Kevin M. Nelson

Mayo Clinic in Arizona

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Bradley F. Boeve

Mayo Clinic in Arizona

Leah K. Forsberg

Mayo Clinic

Hilary W. Heuer

University of California, San Francisco

Howard J. Rosen

University of California, San Francisco

Adam L. Boxer

University Memory and Aging Center

Julie A. Fields

Mayo Clinic

Danielle Brushaber

Mayo Clinic in Arizona

Jeremy A. Syrjanen

Mayo Clinic in Florida

Matthew Stauder

Massachusetts General Hospital

Rodney Pearlman

University College London

Cooperative Institutions

Mayo Clinic in Arizona

Mayo Clinic in Florida

WinnMed

Mayo Clinic

University of California, Los Angeles

University of California, San Francisco

VIB-UAntwerp Center for Molecular Neurology

University of Antwerp

Alzheimer’s Disease Neuroimaging Initiative

Harvard University

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Analyses of Quality of Life in Frontotemporal Lobar Degeneration: Findings from the ALLFTD Consortium

Alzheimer s & Dementia (2023)

Kevin M. Nelson Leah K. Forsberg Danielle Brushaber Jeremy A. Syrjanen Maria I. Lapid

Abstract Background The DEMQOL (Dementia Quality of Life) scale is a patient reported questionnaire and proxy form that captures subjective life quality. Participants in ALLFTD and their Study Partners (SP) complete these questionnaires at each study visit. Method We analyzed the DEMQOL in participants and their SPs when the SP was reported to be a spouse or equivalent. Analyses focused on the final overall quality of life (QoL) rating for the participant (poor, fair, good, or very good). Result DEMQOL responses from 907 dyads (participant: mean age 58.3±13.4 years, 44% female, and mean education 15.9±2.5 years) were analyzed. Participants rated their overall QoL as very good (45.8%), good (36.5%), fair (14%), and poor (3.5%). SPs rated their participant’s overall QoL as very good (33.6%), good (41%), fair (19.4%), and poor (6%). There was a discordance in ratings between participants and SPs (p<0.0001); in almost 50% of cases, participants rated their QoL better (33.2%) or worse (15.2%) than their SP rated their QoL. When considering disease severity (CDR®+NACC‐FTLD global score), participants rated their QoL better than their SP rated their QoL (CDR®+NACC‐FTLD = 0: 19.4%, CDR®+NACC‐FTLD = 0.5: 42%, and CDR®+NACC‐FTLD = 1+: 33.2%), worse than (CDR®+NACC‐FTLD = 0: 15.1%, CDR®+NACC‐FTLD = 0.5: 13.3%, and CDR®+NACC‐FTLD = 1+: 15.2%), or the same (CDR®+NACC‐FTLD = 0: 65.6%, CDR®+NACC‐FTLD = 0.5: 44.8%, and CDR®+NACC‐FTLD = 1+: 51.6%). Conclusion Among participants and SPs, similarities and differences in QoL ratings are fairly consistent regardless of global CDR®+NACC‐FTLD rating. Generally, participants are equally or more optimistic about QoL than their SPs. Longitudinal analyses are forthcoming.

Frontotemporal lobar degeneration

Spouse

Clinical Dementia Rating

10.1002/alz.080591

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Direct-Acting Antiviral Therapy in Liver Transplant Patients With Hepatocellular Carcinoma and Hepatitis C

Transplantation Direct (2020)

