Caroline Tanner

• Professor at University of California, San Francisco

Background Neuronal α‐synuclein disease (NSD) is defined by the presence of an in vivo biomarker of neuronal alpha‐synuclein (n‐asyn) pathology. The NSD integrated staging system (NSD‐ISS) for research describes progression across the disease continuum as stages 0 to 6. Objective The aim was to assess 5‐year longitudinal change in NSD‐ISS in early...

Mood dysfunction is highly prevalent in Parkinson’s disease (PD), a main predictor of functional decline, and difficult to treat—novel interventions are critically needed. Psilocybin shows early promise for treating depression and anxiety, but its potential in PD is unknown, as safety concerns have excluded people with neurodegenerative disease fro...

Objective Remote identification of individuals with severe hyposmia may enable scalable recruitment of participants with underlying alpha‐synuclein aggregation. We evaluated the performance of a staged screening paradigm using remote smell testing to enrich for abnormal dopamine transporter single‐photon emission computed tomography imaging (DAT‐SP...

Background. Neuronal alpha-Synuclein Disease (NSD) is defined by presence of an in vivo biomarker of neuronal alpha-synuclein (n-asyn) pathology, independent of presence of clinical syndrome. The NSD integrated staging system (NSD-ISS) describes progression across the disease continuum as stages 0 to 6. The objective of this analysis was to assess...

Objectives: To determine the impact of dopamine deficiency and isolated REM sleep behavior disorder (iRBD) on cognitive performance in early neuronal alpha-synuclein disease (NSD) with hyposmia. Methods: Using Parkinson's Progression Markers Initiative baseline data, cognitive performance was assessed with a cognitive summary score (CSS) developed...

Background REM sleep behavior disorder (RBD) is an early manifestation of alpha-synucleinopathy in many cases. Dream enactment behavior (DEB), the clinical hallmark of RBD, has many etiologies and cannot be used alone to predict underlying alpha-synucleinopathy. We compared the proportion of people with alpha-synucleinopathy, as measured by CSF alp...

Background Electronic medical record (EMR)–based studies hold great potential for epidemiologic investigations of Parkinson's disease (PD) causal factors and phenomenology, but diagnostic misclassification may obscure or bias inferences. Objectives The aims were to determine the validity of PD diagnostic codes in the Veterans Administration (VA) n...

Objectives: Because of the continued transition to older populations, various strategies have been developed to estimate the social impact and burden of health care. Regarding mental health, a strategy in the elderly is the measurement of neuropsychiatric symptoms (NPS), these include a wide range of behavioral and psychological manifestations. The...

Objectives: Studies in PD have traditionally focused on motor features, however, interest in non-motor manifestations has increased resulting in improved knowledge regarding the prognosis of the disease. Although several studies have explored the incidence of dementia in PD cohorts, these studies have been conducted mainly in reference centers in h...

Background: Limited knowledge exists about the association between Parkinsonism or Parkinson’s disease (PD) and cognitive impairment and dementia in Latin America. Objectives: The study aimed to determine the cross-sectional and prospective associations between Parkinsonism and PD with cognitive impairment and dementia in a large multi-country coho...

Long-term longitudinal data on outcomes in sporadic Parkinsons Disease are limited, especially from cohorts with extensive biological characterization. Recent advances in biomarkers characterization of Parkinsons Disease necessitate an updated examination of long-term progression within contemporary cohorts like the Parkinsons Progression Markers I...

The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA, and SPARK studies, we developed and...

Background Little is known about the relationship between parkinsonism or Parkinson's disease (PD) and frailty in Latin America. Objective The study aimed to determine the cross‐sectional and prospective associations between parkinsonism and PD with frailty in a large multi‐country cohort in Latin America. Frailty was assessed using three differen...

Post-traumatic stress disorder (PTSD) may be a risk factor for Parkinson’s disease (PD). We examined the relation between PTSD and PD in a cohort of 158,122 Veterans who had any Veterans Health Administration (VHA) or Medicare health care utilization between 10/1/1999– 2/17/2021. Using a nested case-control design we matched 10 controls to each Vet...

