Chapter 4 - The role of cerebrovascular disease in aging and Alzheimer's disease among people with Down syndrome

Abstract

Cerebrovascular disease is common in older adults and is associated with cognitive decline and Alzheimer's disease (AD) risk. Adults with Down syndrome (DS) have vascular risk profiles that are distinct from individuals in the general population and include lower rates of hypertension and atherosclerosis but higher rates of congenital heart disease, obesity, high cholesterol, and sleep apnea. This chapter reviews emerging concepts and observations about cerebrovascular disease from autopsy and neuroimaging studies of older adults with DS. Autopsy studies confirm high rates of cerebral amyloid angiopathy and hemorrhagic lesions. Magnetic resonance imaging (MRI) studies are consistent with postmortem observations in showing high rates of cerebral microbleeds that are likely due to cerebral amyloid angiopathy. In addition, MRI studies in DS highlight evidence of ischemic disease such as white matter intensities and brain infarcts as well as other potential consequences of cerebrovascular disease such as white matter microstructural abnormalities and enlarged perivascular spaces. These abnormalities increase with a clinical diagnosis of AD. The moderators and mediators of the observed postmortem and neuroimaging evidence of cerebrovascular disease have not been studied comprehensively. Further study of the mechanisms leading to cerebrovascular disease in adults with DS will provide insight into the neurobiology of cognitive aging and AD in people with DS and in the general population, as well as highlight potential novel therapeutic avenues.