Chung Sang Tse Ju Dong Yang Omar Y. Mousa Kevin M. Nelson Surakit Pungpapong

Background: Direct-acting antivirals (DAA) are highly effective for the treatment of hepatitis C (HCV), although there are limited data on the safety and efficacy of DAA therapy in hepatitis C-positive individuals awaiting liver transplantation for hepatocellular carcinoma (HCC). Methods: We conducted a retrospective cohort study of HCV-positive patients who underwent liver transplantation for HCC at 3 liver transplant centers across the United States from 2014 to 2017 with follow-up to July 2018. Transplant recipients who received DAA before transplant were compared with those who did not (DAA naive) for posttransplant HCC recurrence rate, sustained virological response (SVR), allograft failure, and death using Kaplan-Meier analysis and Cox proportional hazard models. Results: A total of 171 HCV-HCC transplant recipients (99 pretransplant DAA; 72 DAA naive controls) were included, with a median follow-up of 24 months. The overall posttransplant HCC recurrence rate was 9% (15/171). Pretransplant DAA was not associated with HCC recurrence (5% versus 14%; P = 0.07), graft failure (7% versus 3%; P = 0.21), or death (12% versus 19%; P = 0.19) as compared with DAA naive patients. SVR rates were significantly lower ( P < 0.01) with pretransplant DAA (75%, 39/52) than posttransplant DAA (97%, 59/61) therapies. Those who received pretransplant DAA and those who did not were not statistically different in age, gender, alpha fetal protein levels, model for end-stage liver disease scores, or transplant wait time. Conclusions: Pretransplant DAA for HCV was not associated with an increased risk of posttransplant HCC recurrence, though pretransplant DAA had lower efficacy than posttransplant DAA in HCV-HCC transplant recipients.

Hepatitis C

Liver disease

10.1097/txd.0000000000001049

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Citations (5)

Molecular dynamics simulations of atomic clusters

PPSC (1993)

Kevin M. Nelson S. T. Smith L. T. Wille

We discuss the implementation of massively parallel computer simulations of the molecular dynamics of atomic clusters. We analyze several algorithms appropriate for SIMD-computers with a two-dimensional mesh-architecture, with specific attention to the MasPar-1 (DECmpp 12000) series. For clusters sizes of the same order as the square root of the processor array size, a double shift algorithm is an alternative to the Boyer-Pawley method, while for larger cluster sizes an orrery shift algorithm is indicated. We also propose a systolic shift algorithm for particles interacting through three-body potentials.

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The North American Prodromal Synucleinopathy (NAPS) Consortium: Baseline neuropsychological findings in 136 participants

Alzheimer s & Dementia (2020)

Julie A. Fields Bradley F. Boeve Leah K. Forsberg Erik K. St. Louis Ruth Kraft

Abstract Background It is important to determine the natural history of individuals with RBD and generate clinical and neuropsychological data for planning disease‐modifying trials to delay or prevent phenoconversion of RBD to an overt synucleinopathy such as dementia with Lewy bodies, Parkinson’s disease, or multiple system atrophy. Our objective is to present initial neuropsychological data on 136 participants with REM sleep behavior disorder (RBD) without an overt synucleinopathy who are in the North American Prodromal Synucleinopathy (NAPS; R34AG056639) Consortium. Method As part of the NAPS protocol (www.naps‐rbd.org), investigators at 10 centers in North America are enrolling a target of 360 participants with RBD. A comprehensive clinical battery and a set of neuropsychological measures (using the National Alzheimer Coordinating Center Uniform Data Set version 3 or UDS3) are performed at each visit. Result Participants were 82% male, ranging in age from 35‐85 (Mean=65.9, SD=15.9) and education from 8‐20 years (Mean=15.9, SD=3.1). Only 17 participants (13%) were impairment‐free across all tests administered. The proportions of participants with impaired scores were tabulated as follows ( < ‐1.5 SD after adjustment for age, sex, and education): global cognition – 17%; attention/executive functioning – 10‐20% across measures; language – 14‐24% across measures; visuospatial – 16%; and episodic learning/memory – 18‐25% across measures. Of all participants, 79 (58%) showed impairments < ‐2 SD. Moreover, 53% of those with cognitive impairment involved impact in 2 domains, an additional 20% in 3 domains, and another 4% was impaired in all domains. The combination of attention/executive and language was most often observed. Conclusion Collection of a comprehensive set of clinical and neuropsychological measures is feasible and tolerated in RBD patients. Using the UDS3 neuropsychological test battery, impairment in one or more measures was present in 87% of participants, and 58% showed impairments greater than 2 SD below the mean in the absence of a clinical diagnosis of dementia. Impairments in > 2 domains was common, most frequently involving attention/executive and language. Future longitudinal assessments will be required to determine the predictive utility of neuropsychological performance for phenoconversion of RBD to an overt synucleinopathy.

