Alzheimer’s Disease Research

Insulin and Aging
A new study, to be published, says that high insulin levels, among both diabetics and non-diabetics, may contribute to Alzheimer’s disease.

To quote the authors of the study “Although this model has obvious relevance for diabetes mellitus, hyperinsulinemia and insulin resistance are widespread conditions that affect many nondiabetic adults with obesity, impaired glucose tolerance, cardiovascular disease, and hypertension. Our results provide a cautionary note for the current epidemic of such conditions, which, in the context of an aging population, may provoke a dramatic increase in the prevalence of AD (Alzheimer’s).”

You can read the entire article at the Journal of Neurology

Obesity and vascular risk factors at midlife and the risk of dementia and Alzheimer disease.
Kivipelto M, Ngandu T, Fratiglioni L, Viitanen M, Kareholt I, Winblad B, Helkala EL, Tuomilehto J, Soininen H, Nissinen A. Arch Neurol. 2005 Oct;62(10):1556-60.

From the abstract: “Obesity at midlife is associated with an increased risk of dementia and AD (Alzheimer’s Disease) later in life. Clustering of vascular risk factors increases the risk in an additive manner. The role of weight reduction for the prevention of dementia needs to be further investigated.”
Read the abstract

Brain Estrogen Deficiency and Alzheimer’s Disease
Writing in the Proceedings of the National Academy of Sciences (USA), researchers studied the effects of estrogen deficiency and Alzheimer’s Disease. They wrote: “Much evidence indicates that women have a higher risk of developing Alzheimer’s disease (AD) than do men. The reason for this gender difference is unclear. We hypothesize that estrogen deficiency in the brains of women with AD may be a key risk factor….Our results indicate that estrogen depletion in the brain may be a significant risk factor for developing AD neuropathology.”

Yue X, Lu M, Lancaster T, Cao P, Honda SI, Staufenbiel M, Harada N, Zhenyu Z, Shen Y, Rena Li R Brain estrogen deficiency accelerates Aβ plaque formation in an Alzheimer’s disease animal model Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0505203102

Melatonin and Alzheimer-like neurodegeneration
Writing in the medical journal Acta Pharmacologica Sinica, researchers studied the effect of melatonin and cognitive impairment. They wrote: “Alzheimer disease (AD), an age-related neurodegenerative disorder with progressive loss of memory and deterioration of comprehensive cognition, is characterized by extracellular senile plaques of aggregated beta-amyloid (Abeta), and intracellular neurofibrillary tangles that contain hyperphosphorylated tau protein. Recent studies showed that melatonin, an indoleamine secreted by the pineal gland, may play an important role in aging and AD as an antioxidant and neuroprotector. Melatonin decreases during aging and patients with AD have a more profound reduction in this hormone. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning, and slows down the progression of cognitive impairment in Alzheimer patients.” Wang JZ, Wang ZF. Acta Pharmacol Sin. 2006 Jan;27(1):41-9.

Read the abstract here

Obesity and Alzheimer’s Disease
Researchers say that obesity can lead to higher risk of Alzheimer’s disease.

From the press release issued by Thomas Jefferson University Hospital: “A team led by researchers at the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia and Edith Cowan University in Joondalup, Western Australia has shown that being extremely overweight or obese increases the likelihood of developing Alzheimer’s. They found a strong correlation between body mass index and high levels of beta-amyloid, the sticky protein substance that builds up in the Alzheimer’s brain and is thought to play a major role in destroying nerve cells and in cognitive and behavioral problems associated with the disease.”

Exercise Delays Onset of Dementia and Alzheimer’s
Larson EB, Wang L, Bowen JD,McCormick WC, Teri L, Crane P, Kukull W. Exercise Is Associated with Reduced Risk for Incident Dementia among Persons 65 Years of Age and Older. Annals of Internal Medicine January 17, 2006 Volume 144 Issue 2 Pages 73-81.

A new study reports a reduced incidence rate of dementia for people who exercised 3 or more times a week compared with those who exercised fewer than 3 times per week.

Say the study authors: “We believe these findings may be useful if they are confirmed because Alzheimer disease is one of the most feared illnesses of aging and is frequently cited as a reason for not wanting to “get old”: People do not want to lose their independence and quality of life as a consequence of aging.”

