Digitally-enhanced, Decentralized, Multi-omics Observational Cohort

NCT04701177 | Enrolling By Invitation DMC FDA Device

• 2 other identifiers: ANANEOS-GP2GR-00546
• Study Type: observational
• Target: 100,000
• Locations: 2 countries
• Sites: 4

Brief Summary

The study is carried out as part of the GR2021 Priority project "Healthy Brains for life (Age 20-99): Digitally-enhanced personalized medicine study ANANEOS" and code numbered GR-00546 and it will look at the decentralized and remote assessment of the symptoms of preclinical stages in Alzheimer's disease and movement disorders, e.g. Parkinson's. For this study we are looking for participants aged over 45 without cognitive complaints or with subjective perception of cognitive decline or with mild cognitive complaints. Specific aims for the proposed study: a) to develop novel sensitive measures that can provide an early identification of those SCD and MCI individuals harboring AD pathology that are at high risk of cognitive worsening over time; b) to track pre-motor stages in Parkinson's disease and trials that enable active digital functional biomarkers; c) to track disease progression during pre-dementia and pre-motor stages in clinical practice and trials with measures that enable to capture subtle changes.

Conditions

Mild Cognitive Impairment; Memory Loss (Excluding Dementia); Cognitive Change; Alzheimer Disease; Parkinson's Disease and Parkinsonism; Presymptomatic Disease; Dementia

Keywords

Digital Biomarkers

Outcome Measures

Primary Outcomes (3)

• Establish standardized protocols for acquisition, transfer & analysis of clinical, digital, imaging, biologic and genetic data that can be used in the AD & PD research community.

  This protocol will build on the existing Greek Brain Registry infrastructure

  baseline to 60 months

• Comprehensive and uniformly acquired dataset

  Develop a comprehensive and uniformly acquired clinical, digital and imaging dataset and repository of biological and genetic samples that would be available to the PD research community to test hypotheses of the underlying molecular pathobiology of PD, enable modeling of PD progression to identify clinical and/or data driven PD progression sub-sets, and inform studies testing PD therapeutics (for examples, clinical trials targeting synuclein, LRRK2, GBA as well as other targets)

  baseline to 60 months

• Change in Diagnostic Area Under the Receiver Operating Characteristic Curve (ROC-AUC)

  The machine learning models capturing voice data, hands micromovements \& micro-errors, posture changes, eye tracking, visuospatial navigation micro-errors and spatio-temporal gait parameters developed for the Altoida system will be tested in this prospective cohort. Sensitivity, specificity and accuracy of the model will be tested in differential diagnosis between the study groups as well as the accuracy of predicting cognitive trajectories as measured by neuropsychological test battery in both groups.

  60 months of follow up

Secondary Outcomes (1)

• Establish the probability of phenoconversion to PD

  study intervals ranging from baseline to 60 months

Study Arms (3)

Mild Behavioural Impairment (MBI)

Mild Behavioral Impairment (MBI) is a neurobehavioral syndrome characterized by new, persistent psychiatric symptoms in older adults (aged 50+) who do not have dementia. Often together with subjective perception of cognitive decline in the absence of cognitive impairment in formal neuropsychological assessment.

Diagnostic Test: Teleph0s digital phenotyping platform

Mild cognitive impairment (MCI)

Single or multidomain cognitive deficits with preservation of activities of daily living.

Diagnostic Test: Teleph0s digital phenotyping platform

Prodromal Parkinson's Disease

Parkinson's disease (PD) has a prodromal phase during which nonmotor clinical features as well as physiological abnormalities may be present.

Diagnostic Test: Teleph0s digital phenotyping platform

Interventions

Teleph0s digital phenotyping platform DIAGNOSTIC_TEST

Computerized multimodal assessment of complex neurological and psychiatric interviews (AI-COPE).

Mild Behavioural Impairment (MBI); Mild cognitive impairment (MCI); Prodromal Parkinson's Disease

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study is a decentralized, observational, digital assessment cohort study in healthy volunteers with negative AD biomarkers as control, subjects with MBI, preclinical AD and MCI due to AD dementia.