10.1002/alz.044834

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Studying the natural history of frontotemporal lobar degeneration (FTLD): The ARTFL LEFFTDS longitudinal FTLD (ALLFTD) protocol

Alzheimer s & Dementia (2020)

Bradley F. Boeve Adam L. Boxer Howard J. Rosen Leah K. Forsberg Hilary W. Heuer

Abstract Background It is important to determine the natural history of sporadic and familial frontotemporal lobar degeneration (FTLD) and generate clinical, neuropsychological, neuroimaging and biofluid data for planning disease‐modifying trials. Method As part of the ARTFL LEFFTDS Longitudinal Frontotemporal Lobar Degeneration (ALLFTD; U19 AG063911) protocol, investigators at 19 centers in North America will enroll 2100 participants with FTLD over the next 5 years beginning in early 2020. Result As of 1/20/20, the ARTFL/LEFFTDS (A/L) Consortium had enrolled 1832 participants, including 850 in kindreds with familial FTLD (239 associated with mutations in MAPT , 192 in GRN , 370 in C9orf72 , 4 with mutations in both GRN and C9orf72 , and 45 with a mutation in a different gene or no mutation in any known FTLD‐associated gene). Over 500 participants have undergone 2 or more annual visits to date. MRI has been performed in 1105. Biofluid samples have also been collected, with blood (DNA, plasma, serum, mRNA, PBMC) in 1413 and CSF in 303. Over 60 manuscripts using A/L data or samples have been published to date. Five clinical trials involving A/L and ALLFTD participants are in progress or planned. The longitudinal arm in ALLFTD will enroll 500 of existing A/L and 600 future participants for annual assessments with similar methodology to A/L. An additional 1000 FTLD patients will undergo focused one‐time clinical evaluations and biofluid collection. Conclusion The data/samples from already‐enrolled and planned participants in ALLFTD and findings published to date underscore the utility of evaluating FTLD subjects. The absence of identifiable mutations in some with familial FTLD suggests that other genes are yet to be discovered. ALLFTD data will inform clinical trial design, and many participants will be eligible for future trials. The key data and samples in ALLFTD are available to interested investigators worldwide. Supported by: AG063911, AG045390, NS092089, AG016976, AG21886.

Frontotemporal lobar degeneration

Natural history study

C9ORF72

10.1002/alz.045482

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(157) Advanced Practice Providers Deliver Equivalent Outcomes with CCH Injection for Peyronie’s Disease

The Journal of Sexual Medicine (2023)

Stephanie K. Carlson E Tentis Kevin M. Nelson Reza Roshandel M. Alom

Demographics

10.1093/jsxmed/qdad060.152

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The North American Prodromal Synucleinopathy (NAPS) Consortium: Baseline Neuropsychological Findings in 70 Participants (4874)

Neurology (2020)

Julie A. Fields Bradley F. Boeve Leah K. Forsberg Erik K. St. Louis Ruth Kraft

Thursday, April 30April 14, 2020Free AccessThe North American Prodromal Synucleinopathy (NAPS) Consortium: Baseline Neuropsychological Findings in 70 Participants (4874)Julie Fields, Bradley Boeve, Leah Forsberg, Erik St. Louis, Ruth Kraft, Kevin Nelson, Paul Timm, … Show All … , Luke Teigen, Alon Avidan, Adreanne Rivera, Ronald Postuma, Amelie Pelletier, Michael Howell, Josh De Kam, Kelly Ryberg, Rebekah Summers, Donald Bliwise, Daniel Huddleston, Cathy Wood-Siverio, Carole Seeley, Aleksandar Videnovic, Matthew Stauder, Samantha Hersh, Walter Kukull, Jennifer McLeland, and Yo-El Ju Show FewerAuthors Info & AffiliationsApril 14, 2020 issue94 (15_supplement)https://doi.org/10.1212/WNL.94.15_supplement.4874 Letters to the Editor

