. White matter hyperintensities and CSF Alzheimer disease biomarkers in preclinical Alzheimer disease. Neurology. 2020 Mar 3;94(9):e950-e960. Epub 2019 Dec 30 PubMed.


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  1. This a wonderful discussion of an important topic in the vascular contributions to dementia. It is important to contextualize that these results pertain specifically to atherosclerosis and not other forms of vascular dysfunction. Gottesman et al. is consistent with the literature showing atherosclerosis is weakly or not associated with dementia and its pathology.

    Atherosclerosis is one focal form of vascular disease that can impact brain health, most often through acute cerebrovascular insult. In the case of severe stenosis, a diffuse pattern of ischemia is also observed. It is more difficult to measure and disentangle more diffuse forms of vascular pathology and dysfunction (e.g. arterial stiffness, arteriolosclerosis, endothelial dysfunction) from atherosclerosis.

    Yet, there are data emerging that more diffuse function disorders (e.g., arterial stiffness) are associated with both cerebral small-vessel disease and amyloid pathology in older adults, while atherosclerosis is not. Additional basic models are needed to determine if arterial dysfunction and stiffening plays a potential role inhibiting amyloid clearance or as a consequence of amyloid deposition in the vascular wall. Currently, our amyloid PET ligands cannot differentiate vascular from parenchymal fibrillar amyloid deposits. Given the common nature of extensive amyloid deposition in older adults, it is important to specify what forms of amyloid deposition are exhibited in older adults.

    For more detailed reading: Hughes, Craft and Lopez. "Review of 'The Potential Role of Arterial Stiffness in the Pathogenesis of Alzheimer's Disease.'" 


    . Review of 'the potential role of arterial stiffness in the pathogenesis of Alzheimer's disease'. Neurodegener Dis Manag. 2015;5(2):121-35. PubMed.

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  1. Vascular Dysfunction Taxes Cognition, but Not Via Amyloid, AD