Clinical trial NCT05059158: Amyloid-β Clearance Mechanisms in Alzheimer's Disease
Official title: Amyloid-β Clearance Mechanisms: A Multi-modal Study on Lymphatic, Glymphatic and Blood-brain-barrier Function in Alzheimer's Disease
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Alzheimer's Disease (AD)
Keywords: Alzheimer's Disease
Mild Cognitive Impairment
Sleep
Actigraphy
Blood-brain-barrier
Amyloid-β Clearance Mechanisms
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2021-09-28
Enrollment: 60
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: SCD, MCI or AD

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Differences in the disruption of the brain-blood-barrier between the subgroups
timeFrame: Baseline
measure: Clearance mechanisms and glymphatic or cerebral lymphatic system
timeFrame: Baseline
measure: Connection between the structural/functional connectivity of the resting networks and the clearance mechanisms
timeFrame: Baseline
measure: 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?
timeFrame: Baseline
measure: Connection between clinical symptoms, Aß pathology and BBB disorder
timeFrame: Baseline
Secondary outcomes:
Other outcomes:
Locations:
city: München
country: Germany
facility: Klinik und Poliklinik für Psychiatrie und Psychotherapie des LMU Klinikums
state: Bayern
Study officials:
affiliation: Klinik und Poliklinik für Psychiatrie und Psychotherapie des LMU Klinikums
name: Robert Perneczky, Prof.Dr.med.
role: PRINCIPAL_INVESTIGATOR
References: