Hemodynamic Factors Underlying The Pathogenesis And Clinical Expression Of Alzheimer’s Disease

As the population ages, unhealthy cognitive decline and dementia are increasingly important public health issues. Vascular risk factors, such as hypertension, diabetes mellitus, and atherosclerosis, are associated with abnormal neuroanatomic changes, cognitive impairment, and clinical dementia in older adults. A poorly understood aspect of compromised vascular health and cognitive aging is the association between systemic hemodynamics (cardiac output or the amount of blood exiting the heart to perfuse the system) and brain aging. Clinical and epidemiological data from my laboratory suggests that, independent of shared vascular risk factors, modest reductions in cardiac output are associated with clinically detectable cognitive impairment, reduced gray matter volume, increased white matter hyperintensities, reduced normative cerebral blood flow (CBF) values, and incident dementia. These observations may be due to subclinical systemic blood flow altering CBF homeostasis. Such alterations are especially likely among older adults with age-related compromises in cerebral circulation control mechanisms, placing the brain at greater risk for cerebrovascular injury and Alzheimer’s disease (AD) pathogenesis. While vascular pathology and AD pathology may develop independently, compromised cerebrovascular health propagates amyloid deposition, compromised β-amyloid clearance, and faster clinical manifestation and trajectory of AD. Thus, systemic hemodynamics may affect cerebral hemodynamics in older adults with compromised cerebral circulation control mechanisms by not only contributing to cerebrovascular injury but also proliferating the pathogenesis or exacerbation of amyloid deposition and subsequent neuronal injury. This presentation will review evidence to date from my laboratory linking hemodynamics and abnormal brain aging and highlight future strategies to delay abnormal cognitive aging