Cerebral amyloid angiopathy and cognitive outcomes in community-based older persons

Abstract

Objective: We tested the hypothesis that cerebral amyloid angiopathy (CAA) is related to Alzheimer disease (AD) dementia and decline in multiple cognitive systems in old age, independent of AD plaque and tangle pathology and other common age-related neuropathologies.Methods: Participants (n 5 1,113) came from 2 longitudinal clinical-pathologic studies of aging, the Rush Memory and Aging Project and the Religious Orders Study. All underwent annual clinical evaluations including detailed cognitive testing for a mean of 7.1 years before death. Clinical diagnoses of AD were established after reviewing all clinical data, blinded to neuropathologic information. Neuropathologic examinations provided measures of CAA, AD pathology, macroscopic infarcts, microinfarcts, and neocortical Lewy bodies. The association of CAA with AD dementia was examined using logistic regression models, and its association with cognitive decline was examined using linear mixed models.Results: CAA was common, present in 78.9% of participants, and moderately related to AD pathology (r 5 0.401, p , 0.0001). In analyses adjusted for plaques, tangles, and other common age-related neuropathologies, CAA was associated with an increased odds of AD dementia (odds ratio 5 1.237, 95% confidence interval 1.082-1.414) and an increased rate of decline in global cognition, perceptual speed, episodic memory, and semantic memory. The associations of CAA with cognitive outcomes were not driven by the presence of capillary involvement.Conclusions: CAA is an important determinant of AD dementia and decline in multiple cognitive systems in old age. Cerebral amyloid angiopathy (CAA) is frequently observed in the brains of older persons and cooccurs with Alzheimer disease (AD) pathology.1,2 However, the independent relation of CAA with late-life cognitive outcomes is unclear. Although several studies suggest a link between CAA and dementia, 3-7 findings come mainly from highly selected samples, and AD and other common age-related neuropathologies have infrequently been considered. [8][9][10][11] Furthermore, little is known about the relation of CAA with cognitive decline. We previously reported associations between CAA, perceptual speed, and episodic memory proximate to death in a sample a third the size of that in this study, 12 but studies examining the relation of CAA with the rate of change in multiple cognitive systems over time are rare.We tested the hypothesis that CAA is related to cognitive outcomes over and above other common age-related neuropathologies, particularly AD. Participants and data came from 2 longitudinal clinical-pathologic studies of aging. 13 We first examined the independent relation of CAA with likelihood of AD dementia, and then examined the association of CAA with cognitive decline using data collected annually for up to 19 years before death.METHODS Standard protocol approvals, registrations, and patient consents. Data for this study came from 2 ongoing longitudinal cohort studies of aging. 13,14 These studies were approved b...

Strictly Lobar Cerebral Microbleeds Are Associated With Cognitive Impairment

“…Because CAA pathology is frequently observed in AD, 32,34 the relationship between CAA, independent of AD pathology, and cognition has been a topic of debate. A recent autopsy study reported that CAA pathology is associated with an increased rate of decline in cognitive functions proximate to death (mean age at death: 88.5 years).…”

MRI-visible perivascular space location is associated with Alzheimer's disease independently of amyloid burden

“…Arteriolosclerosis is associated with hypertension, diabetes and increasing age, and "vascular" dementia (the most common form of which is subcortical vascular cognitive impairment, SVCI), whereas CAA is the result of amyloid-beta (Aβ) deposition in the walls of small to medium vessels in the cortex and leptomeninges, and found in over 90% of those with AD (Charidimou et al, 2012). As well as being a risk factor for spontaneous intracerebral haemorrhage (Samarasekera et al, 2012), CAA can result in cognitive deficits independently of AD (Arvanitakis et al, 2011;Boyle et al, 2015;Reijmer et al, 2015), although the exact interaction between these two processes remains unclear. Traditionally AD and SVCI have been described as having distinct neuroimaging profiles (Wardlaw et al, 2013b;Greenberg et al, 2014), but clinically differentiating between the two remains difficult, as both the cognitive symptoms and the imaging findings frequently overlap (Lee et al, 2011;Wardlaw et al, 2013a;Wardlaw et al, 2013b;Greenberg et al, 2014;Lee et al, 2014).…”

Small vessel disease burden in cerebral amyloid angiopathy without symptomatic hemorrhage

“…By contrast, those seen for cognitive symptoms may have a more progressive silent expression of the disease, or may be more frequently associated with neurodegenerative processes including Alzheimer disease. 35 Interestingly, patients first seen for TFNEs demonstrated a significantly more posterior distribution of WMH lesions. The posterior distribution of WMH lesions has been described in patients with sporadic CAA without ICH 26 but the influence of CAA subtype on WMH distribution had not been previously defined.…”

“…17,40,41 It could be hypothesized that SVD-related damage in patients seen for acute neurologic symptoms more strongly influences cortical atrophy 41,42 whereas in patients with CAA presenting with cognitive symptoms both SVD pathology and neurodegenerative processes drive atrophy. 35,43,44 Quantitative cortical atrophy measures coupled with in vivo molecular imaging of amyloid and tau deposition may shed further insight into this possibility.…”