They conclude: “These results suggest that regular exercise is associated with a delay in onset of dementia and Alzheimer disease, further supporting its value for elderly persons.”

Read the full article here at the Annals of Internal Medicine

Obesity and Alzheimer’s
Midlife Obesity Raises Risk of Alzheimer’s Disease Later
Researchers reporting at the American Academy of Neurology 58th Annual Meeting in San Diego this week say that midlife obesity raises the risk for Alzheimer’s. Read more

Testosterone, Alzheimer’s, Mood and Quality of Life
A study suggets that that testosterone replacement therapy improved overall quality of life in patients with Alzheimers Disease.

Brain Estrogen Deficiency and Alzheimer’s Disease
Writing in the Proceedings of the National Academy of Sciences (USA), researchers studied the effects of estrogen deficiency and Alzheimer’s Disease. They wrote: “Much evidence indicates that women have a higher risk of developing Alzheimer’s disease (AD) than do men. The reason for this gender difference is unclear. We hypothesize that estrogen deficiency in the brains of women with AD may be a key risk factor….Our results indicate that estrogen depletion in the brain may be a significant risk factor for developing AD neuropathology.”

Yue X, Lu M, Lancaster T, Cao P, Honda SI, Staufenbiel M, Harada N, Zhenyu Z, Shen Y, Rena Li R Brain estrogen deficiency accelerates Aβ plaque formation in an Alzheimer’s disease animal model Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0505203102

Melatonin and Alzheimer-like neurodegeneration
Writing in the medical journal Acta Pharmacologica Sinica, researchers studied the effect of melatonin and cognitive impairment. They wrote: “Alzheimer disease (AD), an age-related neurodegenerative disorder with progressive loss of memory and deterioration of comprehensive cognition, is characterized by extracellular senile plaques of aggregated beta-amyloid (Abeta), and intracellular neurofibrillary tangles that contain hyperphosphorylated tau protein. Recent studies showed that melatonin, an indoleamine secreted by the pineal gland, may play an important role in aging and AD as an antioxidant and neuroprotector. Melatonin decreases during aging and patients with AD have a more profound reduction in this hormone. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning, and slows down the progression of cognitive impairment in Alzheimer patients.” Wang JZ, Wang ZF. Acta Pharmacol Sin. 2006 Jan;27(1):41-9.

Read the abstract here

Cortisol Concentrations Predict a Decline in Memory Function
Researchers writing in the medical journal Neurobiology of Aging say their “results partially confirm previous findings that high cortisol is associated with impaired declarative memory function in non-demented older persons. In addition, our data show that high salivary cortisol concentrations predict a decline in memory function over the next 3 years.” Read more

Melatonin Research

Blood Pressure
Scheer FA, Van Montfrans GA, van Someren EJ, et al. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 2004;43:192-7.

Study: Researchers sought to examine whether hypertension could be lowered by better sleep.

The researchers stated: “In patients with essential hypertension, repeated bedtime melatonin intake significantly reduced nocturnal blood pressure. Future studies in larger patient group should be performed to define the characteristics of the patients who would benefit most from melatonin intake. The present study suggests that support of circadian pacemaker function may provide a new strategy in the treatment of essential hypertension.”

Melatonin’s Beneficial Effects on Night-Time Blood Pressure and Women Aged 47 to 63
Researchers writing in the American Journal of Hypertension examined the question: “The nocturnal decline of blood pressure (BP) is almost coincident with the elevation of melatonin, which may exert vasodilatating and hypotensive effects. In this study we investigated whether prolonged nocturnal administration of melatonin could influence the daily rhythm of BP in women.”

How was the study conducted?
“In a randomized double-blind study, 18 women, 47 to 63 years of age (nine with normal blood pressure and nine being treated treated for essential hypertension) received a 3-week course of a slow-release melatonin pill (3 mg) or placebo 1 hour before going to bed. They were then crossed over to the other treatment for another 3 weeks.”

What did they conclude?
“In comparison with placebo, melatonin administration did not influence (daytime) BP but did significantly decrease nocturnal systolic, diastolic, and mean BP without modifying heart rate. The effect was inversely related to the day–night difference in BP…These data indicate that prolonged administration of melatonin may improve the day–night rhythm of BP, particularly in women with a blunted nocturnal decline.”

