Specifically, there is ongoing debate as to whether vascular risk factors contribute to the deposition of the neuritic plaques and neurofibrillary tangles (NFTs) that represent the pathological hallmarks of Alzheimer’s dementia ( Hyman et al., 2012), lead to cerebrovascular changes that in turn lower the threshold for the clinical expression of Alzheimer’s dementia pathology, or operate through both mechanisms ( Zlokovic, 2011 Chui et al., 2012). However, the role of vascular risk factors in Alzheimer’s dementia pathophysiology remains unclear. Hypertension is believed to increase susceptibility to Alzheimer’s dementia ( Skoog et al., 1996 Launer et al., 2000 Walker et al., 2017). Circle of Willis atherosclerosis may be an important point of convergence between vascular risk factors, cerebrovascular changes and Alzheimer’s disease neuropathology. These results suggest that hypertension may promote Alzheimer’s disease pathology indirectly through intracranial atherosclerosis by limiting cerebral blood flow and/or dampening perivascular clearance. Similar indirect effects were observed for continuous measures of systolic and diastolic blood pressure. Within the overall sample and among Alzheimer’s dementia decedents, hypertension was indirectly associated with increased neuritic plaques and neurofibrillary tangles through its association with circle of Willis atherosclerosis. To examine the role of circle of Willis atherosclerosis in the association between hypertension and Alzheimer’s disease neuropathology, we analysed post-mortem neuropathological data on 2198 decedents from the National Alzheimer’s Coordinating Center database using joint simultaneous (i.e. Hypertension also promotes circle of Willis atherosclerosis, which contributes to cerebral hypoperfusion and arterial wall stiffening, two potential mechanisms linking hypertension to Alzheimer’s disease. Hypertension is common among older adults and is believed to increase susceptibility to Alzheimer’s disease, but mechanisms underlying this relationship are unclear.
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