Background We recently reported an increased risk of Parkinson's disease (PD) in service members who resided at Marine Base Camp Lejeune, North Carolina, when water supplies were contaminated with trichloroethylene and other volatile organic compounds (VOCs). Prior studies suggest that environmental exposures may affect PD phenotype or progression,...

Fox Insight is an online, longitudinal study of over 54,000 people with and without Parkinson’s disease, facilitating discovery, validation, and reproducibility in Parkinson’s disease research. The study administers routine longitudinal assessments, one-time questionnaires on an array of topics such as environmental exposure or COVID-19, plus genet...

Importance: Identifying individuals in the earliest stages of synucleinopathy is essential to evaluate drugs aimed to slow progression or prevent manifest disease. Remote identification of hyposmic individuals may enable scalable recruitment of participants with underlying alpha synuclein pathology. Objective: To evaluate the performance of a stage...

Background The penetrance of common genetic risk variants for Parkinson’s disease (PD) is low. Pesticide exposure increases PD risk, but how exposure affects penetrance is not well understood. Objective To determine the relationship between occupational pesticide exposure and PD in people with LRRK2 and GBA risk variants. Methods Participants of...

Introduction Between 1953 and 1987, over one million Veterans were exposed to contaminated water at Marine Corps Base Camp Lejeune, North Carolina. We examined the relationship between toxicant exposure and subsequent disability ratings in female veterans. Materials and Methods Comparisons were made between females stationed at Camp Lejeune and fr...

In 2011, the UK medical research charity Cure Parkinson’s set up the international Linked Clinical Trials (iLCT) committee to help expedite the clinical testing of potentially disease modifying therapies for Parkinson’s disease (PD). The first committee meeting was held at the Van Andel Institute in Grand Rapids, Michigan in 2012. This group of PD...

Background Environmental exposure to trichloroethylene (TCE), a carcinogenic dry‐cleaning chemical, may be linked to Parkinson's disease (PD). Objective The objective of this study was to determine whether PD and cancer were elevated among attorneys who worked near a contaminated site. Methods We surveyed and evaluated attorneys with possible exp...

The Neuronal alpha-Synuclein Disease (NSD) biological definition and Integrated Staging System (NSD-ISS) provide a research framework to identify individuals with Lewy body pathology and stage them based on underlying biology and increasing degree of functional impairment. Utilizing data from the PPMI, PASADENA and SPARK studies, we developed and a...

Background and Objectives: In Parkinson disease (PD), Alzheimer disease (AD) copathology is common and clinically relevant. However, the longitudinal progression of AD CSF biomarkers—β-amyloid 1-42 (Aβ42), phosphorylated tau 181 (p-tau 181 ), and total tau (t-tau)—in PD is poorly understood and may be distinct from clinical AD. Moreover, it is uncl...

Background Parkinson's disease (PD) is a rapidly growing neurodegenerative disorder, but up‐to‐date epidemiological data are lacking in Latin America. We sought to estimate the prevalence and incidence of PD and parkinsonism in Latin America. Methods We searched Medline, Embase, Scopus, Web of Science, Scientific Electronic Library Online, and Lit...

Background Little is known about the burden of parkinsonism and Parkinson’s disease (PD) in Latin America. Better understanding of health service use and clinical outcomes in PD is needed to improve its prognosis. Objective The aim of the study was to estimate the burden of parkinsonism and PD in six Latin American countries. Methods 12,865 parti...

To elucidate the molecular basis of multiple system atrophy (MSA), a neurodegenerative disease, we conducted a genome-wide association study (GWAS) in a Japanese MSA case/control series followed by replication studies in Japanese, Korean, Chinese, European, and North American samples. In the GWAS stage, rs2303744 on chromosome 19 showed a suggestiv...

Background Identifying a meaningful progression metric for Parkinson’s disease (PD) that reflects heterogeneity remains a challenge. Objective To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones. Methods Using data from the Parkinson’s Progression Markers Initiative (PPMI) de nov...

