To examine the differences in the capacity to activate microglia in patients with Alzheimer's Disease (AD) compared to age-comparable cognitively normal subjects and younger healthy controls.
The primary outcome is Microglia Activation Reserve Index (MARI) (calculated in the parietal region of interest (ROIs)) in AD patients compared to elderly controls. The researchers will recruit up to 20 participants. The investigators will use 7 AD and 7 comparably aged cognitively normal successfully scanned subjects to calculate the microglial activation reserve index. The expectations are significant differences between the two groups suggesting altered reactivity of the microglia in AD. The result would be an exciting one suggesting at least one mechanism by which some patients with significant amyloid load have progressive dementia while comparable others are either cognitively normal or have stable Mild Cognitive Impairment (MCI). It will also suggest avenues for intervention in amyloid positive MCIs to prevent progression to Alzheimer's dementia. The exploratory analysis will include: 1. Effects of aging on MARI: The researchers will evaluate the effects of aging on MARI. Comparisons will be made for MARI between cognitively normal elderly and the 8 healthy individuals to whom the investigators applied this protocol in an earlier study. The reactivity of microglia is reported to change with age and so the investigators expect MARI to change in the cognitively normal elderly. However, the expectation is that the differences between the young and elderly cognitively normal subjects to be small relative to the comparison of AD and elderly normal controls. 2. Effects of amyloid on MARI: The researchers will look at the relationship of regional and global amyloid load to MARI. The presence of a relationship suggests that one of the reasons for altered microglial reactivity might be interactions of microglia with pathologic amyloid. 3. Effects of MARI on cognition: The researchers will explore whether MARI would correlate with the measure of disease stage, with higher MARIs associated with worse neuropsychological score and more severe disease. The researchers will look for correlations between MARI and the individual neuropsychological scores. This would determine if disease severity is correlated with microglial activation reserve.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
18
LPS (0.4 ng/kg)
Alzheimer's Disease Research Unit
New Haven, Connecticut, United States
Microglial Activation Reserve Index (MARI)
Participants will undergo \[11C\]PBR PET scanning both before and then after LPS injection. Parametric images of volume of distribution (VT)were generated for each using multilinear analysis (MA1) and MARI was calculated in the parietal cortex using the equation \[(VT post LPS - VT pre LPS)/VT post LPS\] x 100%. Higher values of MARI are thought to represent higher levels of microglial activation. There are no clinically relevant thresholds for this measure.
Time frame: 180 minutes post intervention
Effects of MARI on Cognition
The Pearson's correlation between MARI and performance on the Montreal Cognitive Assessment (MOCA) will be calculated. The MOCA is a global assessment of cognitive function ranging from 0 to 30 where higher scores represent better cognitive performance.
Time frame: 180 minutes post intervention
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