The BRidge Towards Implementation of Blood-based Biomarkers to Enable Early and Accurate Diagnosis of Alzheimer's Disease (BRIDGE-AD2)

The BRidge Towards Implementation of Blood-based Biomarkers to Enable Early and Accurate Diagnosis of Alzheimer's Disease (BRIDGE-AD2)

Cognitive disorders have a broad differential diagnosis, and a precise, timely diagnosis is essential for personalized treatment and care. Currently, dementia diagnoses are often not further specified according to the underlying pathology and are frequently delayed by several years. However, with the upcoming disease-modifying treatments (DMTs) for AD, an accurate, pathology-driven (i.e., etiological) diagnosis will become necessary.

Blood-based biomarkers (BBMs) are promising tools for detecting Alzheimer's disease (AD), with current research showing high concordance with cerebrospinal fluid (CSF) biomarkers and amyloid PET imaging. However, it remains unclear how physicians would value the availability of BBMs for AD in routine clinical practice. The investigators hypothesize that BBMs will benefit both patients and physicians in the diagnostic process within a memory clinic setting.

This study aims to investigate clinical impact and diagnostic utility of blood-based biomarkers for AD in the diagnostic process of a memory clinic. The main objectives are to investigate change in diagnosis, diagnostic certainty and patient management, due to BBM results.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer's Disease (AD); Alzheimer Blood Biomarkers
• Intervention / Treatment: Diagnostic test: Plasma p-tau217 and neurofilament light chain results

• Study Type: Interventional
• Enrollment (Estimated): 550
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Floor Duits, PhD; Phone Number: 020 - 4440816; Email: f.duits@amsterdamumc.nl

Study Locations

• Netherlands
  • 's-Hertogenbosch, Netherlands
    • Recruiting
    • Jeroen Bosch Ziekenhuis
    • Contact: A van Strien, MD PhD; Phone Number: 0031735532000
    • Principal Investigator: A van Strien, MD PhD
  • Almere Stad, Netherlands
    • Recruiting
    • Flevoziekenhuis
    • Contact: M I Kester, MD PhD; Phone Number: 0031368688720; Email: mkester@flevoziekenhuis.nl
    • Principal Investigator: M I Kester, MD PhD
  • Haarlem, Netherlands
    • Recruiting
    • Spaarne Gasthuis
    • Contact: N SM Schoonenboom, MD PhD; Phone Number: 0031232240110; Email: schoonenboom@spaarnegasthuis.nl
    • Principal Investigator: N SM Schoonenboom, MD PhD
  • Hilversum, Netherlands
    • Recruiting
    • Tergooi MC
    • Contact: S S Staekenborg, MD PhD; Phone Number: 0031887531250; Email: sstaekenborg@tergooi.nl
    • Principal Investigator: S S Staekenborg, MD PhD
  • Leeuwarden, Netherlands
    • Recruiting
    • Frisius MC
    • Contact: N A Verwey, MD PhD; Phone Number: 0031582866666; Email: niek.verwey@frisiusmc.nl
    • Principal Investigator: N A Verwey, MD PhD
  • Purmerend, Netherlands
    • Recruiting
    • Dijklander Ziekenhuis
    • Contact: L AR Zwart, MD PhD; Phone Number: 0031299457142; Email: l.a.r.zwart@dijklander.nl
    • Principal Investigator: L AR Zwart, MD PhD
  • Tilburg, Netherlands
    • Not yet recruiting
    • Elisabeth-TweeSteden Ziekenhuis
    • Contact: H P Aben, MD PhD; Phone Number: 0031132210000; Email: h.aben@etz.nl
    • Principal Investigator: H P Aben, MD PhD
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081HV
      • Recruiting
      • Amsterdam UMC
      • Contact: F H Duits, MD PhD; Phone Number: 0031204440816; Email: fduits@amsterdamumc.nl
      • Principal Investigator: F H Duits, MD PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Patient presents in memory clinic with cognitive complaints.
• The physician is concerned about underlying AD as etiology of the complaints.
• Adequate fluency in Dutch to understand informed consent procedure.

Exclusion Criteria:

