White matter neuroinflammation correlates cognition in preclinical Alzheimer disease

Abstract

AbstractBackgroundAlthough neuroinflammation plays a critical role in the progression of Alzheimer disease (AD), the exact mechanism underlying neuroinflammation remains largely unclear. Neuro‐inflammation imaging (NII), a diffusion‐based MRI method for neuroinflammation, has been used to quantify white matter (WM) neuroinflammation in the sporadic AD. This study aims to evaluate WM neuroinflammation in reference to the A/T/N framework of AD and assess its associations with cognition.Method266 participants enrolled in ongoing studies at the Knight ADRC at Washington University underwent NII measures, CSF biomarker measures, and a test battery of cognitive tasks. The CSF levels of Aβ42/Aβ40, ptau181, and total‐tau were measured with the automated Lumipulse platform and used to classify the participants into the following groups – A‐T‐N‐ (n=145), A+T‐N‐ (n=71), and A+T+N+(n=50) (Table 1). The preclinical Alzheimer Cognitive Composite (PACC) and Global Composite scores for each individual were derived from a subset of the Knight ADRC cognitive battery to assess cognitive performance. NII was acquired with a multi‐b value scheme (bmax =1400s/mm2 and 25 directions). The whole WM neuroinflammation (unit, mm2/ms) was quantified using the Tract Based Spatial Statistics (http://www.fmrib.ox.ac.uk/fsl) based WM skeleton. All statistical tests were conducted in R (R Core Team, 2020). Continuous and categorical variables in characteristics across all the three groups were compared using the Kruskal‐Wallis test and the Chi‐square tests where appropriate. The correlation between the NII WM neuroinflammation and cognition was determined by Spearman correlation. Analyses were adjusted for covariates, including age, sex, education, and APOE ε4 carrier status.ResultNII WM neuroinflammation was significantly correlated with the PACC (Figure 1A) and Global Composite score (Figure 1B) in all participants. Significant correlations between NII WM neuroinflammation and cognition composite scores were found in the A‐T‐N‐ and the A+T+N+ groups (Figure 1).ConclusionOur findings suggest that NII WM neuroinflammation is associated with cognitive performance both in individuals with no evidence of brain amyloidosis and in individuals with biomarkers consistent with Alzheimer disease. Given that this measure is acquired without using a contrast agent or radioactive tracer, NII holds great promise as an accessible measure for quantifying neuroinflammation in AD pathogenesis.