Vascular and Alzheimer’s pathology: A mixed affair

Background In‐vivo indicators of the central pathologies that define Alzheimer’s disease (AD) have transformed research in dementia. The AT(N) framework was proposed to standardize nomenclature when using these biomarkers in the research setting of suspected Alzheimer’s dementia. However, in‐vivo amyloid and tau biomarkers provide an incomplete picture of the brain in persons living with Alzheimer’s dementia, a heterogeneous syndrome that not only includes prominent episodic memory impairment, but often deficits in multiple other cognitive domains, motoric abilities and behavior. Method Presentation of human data from autopsy studies that support a role for vascular pathology in accelerating neurodegeneration and worsening cognitive impairment. Result Brain vascular disease is extraordinarily common in the aging brain with and without AD pathology and contributes to cognitive impairment. In spite of the prevalence of vascular pathology, most persons have no history of stroke. Vascular brain pathologies include but are not limited to small and large vessel diseases and macro and microscopic tissue injuries. Each vascular pathology adds to cognitive impairment and lowers the threshold for Alzheimer's dementia. In some studies, vascular pathologies contribute to about 1/3 of association between age and dementia. Changes in endothelial cells, the blood brain barrier and the neurovascular unit are also implicated. Moreover, vascular risk factors and vessel diseases may promote or interact with amyloid and/or tau to accelerate tissue injury. Conclusion Preventing and treating cognitive impairment requires an integrated understanding of beta‐amyloid, hyperphosphorylated tau, and the vascular pathologies and processes that lead to tissue injury, neurodegeneration, and ultimately cognitive decline.