Importance: Parkinsonism and Parkinson disease (PD) are known to result from repetitive head impacts from boxing. Repetitive head impacts from American football may also be associated with increased risk of neurodegenerative pathologies that cause parkinsonism, yet in vivo research on the association between football play and PD is scarce and limi...

Little is known about electrocardiogram (ECG) markers of Parkinson’s disease (PD) during the prodromal stage. The aim of the study was to build a generalizable ECG-based fully automatic artificial intelligence (AI) model to predict PD risk during the prodromal stage, up to 5 years before disease diagnosis. This case–control study included samples f...

Background Free-text, verbatim replies in the words of people with Parkinson’s disease (PD) have the potential to provide unvarnished information about their feelings and experiences. Challenges of processing such data on a large scale are a barrier to analyzing verbatim data collection in large cohorts. Objective To develop a method for curating...

Background: Neuropsychiatric symptoms (NPSs) are common in neurodegenerative diseases; however, little is known about the prevalence of NPSs in Hispanic populations. Methods: Using data from community-dwelling participants age 65 years and older enrolled in the 10/66 study (N = 11,768), we aimed to estimate the prevalence of NPSs in Hispanic pop...

Background: Identifying a meaningful progression metric for Parkinson's disease (PD) that reflects heterogeneity remains a challenge. Objective: To assess the frequency and baseline predictors of progression to clinically relevant motor and non-motor PD milestones. Methods: Using data from the Parkinson's Progression Markers Initiative (PPMI) de no...

Importance: An increased risk of Parkinson disease (PD) has been associated with exposure to the solvent trichloroethylene (TCE), but data are limited. Millions of people in the US and worldwide are exposed to TCE in air, food, and water. Objective: To test whether the risk of PD is higher in veterans who served at Marine Corps Base Camp Lejeune...

To elucidate the molecular basis of multiple system atrophy (MSA), a neurodegenerative disease, we conducted a genome-wide association study (GWAS) in a Japanese MSA case/control series followed by replication studies in Japanese, Korean, Chinese, European and North American samples. In the GWAS stage rs2303744 on chromosome 19 showed a suggestive...

Background and Objectives: In Parkinson's disease (PD), Alzheimer's disease (AD) co-pathology is common and clinically relevant. However, the longitudinal progression of AD cerebrospinal fluid (CSF) biomarkers - β-amyloid 1-42 (Aβ42), phosphorylated tau 181 (p-tau181) and total tau (t-tau) - in PD is poorly understood, and may be distinct from clin...

Background: Emerging evidence shows that α-synuclein seed amplification assays (SAAs) have the potential to differentiate people with Parkinson's disease from healthy controls. We used the well characterised, multicentre Parkinson's Progression Markers Initiative (PPMI) cohort to further assess the diagnostic performance of the α-synuclein SAA and...

The etiologies of Parkinson’s disease (PD) remain unclear. Some, such as certain genetic mutations and head trauma, are widely known or easily identified. However, these causes or risk factors do not account for the majority of cases. Other, less visible factors must be at play. Among these is a widely used industrial solvent and common environment...

Background: Tardive dyskinesia (TD) is a persistent and potentially disabling movement disorder associated with antipsychotic use. Data from RE-KINECT, a real-world study of antipsychotic-treated outpatients, were analyzed to assess the effects of possible TD on patient health and social functioning. Methods: Analyses were conducted in Cohort 1...

Background Recent research demonstrates that α-synuclein seed amplification assays (αSyn-SAA) accurately differentiate Parkinson’s disease (PD) patients from healthy controls (HC). We used the well-characterized, multicenter Parkinson’s Progression Markers Initiative (PPMI) cohort to further assess the diagnostic performance of αSyn-SAA and to exam...

Background Since the onset of the coronavirus disease 2019 pandemic, the caregiving routine for care partners of people with Parkinson's disease (PwPD) changed substantially. Objectives To understand the nature and severity of burden in care partners of PwPD during the ongoing pandemic. We also sought to describe care partners' perceived change in...

