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Enrolling by invitationNCT04701177ANANEOSUpdated Sep 10, 2026

Digitally-enhanced, Decentralized, Multi-omics Observational Cohort

An observational study in Presymptomatic Disease, Mild Cognitive Impairment and Memory Loss (Excluding Dementia), sponsored by Greece 2021 Committee. Enrolling by invitation at 4 sites in 2 countries. Open to participants aged 45 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-09-10.

Sponsored by Greece 2021 Committee · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
100,000
Ages
45 Years and older
Sex
All
01

Study 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.

Read the detailed description

Digital technologies, particularly those based on the use of smartphones, wearables and/or home-based monitoring devices, here defined as 'Remote Measurement Technologies' (RMTs), provide an opportunity to change radically the way in which functional assessment is undertaken in AD, RMTs have the potential to obtain better measurements of behavioural and biological parameters associated with individual Activities of Daily Living (ADL) when compared to the current subjective scales or questionnaires. Divergence from normative ADL profiles could objectively indicate the presence of specific incipient functional impairments even at the very early stages of AD.

Therefore, the main hypothesis of this project is that RMTs should allow the detection of impairments in functional components of ADLs that occur below the threshold of clinical scale detection or disability questionnaires.

ANANEOS is an independent Brain Registry (patient registry), created as an organized system to collect uniform data (clinical and other) to evaluate specified outcomes for the Neuropsychiatric Progression Index (NPI) and serves as a real-world view of clinical practice, patient outcomes, safety, and can serve a number of evidence development and decision making purposes.

02

Conditions studied

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

Keywords

  • Digital Biomarkers
03

Who can participate

Ages eligible
45 Years and older
Sexes eligible
All
Accepts healthy volunteers
Yes
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.

Eligibility criteria

Inclusion Criteria for Cohort participants:

  • 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.

Inclusion Criteria for Healthy volunteers:

  • 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.
  • MMSE >27, CDR=0.
  • In otherwise good health conditions, or with diagnosis mild chronic disorders (of metabolic, respiratory, immunological, cardiologic, and metabolic origin) or any other affections that are controlled by the therapy and do not importantly limit ADLs or social interactions.
  • Able to read and to communicate in the language of the recruitment centre.
  • nformed consent signed by the subject and caregiver.
  • Subject and informant own a smartphone.

Exclusion Criteria for Cohort participants:

  • 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.

Exclusion Criteria for Healthy volunteers:

  • 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.
04

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
100,000 participants (estimated)
Target follow-up
5 Years
Patient registry
Yes
Biospecimen retention
Samples with dna

Groups and cohorts

  • 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

  • Symptomatic Parkinson's

    To be classified in a symptomatic cohort, individuals typically meet the Movement Disorder Society (MDS) clinical diagnostic criteria, which require the presence of parkinsonism as the foundational baseline.

    Diagnostic Test: Teleph0s digital phenotyping platform

Interventions

  • Diagnostic testTeleph0s digital phenotyping platform

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

05

What researchers measure

Primary outcomes

  1. 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

    Time frame: baseline to 60 months

  2. 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)

    Time frame: baseline to 60 months

  3. 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.

    Time frame: 60 months of follow up

Secondary outcomes

  1. Establish the probability of phenoconversion to PD

    Evaluate the probability of phenoconversion to PD for individuals with prodromal PD enrolled in the prodromal cohorts (including individuals with RBD, olfactory loss, a LRRK2, GBA, SNCA or rare genetic mutations (such as Parkin or Pink1) and/ or other risk factors for PD with and without DAT deficit).

    Time frame: study intervals ranging from baseline to 60 months

06

Study locations

4 sites
  • Ionian University
    Corfu, Corfu 49100, Greece
  • Panhellenic Federation Of Alzheimer's Disease And Related Disorders
    Thessaloniki, 54643, Greece
  • Greek Alzheimer's Association and Related Disorders
    Thessaloniki, 55250, Greece
  • Hospital Clinic Barcelona
    Barcelona, Spain
07

References and documents

Publications

  • 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. PubMed 32832589 ↗
  • 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. PubMed 34168269 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT04701177
Lead sponsor
Greece 2021 Committee
Collaborators
Ionian University, Greek Alzheimer's Association and Related Disorders, Panhellenic Federation of Alzheimer's Disease and Related Disorders, Hospital Clinic of Barcelona, Teleph0s LLC
Responsible party
Ioannis Tarnanas (Brainregistry Task Force, Greece 2021 Committee) — Principal investigator
First posted
Jan 8, 2021
Start date
Mar 15, 2021
Primary completion
Oct 30, 2031 (estimated)
Completion
Nov 30, 2031 (estimated)
Last update
Sep 10, 2026

Study contacts

Panagiotis Vlamos, PhD
study chair · Bioinformatics and Human Electrophysiology Laboratory, Department of Informatics, Ionian University

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
Yes
View the source record on ClinicalTrials.gov ↗

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