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INTRODUCTION: The objective of this pilot study was to establish the feasibility of recruiting older Vietnamese Americans for research addressing genetic and nongenetic risk factors for Alzheimer disease (AD). METHODS: Twenty-six Vietnamese Americans were recruited from communities in San Diego. A Community Advisory Board provided cultural and linguistic advice. Bilingual/bicultural staff measured neuropsychological, neuropsychiatric, lifestyle, and medical/neurological functioning remotely. Saliva samples allowed DNA extraction. A consensus team reviewed clinical data to determine a diagnosis of normal control (NC), mild cognitive impairment (MCI), or dementia. Exploratory analyses addressed AD risk by measuring subjective cognitive complaints (SCC), depression, and vascular risk factors (VRFs). RESULTS: Twenty-five participants completed the study (mean age=73.8 y). Eighty percent chose to communicate in Vietnamese. Referrals came primarily from word of mouth within Vietnamese communities. Diagnoses included 18 NC, 3 MCI, and 4 dementia. Participants reporting SCC acknowledged more depressive symptoms and had greater objective cognitive difficulty than those without SCC. Eighty-eight percent of participants reported at least 1 VRF. DISCUSSION: This pilot study supports the feasibility of conducting community-based research in older Vietnamese Americans. Challenges included developing linguistically and culturally appropriate cognitive and neuropsychiatric assessment tools. Exploratory analyses addressing nongenetic AD risk factors suggest topics for future study.

IntroductionClinical research in Alzheimer's disease (AD) lacks cohort diversity despite being a global health crisis. The Asian Cohort for Alzheimer's Disease (ACAD) was formed to address underrepresentation of Asians in research, and limited understanding of how genetics and non-genetic/lifestyle factors impact this multi-ethnic population.MethodsThe ACAD started fully recruiting in October 2021 with one central coordination site, eight recruitment sites, and two analysis sites. We developed a comprehensive study protocol for outreach and recruitment, an extensive data collection packet, and a centralized data management system, in English, Chinese, Korean, and Vietnamese.ResultsACAD has recruited 606 participants with an additional 900 expressing interest in enrollment since program inception.DiscussionACAD's traction indicates the feasibility of recruiting Asians for clinical research to enhance understanding of AD risk factors. ACAD will recruit > 5000 participants to identify genetic and non-genetic/lifestyle AD risk factors, establish blood biomarker levels for AD diagnosis, and facilitate clinical trial readiness.HighlightsThe Asian Cohort for Alzheimer's Disease (ACAD) promotes awareness of under-investment in clinical research for Asians. We are recruiting Asian Americans and Canadians for novel insights into Alzheimer's disease. We describe culturally appropriate recruitment strategies and data collection protocol. ACAD addresses challenges of recruitment from heterogeneous Asian subcommunities. We aim to implement a successful recruitment program that enrolls across three Asian subcommunities.

INTRODUCTION: The A/T/N (amyloid/tau/neurodegeneration) framework provides a biological basis for Alzheimers disease (AD) diagnosis and can encompass additional changes such as inflammation (I). A spectrum of T/N/I imaging and plasma biomarkers was acquired in a phase 2 clinical trial of rasagiline in mild to moderate AD patients. We evaluated these to understand biomarker distributions and relationships within this population. METHODS: Plasma biomarkers of pTau-181, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), other inflammation-related proteins, imaging measures including fluorodeoxyglucose (FDG) positron emission tomography (PET), flortaucipir PET, and volumetric magnetic resonance imaging (MRI), and cognitive endpoints were analyzed to assess characteristics and relationships for the overall population (N = 47 at baseline and N = 21 for longitudinal cognitive comparisons) and within age-decade subgroups (57-69, 70-79, 80-90 years). RESULTS: Data demonstrate wide clinical and biomarker heterogeneity in this population influenced by age and sex. Plasma