Neuroinflammation and amyloid deposition in the progression of mixed Alzheimer and vascular dementia.

BACKGROUND

Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) pathologies coexist in patients with cognitive impairment. Abnormal amyloid beta (Aβ) deposition is the hallmark pathologic biomarker for AD. Neuroinflammation may be a pathophysiological mechanism in both AD and VCID. In this study, we aimed to understand the role of neuroinflammation and Aβ deposition in white matter hyperintensities (WMH) progression and cognitive decline over a decade in patients with mixed AD and VCID pathologies.

METHODS

Twenty-four elderly participants (median [interquartile range] age 78 [64.8, 83] years old, 14 female) were recruited from the Knight Alzheimer Disease Research Center. C-PK11195 standard uptake value ratio (SUVR) and C-PiB mean cortical binding potential (MCBP) were used to evaluate neuroinflammation and Aβ deposition in-vivo, respectively. Fluid-attenuated inversion recovery MR images were acquired to obtain baseline WMH volume and its progression over 11.5 years. Composite cognitive scores (global, processing speed and memory) were computed at baseline and follow-up over 7.5 years. Multiple linear regression models evaluated the association between PET biomarkers (C-PK11195 SUVR and C-PiB MCBP) and baseline WMH volume and cognitive function. Moreover, linear mixed-effects models evaluated whether PET biomarkers predicted greater WMH progression or cognitive decline over a decade.

RESULTS

Fifteen participants (62.5%) had mixed AD (positive PiB) and VCID (at least one vascular risk factor) pathologies. Elevated C-PK11195 SUVR, but not C-PiB MCBP, was associated with greater baseline WMH volume and predicted greater WMH progression. Elevated C-PiB MCBP was associated with baseline memory and global cognition. Elevated C-PK11195 SUVR and elevated C-PiB MCBP independently predicted greater global cognition and processing speed declines. No association was found between C-PK11195 SUVR and C-PiB MCBP.

CONCLUSIONS

Neuroinflammation and Aβ deposition may represent two distinct pathophysiological pathways, and both independently contributed to the progression of cognitive impairment in mixed AD and VCID pathologies. Neuroinflammation, but not Aβ deposition, contributed to WMH volume and progression.