ESR1 and dementia: Given the key role of estrogen in cholinergic transmission relevant to congestion and mood—association with the development of dementia—and understanding that estrogen activity in the brain is mediated through activation of intracellular, transmembrane, and membrane-bound estrogen receptors (ERs), along with non-genomic mechanisms, certain estrogen receptor α (ESR1) polymorphisms have been linked to an increased risk of cognitive impairment in older women [14,15] and diminution of the cerebral cortex [16].