Cerebral amyloid angiopathy impacts neurofibrillary tangle burden and cognition

Cerebral amyloid angiopathy commonly co-occurs with amyloid beta plaques and neurofibrillary degeneration and is proposed to con-tribute to cognitive impairment. However, the interplay among these pathologic changes of Alzheimer disease is not well understood. Here we replicate and extend findings of a recent study that suggested the association of cerebral amyloid angiopathy and cognitive impairment is mediated by neurofibrillary degeneration. We employed similar approaches but in a larger, clinical-based (as opposed to community-based) set of 4915 autopsied National Alzheimer's Coordinating Center participants (60% with dementia). Neuropathologic lesions were measured ordinally; longitudinal change in cognition was used to measure cognitive impairment. Statistical analyses included ordinal logistic regression, mediation analyses and extension of models to include presence of APOE e4. We show a statistical interaction between cerebral amyloid angiopathy and neuritic plaques that impacts the burden of neurofib-rillary tangles. Mediation analyses show that cerebral amyloid angiopathy is associated with cognitive impairment, but only by modi-fying the impact of neurofibrillary tangles on cognition. We expanded the mediation analysis to include APOE e4 and show similar results. Findings indicate that cerebral amyloid angiopathy plays an important role in the burden and impact of neurofibrillary degen-eration contributing to cognitive impairment