Cerebral Amyloid Angiopathy and Neuritic Plaque Pathology Correlate with Cognitive Decline in Elderly Non-Demented Individuals

Abstract

Background: Cerebral amyloid angiopathy (CAA) is a vascular neuropathology commonly reported in non-cognitively impaired (NCI), mild cognitive impairment, and Alzheimer's disease (AD) brains. However, it is unknown whether similar findings are present in non-demented elderly subjects.

Objective: This study determined the association between CAA and cognition among elderly NCI subjects with varying levels of AD pathology.

Methods: Data from 182 cases that received a diagnosis of NCI at their first clinical assessment were obtained from the Rush Religious Orders study (RROS). A cognitive composite score was used to measure cognitive decline. CAA was dichotomized as present or absent. Cases were also dichotomized according to CERAD neuropathological diagnosis and Braak staging. A mixed model-repeated measures analysis assessed decline on the cognitive composite score.

Results: CAA, alone, was not associated with cognitive decline [-0.87 (95% CI: -3.33, 1.58), p = 0.49]. However, among those with CAA, the High CERAD group had significantly greater decline relative to the Low CERAD group [-4.08 (95% CI: -7.10, -1.06), p = 0.008]. The High and Low CERAD groups were not significantly different [-1.77 (95% CI: -6.14, 2.60), p = 0.43] in those without CAA. Composite score decline in the High and Low Braak groups with [-1.32 (95% CI: -4.40, 1.75), p = 0.40] or without [0.27 (95% CI: -4.01, 4.56), p = 0.90] CAA was not significantly different.

Conclusion: The current data shows that an interaction between CAA and plaque load is associated with greater decline on a cognitive composite score used to test non-cognitively impaired elderly participants in AD prevention trials.

Keywords: Amyloid; dementia; episodic memory; executive function; neuropathology; preclinical; prevention; vascular.

Fig. 1.

Composite Score Change from Baseline Estimates for CAA Status. Change from baseline group difference: −0.87, 95% CI (−3.33, 1.58), p = 0.49. Error bars represent the standard error.

Fig. 2.

A Composite Score Change from Baseline Estimates for CERAD Status without CAA. Change from baseline group difference: −1.61, 95% CI (−5.31, 2.09), p = 0.39. Error bars represent the standard error. B Composite Score Change from Baseline Estimates for CERAD Status with CAA. Change from baseline group difference: −3.92, 95% CI (−7.12, −0.71), p = 0.02. Error bars represent the standard error.

Fig. 3.

A Composite Score Change from Baseline Estimates for High CERAD by CAA Status. Change from baseline group difference: −1.13, 95% CI (−4.83, 2.57), p = 0.55. Error bars represent the standard error. B Composite Score Change from Baseline Estimates for Low CERAD by CAA Status. Change from baseline group difference: −3.19, 95% CI (−6.95, 0.57), p = 0.10. Error bars represent the standard error.