Cerebral amyloid angiopathy and its co-occurrence with Alzheimer's disease and other cerebrovascular neuropathologic changes

Abstract

We examined the relationship between cerebral amyloid angiopathy (CAA), Alzheimer's disease neuropathologic changes, other vascular brain pathologies, and cognition in a large multicenter autopsy sample. Data were obtained from the National Alzheimer's Coordinating Center on autopsied subjects (N = 3976) who died between 2002 and 2012. Descriptive statistics and multivariable regression models estimated the associations between CAA and other pathologies, and between CAA severity and cognitive test scores proximal to death. CAA tended to co-occur with Alzheimer's disease neuropathologic changes but a minority of cases were discrepant. CAA was absent in 22% (n = 520) of subjects with frequent neuritic plaques but present in 20.9% (n = 91) of subjects with no neuritic plaques. In subjects with no/sparse neuritic plaques, nonhemorrhagic brain infarcts were more common in those with CAA pathology than without (p = 0.007). In subjects without the APOE ε4 allele, CAA severity was associated with lower cognition proximal to death, factoring in other pathologies. The presence of CAA in patients without Alzheimer's disease may indicate a distinct cerebrovascular condition.

Keywords: Alzheimer's disease neuropathologic change; Cerebral amyloid angiopathy; Cerebrovascular disease; Cognition; Neuropathology.

Figure 1

Presence of cerebral amyloid angiopathy (CAA), Alzheimer’s disease neuropathologic change (ADNC), and at least one APOE ε4 allele by age at death. The proportion of subjects with CAA (a), ADNC (b), and at least one APOE ε4 allele (c) was plotted according to age at death using fitted polynomial curves.

Figure 2

Percentage of autopsies with none, mild, moderate, and severe cerebral amyloid angiopathy (CAA) according to CERAD neuritic plaque densities.

Figure 3

Gross or microscopic infarcts in subjects with cerebral amyloid angiopathy (CAA+) compared to those without (CAA−). This figure focuses on 824 subjects (of 846) with no/sparse neuritic plaques and non-missing vascular pathology details.