Cagnaccia A, Cannolettaa M, Renzia A, Baldassaria F, Aranginob S, Volpea A. Prolonged Melatonin Administration Decreases Nocturnal Blood Pressure in Women. American Journal of Hypertension. Volume 18, Issue 12, Pages 1614-1618

Immune Stimulation
Poon AM, Liu ZM, Pang CS, et al. Evidence for a direct action of melatonin on the immune system. Biol Signals. 1994 Mar-Apr;3(2):107-17.

From the abstract: “Pineal melatonin modulates the mammalian immune system. In vivo studies showed that melatonin enhanced the natural and acquired immunity while in vitro studies demonstrated its inhibitory influence.”

Melatonin, Immune Function and Aging
Researchers writing in the medical Journal Immunity & Aging say: (From the abstract) “Aging is associated with a decline in immune function (immunosenescence), a situation (sp) known to correlate with increased incidence of cancer, infections and degenerative diseases….Melatonin has the potential therapeutic value to enhance immune function in aged individuals and in patients in an immunocompromised state.”

Venkatramanujam Srinivasan, Georges J.M. Maestroni, Daniel P. Cardinali, Ana I. Esquifino, S. R. Pandi-Perumal and Sandra C. Miller. Melatonin, Immune Function and Aging. Immunity & Ageing 2005, 2:17

Read the abstract

Melatonin Randomized Trial for Insomnia in the Elderly
Nalaka S. Gooneratne, MD,MSc, Principal Investigator, University of Pennsylvania
Study start: October 2004; Expected completion: July 2007

From the study details “Melatonin is a hormone secreted predominantly during the sleep period, suspected to have a strong link to the circadian sleep-wake cycle. Melatonin is also available in a pill form and, when administered during the day, tends to have a sedative effect. Clinical trials that have examined the nocturnal effects of melatonin have focused on patients of any age who have insomnia, regardless of their endogenous melatonin levels. Data indicate, however, that individuals with low endogenous melatonin levels may be more responsive to exogenous melatonin. Generally, melatonin levels decrease with age; therefore, older individuals with insomnia represent an ideal population in which to study the effects of exogenous melatonin on sleep. This study will provide older adults with insomnia melatonin tablets to determine whether the tablets will increase their sleep.”

Read more about this current research

Melatonin and Alzheimer-like Neurodegeneration
Writing in the medical journal Acta Pharmacologica Sinica, researchers studied the effect of melatonin and cognitive impairment. They wrote: “Alzheimer disease (AD), an age-related neurodegenerative disorder with progressive loss of memory and deterioration of comprehensive cognition, is characterized by extracellular senile plaques of aggregated beta-amyloid (Abeta), and intracellular neurofibrillary tangles that contain hyperphosphorylated tau protein. Recent studies showed that melatonin, an indoleamine secreted by the pineal gland, may play an important role in aging and AD as an antioxidant and neuroprotector. Melatonin decreases during aging and patients with AD have a more profound reduction in this hormone. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning, and slows down the progression of cognitive impairment in Alzheimer patients.” Wang JZ, Wang ZF. Acta Pharmacol Sin. 2006 Jan;27(1):41-9.

Read the abstract here

Does Melatonin Protect Vision As We Age?
Researchers writing in the Journal of Pineal Research say that Melatonin maybe beneficial in preserving visual functions.

Excerpts from the study abstract:
“Current evidence suggests that melatonin may act as a protective agent in ocular conditions such as photo-keratitis, cataract, glaucoma, retinopathy of prematurity and ischemia/reperfusion injury.

These diseases are sight-threatening and they currently remain, for the most part, untreatable. The pathogenesis of these conditions is not entirely clear but oxidative stress has been proposed as one of the causative factors.

Oxidative damage in the eye leads to apoptotic degeneration of retinal neurons and fluid accumulation. Retinal degeneration decreases visual sensitivity and even a small change in the fluid content of the cornea and crystalline lens is sufficient to disrupt ocular transparency. In the eye, melatonin is produced in the retina and in the ciliary body. Continuous regeneration of melatonin in the eye offers a frontier antioxidative defense for both the anterior and posterior eye.

