Precision Medicine in Alzheimer's Disease : Integration of Resilience Metrics and Risk Factors - Validation Cohort BioCogBank-AD (BioCogBank-AD)

Precision Medicine in Alzheimer's Disease: Integration of Resilience Metrics and Risk Factors - Validation Cohort BioCogBank-AD

BioCogBankAD aims at building a prospective clinical practice cohort of 244 patients with biologically confirmed mild cognitive impairment due to Alzheimer's Disease (AD) or mild AD in order to validate data regarding markers of resilience toward AD pathophysiological process discovered in an upstream project called AD-Resilience.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Other: Blood sample; Behavioral: Neuropsychological battery tests

Detailed Description

Alzheimer's disease (AD) is a leading cause for individual and caregiver burden associated with neurodegenerative diseases (NDs) in an aging population, afflicting + 35 million people worldwide, and spiraling costs. Major advances have been made during the last 20 years in the understanding of AD pathophysiological process. It is now well demonstrated that the course of the disease extend over more than 20 years with long pre and pauci-symptomatic periods.

A major need and challenge in translational research on Alzheimer's disease (AD) is to predict disease progression rate and/or time to clinical conversion, notably in the early phases of the AD process, such as mild cognitive impairment (MCI). Current markers such as Aß and tau species measured in cerebrospinal fluid (CSF) can differentiate AD from control and are currently used in daily clinical practice to assess presence of AD pathological process in patients with cognitive complaints. However, they do not account for cellular compensation and resistance mechanisms, the so-called "resilience" process.

Consequently, both prediction of AD progression in single patients and personalized adaptation of management and treatment remain highly limited. Moreover, there is an important unmet need regarding targeted prevention.

AD-Resilience is a translational research study funded by Agence Nationale pour la Recherche (ANR) and Direction Générale de l'Organisation des Soins (DGOS) that aims at identifying and validating markers of the biological processes underlying the mechanisms of brain resilience toward AD pathological process. Using blood samples, the investigators will produce the molecular-profile data that are needed to assess the resilience and brain homeostasis status of patients facing the AD process. Results will be processed using high-end machine learning (ML) to overcome the limitations associated with sub-optimal reliability and precision of dimensional data analysis.

These biomarkers will be identified using data and samples from an already available nationwide research cohort (BALTAZAR). In order to ensure validity and facilitate transfer to clinical practice, results from this preliminary study will have to be confirmed in an independent, prospective cohort of patients reflecting the full spectrum and real-life heterogeneity of AD.

For this purpose, BioCogBankAD study aims at building this validation cohort. 244 patients with MCI or early dementia due to AD will be recruited in the present study and prospectively followed during three years. Blood samples (plasma, DNA and PaxGen) will be taken from these patients in order to measure the biomarkers previously identified in the exploratory study. Clinical follow-up including including standardized neuropsychological examination and blood sampling (plasma) will be performed annually.

• Study Type: Interventional
• Enrollment (Estimated): 244
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Valérie PLENCE, MSc; Phone Number: +33 1 54 41 11 78; Email: valerie.plence@aphp.fr
• Study Contact Backup: Name: Olivier HANON, MD, PhD; Phone Number: + 1 44 08 33 81; Email: olivier.hanon@aphp.fr

Study Locations

• France
  • Paris, France, 75014
    • Recruiting
    • Hopital Cochin
    • Contact: Olivier HANON, MD, PhD; Phone Number: +33 1 44 08 33 81; Email: olivier.hanon@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of AD according to IWG-2 2014 criteria
• Age 50-90 year old
• Affiliated or beneficiary of a social security scheme
• MMSE ≥ 20
• Abnormal CSF Aβ42 or Aβ40/Aβ42 ratio according to local cut-offs
• Abnormal CSF phosphorylated and total Tau according to local cut-offs
• Ability to pass neuropsychological assessments
• Availability of a brain MRI with T1 volumetric sequence performed within 1 year

Exclusion Criteria:

