Objective. To investigate the peculiarities of the metabolic activity of neurons and the expression of estrogen receptors and their splice variants in aging and two most common types of dementia: Alzheimer’s disease (AD) and vascular dementia (VD). Subjects and methods. Autopsy brain specimens were examined in 95 men and women: 54 control cases divided into 4 age groups from young to old age according to the WHO periodization, 30 cases with AD and 11 with VD. The methods included thionine or cresyl violet staining; immunocytochemical staining of the Golgi complex middle cistern protein, estrogen receptors (ER), and aromatase with polyclonal antibodies, polymerase chain reaction to determine splice variants of ER, morphometry, and statistical material processing. Results. Neuronal metabolic activity in most hypothalamic and basal forebrain structures increases with aging; it is mosaic in AD and decreases in VD. The age- and gender-related features of neuronal metabolic activity are associated with the level of the estrogens circulating and locally produced in the brain and with the expression of ER. The presence of gliosis in the studied brain structures in AD and VD may suggest that there is a compensatory response to lower neuronal metabolic activity. The expression of nuclear ERα in the brain is pathognomonically increased in the anterior basal forebrain and hypothalamus in AD and can be considered as one of the markers for this disease. Accumulation of the splice variants of ERα occurs in the brain of women with aging. Conclusion. The authors have investigated neuronal metabolic activity changes and ER expression in aging and two most common types of dementia. The splice variants have been isolated for the first time from the human brain and their expression was determined in relation to gender and age.