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P1‐284: Grey Matter Connectivity is Associated With Clinical Progression in Non‐Demented, Amyloid Positive Patients
Author(s) -
Tijms Betty M.,
Kate Mara ten,
Verfaillie Sander C.J.,
Gouw Alida A.,
Teunissen Charlotte E.,
Barkhof Frederik,
Scheltens Philip,
van der Flier Wiesje M.
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1034
Subject(s) - grey matter , dementia , hazard ratio , medicine , cohort , proportional hazards model , psychology , clinical dementia rating , cognitive decline , oncology , disease , magnetic resonance imaging , white matter , radiology , confidence interval
ease progression is still unclear. Methods: In this longitudinal study we have evaluated the relationship between amyloid fibrillar load and microglial activation at baseline and follow up in amnestic MCI subjects. 30 subjects (8 MCIs, 8 ADs and 14 controls) underwent [11C](R)PK11195, [11C]PIB PET and volumetric MRI. MCI subjects were followed up after 1464 months, and findings compared with those of AD subjects. Region of interest analysis and SPM were used to determine longitudinal alterations. Correlations between levels of microglial activation and amyloid deposition at a voxel level were assessed with Biological Parametric Mapping while hippocampal volume changes were analysed using FreeSurfer. Results: Baseline microglial activation was raised by 41% in the MCI cohort compared with controls. There was a longitudinal reduction of 18% in microglial activation in MCI subjects over 14 months, which was associated with a mild elevation in fibrillar amyloid load. Cortical clusters of microglial activation and amyloid deposition spatially overlapped in the MCI subjects. Baseline microglial activation was raised by 36% in AD subjects compared with controls. This increased further by 10% after 14 months and was correlated with progressive reduction in hippocampal volume. Conclusions: This study demonstrated that while neuroinflammation is initially present in MCI subjects, this diminishes over time, while in AD subjects microglial activation continues to rise giving two peaks of glial activation in the disease trajectory suggesting that microglial activation is a dynamic process, which could be detected in vivo. We speculate that activated microglia in MCI subjects initially adopt a protective M2 phenotype but change to a cidal M1 phenotype as disease progresses resulting in two peaks. This results suggests that antimicroglial agents may have their most beneficial effect in later stages of the disease when they target the proinflammatory phenotypes.