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The goal of this observational study is to determine whether the early adoption of blood-based biomarkers for Alzheimer's disease is associated with an impact on etiological diagnosis, patient's management, emotional impact, patient's preferences and cost-effectiveness in patients presenting with cognitive complaints in a Cognitive Disorders Unit from a public hospital.
The main questions it aims to answer are:
Participants will be asked to:
Researchers will compare the group in which blood biomarkers are delivered at 3 months with the group in which they are delivered at 9 months to assess whether early adoption of blood-based biomarkers is associated with an impact on etiological diagnosis, patient's management, emotional impact, patient's preferences and cost-effectiveness in a specialized memory unit.
Blood-based biomarkers that accurately detect Alzheimer's disease (AD) and neurodegeneration now offer a realistic, cost-effective and non-invasive assessment that will aid the diagnostic process in patients presenting with cognitive clinical manifestations. Plasma measures of Amyloid-β (Aβ) 42/40, phosphorylated tau (p-tau) 181, p-tau217, p-tau231 and Glial fibrillary acidic protein (GFAP) have shown high diagnostic accuracy to detect AD, while plasma Neurofilament light chain (NfL) indicates neuronal injury. Despite these promising results, there is still no clear real-word evidence of their clinical applications. Here, the PLASMAR project aims to determine whether blood-based biomarkers have an impact on the clinical management of patients presenting with cognitive complaints in a Cognitive Disorders Unit from a public hospital, which provides care to a heterogeneous population. The project is divided into two specific objectives. First, the investigators will determine, in a research cohort, which blood biomarker or biomarkers' combination have the highest accuracy to detect AD. Second, a prospective clinical cohort of consecutive patients coming to the memory unit will be recruited. The investigators will assess whether early adoption of blood-based biomarkers is associated with an impact on etiological diagnosis, patient's management, emotional impact, patient's preferences and cost-effectiveness in a specialized memory unit. Answering the question of whether blood-based biomarkers have a clinical impact in the real-world scenario of a memory unit, the PLASMAR project is crucial for the healthcare system and can guide the developing of guidelines and protocols on the use of blood-based biomarkers.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Early Blood-based biomarkers Arm | The results of the blood-based biomarkers will be communicated to the managing neurologist at visit 1 (at 3 months from baseline visit). |
| |
| Late Blood-based biomarkers Arm | The results of the blood-based biomarkers will be communicated to the managing neurologist at visit 2 (at 9 months from baseline visit). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Early adoption of blood-based biomarkers for Alzheimer's disease | Diagnostic Test | A blood test will be performed to obtain plasma measures of Amyloid-β (Aβ) 42/40, phosphorylated tau (p-tau) 181, p-tau217, p-tau231 and Glial fibrillary acidic protein (GFAP) and Neurofilament light chain (NfL) and results will be disclosure to the early and late arms at different time points. |
| Measure | Description | Time Frame |
|---|---|---|
| Etiological diagnosis | The proportion of patients for whom an etiologic diagnosis is reached with very high confidence (≥90%) in each group at 3 and 9 months. | 9 months |
| Suspicion of neurodegenerative disease | The proportion of patients for whom a suspicion of neurodegenerative disease is reached as etiology with very high confidence (≥90%) in each group at 3 and 9 months. | 9 months |
| Measure | Description | Time Frame |
|---|---|---|
| Number of tests for etiological diagnosis | The number of tests necessary to reach an etiological diagnosis with very high confidence (≥90%) in each group at 3 and 9 months. | 9 months |
| Number of tests for a suspicion of neurodegenerative disease |
| Measure | Description | Time Frame |
|---|---|---|
| Number of patients whose clinical management in the Cognitive Disorders Unit changes | Changes in the prescription or withdrawal of disease-specific pharmacologic treatments (cholinesterase inhibitors, Memantine) and other pharmacologic or non-pharmacological interventions in addition to the number of patients who are discharged from the Cognitive Disorders Unit during the time of the study. | 9 months |
Inclusion Criteria:
Exclusion Criteria:
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PLASMAR is prospective, unicentric, unblinded and randomized controlled study with blinded outcome ascertainment. Two hundred new patients will be consecutively recruited. All consecutive new patients who are visited for the first time to the outpatients' Memory Clinic at the Neurology Service (Hospital del Mar, Barcelona, Spain) will be considered for the study. Each patient will name a study partner to participate in this study, who will be considered for the study as well. In case the patient is diagnosed with dementia, a caregiver will be considered.