pTau-181 and GFAP correlate with tau PET, most strongly in left inferior temporal cortex (p = 0.0002, p = 0.0006, respectively). In regions beyond temporal cortex, tau PET uptake decreased with age for the same pTau-181 or GFAP concentrations. FDG PET and brain volumes correlate with tau PET in numerous regions (such as inferior temporal: p = 0.0007, p = 0.00001, respectively). NfL, GFAP, and all imaging modalities correlate with baseline MMSE; subsequent MMSE decline is predicted by baseline parahippocampal and lateral temporal tau PET (p = 0.0007) and volume (p = 0.0006). Lateral temporal FDG PET (p = 0.006) and volume (p = 0.0001) are most strongly associated with subsequent ADAS-cog decline. NfL correlates with FDG PET and baseline MMSE but not tau PET. Inflammation biomarkers are intercorrelated but correlated with other biomarkers in only the youngest group. DISCUSSION: Associations between plasma biomarkers, imaging biomarkers, and cognitive status observed in this study provide insight into relationships among biological processes in mild to moderate AD. Findings show the potential to characterize AD patients regarding likely tau pathology, neurodegeneration, prospective clinical decline, and the importance of covariates such as age. HIGHLIGHTS: Plasma pTau-181 and GFAP correlated with regional and global tau PET in mild to moderate AD.NfL correlated with FDG PET and cognitive endpoints but not plasma pTau-181 or tau PET.Volume and FDG PET showed strong relationships to tau PET, one another, and cognitive status.Temporal volumes most strongly predicted decline in both MMSE and ADAS-cog.Volume and plasma biomarkers can enrich for elevated tau PET with age a significant covariate.

BACKGROUND: Benfotiamine provides an important novel therapeutic direction in Alzheimers disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. OBJECTIVE: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. METHODS: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. CONCLUSION: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360.

IntroductionPhysical exercise and cognitive training have the potential to enhance cognitive function and mobility in older adults at risk of Alzheimer's disease and related dementia (ADRD), but little is known about the feasibility of delivering multidomain interventions in home settings of older adults at risk of ADRD. This study aims to assess the feasibility of home-based delivery of exercise and cognitive interventions, and to evaluate the relationship between participants' intervention preferences and their subsequent adherence. Secondary objectives include the effect of the interventions on ADRD risk factors, including frailty, mobility, sleep, diet and psychological health.Methods and analysisThe SYNchronising Exercises, Remedies in GaIt and Cognition at Home (SYNERGIC@Home) feasibility trial is a randomised control trial that follows a 2×2 factorial design, with a 16-week home-based intervention programme (3 sessions per week) of physical exercises and cognitive training. Participants will be randomised in blocks of four to one of the following four arms: (1) combined exercise (aerobic and resistance)+cognitive training (NEUROPEAK); (2) combined exercise+control cognitive training (web searching); (3) control exercise (balance and toning)+cognitive training; and (4) control exercise+control cognitive training. SYNERGIC@Home will be implemented through video conferencing. Baseline and post-intervention assessments at 4-month and 10-month follow-up will include measures of cognition, frailty, mobility, sleep, diet and psychological health. Primary feasibility outcome is adherence to the interventions. Primary analytic outcome is the relationship between pre-allocation preference for a given intervention and subsequent adherence to the allocated intervention. A series of secondary analytic outcomes examining the potential effect of the individual and combined interventions on cognitive, mobility and general well-being will be measured at baseline and follow-up.Ethics and disseminationEthics approval was granted by the relevant research ethics boards. Findings of the study will be presented to stakeholders and published in peer-reviewed journals and at provincial, national and international conferences.Trial registration numberNCT04997681, Pre-results.

