Markers of Inflammation Correlate With Longitudinal Cognitive Decline in People With Mild Cognitive Impairment
At 9 and 15 months of follow up, higher cerebrospinal fluid (CSF) levels of the inflammatory marker monocyte chemoattractive protein-1 (CCL2) and lower levels of the anti-inflammatory molecule plasma α1-antitrypsin both correlated with greater cognitive declines in people with mild cognitive impairment. Plasma α1-antitrypsin is an acute phase reactant with anti-inflammatory, anti- leukocyte migratory activity and CCL2 is a key regulator of monocyte and macrophage migration and infiltration that occurs in inflammation.
For this study, 48 participants with mild cognitive impairment and positive amyloid, tau, and neurodegeneration status had blood and CSF tests for a panel of 53 markers of inflammation. The Dementia Rating Scale (DRS) and MMSE (Mini Mental Status exam), and Clinical Dementia Rating: Sum of Boxes (CDR-SB) were also administered at these time points. Results were further evaluated after adjusting for age, sex, APOE ε4 status, baseline cognitive score and corrected for false discovery rate (0.05).
The MMSE scores change from baseline to 15 months was 2.3±3.7, CDR-SB was 2.4±2.0, and DRS was 9.6±10.4 points. The CSF CCL2 levels correlated with cognitive decline on the CDR-SB (0.54, 95% CI 0.25,0.73) and CSF plasma α1-antitrypsin inversely correlated to cognitive change on the DRS (-0.54, 95% CI -0.74,-0.23). No inflammatory marker correlated with scores on more than 1 measure of cognitive function. At baseline, inflammatory analytes in CSF were more closely correlated with markers of neurodegeneration and did not correlate with cognitive test measures.
Together these results support the hypothesis that the inflammatory process is an important component of MCI and progression to Alzheimer’s disease (AD). Further, the data suggest that inflammatory changes that are independent of neurodegeneration may play a critical role in AD pathophysiology.
First author of the study, Jagan A. Pillai, MD, PhD of the Cleveland Clinic Lou Ruvo Center for Brain Health in Cleveland, OH, noted, “These results potentially could lead to better prognostication of who might progress from MCI to AD more quickly and also give us potential new therapeutic targets. Of note, this study suggests that some, but not all, inflammation may drive clinical decline. We are narrowing down the nature of inflammation-related changes that are related to rapid cognitive decline.”
Ilana E. Green; Andrew M. Southerland, MD, MSc; and Bradford B. Worrall, MD, MSc
Jennifer E. Fugate, DO
Shruti Bhandari, MD; Rohit Kumar, MD; Megan Nelson, MD; Donald Miller, MD; and Brian J. Williams, MD