Gender-Specific Degeneration of Dementia-Related Subcortical Structures Throughout the Lifespan

Abstract

Age-related changes in brain structure are a question of interest to a broad field of research. Structural decline has been consistently, but not unambiguously, linked to functional consequences, including cognitive impairment and dementia. One of the areas considered of crucial importance throughout this process is the medial temporal lobe, and primarily the hippocampal region. Gender also has a considerable effect on volume deterioration of subcortical grey matter (GM) structures, such as the hippocampus. The influence of age×gender interaction on disproportionate GM volume changes might be mediated by hormonal effects on the brain. Hippocampal volume loss appears to become accelerated in the postmenopausal period. This decline might have significant influences on neuroplasticity in the CA1 region of the hippocampus highly vulnerable to pathological influences. Additionally, menopause has been associated with critical pathobiochemical changes involved in neurodegeneration. The micro- and macrostructural alterations and consequent functional deterioration of critical hippocampal regions might result in clinical cognitive impairment-especially if there already is a decline in the cognitive reserve capacity. Several lines of potential vulnerability factors appear to interact in the menopausal period eventually leading to cognitive decline, mild cognitive impairment, or Alzheimer's disease. This focused review aims to delineate the influence of unmodifiable risk factors of neurodegenerative processes, i.e., age and gender, on critical subcortical GM structures in the light of brain derived estrogen effects. The menopausal period appears to be of key importance for the risk of cognitive decline representing a time of special vulnerability for molecular, structural, and functional influences and offering only a narrow window for potential protective effects.

Sirtuin 3 protects against anesthesia/surgery-induced cognitive decline in aged mice by suppressing hippocampal neuroinflammation

“…In addition, anesthesia/surgery may induce microglial activation, resulting in the release of inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 [11,12]. Furthermore, the hippocampal CA1 region is critical for cognition [13], and overactivated microglia and neuroinflammation create a neurotoxic response and cause synaptic dysfunction, resulting in cognitive dysfunction [14].…”

Technologies for Cognitive Training and Cognitive Rehabilitation for People With Mild Cognitive Impairment and Dementia. A Systematic Review

“…Despite the advances in treatments of chronic diseases related to old age, dementia is considered one of the most significant public health challenges (Nemeth et al, 2017). It is estimated that 74.7 million people around the world will be living with dementia by the year 2030 (Alzheimer's Disease International., 2015).…”

Aging and aging-associated diseases: a microRNA-based endocrine regulation hypothesis

“…Two-thirds of Americans living with AD dementia are women, and neither their longer lifespans nor differences in lifestyle compared to men can explain these numbers. It has been suggested that the higher frequency of female AD morbidity is caused by increased chances of AD initiation earlier in life due to menopause [ 111 , 112 ], although the mechanisms underlying this phenomenon are not clear. The proposed hypothesis explains these sex differences by changes in the spectrum of secreted PG miRNA hormones from pro-developmental to anti-carcinogenic, changes that are associated with decreased levels of estrogen.…”