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer's disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid β peptides (Aβ1-40, Aβ1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

BackgroundA Phase II proof of concept (POC) randomized clinical trial was conducted to evaluate the effects of rasagiline, a monoamine oxidase B (MAO-B) inhibitor approved for Parkinson disease, in mild to moderate Alzheimer's disease (AD). The primary objective was to determine if 1 mg of rasagiline daily for 24 weeks is associated with improved regional brain metabolism (fluorodeoxyglucose-positron emission tomography [FDG-PET]) compared to placebo. Secondary objectives included measurement of effects on tau PET and evaluation of directional consistency of clinical end points.MethodsThis was a double-blind, parallel group, placebo-controlled, community-based, three-site trial of 50 participants randomized 1:1 to receive oral rasagiline or placebo (NCT02359552). FDG-PET was analyzed for the presence of an AD-like pattern as an inclusion criterion and as a longitudinal outcome using prespecified regions of interest and voxel-based analyses. Tau PET was evaluated at baseline and longitudinally. Clinical outcomes were analyzed using an intention-to-treat (ITT) model.ResultsFifty patients were randomized and 43 completed treatment. The study met its primary end point, demonstrating favorable change in FDG-PET differences in rasagiline versus placebo in middle frontal (P

BackgroundContinuous morphine infusions (CMIs) treat pain and dyspnea at the end of life (EOL). CMIs may be initiated at an empiric rate and/or are rapidly escalated without proper titration.ObjectiveThe study objective was to evaluate CMI patterns at the EOL.MethodsThis single-center, retrospective chart review evaluated adult patients who died while receiving CMI at EOL. Patient demographics and opioid dosing information were extracted from an electronic medical record. Twenty-four hour IV morphine equivalent was calculated prior to CMI initiation and at the time of death.ResultsOf the 190 patient charts, 63.2% (n=120) received no bolus doses prior to CMI initiation. Mean 24-hour IV morphine equivalent prior to CMI initiation was 49.3 mg (range: 0-1200 mg, SD 384.9) and at time of death was 267.1 mg (12.0-5193.2 mg, SD 442.2), representing an increase of +442%. Mean CMI starting rate was 3.3 mg/hour (0.4-30.0 mg/hour, SD 3.6) with titration at time of death to a mean of 7.7 mg/hour (0.4-70.0 mg/hour, SD 9.4), representing an increase of +130%. Mean number of CMI rate adjustments was 2.5 (0-5, SD 3.3); and number of bolus doses administered between titrations was 4.2 (0-27, SD 4.8). Mean time from CMI initiation to death was 15.5 hours (0.05-126.9 hours, SD 21.7). There was a negative association between rate of infusion increase per hour and total number of hours on CMI (r=-0.2, p=0.0062).ConclusionsHospitalized patients at EOL had a much higher 24-hour IV morphine equivalents and CMI rates at time of death compared to CMI initiation. Variability was observed in the number of CMI rate adjustments and the number of bolus doses administered.

Background: Benfotiamine provides an important novel therapeutic direction in Alzheimer's disease (AD) with possible additive or synergistic effects to amyloid targeting therapeutic approaches. Objective: To conduct a seamless phase 2A-2B proof of concept trial investigating tolerability, safety, and efficacy of benfotiamine, a prodrug of thiamine, as a first-in-class small molecule oral treatment for early AD. Methods: This is the protocol for a randomized, double-blind, placebo-controlled 72-week clinical trial of benfotiamine in 406 participants with early AD. Phase 2A determines the highest safe and well-tolerated dose of benfotiamine to be carried forward to phase 2B. During phase 2A, real-time monitoring of pre-defined safety stopping criteria in the first approximately 150 enrollees will help determine which dose (600 mg or 1200 mg) will be carried forward into phase 2B. The phase 2A primary analysis will test whether the rate of tolerability events (TEs) is unacceptably high in the high-dose arm compared to placebo. The primary safety endpoint in phase 2A is the rate of TEs compared between active and placebo arms, at each dose. The completion of phase 2A will seamlessly transition to phase 2B without pausing or stopping the trial. Phase 