Cerebral β-Amyloid Angiopathy Is Associated with Earlier Dementia Onset in Alzheimer's Disease

Abstract

Background: Cerebral β-amyloid angiopathy (CAA) occurs when β-amyloid (Aβ) is deposited in the vascular media and adventitia. It is a common pathology in the brains of older individuals and has been linked to cognitive decline, but relatively little is known about the influence that CAA has on the clinical manifestation of Alzheimer's disease (AD). The aim of this retrospective analysis was to quantify the effect that CAA had on the manifestation of initial AD-related cognitive change and subsequent progression of dementia.

Methods: We analyzed neuropathological data from the National Alzheimer's Coordinating Center's data set, performing parametric analyses to assess differences in age of progression to moderate-stage dementia.

Results: We found that individuals with both CAA burden and Aβ neuritic plaque burden at death had the greatest risk of earlier conversion to very mild and moderate-stage dementia, but not necessarily faster progression.

Conclusions: Our results suggest that CAA contributes to changes in early AD pathogenesis. This supports the idea that vascular change and neuritic plaque deposition are not just parallel processes but reflect additive pathological cascades that influence the course of clinical AD manifestation. Further inquiry into the role of CAA and its contribution to early cognitive change in AD is suggested.

Figure 1

This plot shows the cumulative probability of cognitive change against age for each of our neuropathologic classifications: no significant neuritic plaque (NP) or cerebral amyloid angiopathy burden (CAA−/NP−, black line), no significant CAA burden but significant NP burden (CAA−/NP+, blue line), significant CAA burden with no NP burden (CAA+/NP−, green line), significant CAA and NP burden (CAA+/NP+, red line). The light gray horizontal line at denotes at least 50% of individuals experiencing cognitive change. Note how the CAA+/NP+ and CAA−/NP+ groups have high likelihood for experiencing cognitive change even at an early age.

Figure 2

This plot shows the cumulative probability of moderate-stage dementia classification against age for each of our neuropathologic classifications: no significant neuritic plaque (NP) or cerebral amyloid angiopathy (CAA) burden (CAA−/NP−, black line), no significant CAA burden but significant NP burden (CAA−/NP+, blue line), significant CAA burden with no NP burden (CAA+/NP−, green line), significant CAA and NP burden (CAA+/NP+, red line). The light gray horizontal line at denotes at least 50% of individuals experiencing moderate-stage dementia. Note again how the CAA+/NP+ and CAA−/NP+ groups have high likelihood for experiencing earlier classification as moderately demented.

Figure 3

This plot shows the estimated cumulative probability of time to progress from early-stage to moderate-stage dementia classification based on neuropathologic classification at autopsy: no significant neuritic plaque (NP) or cerebral amyloid angiopathy (CAA) burden (CAA−/NP− or CAA+/NP−, blue line), no significant CAA burden but significant NP burden (CAA−/NP+, green line), significant CAA and NP burden (CAA+/NP+, red line). The light gray horizontal line at denotes at least 50% of individuals transitioning to moderate-stage dementia.