You may qualify if:

• Male or female over 45 years of age.
• Subject is seen at a memory clinic or is part of an observational study.
• An informant (caregiver/family member) is available to collaborate.
• Diagnosis of individuals in the AD biological continuum with evidence of amyloid-beta accumulation based on the presence of Aβ load AD biomarkers (either in CSF or PET scan), MMSE, CDR score and cognitive tests as defined by the Guidance document of EMA (2016) or FDA (2018):
• preclinical AD: MMSE≥27 and CDR=0, either none or borderline cognitive deficits (compatible with FDA stages 1 and 2, with positive AD biomarkers). Patients reporting subjective cognitive decline who meet the criteria above are eligible for assignment to the preclinical AD group.
• prodromal AD/MCI due to AD: MMSE \>23, CDR=0.5, impairment on cognitive testing with RBANS (compatible with stage 3 FDA, with positive AD biomarkers).
• Prodromal PD: Male or female age 60 years or older (except age 30 years or older for SNCA, or rate genetic mutations (such as Parkin or Pink1) participants).
• Individuals taking any of the following drugs: alpha methyldopa, methylphenidate, amphetamine derivatives or modafinil, must be willing and medically able to hold the medication for at least 5 half-lives before DaTscan imaging.
• Informed consent signed by the subject and informant.
• Informant should be able to read and communicate in the language of the recruitment centre and available to actively engage in tests and questionnaires.
• Subject and the informant own a smartphone.
• Male or female over 45 years of age.
• Individuals with no evidence of amyloid-beta accumulation based on the presence of Aβ load AD biomarkers (either in CSF or PET scan).
• Approximately age and gender matched to AD subjects on a group level.
• An informant is available to collaborate.

You may not qualify if:

• Presence of an additional neurological or psychiatric disease that may affect ADL, cognitive function or social interactions.
• Clinical diagnosis of PD, other parkinsonism, or dementia.
• Received any of the following drugs: dopamine receptor blockers (neuroleptics), metoclopramide and reserpine within 6 months of Screening visit.
• Current treatment with anticoagulants (e.g. coumadin, heparin) that might preclude safe completion of the lumbar puncture.
• Abnormal VB12 value.
• Any other kind of disorders that relevantly affect mobility and/or ADL, cognitive function or social interactions (e.g., immune-mediated inflammatory disorders, recovery from recent trauma, stroke, etc.).
• TSH above normal range
• T3 or T4 outside normal range with clinically significant.
• Presence of an additional neurological or psychiatric disease that may affect ADL, cognitive function or social interactions.
• Diagnosis of any disorders or post traumatic conditions that are not fully controlled by the therapy and produce relevant limitations of ADL, cognitive function or social interactions.

Sponsors & Collaborators

• Ionian University: collaborator
• Greece 2021 Committee: lead
• Greek Alzheimer's Association and Related Disorders: collaborator
• Panhellenic Federation of Alzheimer's Disease and Related Disorders: collaborator
• Barcelona Clinic Hospital (HCB), Spain: collaborator
• Teleph0s LLC: collaborator

Study Sites (4)

Ionian University

Corfu, Corfu, 49100, Greece

Location

Panhellenic Federation Of Alzheimer's Disease And Related Disorders

Thessaloniki, 54643, Greece

Location

Greek Alzheimer's Association and Related Disorders

Thessaloniki, 55250, Greece

Location

Hospital Clinic Barcelona

Barcelona, Spain

Location

Related Publications (2)

• Buegler M, Harms R, Balasa M, Meier IB, Exarchos T, Rai L, Boyle R, Tort A, Kozori M, Lazarou E, Rampini M, Cavaliere C, Vlamos P, Tsolaki M, Babiloni C, Soricelli A, Frisoni G, Sanchez-Valle R, Whelan R, Merlo-Pich E, Tarnanas I. Digital biomarker-based individualized prognosis for people at risk of dementia. Alzheimers Dement (Amst). 2020 Aug 19;12(1):e12073. doi: 10.1002/dad2.12073. eCollection 2020.

  BACKGROUND

• Meier IB, Buegler M, Harms R, Seixas A, Coltekin A, Tarnanas I. Using a Digital Neuro Signature to measure longitudinal individual-level change in Alzheimer's disease: the Altoida large cohort study. NPJ Digit Med. 2021 Jun 24;4(1):101. doi: 10.1038/s41746-021-00470-z.

  PMID: 34168269 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Whole exome sequencing and GWAS analysis from buccal swab or saliva swab. For a subset of 3'000 deeper phenotyped individuals, the DNA would be extracted from blood.

MeSH Terms

Conditions

Asymptomatic Diseases; Cognitive Dysfunction; Memory Disorders; Dementia; Alzheimer Disease; Parkinson Disease; Parkinsonian Disorders

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies

Study Officials

• Panagiotis Vlamos, PhD

  Bioinformatics and Human Electrophysiology Laboratory, Department of Informatics, Ionian University

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 5 Years
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Brainregistry Task Force

Study Record Dates

• First Submitted: January 6, 2021
• First Posted: January 8, 2021
• Study Start: March 15, 2021
• Primary Completion (Estimated): October 30, 2031
• Study Completion (Estimated): November 30, 2031
• Last Updated: March 18, 2026

Record last verified: 2026-03

Locations

ES (1); GR (3)