2B will assess efficacy and longer-term safety of benfotiamine in a larger group of participants through 72 weeks of treatment, at the selected dose. The co-primary efficacy endpoints in phase 2B are CDR-Sum of Boxes and ADAS-Cog13. Secondary endpoints include safety and tolerability measures; pharmacokinetic measures of thiamine and its esters, erythrocyte transketolase activity as blood markers of efficacy of drug delivery; ADCS-ADL-MCI; and MoCA. Conclusion: The BenfoTeam trial utilizes an innovative seamless phase 2A-2B design to achieve proof of concept. It includes an adaptive dose decision rule, thus optimizing exposure to the highest and best-tolerated dose. Trial registration: ClinicalTrials.gov identifier: NCT06223360, registered on January 25, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06223360. [ABSTRACT FROM AUTHOR]

Introduction: The "A/T/N" (amyloid/tau/neurodegeneration) framework provides a biological basis for Alzheimer's disease (AD) diagnosis and can encompass additional changes such as inflammation ("I"). A spectrum of T/N/I imaging and plasma biomarkers was acquired in a phase 2 clinical trial of rasagiline in mild to moderate AD patients. We evaluated these to understand biomarker distributions and relationships within this population., Methods: Plasma biomarkers of pTau-181, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), other inflammation-related proteins, imaging measures including fluorodeoxyglucose (FDG) positron emission tomography (PET), flortaucipir PET, and volumetric magnetic resonance imaging (MRI), and cognitive endpoints were analyzed to assess characteristics and relationships for the overall population ( N = 47 at baseline and N = 21 for longitudinal cognitive comparisons) and within age-decade subgroups (57-69, 70-79, 80-90 years)., Results: Data demonstrate wide clinical and biomarker heterogeneity in this population influenced by age and sex. Plasma pTau-181 and GFAP correlate with tau PET, most strongly in left inferior temporal cortex ( p = 0.0002, p = 0.0006, respectively). In regions beyond temporal cortex, tau PET uptake decreased with age for the same pTau-181 or GFAP concentrations. FDG PET and brain volumes correlate with tau PET in numerous regions (such as inferior temporal: p = 0.0007, p = 0.00001, respectively). NfL, GFAP, and all imaging modalities correlate with baseline MMSE; subsequent MMSE decline is predicted by baseline parahippocampal and lateral temporal tau PET ( p = 0.0007) and volume ( p = 0.0006). Lateral temporal FDG PET ( p = 0.006) and volume ( p = 0.0001) are most strongly associated with subsequent ADAS-cog decline. NfL correlates with FDG PET and baseline MMSE but not tau PET. Inflammation biomarkers are intercorrelated but correlated with other biomarkers in only the youngest group., Discussion: Associations between plasma biomarkers, imaging biomarkers, and cognitive status observed in this study provide insight into relationships among biological processes in mild to moderate AD. Findings show the potential to characterize AD patients regarding likely tau pathology, neurodegeneration, prospective clinical decline, and the importance of covariates such as age., Highlights: Plasma pTau-181 and GFAP correlated with regional and global tau PET in mild to moderate AD.NfL correlated with FDG PET and cognitive endpoints but not plasma pTau-181 or tau PET.Volume and FDG PET showed strong relationships to tau PET, one another, and cognitive status.Temporal volumes most strongly predicted decline in both MMSE and ADAS-cog.Volume and plasma biomarkers can enrich for elevated tau PET with age a significant covariate., Competing Interests: Dawn Matthews is CEO of ADM Diagnostics, Inc., Scientific Advisor to the Alzheimer's Drug Development Foundation, and Co‐Chair of the Radiological Society of North America PET Tau Profile Working Group and PET Amyloid Profile Working Group, and reports that ADM Diagnostics received grant funding (2R44AG060861‐02) from the National Institutes of Aging, University of Arizona subaward (R01 AG063826), and University of Arizona subaward (R01 AG075122‐01 during the conduct of this work. She reports support for attending meetings and/or travel hotel and registration fees from Alzheimer's Drug Discovery Foundation, and stock or stock options in ADM Diagnostics and Abiant. Jefferson Kinney reports a grant from the National Institutes