Thursday

10.1212/wnl.94.15_supplement.4874

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Efficacy and safety of curcumin in primary sclerosing cholangitis: an open label pilot study

Scandinavian Journal of Gastroenterology (2019)

John E. Eaton Kevin M. Nelson Andrea A. Gossard Elizabeth J. Carey James H. Tabibian

Goals: To assess if curcumin improves markers of cholestasis among subjects with primary sclerosing cholangitis (PSC).Background: PSC is a chronic cholestatic liver disorder for which there is no established medical therapy. Preclinical data suggest curcumin may have a beneficial effect in PSC.Study: Subjects with PSC and a serum alkaline phosphatase (SAP) greater than 1.5 times the upper limit of normal (ULN) received curcumin 750 mg orally twice daily for 12 weeks in an open-label pilot study. The primary composite endpoint was proportion of subjects who had a reduction of SAP to less than 1.5 times ULN or a 40% reduction in SAP between baseline and week 12. Secondary endpoints included changes in serum aspartate aminotransferase, total bilirubin, Mayo PSC risk score and self-reported health questionnaires.Results: Two-hundred and fifty-eight patients with PSC were screened and 15 subjects were enrolled and all completed 12 weeks of therapy. The most common reason for subject exclusion was SAP less than 1.5 times the ULN (n = 98). Curcumin did not result in a significant median (interquartile range) change in SAP times the ULN [3.43 (2.10–4.32) to 2.46 (1.89–4.41), p = .36], and only 20% (3/15) subjects achieved the primary endpoint. Similarly, there was no significant change in the secondary endpoints. There were no serious adverse events reported.Conclusion: While curcumin was well tolerated, it was not associated with significant improvements in cholestasis or symptoms. Moreover, this study also illustrates that a low SAP is common among those with PSC.AbbreviationsPSC: Primary sclerosing cholangitis; IBD: inflammatory bowel disease; CCA: cholangiocarcinoma; SAP: serum alkaline phosphatase; ULN: upper limit of normal; UDCA: ursodeoxycholic acid; CRP: c-reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; INR: international normalized ratio; FIS: fatigue impact scale; AE: adverse events; PREsTo: PSC risk estimate tool; IQR: interquartile range; ELF: enhanced liver fibrosis

Primary Sclerosing Cholangitis

Interquartile range

Clinical endpoint

10.1080/00365521.2019.1611917

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The Neurofilament Surveillance Project (NSP): A biomarker study to sample blood quarterly in familial frontotemporal lobar degeneration

Alzheimer s & Dementia (2022)

Rachel Acuna‐Narvaez Hilary W. Heuer Leah K. Forsberg Anne Alward Danielle Graham

