Exploring Vascular Contributions to Cognitive Impairment with Focus on Small-Vessel Disease of White Matter and Micro/nanoplastics

Cognitive impairment due to vascular pathology was recognized by Otto Binswanger in 1894, before Alois Alzheimer presented his findings in 1907. Vascular causes of cognitive impairment are likely due to a range of pathologies that are still, a hundred years later, unknown. Recent epidemiologic evidence from post-mortem human brains reports cases may be afflicted by Alzheimer's disease, vascular disease, or both. Although it is well known that hypertension and diabetes affect vasculature throughout the body as well as brain, other types of underlying causes that primarily affect cerebral vessels are understudied. Consensus guidelines exist for histopathologic diagnosis of Alzheimer's disease, but are limited for cerebrovascular diseases. Here, first, the anatomy of brain vasculature is reviewed. Next, a schema for categorization of vascular pathologies is proposed, followed by examples that illustrate these pathologies together with stains useful for their detection. Scoring pathologies across many cases according to this schema will subdivide vascular dementias into their underlying, potentially treatable, categories. The recent discovery of micro/nanoplastics in the brain and their association with vasculature will have a profound influence on how vascular-pathology-associated cognitive impairment is understood and diagnosed. Going forward, anatomic pathologists will need to apply this categorization to triage types of cerebrovascular pathology and begin to dissect its underlying causes, consequences, and potential treatments.