Beijing You’an Hospital of Capital Medical University, Beijing, China; 2Department of Infectious Disease, Division III, 302 Military Hospital of China, Beijing, China; 3Research and Development, Vital Therapies, Inc, San Diego, CA, USA; 4Department of Surgery, University of Chicago, Chicago, IL, USA *These authors contributed equally to this work Background: Preliminary evidence of safety and efficacy of an extracorporeal cellular therapy (ELAD®) has been demonstrated in subjects with acute forms of liver failure. This study compared ELAD with standard of care in Chinese subjects with acute-on-chronic liver failure (ACLF), predominantly secondary to chronic viral hepatitis.Subjects and methods: Subjects meeting eligibility criteria were randomized to either the ELAD group or the control group. All subjects received plasma exchange and venovenous hemofiltration and either ELAD treatment for 3–5 days, unless terminated early, along with standard of care or standard of care alone (control) and were then followed up for 12 weeks.Results: Forty-nine subjects (ELAD subjects, 32; controls, 17) were randomized under this protocol. Kaplan–Meier analysis of transplant-free survival (TFS) revealed a significant difference in favor of ELAD vs control (P=0.049, Wilcoxon signed-rank test). There was a significant difference in TFS on day 28 in ELAD vs control (P=0.022). In a multiple regression model, the relationship between group assignment and outcome was significant (P=0.031) when changes in food intake and Model for End-Stage Liver Disease (MELD) scores at screening were included as additional independent variables. The duration of ELAD treatment alone was a significant predictor of TFS (P=0.043). Median time to a 5-point increase in MELD, transplant, or death was longer than 72 days with ELAD vs 26 days for control (P=0.036). Total bilirubin level decreased by 25% during ELAD treatment vs 37% increase in the control group (P

Yan Zhou,1,2 Genyan Zhang,2 Feng Wang,2 Jin Wang,2 Yanwei Ding,2 Xinyu Li,2 Chongtie Shi,2 Jiakui Li,2 Chengkon Shih,2 Song You1 1The School of Life Science and Biopharmaceutical, Shenyang Pharmaceutical University, Shenyang, 2Department of Project Management, Medicinal Chemistry, Pharmacology, Drug Metabolism, and Pharmacokinetics, Toxicology, Xuanzhu Pharma, Jinan, China Abstract: This study presents a process of developing a novel PI3K–mTOR inhibitor through the prodrug of a metabolite. The lead compound (compound 1) was identified with similar efficacy as that of NVP-BEZ235 in a tumor xenograft model, but the exposure of compound 1 was much lower than that of NVP-BEZ235. After reanalysis of the blood sample, a major metabolite (compound 2) was identified. Compound 2 exerted similar in vitro activity as compound 1, which indicated that compound 2 was an active metabolite and that the in vivo efficacy in the animal model came from compound 2 instead of compound 1. However, compound 1 was metabolized into compound 2 predominantly in the liver microsomes of mouse, but not in the liver microsomes of rat, dog, or human. In order to translate the efficacy in the animal model into clinical development or predict the pharmacokinetic/pharmacodynamic parameters in the clinical study using a preclinical model, we developed the metabolite (compound 2) instead of compound 1. Due to the low bioavailability of compound 2, its prodrug (compound 3) was designed and synthesized to improve the solubility. The prodrug was quickly converted to compound 2 through both intravenous and oral administrations. Because the prodrug (compound 3) did not improve the oral exposure of compound 2, developing compound 3 as an intravenous drug was considered by our team, and the latest results will be reported in the future. Keywords: PI3K, mTOR, NVP-BEZ235, prodrug, metabolite, antitumor

Effective self-report screening tools for emerging adults are understudied. The present study examined the latent structure of the Depression, Anxiety, and Stress Scales (DASS-21) with U.S. undergraduates. Data were collected from 1,413 undergraduates surveyed online. Three models were tested: (a) a one-factor model, (b) the original correlated three-factor model, and (c) a bifactor model that included a general negative affectivity factor and three specific factors of depression, anxiety, and stress. The bifactor model with three specific orthogonal factors yielded the best fit. All items loaded onto the general negative affectivity factor. This study provides an important evaluation of alternative models of the latent structure of the DASS among U.S. undergraduates, with results supporting it as an assessment of general distress for emerging adults.