• Other cause of dementia
• Participation in an AD therapeutic clinical trial
• Protected adults (including individual under guardianship by court order),

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Exploratory group

Other: Blood sample; Plasma, DNA, RNA and PBMC Sampling; Behavioral: Neuropsychological battery tests; Short term memory: Digit span (forward and backward); Long term memory: Free and Cued selective reminding Test; Language and semantic Memory : Verbal Fluency (Category and Litteral), Image Naming (DO 40); Praxis; Visuo Spatial abilities: Rey-Osterrieth Complex Figure Test; Attention and executive functions: Trail Making Test (TMT) Part A and B, Frontal Assessment Battery (FAB); Autonomy in daily life activities : Alzheimer's Disease Cooperative Study - Activities of Daily Living Inventory (ADCS-ADL), Instrumental Activities of Daily Living (IADL); Mood and anxiety: Hospital Anxiety and Depression Scale (HADS); Cognitive reserve : Cognitive Reserve Index questionnaire (CRIq)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean levels of new blood biomarkers	assess biomarkers of biological resilience toward AD pathological process	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mini-Mental State examination (MMSE)	assess relationship between new biomarkers (biomarkers identified in the current study on the analysis of study samples Baltazar) and cognitive decline - MMSE: 0 to 30 evaluates memory, orientation in space and time, learning and immediate memory, attention and reasoning, language and ability to perform tasks.; Score of 27 or more: no cognitive impairment; Score between 21 and 26: slight impairment; Score between 11 and 20: moderate impairment; Score below 10: severe impairment	36 months
Cognitive performance (zScore)	assess relationship between new biomarkers (biomarkers identified in the current study on the analysis of study samples Baltazar) and cognitive decline -	36 months
Instrumental Activities of Daily Living (IADL)	assess relationship between new biomarkers and loss of autonomy (decline on IADL) - 0 dependent to 17 Assessment of autonomy in instrumental activities of daily living - The score shows the level of autonomy: a maximum score represents maximum autonomy, and the lower the score, the lower the level of autonomy.	36 months
Hospital Anxiety and Depression Scale (HADS)	The HAD scale is a screening instrument for anxiety and depressive disorders. It comprises 14 items rated from 0 to 3. Seven questions relate to anxiety (total A) and seven to depression (total D), giving two scores (maximum score for each = 21). 0 = no anxiety 21= anxiety and depressive disorders max	36 months
Cognitive Reserve Index questionnaire (CRIq)	CRI schooling min = 0 no schooling, training or internship - Max = undefined because "+1" corresponds to each year of schooling and +0.5 for any internship of more than 6 months - CRI work is the number of years of work, rounded to a scale of 5 (0-5-10-15-20) to assess the degree of intellectual effort and personal responsibility - CRI leisure from never/rarely to often/always (checkboxes) multiplied by number of years of practice. Score CRI : ≤70 = low; 70 to 84 = low average; 85 to 114 = average From 115 to 130 = high average; ≥ = high	36 months
Cerebrospinal Fluid (CSF) biomarkers of AD	correlate the new blood biomarkers levels and CSF biomarkers of AD (Aβamyloid, Tau, P Tau)	36 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; National Research Agency, France; URC-CIC Paris Descartes Necker Cochin; Centre National de la Recherche Scientifique, France
• Investigators: Study Director: Emmanuel GOGNAT, MD, PhD, Assistance Publique - Hopitaux de Paris; Study Chair: Christian NERRI, PhD, Institut National de la Santé Et de la Recherche Médicale, France

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2024
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: July 23, 2024
• First Submitted That Met QC Criteria: August 30, 2024
• First Posted (Actual): September 3, 2024

Study Record Updates

• Last Update Posted (Actual): March 27, 2026
• Last Update Submitted That Met QC Criteria: March 24, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Alzheimer Disease; Cohort; Biomarkers; Mild cognitive impairment; Resilience; Clinical practice
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Blood Specimen Collection
• Other Study ID Numbers: APHP210991; 2024-A00457-40 (Other Identifier: ID-RCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No