Parkinson disease (PD) is the second most common age-related neurodegenerative condition diagnosed in North America. We recently demonstrated, using multiple epidemiological data sources, that the prevalence of PD diagnoses was greater than previously reported and currently used for clinical, research, and policy decision-making. Prior PD incidence...

We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually with comprehensive m...

Background The Unified Dyskinesia Rating Scale (UDysRS) evaluates dyskinesia in patients with Parkinson's disease (PD). A minimal clinically important change (MCIC)—the smallest change in a treatment outcome that a patient considers important—remains undefined for the UDysRS. Objective To utilize pivotal amantadine delayed-release/extended-release...

Background To date, no medication has slowed the progression of Parkinson’s disease (PD). Preclinical, epidemiological, and experimental data on humans all support many benefits of endurance exercise among persons with PD. The key question is whether there is a definitive additional benefit of exercising at high intensity, in terms of slowing disea...

Background and Objectives To recruit and characterize a national cohort of individuals who have a genetic variant ( LRRK2 G2019S) that increases risk of Parkinson disease (PD), assess participant satisfaction with a decentralized, remote research model, and evaluate interest in future clinical trials. Methods In partnership with 23andMe, Inc., a p...

We quantified concentrations of three isoforms of the endolysosomal lipid, bis(monoacylglycerol) phosphate (BMP) in urine of deeply phenotyped cohorts in the Parkinson’s Progression Markers Initiative: LRRK2 G2019S PD (N = 134) and non-manifesting carriers (NMC) (G2019S + NMC; N = 182), LRRK2 R1441G PD (N = 15) and R1441G + NMC (N = 15), GBA1 N409S...

Now that wearable sensors have become more commonplace, it is possible to monitor individual healthcare-related activity outside the clinic, unleashing potential for early detection of events in diseases such as Parkinson’s disease (PD). However, the unsupervised and “open world” nature of this type of data collection make such applications difficu...

Tremendous progress in our understanding of the pathophysiology and clinical manifestations of the prodromal phase of Parkinson disease (PD) offers a unique opportunity to start therapeutic interventions as early as possible to slow or even stop the progression to clinically manifest motor PD. A Parkinson's Prevention Conference, “Planning for Prev...

Background: Aggregated α-synuclein plays an important role in Parkinson's disease pathogenesis. Cinpanemab, a human-derived monoclonal antibody that binds to α-synuclein, is being evaluated as a disease-modifying treatment for Parkinson's disease. Methods: In a 52-week, multicenter, double-blind, phase 2 trial, we randomly assigned, in a 2:1:2:2...

We report on the initial 17 (11 male:6 female) brain autopsies from across Europe and the United States in the Parkinson's Progression Markers Initiative (PPMI). Clinical diagnoses were Parkinson's disease (n = 15), multiple system atrophy (n = 1), and Dementia with Lewy bodies (n = 1); average age of death = 72 ± 8 yr. Cognitive assessment at last...

Background: We examined 2-year longitudinal change in clinical features and biomarkers in LRRK2 non-manifesting carriers (NMCs) versus healthy controls (HCs) enrolled in the Parkinson’s Progression Markers Initiative (PPMI). Methods: We analyzed 2-year longitudinal data from 176 LRRK2 G2019S NMCs and 185 HCs. All participants were assessed annually...

Autonomic nervous system pathology manifests early in Parkinson’s disease (PD) course. Although heart rate variability measured by a 5-minute electrocardiogram (ECG) is reported to be reduced in PD, little is known about ECG markers during prodromal stage, and brief 10-second ECGs have been rarely studied. The aim of the study is to build externall...

Background There is growing interest in health-related quality of life (HRQOL) as a comprehensive view of the patient’s well-being, guiding concept for the treating clinician, and therapeutic trial outcome measure for patients with PD. The key determinants of HRQOL have not been investigated in large populations of people with PD (PwPD). Our object...