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| Name | Affiliation | Role |
|---|---|---|
| Marc Suárez-Calvet, MD PhD | Hospital del Mar Research Insititute (IMIM) | Principal Investigator |
| Albert Puig-Pijoan, MD | Hospital del Mar Research Insititute (IMIM) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital del Mar | Barcelona | Catalonia | 08003 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37155177 | Background | Altomare D, Barkhof F, Caprioglio C, Collij LE, Scheltens P, Lopes Alves I, Bouwman F, Berkhof J, van Maurik IS, Garibotto V, Moro C, Delrieu J, Payoux P, Saint-Aubert L, Hitzel A, Molinuevo JL, Grau-Rivera O, Gispert JD, Drzezga A, Jessen F, Zeyen P, Nordberg A, Savitcheva I, Jelic V, Walker Z, Edison P, Demonet JF, Gismondi R, Farrar G, Stephens AW, Frisoni GB; Amyloid Imaging to Prevent Alzheimer's Disease (AMYPAD) Consortium. Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients: The AMYPAD-DPMS Randomized Clinical Trial. JAMA Neurol. 2023 Jun 1;80(6):548-557. doi: 10.1001/jamaneurol.2023.0997. | |
| 34266917 |
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There is not a plan to make IPD available.
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Cerebrospinal fluid samples, serum and plasma samples will be processed and stored in the BIODEGMAR collection at the facilities of the Hospital del Mar Research Institute (IMIM). The sample collection of the present study has been registered in the National Registry of Biobanks, Instituto de Salud Carlos III (ISCIII), code: 0005744.
|
The number of tests to reach a suspicion of neurodegenerative disease as etiology with very high confidence (≥90%) in each group at 3 and 9 months.
| 9 months |
| Neurologist diagnoses over time | Changes in the neurologist's etiologic diagnosis in each group during the time of the study. | 9 months |
| Neurologist confidence in the etiological diagnosis, which is is collected through the PLASMAR questionnaire at each visit. | Changes in the neurologist's estimate of the likelihood that the patient's symptoms are due to AD in each group during the time of the study. | 9 months |
| Neurologist confidence in the suspicion of neurodegenerative disease, which is is collected through the PLASMAR questionnaire at each visit. | Changes in the neurologist's estimate of the likelihood that the patient's symptoms are due to a neurodegenerative disease as etiology in each group during the time of the study. | 9 months |
| Emotional impact of blood-based biomarkers on patient and study partner/caregiver | Changes in Hospital Anxiety and Depression Scale (HADS; score: 0-42, with higher scores indicating higher anxiety or depression) and The Perceived Stress Scale (PSS; score: 0-40, with higher scores indicating higher perceived stress) during the time of the study. | 9 months |
| Impact of blood-based biomarkers on patient's quality of life | Changes in the 5-level European Quality of Life-5 Dimensions scale (EQ-5D-5L; score: 5-25, with higher scores indicating worse severity index) during the time of the study. | 9 months |
| Patient's tolerance to biomarkers tests and their preferences in how they want to be diagnosed | Tolerance score for each of the tests performed as part of clinical practice during the time of the study. | 9 months |
| Relative cost savings from the Implementation of blood-based biomarkers in the Cognitive Disorders Unit. | The cost of the diagnostic work-up to achieve an etiologic diagnosis with very high confidence (≥90%) and the cost savings in resources (arising from pharmacological or non-pharmacological interventions, as well as discharges) will be combined to determine the relative cost of implementing blood-based biomarkers compared to their non-implementation. | 9 months |
| Background |
