Baseline Microglial Activation Correlates With Brain Amyloidosis and Longitudinal Cognitive Decline in Alzheimer Disease.
Level 3 - non-randomized controlled study
Prospective longitudinal cohort study assessing baseline neuroimaging and fluid biomarkers against cognitive trajectory.
PubMed 35260470 · doi:10.1212/NXI.0000000000001152
What was done
Twenty-four participants from the Knight Alzheimer Disease Research Center were classified into stable cognitively normal, progressor, and symptomatic Alzheimer disease (AD) groups using Clinical Dementia Rating (CDR) scores across two or more assessments. Baseline microglial activation was quantified via [11C]PK11195 TSPO PET standard uptake value ratios (SUVRs) in the hippocampus and precuneus. Baseline CSF biomarkers (Aβ42, Aβ42/Aβ40 ratio, p-tau181, and t-tau) were measured in a subcohort (n = 16). Cognitive progression was evaluated longitudinally using CDR and composite scores (Global and Knight ADRC-PACC).
What was found
Participants in the progressor and symptomatic AD groups had significantly elevated [11C]PK11195 SUVRs in the hippocampus, but not in the precuneus. In the CSF subset (16 of 24), hippocampal and precuneus [11C]PK11195 SUVRs significantly negatively correlated with CSF Aβ42 and Aβ42/Aβ40 ratios, with no correlation observed for CSF p-tau181 or t-tau. Higher baseline [11C]PK11195 SUVR averaged across whole cortical regions predicted longitudinal decline on cognitive tests. The abstract reported no exact numerical values, correlation coefficients, or effect sizes.
Why it matters
This study provides in vivo human longitudinal evidence that neuroinflammation via microglial activation correlates with amyloid pathology and may predict future cognitive decline in Alzheimer disease.
Limits
The study is limited by a very small sample size (n = 24 total; n = 16 for CSF biomarkers). The abstract does not report specific follow-up durations, correlation coefficients, or effect sizes.
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