Evaluation of Autonomic, Imaging and Genetic Markers for Parkinson-related Dementia : Longitudinal Assessment of a PD Cohort.

NCT06156917 | Completed DMC

• 1 other identifier: AIG/PD CARIPLO grant 2014-0832
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Neuropathologically, Parkinson disease (PD) is characterized by the accumulation of intra-neuronal protein aggregates (Lewy bodies and Lewy neurites). It is believed that altered rt-synuclein protein handling plays a key role in the etiopathogenesis of PD, because it is the principal component of Lewy pathology. Recent evidence now suggests the possibility that a-synuclein is a prion-like protein and that PD is a prion-like disease. Some studies have suggested that environmental toxins promote the release of a-synuclein by enter- ic neurons and that released enteric a-synuclein is taken up by presynaptic sympathetic neurites and retro- gradely transported to the soma, where it accumulates, thus mediating the progression of PD pathology. These data indicate the precocity of autonomic nervous system involvement with reference to further spread of a-synuclein pathology. We have evidence from a previous study that the vagal preganglionic pro- jections to the gut express a-synuclein, thus providing a candidate a-synuclein-expressing pathway for the retrograde transport of pathogens to the central nervous system. Cardiovascular autonomic dysfunction explores the reactivity of sympathetic and parasympathetic pathways to a predefined set of tests, allowing to quantify the degree of dysfunction in each of the two components of the autonomic nervous system. Mutations in the GBA gene influence the risk for dementia in PD 21; this effect of GBA is not synergistic with that of increasing age. Heterozygous GBA mutations are considered an important risk factor for PD and dementia, possibly causing a wider protein accumulation in the brain. In vitro models of alpha-synuclein aggregation have provided evidence for co-localization with mutant GBA . It has been proposed that a gain of function mechanism operates in patients with PD carrying GBA gene mutations, whereby mutant G8A promotes alpha-synuclein aggregation, accelerating Lewy body formation and neuronal loss. Each of the selected variables provides a unique window to ascertain the association between PD patho- physiology and the risk of related dementia. Our hypothesis is that PD patients who develop incident dementia will have a number of statistically different abnormalities that will be evidenced as individual predictors and will also be assembled into a predictive algorithm. This project addresses a key issue in Parkinson disease, a progressive neurodegenerative condition, related to the assessment of variables associated to the development of dementia. The project is focused on dementia as a significant and important clinical milestone that constitutes the main cause of non-reversible functional impairment in PD patients.

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (1)

• correlation of dysautonomia with incident dementia associated to PD

  .At the end of the study, the patients will be divided in two groups: demented and non-demented. Dysauto- nomia measures wili be based on autonomic testing and MIBG scintigraphy.

  2 years

Interventions

diagnostic accuracy DIAGNOSTIC_TEST

Aims of the present project are: to investigate the relationship between incident PD dementia and multimodal parameters as cardiovascular autonomic dysfunction, altered cerebral glucose metabolism, and genetic biomarkers; development of an algorithm predictive for PD-related dementia, combining the rele- vant multidimensional parameters under study; longitudinal follow-up of clinical and cognitive status in PD patients with and without dementia along four years.

Eligibility Criteria

• Age: 40 Years - 70 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

This project provides the opportunity to collect and characterize a large cohort of PD patients to be studied prospectively. We will evaluate whether dlfferences In the measured variables exist between patients who will develop dementia (primary endpoint) within the observatlon time frame and those who will remain free from cognitive impairment at follow-up. We will compare PD patients who reach this endpoint before 10 years from disease onset to those who by that tlme remain cognitively preserved.

You may qualify if:

• Diagnosis of "clinically established PD" based on the MDS clinical diagnostic criteria.
• Age at disease onset will be between 40 and 70.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

Irccs San Raffaele

Milan, Italia, Italy

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor in Diagnostic Imaging and Radiotherapy Faculty of Medicine and Surgery, Vita-Salute San Raffaele University Director, Department of Nuclear Medicine, IRCCS Ospedale San Raffaele

Study Record Dates

• First Submitted: November 27, 2023
• First Posted: December 5, 2023
• Study Start: September 1, 2018
• Primary Completion: September 1, 2020
• Study Completion: September 1, 2020
• Last Updated: December 5, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)