| Grothe MJ, Moscoso A, Ashton NJ, Karikari TK, Lantero-Rodriguez J, Snellman A, Zetterberg H, Blennow K, Scholl M; Alzheimer's Disease Neuroimaging Initiative. Associations of Fully Automated CSF and Novel Plasma Biomarkers With Alzheimer Disease Neuropathology at Autopsy. Neurology. 2021 Sep 20;97(12):e1229-e1242. doi: 10.1212/WNL.0000000000012513. |
| 32123385 | Background | Janelidze S, Mattsson N, Palmqvist S, Smith R, Beach TG, Serrano GE, Chai X, Proctor NK, Eichenlaub U, Zetterberg H, Blennow K, Reiman EM, Stomrud E, Dage JL, Hansson O. Plasma P-tau181 in Alzheimer's disease: relationship to other biomarkers, differential diagnosis, neuropathology and longitudinal progression to Alzheimer's dementia. Nat Med. 2020 Mar;26(3):379-386. doi: 10.1038/s41591-020-0755-1. Epub 2020 Mar 2. |
| 32333900 | Background | Karikari TK, Pascoal TA, Ashton NJ, Janelidze S, Benedet AL, Rodriguez JL, Chamoun M, Savard M, Kang MS, Therriault J, Scholl M, Massarweh G, Soucy JP, Hoglund K, Brinkmalm G, Mattsson N, Palmqvist S, Gauthier S, Stomrud E, Zetterberg H, Hansson O, Rosa-Neto P, Blennow K. Blood phosphorylated tau 181 as a biomarker for Alzheimer's disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020 May;19(5):422-433. doi: 10.1016/S1474-4422(20)30071-5. |
| 35865350 | Background | Simren J, Andreasson U, Gobom J, Suarez Calvet M, Borroni B, Gillberg C, Nyberg L, Ghidoni R, Fernell E, Johnson M, Depypere H, Hansson C, Jonsdottir IH, Zetterberg H, Blennow K. Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5-90 years. Brain Commun. 2022 Jul 4;4(4):fcac174. doi: 10.1093/braincomms/fcac174. eCollection 2022. |
| 33169916 | Background | Suarez-Calvet M, Karikari TK, Ashton NJ, Lantero Rodriguez J, Mila-Aloma M, Gispert JD, Salvado G, Minguillon C, Fauria K, Shekari M, Grau-Rivera O, Arenaza-Urquijo EM, Sala-Vila A, Sanchez-Benavides G, Gonzalez-de-Echavarri JM, Kollmorgen G, Stoops E, Vanmechelen E, Zetterberg H, Blennow K, Molinuevo JL; ALFA Study. Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer's continuum when only subtle changes in Abeta pathology are detected. EMBO Mol Med. 2020 Dec 7;12(12):e12921. doi: 10.15252/emmm.202012921. Epub 2020 Nov 10. |
| 34418401 | Background | Thijssen EH, La Joie R, Strom A, Fonseca C, Iaccarino L, Wolf A, Spina S, Allen IE, Cobigo Y, Heuer H, VandeVrede L, Proctor NK, Lago AL, Baker S, Sivasankaran R, Kieloch A, Kinhikar A, Yu L, Valentin MA, Jeromin A, Zetterberg H, Hansson O, Mattsson-Carlgren N, Graham D, Blennow K, Kramer JH, Grinberg LT, Seeley WW, Rosen H, Boeve BF, Miller BL, Teunissen CE, Rabinovici GD, Rojas JC, Dage JL, Boxer AL; Advancing Research and Treatment for Frontotemporal Lobar Degeneration investigators. Plasma phosphorylated tau 217 and phosphorylated tau 181 as biomarkers in Alzheimer's disease and frontotemporal lobar degeneration: a retrospective diagnostic performance study. Lancet Neurol. 2021 Sep;20(9):739-752. doi: 10.1016/S1474-4422(21)00214-3. |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D060825 | Cognitive Dysfunction |
| D003704 | Dementia |
| D019636 | Neurodegenerative Diseases |
| D057180 | Frontotemporal Dementia |
| D020961 | Lewy Body Disease |
| D015140 | Dementia, Vascular |
| D004194 | Disease |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
| D057174 | Frontotemporal Lobar Degeneration |
| D057177 | TDP-43 Proteinopathies |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D020734 | Parkinsonian Disorders |
| D001480 | Basal Ganglia Diseases |
| D009069 | Movement Disorders |
| D000080874 | Synucleinopathies |
| D002561 | Cerebrovascular Disorders |
| D002537 | Intracranial Arteriosclerosis |
| D020765 | Intracranial Arterial Diseases |
| D056784 | Leukoencephalopathies |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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