Amyloid-β Clearance Mechanisms in Alzheimer's Disease (AmyClearAD)

Amyloid-β Clearance Mechanisms: A Multi-modal Study on Lymphatic, Glymphatic and Blood-brain-barrier Function in Alzheimer's Disease

The focus of this study is to examine the protein-plaque clearance (Aß) in relation to the blood-brain-barrier, the glymphatic system, brain lymphatic system and enzymatic degradation. In order to achieve this aim the investigators intend to study participants with a Subjective Cognitive Decline, Mild Cognitive Impairment and a mild Alzheimer's disease.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer's Disease (AD)
• Intervention / Treatment: Radiation: positron emission tomography (PET)

Detailed Description

In this study, the investigators want to examine the different mechanisms of the accumulation and the clearance of Aß- deposits with imaging methods. One focus of the study is an improved characterisation of a blood-brain-barrier disorder (which seems to have an impact on the Aß-accumulation). Another main aim is to provide an improved mechanistic clearance model, which integrates crucial components such as the recently proposed cerebral glymphatic and lymphatic pathways, and which addresses the interaction between the different components and their individual contribution to Aβ removal from the brain. A possible connection between sleep and an altered transport mechanism will be analysed. The prospective study cohort (N ~60) will include patients with Mild Cognitive Impairment, mild clinical AD and Subjective Cognitive Decline. All study participants will undergo a detailed clinical and neuropsychological assessment according to a standardised protocol (i.a. MRI, PET, CSF, actigraphy). Follow-up assessments will not be performed in the present project, but are planned in a subsequent study, pending further funding.

• Study Type: Observational
• Enrollment (Estimated): 60

Contacts and Locations

• Study Contact: Name: Lena Burow, M.Sc.; Phone Number: +4989440055898; Email: lena.burow@med.uni-muenchen.de
• Study Contact Backup: Name: Robert Perneczky, Prof.Dr.med.; Phone Number: +4989440055863; Email: PSY.Alzheimerzentrum@med.uni-muenchen.de

Study Locations

• Germany
  • Bayern
    • München, Bayern, Germany, 80336
      • Recruiting
      • Klinik und Poliklinik für Psychiatrie und Psychotherapie des LMU Klinikums
      • Contact: Robert Perneczky, Prof. Dr.; Phone Number: +49 89 4400 55863; Email: PSY.Alzheimerzentrum@med.uni-muenchen.de
      • Contact: Lena Burow, M.Sc.; Phone Number: +49 89 4400 55898; Email: lena.burow@med.uni-muenchen.de
      • Sub-Investigator: Carolin Kurz, Dr.med.
      • Sub-Investigator: Boris-Stephan Rauchmann, Dr. med.
      • Sub-Investigator: Selim Gürsel
      • Sub-Investigator: Matthias Brendel, PD Dr. med.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

SCD, MCI or AD

Description

Inclusion Criteria:

• Diagnosis of amnestic MCI or AD dementia or clinical normal
• Able to provide written informed consent
• Unchanged pharmacotherapy within 4 days prior to the study specific assessments
• Fluent in German

Exclusion Criteria:

• Unable to give informed consent or has a legal guardian
• Other severe mental disorder, e.g. schizophrenia or bipolar affective disorder
• Clinically relevant depression
• Acute suicidality
• Current alcohol, drug or medication abuse
• History of severe traumatic brain injury within 3 months prior to inclusion
• Structural lesions of the basal ganglia or brain stem
• Severe neurological disorder including (but not limited to) epilepsy, systemic disorders, stroke, repeated transient ischaemic attacks, increased brain intracranial pressure, normal pressure hydrocephalus
• Severe medical disorders including (but not limited to) heart failure, respiratory failure, uncontrolled severe arterial hypertension
• Electronic implants (e.g. cardiac pacemaker) or other MRI contraindication
• Renal failure > stage 3 (GFR < 30 mL/min)
• Pregnancy
• Unresolved malignancies within two years prior to inclusion
• Severe current infections or other chronic or systemic disorders
• Other circumstances which preclude participation based on the investigator's judgement

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Alzheimer's Disease; Patients with a Alzheimer's Disease diagnosis	Radiation: positron emission tomography (PET); 18-Flutemetamol PET (clinical indicated) is going to be performed at the visit.
Mild Cognitive Impairment; Patients with a mild cognitive impairment diagnosis	Radiation: positron emission tomography (PET); 18-Flutemetamol PET (clinical indicated) is going to be performed at the visit.
Subjective Cognitive Decline; Patients with a subjective cognitive decline diagnosis	Radiation: positron emission tomography (PET); 18-Flutemetamol PET (clinical indicated) is going to be performed at the visit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in the disruption of the brain-blood-barrier between the subgroups	Name of Measurement: Ktrans; Measurement Tool: DCI sequence (MRI); Unit: min -1	Baseline
Clearance mechanisms and glymphatic or cerebral lymphatic system	Can a disruption in the cerebral clearance through the glymphatic or cerebral lymphatic system be proven in patients with AD, MCI or SCD? Name of Measurement: DTI ALPS; Measurement Tool: DTI MRI; Unit: mean (Dxpro, Dypro)/ mean (Dypro, Dzasc)	Baseline
Connection between the structural/functional connectivity of the resting networks and the clearance mechanisms	Correlations between correlations of bold fluctuations/ number of tracts and DTI ALPS Index	Baseline
Differences between sleep and activity in SCD, MCI and AD; Do they have a mediator role in association of the BBB disruption and Aß pathology?	Name of Measurement: Sleep Efficiency, Sleep Time, PIM, TAT, ZCM ;Measurement Tool: Actigraphy; Units: minutes, count	Baseline
Connection between clinical symptoms, Aß pathology and BBB disorder	Correlations between Clinical Dementia Rating Sum of Boxes, CSF markers (pg/ml) and Aß PET, SUVr and Ktrans map	Baseline

Collaborators and Investigators

• Sponsor: Ludwig-Maximilians - University of Munich
• Investigators: Principal Investigator: Robert Perneczky, Prof.Dr.med., Klinik und Poliklinik für Psychiatrie und Psychotherapie des LMU Klinikums

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2021
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: July 15, 2021
• First Submitted That Met QC Criteria: September 16, 2021
• First Posted (Actual): September 28, 2021

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Mild Cognitive Impairment; Sleep; Blood-brain-barrier; Actigraphy; Amyloid-β Clearance Mechanisms
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 18-606 (Other Grant/Funding Number: Stiftung Verum); 1081 (Other Grant/Funding Number: Förderung, Forschung und Lehre der LMU;)

Drug and device information, study documents

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