Blood-based Biomarkers for Diagnosis of Alzheimer's

Accuracy of Blood-based Biomarkers in Diagnosing Alzheimer's Disease in Clinical Practice

Alzheimer's disease (AD) may currently be diagnosed using molecular biomarkers in cerebrospinal fluid (CSF) and/or positron emission tomography (PET). These diagnostic procedures are highly accurate, but the high cost and low availability hamper their feasibility. Recently, ultrasensitive blood tests predicting Alzheimer pathologies in the brain have been developed. These tests have a reliable ability to differentiate AD from other neurodegenerative disorders and identify AD across the clinical continuum with high sensitivity and specificity in research cohorts with a high prevalence of AD.

This project will assess the predictive value of these tests in a general practice population.

The hypothesis is that the actual blood panel will have high positive predictive value for a diagnosis of Alzheimer's disease in the primary health care setting.

Study Overview

• Status: Recruiting
• Conditions: Dementia Alzheimers
• Intervention / Treatment: Diagnostic test: predictive value of a blood test

Detailed Description

A correct diagnosis of dementia is important in order to provide the patient and relatives with right information, and to give adequate treatment and support, but also to improve research and further development of treatment. Alzheimer's disease (AD) is the cause of nearly 2/3 of cases of dementia. Current diagnostic methods to ensure accurate diagnosis include analysis of cerebrospinal fluid and molecular PET, but these methods are expensive and not widely available.

Progress has been made in the development of blood-based diagnostic biomarkers for Alzheimer's disease. It will lead to significant simplification and improvement of clinical practice if simple blood tests that can be taken in general practice can provide a reliable diagnosis of Alzheimer's disease.

Several biomarkers (including phosphorylated tau 181, phosphorylated tau 217, phosphorylated tau 231, plasma glial fibrillary acidic protein, plasma β-amyloid 42 to β-amyloid 40 ratio, and plasma neurofilament light) has documented to be useful to distinguish Alzheimer's dementia from non-Alzheimer's dementia in research cohorts with a high prevalence of AD. This project aims to analyze the diagnostic ability of such biomarkers in a primary care cohort with a lower prevalence of AD.

The Stavanger region in Norway will be the catchment area for recruitment of study participants. The region is geographically distinct with 373,000 inhabitants, 15 municipalities with 320 GPs in 94 clinics, all served by one hospital. Consequently, the region offers unique opportunities for community-wide implementation research.

All General Practitioners (GPs) in the region will be invited to, upon consent, select participants for the study. To reflect real-life medical practice in primary care, broad inclusion criteria have been chosen. Blood samples will be taken at the GP offices. First, the robustness of the samples regarding temperature, time and transportation to the laboratory will be studied. Second, the results of the blood samples will be compared with the results of standard diagnostic procedures at the memory outpatient clinic at the hospital. A random sample of an equal number of patients with positive and negative blood biomarker test-results will undergo blinded specialist examination, including MRIs of the brain and analysis of the cerebrospinal fluid for Alzheimer biomarkers. The diagnosis made by the specialists will then be compared to the blood-test results in order to estimate the positive and negative predictive value of such biomarkers for the diagnosis of AD in general practice.

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Svein R Kjosavik, MD PhD; Phone Number: +4790414252; Email: svein.kjosavik@sus.no
• Study Contact Backup: Name: Anita L. Sunde, MD; Phone Number: +4746696494; Email: anita.lenora.sunde@sus.no

Study Locations

• Norway
  • Stavanger, Norway, 4068
    • Recruiting
    • Stavanger University Hospital
    • Contact: Anita Sunde, MD; Phone Number: +47 46696494; Email: anitalenora@gmail.com
    • Contact: Svein Kjosaviki, MD PhD; Phone Number: +47 90414252; Email: svein.kjosavik@sus.no

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants suspected by their GP to have possible dementia, based on history, clinical examination and/or cognitive screening

Exclusion Criteria:

• Lack of capacity for consent as judged by the GP.
• Severe psychiatric disease, use of medication or physical disease that according to the GP may affect participation or likely contribute significantly to the observed cognitive impairment.
• Patients not wanting to be referred to the memory outpatient clinic.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Patients with positive blood test for biomarkers for Alzheimer's disease; The positive blood tests results for this group will be compared with the results from the investigation at the at the memory outpatient clinic to calculate the number of false positive blood tests (using the results from the outpatient clinic as a "gold standard" for the diagnosis)	Diagnostic test: predictive value of a blood test; Evaluation of the clinical value of a new blood based test for diagnosis of Alzheimer's disease in a general practice population.
Active Comparator: Patients with negative blood test for biomarkers for Alzheimer's disease; The negative blood tests results for this group will be compared with the results from the investigation at the at the memory outpatient clinic to calculate the number of false negative blood tests (using the results from the outpatient clinic as a "gold standard" for the diagnosis)	Diagnostic test: predictive value of a blood test; Evaluation of the clinical value of a new blood based test for diagnosis of Alzheimer's disease in a general practice population.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The positive predictive value	The positive predictive value of the blood biomarkers for diagnosing Alzheimer's disease in general practice	2 years
The negative predictive value	The positive predictive value of the blood biomarkers for diagnosing Alzheimer's disease in general practice	2 years

Collaborators and Investigators

• Sponsor: Helse Stavanger HF
• Collaborators: Sahlgrenska University Hospital, Sweden
• Investigators: Study Director: Svein Skeie, MD PhD, Helse Stavanger HF

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: December 24, 2021
• First Submitted That Met QC Criteria: December 24, 2021
• First Posted (Actual): January 12, 2022

Study Record Updates

• Last Update Posted (Actual): September 28, 2023
• Last Update Submitted That Met QC Criteria: September 26, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Diagnosis; Biomarkers; Alzheimer's dementia; Clinical practice
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Dementia; Alzheimer Disease
• Other Study ID Numbers: 2730

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