• Age under 55.
• Previous biomarker-confirmed diagnosis of AD.
• Alcohol or drug abuse to such an extent that treatment would be advisable.
• Patient is incapacitated, and is not able to judge consequences of participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Usual care path; Blood-based biomarker results are not disclosed to the physician and/or patient, patient receives usual care and diagnostics
Experimental: Blood-based biomarker results are made available to the physician; In addition to usual care and diagnostics, blood-based biomarker results are sent to the physician who can disclose the results to the patient	Diagnostic test: Plasma p-tau217 and neurofilament light chain results; Results of the Quanterix Simoa ALZpath p-tau217 and Quanterix Simoa NfL assay.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time from baseline to final diagnosis	The time from baseline visit to final diagnosis will be reported in days.	From enrolment to final diagnosis, assessed up to 100 months
Change in diagnosis	Comparison between the diagnosis (syndrome diagnosis and etiology) before and after BBM testing. Change in diagnosis will be reported as yes/no.	From enrolment to when BBM test results have been disclosed to the physician, assessed up to 3 months
Change in physician's confidence in diagnosis	Comparison between physician's confidence in diagnosis before and after BBM testing within the intervention group. Physician's confidence will be measured on a 7-point Likert scale, with 1 being very uncertain and 7 being very certain.	From enrolment to when BBM test results have been disclosed to the physician, assessed up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference between the intervention group and the control group in use and timing of ancillary tests	Use of ancillary tests (yes/no), including neuropsychological evaluation, brain CT, brain MRI, CSF biomarker analysis, amyloid PET, FDG PET, DaT-SPECT, EEG/MEG, genetic testing, and speech therapy consultation. If performed, the timing in days from enrollment will be reported.	From enrolment to final diagnosis, assessed up to 100 months
Concordance of BBM results with the presence of AD pathology according to CSF or amyloid PET	Concordance will be defined as the percentage of BBM results (positive or negative) that is concordant with CSF or amyloid PET results (positive or negative).	From enrolment to final diagnosis, assessed up to 100 months
Difference between the intervention group and the control group in patient management: follow-up duration	Duration of patient follow-up (reported in days)	From enrolment to final diagnosis, assessed up to 100 months
Difference between the intervention group and the control group in patient management: referral	Referral to another specialist or center (yes/no)	From enrolment to final diagnosis, assessed up to 100 months
Difference between the intervention group and the control group in patient management: prescription of medication	Prescription of medication (yes / no; if yes which medication)	From enrolment to final diagnosis, assessed up to 100 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Usefulness of AD BBMs per case as perceived by the physician	In the intervention group: Usefulness as perceived by the physician measured on a 5-point Likert scale with 1 being extremely unuseful and 5 being extremely useful. In the control group: Hypothetical usefulness (yes/no/maybe) as perceived by the physician in case the BBM results would have been received. In all cases: Desireability of the blood test being performed (yes/no) as perceived by the physician prior to receiving BBM results.	From enrolment to when BBM test results have been disclosed to the physician, assessed up to 3 months
Patients' motivation for participation	Participants will be asked to indicate their motivation for participation.	After the blood test is performed, assessed up to 3 months
Patients' experience with receiving or not receiving BBM results	Intervention group: Experience of receiving BBM results will be assessed by asking participants: Whether not receiving the results would have been preferred (yes/no/I do not know); Whether receiving the results had positive consequences (yes/no); Whether receiving the results had negative consequences (yes/no) In the control group: experience of not receiving BBM results will be assessed by asking participants: - Whether receiving the results would have been preferred (yes/no/I do not know)	After the blood test is performed, assessed up to 3 months
Patient's understanding of the BBM results	Participant's understanding will be assessed by asking participants whether the diagnosis changed after receiving BBM results. If yes, participants will be asked to indicate the initial diagnosis. Additionally, participants will be asked to explain, in their own words, what the BBM results meant.	After the blood test is performed, assessed up to 3 months
Patients' satisfaction with the provision of information	In case the results were disclosed to the patient: Satisfaction will be assessed by rating their agreement with 2 statements on a 5-point agree/disagree scale with 1 being strongly disagree and 5 being strongly agree.	After the blood test is performed, assessed up to 3 months
Patients' satisfaction with the decision to participate	In all cases: Satisfaction will be assessed by asking participants to rate their agreement with 4 statements on a 5-point decision regret scale with 1 being strongly disagree and 5 being strongly agree.	After the blood test is performed, assessed up to 3 months
Cognitive performance measured by the MOCA	Total scores of the Montreal Cognitive Assessment (MoCA) will be registered, if performed during clinical work-up. Scores range from 0 to 30.	From enrolment to final diagnosis, assessed up to 100 months
Cognitive performance measured by the MMSE	Total scores of the Mini-Mental State Examination (MMSE) will be registered, if performed during clinical work-up. Scores range from 0 to 30.	From enrolment to final diagnosis, assessed up to 100 months
Survival	Information on survival will be requested from Statistics Netherlands (Centraal Bureau voor de Statistiek; CBS), provided informed consent has been given for this (optional / separate question in ICF).	Up to 10 years after study completion

Collaborators and Investigators

• Sponsor: Alzheimercentrum Amsterdam
• Collaborators: Davos Alzheimer's Collaborative; Quanterix Corporation (in kind)

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: June 4, 2026
• First Submitted That Met QC Criteria: June 25, 2026
• First Posted (Actual): July 2, 2026

Study Record Updates

• Last Update Posted (Actual): July 2, 2026
• Last Update Submitted That Met QC Criteria: June 25, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Randomised diagnostic trial
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Alzheimer Disease
• Other Study ID Numbers: 2025.0070; 25-01-050817 (Other Identifier: EUDAMED)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: There are plans to share IPD through the ADDI platform, however a contract or data sharing agreement has not yet been established. Therefore it is not yet clear which specific IPD will be shared.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No