Background Parkinson’s disease (PD) is a debilitating neurodegenerative disease with both motor and non-motor manifestations. Available treatment reduces symptoms and is critical for improving quality of life. Treatment options include drugs, device-aided therapies, and non-pharmacological therapies. Complementary and alternative therapies (CATs) a...

Remote health assessments that gather real-world data (RWD) outside clinic settings require a clear understanding of appropriate methods for data collection, quality assessment, analysis and interpretation. Here we examine the performance and limitations of smartphones in collecting RWD in the remote mPower observational study of Parkinson’s diseas...

Background: Age and gender specific prevalence rates for parkinsonism and Parkinson's disease (PD) are important to guide research, clinical practice, and public health planning; however, prevalence estimates in Latin America (LatAm) are limited. We aimed to estimate the prevalence of parkinsonism and PD and examine related risk factors in a cohor...

Maintaining consistent levodopa benefits while simultaneously controlling dyskinesia can be difficult. Recently, an amantadine delayed release/extended release (DR/ER) formulation (Gocovri®) indicated for dyskinesia received additional FDA approval as an adjunct to levodopa for the treatment of OFF episodes. We evaluated OFF time reductions with am...

Epidemiology is the study of the distribution of disease in human populations, which is important in evaluating burden of illness, identifying modifiable risk factors, and planning for current and projected needs of the health care system. Parkinson's disease (PD) is the second most common serious neurodegenerative illness and is expected to furthe...

Background Parkinson’s disease (PD) is a chronic, disabling neurodegenerative disorder. Objective To predict a future diagnosis of PD using questionnaires and simple non-invasive clinical tests. Methods Participants in the prospective Kuakini Honolulu-Asia Aging Study (HAAS) were evaluated biannually between 1995–2017 by PD experts using standard...

Background Traditional in-person Parkinson’s disease (PD) research studies are often slow to recruit and place unnecessary burden on participants. The ongoing COVID-19 pandemic has added new impetus to the development of new research models. Objective To compare recruitment processes and outcomes of three remote decentralized observational PD stud...

Background Investigation of sex-related motor and non-motor differences and biological markers in Parkinson’s disease (PD) may improve precision medicine approach. Objective To examine sex-related longitudinal changes in motor and non-motor features and biologic biomarkers in early PD. Methods We compared 5-year longitudinal changes in de novo, u...

BACKGROUND People with Parkinson’s disease (PD) have a variety of complex medical problems that require detailed review at each clinical encounter for appropriate management. Digital health solutions that efficiently integrate and display this information are needed to improve the care for people with PD. OBJECTIVE To improve the efficacy and effi...

Background: People with Parkinson disease (PD) have a variety of complex medical problems that require detailed review at each clinical encounter for appropriate management. Care of other complex conditions has benefited from digital health solutions that efficiently integrate disparate clinical information. Although various digital approaches hav...

Objective: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. // Methods: We performed the first genomewide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases at...

Background RE-KINECT (NCT03062033), a real-world study of possible tardive dyskinesia (TD) in antipsychotic-treated patients, included a questionnaire to assess the effects of patients’ abnormal involuntary movements on caregivers. Objective To capture the experiences of caregivers who assisted individuals with abnormal involuntary movements that...

At the same time James Parkinson was describing 6 individuals in London, England, with a novel shuffling disease, British meteorologist Luke Howard was detailing great fogs clouding the air. While both Parkinson disease and air pollution predate the early 19th century, their prevalence have risen together (Figure¹). World regions with the most air...

Objective: The aim of this study was to search for genes/variants that modify the effect of LRRK2 mutations in terms of penetrance and age-at-onset of Parkinson's disease. Methods: We performed the first genome-wide association study of penetrance and age-at-onset of Parkinson's disease in LRRK2 mutation carriers (776 cases and 1,103 non-cases a...

Background: Cerebrospinal fluid (CSF) levels of monoamine metabolites may represent biomarkers of Parkinson's disease (PD). Objective: The aim of this study was quantification of multiple metabolites in CSF from PD versus healthy control subjects (HCs), including longitudinal analysis. Methods: Absolute levels of multiple monoamine metabolites...

