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Principal Investigator: ALBERTO ASCHERIO
Organization: HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH
Fiscal Year: 2023
Award: $477,028
Funding agency: National Institute of Neurological Disorders and Stroke
PROJECT SUMMARY The highest priority recommended by NINDS for clinical Parkinson’s research is
to define “the features and natural history of prodromal Parkinson disease (PPD), including the events
that underlie phenoconversion to clinically manifest PD, and biomarkers or other determinants of
prodromal subtypes with the goal of providing sufficient rationale to initiate proof-of-concept prevention
trials....” We are in a privileged position to address this priority by leveraging 25 years of research on
PD in the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), large
cohorts of women and men recruited in mid-adult life and followed prospectively for over 30 years. In
2012, we screened the active participants in these cohorts for probable REM sleep behavior disorder
(pRBD) and constipation, and selected a sub-cohort enriched for these features for further investigation
(the ProPD cohort). This sub-cohort included 20,455 individuals who have so far completed two
olfactory tests and two comprehensive mailed surveys of non-motor and early motor features of PPD,
and have been actively followed until 2018. We are now proposing to extend the longitudinal follow-up
of this unique cohort and its source population to monitor the progression of prodromal features and
phenoconversion to clinically manifest PD (“phenoconversion”, for brevity), thus providing important
insights on the course of PPD and fill the gap between current knowledge and what we need to know
for implementing prevention trials. Further, as part of the proposed project, we will examine the impact
of covid-19 on PPD and its progression and collect new biological samples to evaluate the sebum
volatilome and metabolome, novel promising and non-invasive biomarkers that could play an important
role in the early identification of PPD. The Aims of the study include: i) to obtain an in-depth descriptive
characterization of PPD and its heterogeneity; ii) to identify risk factors for PPD progression and
phenoconversion; iii) to assess the impact of SARS-Cov2/covid-19 on features of prodromal PD and
phenoconversion; and iv) to evaluate the relationship between the sebum volatilome and metabolome
with prodromal features and manifest PD (sebum samples will be collected from individuals with high
probability of PPD, manifest PD, and matched controls). A unique and virtually irreproducible strength
of the proposed study are the data prospectively collected since mid-adult life (men were 40 to 65 at
recruitment, women 30 to 55) on lifestyle and medical history, including risk factors for PD and several
features associated with PPD. If funded, the proposed study stands to lead to groundbreaking
discoveries and create an invaluable resource that will offer numerous opportunities for further in-depth
investigations on PPD and its determinants. Most importantly, the information generated by the
proposed investigation will be pivotal to assess the feasibility of prevention trials and inform their design.
Terms: <2-Phenyl-Benzopyrans><2-Phenyl-Chromenes><2019 novel corona virus><2019 novel coronavirus><2019-nCoV><21+ years old><Active Follow-up><Address><Adrenergic beta-Antagonists><Adrenergic beta-Blockers><Adult><Adult Human><Agonist><Allelism Test><Antigens><Appearance><Biological><Biological Markers><Brain><Brain Nervous System><COVID-19><COVID-19 affected><COVID-19 consequence><COVID-19 effect><COVID-19 impact><COVID-19 impacted><COVID-19 virus><COVID19><COVID19 virus><CV-19><CV19><Caffeine><Carnitine><Clinical><CoV-2><CoV2><Complementation Test><Constipation><Data><Diagnosis><Dietary Practices><Disease Progression><Drugs><Dyskinesia Syndromes><Early Intervention><Early identification><Encephalon><Event><Flavonoids><Follow-Up Studies><Followup Studies><Food><Funding><Future><Genetic Complementation Test><Goals><Health Care Professional><Health Professional><Healthcare professional><Heterogeneity><Individual><Intermediary Metabolism><Intervention><Intervention Strategies><Investigation><Knowledge><Life><Life Style><Lifestyle><Lipids><Machine Learning><Medical History><Medication><Metabolic Processes><Metabolism><Monitor><Motor><Movement Disorder Syndromes><Movement Disorders><NINDS><National Institute of Neurological Diseases and Stroke><National Institute of Neurological Disorders and Stroke><Natural History><Nerve Degeneration><Neuron Degeneration><Nurses' Health Study><Nutrient><Paralysis Agitans><Parkinson><Parkinson Disease><Parkinsonian><Parkinsonian Condition><Parkinsonian Diseases><Parkinsonian Disorders><Parkinsonian Syndrome><Parkinsonism><Participant><Patients><Personal Medical History><Personal Medical History Epidemiology><Pharmaceutic Preparations><Pharmaceutical Preparations><Phase><Physical activity><Play><Population><Position><Positioning Attribute><Prevention trial><Primary Parkinsonism><Probability><REM Behavior Disorder><REM Sleep Behavior Disorder><Rapid Eye Movement Behavior Disorder><Rapid Eye Movement Sleep Behavior Disorder><Recommendation><Research><Research Resources><Resources><Risk Factors><Role><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Sebum><Sebums><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome related corona virus 2><Smoking><Societies><Source><Sphingolipids><Subgroup><Survey Instrument><Surveys><Testing><Time><Training><Trans Test><Volatilization><Woman><Wuhan coronavirus><active followup><adulthood><algorithm training><beta blocker><beta-Adrenergic Blocking Agents><beta-Adrenergic Receptor Blockaders><bio-markers><biologic><biologic marker><biomarker><case control><case-controlled><cohort><complementation analysis><complementation approach><corona virus disease 2019><coronavirus disease 2019><coronavirus disease 2019 consequence><coronavirus disease 2019 effect><coronavirus disease 2019 impact><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 impact><coronavirus disease-19 virus><coronavirus infectious disease-19><design><designing><dietary><dietary pattern><disability><disease risk><disorder risk><drug/agent><experience><follow up><follow-up><followed up><followup><hCoV19><hyposmia><immunogen><insight><interventional strategy><machine based learning><malleable risk><men><metabolome><metabonome><modifiable risk><nCoV2><neural degeneration><neurodegeneration><neurodegenerative><neurological degeneration><neuronal degeneration><new marker><novel><novel biomarker><novel marker><prediction algorithm><predictive algorithm><predictor algorithm><prevent><preventing><prospective><recruit><reduced smell><screening><screenings><sex><social role><virtual>