of General Medical Sciences (NIGMS) COBRE grant #P20GM109025, along with grants NIH NIA R01 AG074392‐01, NIH NIA P20 AG068053‐01, and R01AG062762‐01A1. Aaron Ritter reports payment from Corium Pharmaceuticals and Lundbeck/Otsuka for speaker board and advertisement board. He also has a leadership role in Alzheimer's Association Orange County Board and Alzheimer's Family Center. Ana Lukic, Randolph Andrews, and Lauren Koenig are employees of ADM Diagnostics, Inc. Carolyn Revta has nothing to disclose. Babak Tousi received a grant from the Alzheimer's Drug Discovery Foundation during the study, and has received consulting fees from Eisai, Biogen, Lilly, GE Healthcare, Kisbee, and Otsuka. He received honoraria from Eisai and Lily, support for attending meetings or travel from Novo Nordisk, and participated in a Data Safety Monitoring Board or Advisory Board at Eisai and Lilly. James Leverenz reports the grant P30AG072959, a Scientific Advisory leadership role for the Lewy Body Dementia Association, and receipt of ligands and software for imaging from GE Healthcare. Howard Fillit founding Executive Director and Chief Science Officer of the Alzheimer's Drug Discovery Foundation, which funded the rasagiline clinical trial, and has provided consulting support to the following pharmaceutical companies: Otsuka, LifeWorx, and Alector. He reports royalties from Icahn School of Medicine at Mount Sinai, and participation in a DSMB at Alector. He reports stock or stock options at CarePredict, and other non‐financial interests with the Lilly GERAS study and Roche Genentech Claims study. Howard Feldman reports a service agreement through UCSD with the Cleveland Clinic for data management and biostatistics during the conduct of the original study; grants from Annovis (QR Pharma), Vivoryon (Probiodrug), AC Immune, Biohaven Pharmaceuticals, and LuMind Foundation, and service agreements through UCSD for consulting with LuMind Foundation, Novo Nordisk, Arrowhead Pharmaceuticals, and Axon Neurosciences Roche/Genentech Pharmaceuticals. He reports support for attending meetings and/or travel for Novo Nordisk, and Royal Society of Canada; participation in DMC and DSMB for Tau Consortium, Rooche/Genentech Pharmaceuticals, and Janssen Research and Development; and philanthropic support for Alzheimer therapeutic research. Jeffrey Cummings reports grants from the National Institutes of General Medical Sciences (NIGMS) COBRE grant #P20GM109025; NINDS grant U01NS093334; NIA grant R01AG053798; NIA grant P30AG072959; NIA grant R35AG71476; NIA R25 AG083721‐01; Alzheimer's Disease Drug Discovery Foundation (ADDF); Ted and Maria Quirk Endowment; Joy Chambers‐Grundy Endowment during the conduct of the study. He reports consulting fees from Acadia, Actinogen, Acumen, AlphaCognition, ALZpath, Aprinoia, AriBio, Artery, Biogen, Biohaven, BioVie, BioXcel, Bristol‐Myers Squib, Cassava, Cerecin, Diadem, Eisai, GAP Foundation, GemVax, Janssen, Jocasta, Karuna, Lighthouse, Lilly, Lundbeck, LSP/eqt, Mangrove Therapeutics, Merck, NervGen, New Amsterdam, Novo Nordisk, Oligomerix, ONO, Optoceutics, Otsuka, Oxford Brain Diagnostics, Prothena, ReMYND, Roche, Sage Therapeutics, Signant Health, Simcere, sinaptica, Suven, TrueBinding, Vaxxinity, and Wren pharmaceutical, assessment, and investment companies. He reports participation in Data Safety Monitoring Board or Advisory Board for Acadia, Biogen, Genentech, Grifols, Janssen, Karuna, Otsuka, reMYND, Roche, Signant Health and stock or stock options for Artery, Vaxxinity, Behrens, Alzheon, MedAvante‐Prophase, and Acumen. Finally, outside the submitted work he is Chief Scientific Advisor to CNS Innovations, LLC and owns the copyright for the Neuropsychiatric Inventory (NPI). Kate Zhong and Erin Toledano Strom have nothing to disclose. Author disclosures are available in the supporting information., (© 2024 The Author(s). Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: A Phase II proof of concept (POC) randomized clinical trial was conducted to evaluate the effects of rasagiline, a monoamine oxidase B (MAO-B) inhibitor approved for Parkinson disease, in mild to moderate Alzheimer's disease (AD). The primary objective was to determine if 1 mg of rasagiline daily for 24 weeks is associated with improved regional brain metabolism (fluorodeoxyglucose-positron emission tomography [FDG-PET]) compared to placebo. Secondary objectives included measurement of effects on tau PET and evaluation of directional consistency of clinical end points., Methods: This was a double-blind, parallel group, placebo-controlled, community-based, three-site trial of 50 participants randomized 1:1 to receive oral rasagiline or placebo (NCT02359552). FDG-PET was analyzed for the presence of an AD-like pattern as an inclusion criterion and as a longitudinal outcome using prespecified regions of interest and voxel-based analyses. Tau PET was evaluated at baseline and longitudinally. Clinical outcomes were analyzed using an intention-to-treat (ITT) model., Results: Fifty patients were randomized and 43 completed treatment. The study met its primary end point, demonstrating favorable change in FDG-PET differences in rasagiline versus placebo in middle frontal ( P  < 0.025), anterior cingulate ( P  < 0.041), and striatal ( P  < 0.023) regions. Clinical measures showed benefit in quality of life ( P  < 0.04). Digit Span, verbal fluency, and Neuropsychiatric Inventory (NPI) showed non-significant directional favoring of rasagiline; no effects were observed in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) or activities of daily living. Rasagiline was generally well tolerated with low rates of adverse events and notably fewer neuropsychiatric symptoms in the active treatment group., Discussion: These outcomes illustrate the potential benefits of rasagiline on clinical and neuroimaging measures in patients with mild to moderate AD. Rasagiline appears to affect neuronal activity in frontostriatal pathways, with associated clinical benefit potential warranting a more fully powered trial. This study illustrated the potential benefit of therapeutic repurposing and an experimental medicine proof-of-concept design with biomarkers to characterize patient and detect treatment response., Competing Interests: Dawn C. Matthews, Randolph D. Andrews, and Ana S. Lukic are employees of ADM Diagnostics, Inc., which provides clinical trial imaging services and image analysis products. Carolyn Revta has received grants from Toyama Pharmaceuticals, Biohaven Pharmaceuticals, and Vivoryon (Probiodrug) during the conduct of the study. Babak Tousi has received a grant from the Alzheimer's Drug Discovery Foundation during the study. James B. Leverenz has received research support from the Alzheimer's Association, Avid Radiopharmaceuticals, Department of Defense, GE Healthcare, Lewy Body Dementia Association, Michael J Fox Foundation, National Institutes of Health, and Sanofi/Genzyme. Howard Fillit is founding Executive Director and Chief Science Officer of the Alzheimer's Drug Discovery Foundation, which funded the rasagiline clinical trial, and has provided consulting to the following pharmaceutical companies: Axovant, vTv, Lundbeck, Otsuka, Lilly, Biogen (RTI), Roche, Genentech, Merck, Samus, Pfizer, and Alector. Howard H. Feldman reports a service agreement through UCSD with the Cleveland Clinic for data management and biostatistics during the conduct of this study; grants from Toyama Pharmaceuticals, Biohaven Pharmaceuticals, and Vivoryon (Probiodrug); service agreements through UCSD for consulting with Eisai Pharmaceuticals, Merck Pharmaceuticals, Tau RX, Samus Therapeutics, Arkuda Therapeutics, Samumed, and Axon Neurosciences Roche/Genentech Pharmaceuticals for DMC and DSMB activities; Tau Consortium for Scientific Advisory Board; and Novo Nordisk for Advisory Board. Jeffrey Cummings reports grants from National Institute of General Medical Sciences (NIGMS) COBRE grant #P20GM109025, during the conduct of the study; personal fees from Acadia, Actinogen, AgenBio, Alkahest, Alzheon, Avanir, Axsome, Biogen, Cassava, Cerecin, Cerevel, Cognoptix, Cortexyme, EIP, Eisai, Foresight, Green Valley, Grifols, Idorsia, Karuna, Nutricia, Orion, Otsuka, Probiodrug, QR Pharma, ReMYND, Resverlogix, Roche, Samumed, Samus Therapeutics, Third Rock, Signant Health, Sunovion, Suven, and United Neuroscience pharmaceutical and assessment companies; other from Alzheimer Drug Discovery Foundation; other from ADAMAS, BioAsis, MedAvante, QR Pharma, and United Neuroscience; personal fees from Neuropsychiatric Inventory (NPI), outside the submitted work; and is Chief Scientific Advisor for CNS Innovations. Aaron Ritter, Jefferson Kinney, Ronald G. Thomas, and Kate Zhong have nothing to disclose., (© 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)