Measurements and simulations show that plasma relaxation processes in the reversed field pinch drive and redistribute both magnetic flux and momentum. To examine this relaxation process, a new 3D Mach B-dot probe has been constructed. This probe collects ion saturation currents through six molybdenum electrodes arranged on the flattened vertices of an octahedron made of boron nitride (BN). The ion saturation current flows through configurable voltage dividers for measurement and returns through one of six selectable return electrodes equally spaced along the 12 cm BN probe arm. In addition, the probe arm houses three B-dot magnetic pickup coils in the BN stalk immediately below to the octahedron, to measure the local magnetic field. Inserted in the Madison Symmetric Torus (MST) during deuterium discharges with 220 kA plasma current, density of 0.8 × 1013 cm−3, the probe collects ion saturation currents with sawtooth-like peaks correlated with relaxation events. This compact octahedral design fitting six Mach electrode surfaces within a 1 cm3 cube will enable future multi-point, multi-field probes compatible with the 1.5 in. ports of MST. Such probes will allow for flow circulation, current, and canonical vorticity to be calculated in the center of the finite difference stencil formed by the measurement locations. [ABSTRACT FROM AUTHOR]

ObjectiveTo characterize the cognitive and neuropsychiatric symptoms of patients with behavioral variant frontotemporal dementia (bvFTD) over the natural course of the disease.MethodsWe examined the initial and subsequent neuropsychological test performance and neuropsychiatric symptoms in a large cohort of patients with bvFTD (n = 204) across progressive stages of disease as measured by the Clinical Dementia Rating (CDR). We also compared cognitive and neuropsychiatric impairments of patients with bvFTD to those of an age-matched cohort with Alzheimer disease (AD) dementia (n = 674).ResultsAt the earliest stage (CDR = 0.5), patients with bvFTD had profound neuropsychiatric disturbances, insensitivity to errors, slower response times, and poor naming, with intact attention span, memory, and facial affect naming. Tests continuing to show progressive, statistically significant stepwise declines after the CDR = 1 stage included free recall, visuoconstruction, set-shifting, error insensitivity, semantic fluency, design fluency, emotion naming, calculations, confrontation naming, syntax comprehension, and verbal agility. At CDR = 0.5, patients with bvFTD significantly outperformed patients with AD in episodic memory and were faster in set-shifting, while scoring quantitatively worse in lexical fluency, emotion naming, and error sensitivity. The overall rate of disease progression in bvFTD was more rapid than in AD.ConclusionThere are distinct patterns of cognitive deficits differentiating the earlier and later disease stages in bvFTD, with the pattern of cognitive decline revealing in greater detail the natural history of the disease. These cognitive symptoms are readily apparent clinical markers of dysfunction in the principal brain networks known to undergo molecular and anatomical changes in bvFTD, thus are important indicators of the evolving pathology in individual patients.

BackgroundCognitive deficits are presumed to be the primary driver of functional impairment in Alzheimer's disease (AD); however, functional impairment is likely multifactorially determined.ObjectiveOur objective was to determine the relative contribution of neuropsychiatric symptoms in predicting ratings of functional status.MethodsA total of 223 patients received routine neurological and neuropsychological evaluations and met criteria of probable AD dementia based on the McKhann criteria. Demographic, cognitive, and neuropsychiatric variables were entered in a hierarchical linear regression analysis to predict functional status as measured by the Functional Activities Questionnaire (FAQ).ResultsThe total model explained 29.7% of the variance (p <  0.001) in FAQ. Importantly, neuropsychiatric variables explained 12.7% of the unique variance, with apathy and sleep as significant contributors.ConclusionTwo neuropsychiatric variables, apathy and changes in sleep/nighttime behaviors, predicted ratings of functional status in AD patients independent of age, global cognition, memory and executive function measures, and depressive symptoms. These results highlight the importance of neuropsychiatric symptoms in understanding and potentially treating the functional limitations so prevalent in AD.

BACKGROUND: We investigated the viability of psychometrically robust executive function measures as markers for premanifest Huntingtons disease (HD). METHODS: Fifteen premanifest HD subjects and 42 controls were compared on the NIH EXAMINER executive function battery. This battery yields an overall executive composite score, plus working memory, cognitive control, and fluency scores that are measured on psychometrically matched scales. The scores were correlated with two disease markers, disease burden and striatal volumes, in the premanifest HD subjects. RESULTS: The premanifest HD subjects scored significantly lower on the working memory score. The executive composite positively correlated with striatal volumes, and the working memory score negatively correlated with disease burden. The cognitive control and fluency scores did not differ between the groups or correlate significantly with the disease markers. CONCLUSIONS: The NIH EXAMINER executive composite and working memory scores are sensitive markers of cognitive dysfunction, striatal volume, and disease burden in premanifest HD.

BackgroundWe investigated the viability of psychometrically robust executive function measures as markers for premanifest Huntington's disease (HD).MethodsFifteen premanifest HD subjects and 42 controls were compared on the NIH EXAMINER executive function battery. This battery yields an overall executive composite score, plus working memory, cognitive control, and fluency scores that are measured on psychometrically matched scales. The scores were correlated with two disease markers, disease burden and striatal volumes, in the premanifest HD subjects.ResultsThe premanifest HD subjects scored significantly lower on the working memory score. The executive composite positively correlated with striatal volumes, and the working memory score negatively correlated with disease burden. The cognitive control and fluency scores did not differ between the groups or correlate significantly with the disease markers.ConclusionsThe NIH EXAMINER executive composite and working memory scores are sensitive markers of cognitive dysfunction, striatal volume, and disease burden in premanifest HD.