Abstract Background In familial frontotemporal lobar degeneration (f‐FTLD), plasma levels of neurofilament light (NfL) are elevated at least two years prior to symptom onset and predict future clinical status. The Neurofilament Surveillance Project (NSP), an actively recruiting observational study, seeks to obtain higher resolution data of temporal changes in plasma NfL to better understand its clinical utility in f‐FTLD interventional trials. The NSP is a pre‐competitive collaboration sponsored by the Bluefield Project to Cure FTD and funded by biotechnology and pharmaceutical companies and nonprofit organizations. Method Participants must be members of families with disease‐causing mutations in C9orf72, MAPT or GRN and enrolled in the ALLFTD natural history study. Up to 335 participants, with roughly equal representation across mutation type, provide plasma quarterly for 3 years (4355 samples total) to enable the observation of peripheral NfL levels longitudinally during disease onset and progression. Plasma is collected by certified mobile research nurses during remote visits, and NfL is measured in batch at least every 6 months. NfL measurements from one plasma aliquot per draw will be correlated with annual assessments obtained in the ALLFTD study, including measures of disease severity (CDRÒ+NACC‐FTLD, CGI, etc.), cognitive function from the UDS Neuropsychology Battery, and volumetric MRI data. Additional plasma aliquots are reserved for future analyses of other biomarkers during the course of the study; another subset of aliquots is reserved to share with interested investigators after the study ends. Result As of 1/19/22, the NSP had enrolled 161 participants, including 62 from C9orf72 kindreds, 60 from MAPT kindreds, and 28 from GRN kindreds. One‐hundred forty‐five participants had completed their initial visit, and 109 had completed more than 3, and up to 5, quarterly blood draws. Enrollment and study visits are ongoing despite COVID‐related limitations. Conclusion The quarterly blood sampling from this study, combined with annual comprehensive clinical assessments through the ALLFTD natural history study, will enable a more detailed understanding of when and how NfL levels change during phenoconversion and/or disease progression in f‐FTLD mutation carriers. These data will be especially informative in the context of the targeted investigational therapeutics for f‐FTLD now entering clinical trials.

Frontotemporal lobar degeneration

C9ORF72

10.1002/alz.064959

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Analyses of Progressive Supranuclear Palsy Quality of Life in Frontotemporal Lobar Degeneration: Findings from the ALLFTD Consortium

Alzheimer s & Dementia (2024)

Kevin M. Nelson Jeremy A. Syrjanen Leah K. Forsberg Hilary W. Heuer Adam L. Boxer

Abstract Background The Progressive Supranuclear Palsy Quality of Life (PSP‐QoL) scale is a 45‐question participant‐completed questionnaire used to evaluate physical and cognitive task difficulties. Participants enrolled in the ALLFTD research program are asked to complete this questionnaire annually during their study visits. Method PSP‐QoL responses were analyzed at baseline visits. Our analysis focused on responses to the overall satisfaction of life (range 0‐100, with 0 being extremely dissatisfied and 100 being extremely satisfied) relative to disease severity (CDR®+NACC‐FTLD global scores) and as a function of clinical phenotypes. A Kruskal‐Wallis test was used to compare overall satisfaction ratings against CDR®+NACC‐FTLD global score. Result 788 PSP‐QoL survey responses were analyzed (participant mean age 55.3 ±15 years, 50.5% female). Analysis included responses from 372 (47.2%) asymptomatic participants (CN; CDR®+NACC‐FTLD = 0), 140 prodromal (17.8%) CDR®+NACC‐FTLD = 0.5, 160 (20.3%) CDR®+NACC‐FTLD = 1, 106 (13.5%) CDR®+NACC‐FTLD 2, and 10 (1.3%) CDR®+NACC‐FTLD = 3. All symptomatic groups were similar in PSP‐QOL overall satisfaction of life rating: (mean overall satisfaction CDR®+NACC‐FTLD = 0.5: 74.5 (SD 22.5); CDR®+NACC‐FTLD = 1: 74.1 (SD 24.7) and CDR®+NACC‐FTLD = 2/3: 74.1 (SD 25.8)), but these differed from asymptomatic (cognitively normal): (mean 83.7, (SD 14.6); p<0.0001). Similarly, when including the CN group and symptomatic phenotype groups, a statistically significant difference in ratings was seen: mean overall satisfaction CN = 83.7 (SD 14.7), MCI = 78.3 (SD 16.6), PPA = 71.6 (SD 26.9), PSP = 66.3 (SD 28.2), bvFTD = 76.8 (SD 23.8), and other = 70.6 (SD 23.2). However, even after removing the CN group, a difference amongst symptomatic phenotypes remained (p = 0.036). Conclusion Mean overall life satisfaction as measured by the PSP QoL questionnaire was lower in all symptomatic compared to clinically normal participants, regardless of disease severity or phenotype. Further longitudinal analyses are needed to better understand how clinical progression impacts overall satisfaction of life.

Frontotemporal lobar degeneration

10.1002/alz.092005

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