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Abby's Magazine - November/December 2015 | Page 29 testosterone. Aging is associated with a steep decline in the production of pregnenolone and other steroid hormones. French researchers have shown that pregnenolone directly influences acetylcholine release in several key brain regions. They also demonstrated pregnenolone's ability to promote new nerve growth. Dehydroepiandrosterone (DHEA) DHEA has neuroprotective effects and several studies indicate that patients with Alzheimer's disease have lower levels of DHEA than those without the disease. In animal models, DHEA improved memory in rodents that overexpressed amyloid beta. Estrogen Estrogen is an important regulator of neural function. It has been reported to protect neurons from amyloid beta-mediated toxicity as well as to reduce neuronal death in cell culture. However, the role of estrogen replacement therapy in brain protection is not entirely clear, and may be dependent upon age at initiation. One research team suggested that estrogen therapy could be beneficial when neurons are still healthy, but might exacerbate Alzheimer's disease once neurological health is already compromised. The Cache County Study reported that Alzheimer's risk was reduced with long-term HRT compared to short-term HRT, suggesting that early initiation (near menopause) may be an important factor. Progesterone Like estrogen, progesterone levels decline during normal aging. Declining progesterone levels are linked with increased amyloid beta, increased NFTs, increased neuron death, and impaired cognition; all of which are associated with Alzheimer's disease. Therefore, some scientific evidence suggests that progesterone may be effective for the prevention of degenerative brain diseases including Alzheimer's disease. Risk Factors for Alzheimer's Disease Several factors influence the risk of Alzheimer's disease. Some are modifiable, such as obesity and nutrient deficiencies, but others, such as carrying the ApoE4 gene, are not. Below is a partial list of factors known to be associated with an increased risk of Alzheimer's. • Advancing age • Family history of Alzheimer's disease • Carrying the ApoE4 genetic variant • Certain bacterial infections • Vascular risk factors (e.g., diabetes, atherosclerosis, high blood pressure, high cholesterol) appear to encourage the development of phenomena associated with Alzheimer's disease such as accumulation of amyloid beta. • History of head trauma • High homocysteine levels • Nutrient deficiencies • Silent strokes • Central obesity (i.e., high waist-to-hip ratio) Hormone Replacement Therapy In Alzheimer's Disease A potential strategy to modulate factors that underlie Alzheimer's disease is to target age-related depletion of sex hormones. Following menopause, women experience a rapid loss of estrogen and progesterone. Similarly, men experience an age-related loss of testosterone, a condition known as androgen deficiency or hypogonadism. Since sex hormones have fundamental roles in neural health, hormone replacement therapy (HRT) is an intriguing therapeutic consideration in Alzheimer's disease (Barron 2012). Pregnenolone In humans, the steroid hormone cascade begins with pregnenolone, a hormonal derivative of cholesterol. Subsequently, metabolic modification of pregnenolone gives rise to dehydroepiandrosterone (DHEA), which is then converted into estrogens, progesterone, and