Introduction Parkinson’s disease (PD) research is hampered by slow, inefficient recruitment and burdensome in-person assessments that may be challenging to conduct in a world affected by COVID-19. Fox Insight is an ongoing prospective clinical research study that enables individuals to participate in clinical research from their own homes by comple...

IntroductionGocovri (amantadine) extended release capsules are approved for treatment of dyskinesia and as a levodopa adjunct for OFF episodes in patients with Parkinson’s disease (PD). We report treatment-related effects on non-motor symptoms (NMS) assessed as secondary outcomes in two trials using the Movement Disorder Society–Unified Parkinson’s...

Background: Care partners support people with Parkinson's disease through a long journey ranging from independence to dependence for many daily tasks. Longitudinal studies are important to understand the evolution of this process and predictors of future needs of care partners. Methods: A scoping review was conducted, searching PubMed for longit...

The Trial of Parkinson’s And Zoledronic acid (TOPAZ, https://clinicaltrials.gov/ct2/show/NCT03924414) is a unique collaboration between experts in movement disorders and osteoporosis to test the efficacy of zoledronic acid, an FDA-approved parenteral treatment for osteoporosis, for fracture prevention in people with neurodegenerative parkinsonism....

Objective The expanding power and accessibility of personal technology provide an opportunity to reduce burdens and costs of traditional clinical site‐centric therapeutic trials in Parkinson’s disease and generate novel insights. The value of this approach has never been more evident than during the current COVID‐19 pandemic. We sought to (1) estab...

Introduction Individuals with idiopathic rapid eye movement sleep behavior disorder (iRBD) are at high risk for a clinical diagnosis of an α‐synucleinopathy (aSN). They could serve as a key population for disease‐modifying trials. Abnormal dopamine transporter (DAT) imaging is a strong candidate biomarker for risk of aSN diagnosis in iRBD. Our prim...

Parkinson’s disease (PD) is one of the world’s fastest growing neurological disorders. Much is unknown about PD-associated economic burdens in the United States (U.S.) and other high-income nations. This study provides a comprehensive analysis of the economic burdens of PD in the U.S. (2017) and projections for the next two decades. Multiple data s...

Accurate diagnosis and appropriate treatment of tardive dyskinesia (TD) are imperative, as its symptoms can be highly disruptive to both patients and their caregivers. Misdiagnosis can lead to incorrect interventions with suboptimal or even deleterious results. To aid in the identification and differentiation of TD in the psychiatric practice setti...

Background The effect of the COVID-19 pandemic on people with Parkinson’s disease (PD) is poorly understood. Objective To rapidly identify areas of need and improve care in people with PD during the COVID-19 pandemic, we deployed a survey to assess COVID-19 symptoms and the pandemic’s effect among those with and without COVID-19. Methods People w...

Ongoing biomarker development programs have been designed to identify serologic or imaging signatures of clinico-pathologic entities, assuming distinct biological boundaries between them. Identified putative biomarkers have exhibited large variability and inconsistency between cohorts, and remain inadequate for selecting suitable recipients for pot...

Parkinson disease affects nearly 1 million people in the United States, and the prevalence is expected to increase to at least 1.2 million people by 2030. Parkinson disease is a chronic, incurable disease. Most treatments focus on controlling motor symptoms; however, as the disease progresses, periods of reduced therapeutic benefit, or OFF periods,...

Parkinson disease, the second-most-common neurodegenerative disorder, affects approximately 1 million individuals in the United States, and this number is projected to increase to 1.2 million by 2030. Characterized pathologically by degeneration of dopaminergic neurons, with widespread pathology in nondopaminergic systems, Parkinson disease leads t...

Background Many countries have implemented drastic measures to fight the COVID‐19 pandemic. Restrictions and diversion of resources may have negatively affected patients with Parkinson's disease (PD). Objectives We aimed to examine whether COVID‐19 had an impact on access to PD medication by region and income. Methods This study was conducted as...