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Longitudinal Imaging of Microglial Activation in Different Clinical Variants of Alzheimer's Disease

Phase 2
Recruiting
Conditions
Alzheimer Disease
Interventions
Drug: 18F-MK6240
Drug: 18F-Florbetaben
Procedure: Lumbar Puncture
Registration Number
NCT04576793
Lead Sponsor
Patrick Lao
Brief Summary

The purpose of this study is to determine how inflammation is related to other changes in the brain that occur during the progression of Alzheimer's disease. The investigators are also studying how inflammation is related to the symptoms that first occur in patients with Alzheimer's disease (AD). For this reason, the investigators are asking people with different versions of Alzheimer's disease and/or other related dementias to participate. This includes patients with:

* Mild Cognitive Impairment

* Posterior cortical atrophy - a version of Alzheimer's disease with vision difficulties

* Logopenic variant primary progressive aphasia - a version of Alzheimer's disease with language difficulties

* Amnestic Alzheimer's disease - a "typical" version of Alzheimer's disease with memory difficulties

* The investigators are also enrolling older adults with normal visual, language, and memory function.

Detailed Description

This study is being done to learn about inflammation in Alzheimer's disease so that the investigators can find out new ways to treat patients with this disease. Because Alzheimer's disease usually causes slow changes to the brain over time, in this study the investigators are going to perform different tests and then repeat some of them two years later.

Inflammation can be measured using a type of brain scan called a positron emission tomography (PET) scan. A PET scan uses very small amounts of a radioactive drug that is injected into a vein to create a special picture of the brain. The inflammation PET scan uses a drug called ER176. ER176 is an experimental drug but has been used in several human studies before. Once in the body, ER176 sticks to areas with lots of inflammation, and the PET scan allows us to see these areas.

Inflammation can also be measured by looking at certain proteins in the spinal fluid. In order to measure these proteins in the spinal fluid, the investigators need to perform a lumbar puncture (spinal tap). Certain genes that inherited from parents influence the amount of inflammation in the body. The investigators can study how genes affect inflammation in Alzheimer's disease by looking doing genetic tests on blood that collected from the vein.

The investigators can study how genes affect inflammation in Alzheimer's disease by doing genetic tests on blood. The investigators will also be testing blood for severe acute respiratory syndrome (SARS)- CoV-2 (the virus that causes COVID-19) antibodies. The investigators want to see if exposure to the virus that causes COVID-19 changes the amount of inflammation in the brain or not.

Along with inflammation, Alzheimer's disease is also associated with the build up of the proteins amyloid and tau in the brain. The investigators can measure these proteins using PET scans. The amyloid PET scan uses a drug called florbetaben that has been approved by the FDA to help diagnose Alzheimer's disease. The tau PET scan uses a drug called MK-6240. Like ER176, MK-6240 is experimental but has been used in several human studies before.

A brain MRI creates a high resolution picture of the brain. The brain MRI helps the investigators get more information from the PET scans, and can also tell the investigators the size and appearance of different brain structures. When someone has Alzheimer's disease, some of these brain structures get smaller or have altered appearance on MRI.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
100
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Cognitive impairment18F-MK6240* Mild Cognitive Impairment * Posterior cortical atrophy - a version of Alzheimer's disease with vision difficulties * Logopenic variant primary progressive aphasia - a version of Alzheimer's disease with language difficulties * Amnestic Alzheimer's disease - a "typical" version of Alzheimer's disease with memory difficulties
Cognitive impairment18F-Florbetaben* Mild Cognitive Impairment * Posterior cortical atrophy - a version of Alzheimer's disease with vision difficulties * Logopenic variant primary progressive aphasia - a version of Alzheimer's disease with language difficulties * Amnestic Alzheimer's disease - a "typical" version of Alzheimer's disease with memory difficulties
Cognitive impairmentLumbar Puncture* Mild Cognitive Impairment * Posterior cortical atrophy - a version of Alzheimer's disease with vision difficulties * Logopenic variant primary progressive aphasia - a version of Alzheimer's disease with language difficulties * Amnestic Alzheimer's disease - a "typical" version of Alzheimer's disease with memory difficulties
No cognitive impairment11C-ER176Healthy controls
No cognitive impairment18F-MK6240Healthy controls
No cognitive impairment18F-FlorbetabenHealthy controls
No cognitive impairmentLumbar PunctureHealthy controls
Cognitive impairment11C-ER176* Mild Cognitive Impairment * Posterior cortical atrophy - a version of Alzheimer's disease with vision difficulties * Logopenic variant primary progressive aphasia - a version of Alzheimer's disease with language difficulties * Amnestic Alzheimer's disease - a "typical" version of Alzheimer's disease with memory difficulties
Primary Outcome Measures
NameTimeMethod
18F-MK6240 Standardized Uptake Value RatioUp to 24 months

The standardize uptake value ratio is the concentration of radioactivity measured from the 18F-MK6240 PET scan in the cortex compared to the uptake in the cerebellum (pseudo-reference region).

11C-ER176 Standardized Uptake Value RatioUp to 24 months

The standardize uptake value ratio is the concentration of radioactivity measured from the 11C-ER176 PET scan in the cortex compared to the uptake in the cerebellum (pseudo-reference region).

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Columbia University Irving Medical Center

🇺🇸

New York, New York, United States

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