Alzheimer's DiseaseLife Extension Suggestions
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).
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 testosterone (Miller 2002; Luu-The 2010). 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 (Mayo 2003; Mayo 2005).
DHEA has neuroprotective effects and several studies indicate that patients with Alzheimer’s disease have lower levels of DHEA than those without the disease (Hillen 2000; Polleri 2002; Weill-Engerer 2002). In animal models, DHEA improved memory in rodents that overexpressed amyloid beta (Farr 2004).
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 (Zhang 2003; Bailey 2011). However, the role of estrogen replacement therapy in brain protection is not entirely clear, and may be dependent upon age at initiation (Maki 2012). 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 (Brinton 2005). The Cache County Study reported that Alzheimer’s risk was reduced with long-term HRT (exceeding 10 years) compared to short-term HRT (Zandi 2002), suggesting that early initiation (near menopause) may be an important factor (Carroll 2012; Barron 2012).
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 (Barron 2012). Therefore, some scientific evidence suggests that progesterone may be effective for the prevention of degenerative brain diseases including Alzheimer’s disease (Schumacher 2004).
Unlike the sudden drop of female hormones that occurs during menopause, loss of testosterone is gradual in men, with bioavailable levels declining 2-3% annually from approximately 30 years of age (Barron 2012). Several studies have linked low testosterone to increased risk of Alzheimer’s disease in men. In a clinical trial involving 16 male Alzheimer’s patients and 22 healthy controls, 24 weeks of testosterone replacement therapy was associated with improved quality of life compared to placebo among those with Alzheimer’s disease (Lu 2006).
Endogenous melatonin not only helps regulate the sleep-wake cycle, but is a strong antioxidant (Bubenik 2011). Melatonin secretion within the brain declines with age and lower levels are associated with a higher degree of cognitive impairment (Magri 2004). Melatonin concentration is lower in Alzheimer’s patients than in healthy people of the same age (Cardinali 2011). In animal studies, melatonin improved cognitive function and reduced oxidative injury and deposition of amyloid beta (Cheng 2006). Additional studies have confirmed that melatonin protects brain cells from amyloid beta toxicity by impairing amyloid beta generation and slowing the formation of plaque deposits (Wang 2006a). Melatonin has also been shown to reduce tau tangles and amyloid beta toxicity (Srinivasan 2006).