However, melatonin production is minimal in newborns and its production gradually wanes in aging individuals as indicated by the large drop in circulating blood concentrations of (Melatonin).

These individuals are possibly at risk of contracting degenerative eye diseases that are free radical-based. Supplementation with melatonin, a potent antioxidant, in especially the aged population should be considered as a prophylaxis to preserve visual functions.”

Siu AW, Maldonado M, Sanchez-Hidalgo M, Tan DX, Reiter RJ. Protective effects of melatonin in experimental free radical-related ocular diseases. J Pineal Res. 2006 Mar;40(2):101-9.

Melatonin

Melatonin is secreted by the pea-sized pineal gland in the center of our brains to regulate our sleep patterns. Our bodies make it from the well known sleep inducing amino acid tryptophan.

As we age we seem to produce less melatonin and this has been suggested as one of the reasons why our aging population has difficult sleeping patterns.

The decline of melatonin centers around age 45. The decline is usually a steep one. By age 60, we produce half the melatonin we did during our twenties and by the late seventies nearly none.

What is so important about sleep?
You probably do not need a long litany of medical articles to know that it is probably a pretty good idea to get a good night’s sleep.

The researchers of sleep have broken sleep up into five different stages, Stages I and II are the “light” sleep phases, Stage III and IV are the deep sleep cycles. Dreaming occurs during Rapid Eye Movement sleep (REM). It is during level IV sleep that our body re-energizes and most importantly that the immune system is stimulated. In treating patients with chronic pain, one of the very first things we do is take a history from the patient of their sleep patterns. Melatonin helps restore good sleep architecture. Without deep Stage IV sleep, healing becomes more difficult, there is a decrease in hormones and neurotransmitters produced that can give us a great quality of life.

If regulating sleep was all that melatonin did, that would be important enough to include it in an age management program.

But research has also suggested that melatonin may contribute to the following:
– Enhances the immune system as an anti-oxidant
– Positive effect on the aging process
– Reduce blood pressure
– Improves bowel symptoms
– Decrease cholesterol
– Increase the natural killer cell activity of the immune system
– Helps reset the circadian rhythm in jet lag

Will melatonin make you live longer?
Much has been made of the possibility of melatonin being a life extender. This is based on animal studies in rats and mice that showed a 20% increase in life span. Speculation centers on melatonin’s anti-oxidant properties. No human longevity studies have been reported to date.

The negatives of melatonin
No serious side effects have been reported in the short-term, and long-term effects are unknown. Melatonin is a hormone, and as such, it should be taken under a physician’s guidance.

Other Side Effects
Headaches
Stomach upset
Insomnia
Restlessness
Depression
Strange dreams

Selected Research

Why am I so driven to work in the age management field?

Basically it was for my own personal, mental, and spiritual well being.

A few years back when I was in my early forties, I began to notice a significant decrease in my energy levels. In other words, I was dragging.

I also noticed that I was losing muscle mass, I was getting softer. I didn’t have the energy to “pump up,” anymore and I was not able to exercise at levels I was accustomed to. “Well, that’s it, I am getting old,” I thought.

I was at a medical convention and spoke to a colleague about “my condition,” and he suggested that I should get my hormone levels checked. When I got my test results back my testosterone levels were so low they didn’t make the charts; way below the normal of anyone I had ever seen before.

Suffice to say, my curiosity in hormone supplementation was sparked. Because my testosterone was so very low and testosterone is the well known builder of bone, I immediately got a Bone Densitometry Test to measure my bone density. I was stunned as the tech told me the news in disbelief. It was very low as well, putting me at a high risk for fracture. I was absolutely stunned, I had to stop a lot of sports I was doing, and loved. I realized that snow skiing, snow shoeing, water skiing, and surfing, some of my favorites, no longer existed for me. No more vacations in the snow or ice. No more high-speed water sports.

It was then that I started to study and research HGH (Human growth hormone), pregenenolone, DHEA, thyroid, Melatonin and the affects of diet on all of them and how the body works with this big maze of hormones to keep people feeling good, not only increasing quality of life but making them healthy on many levels. Initially, I used testosterone intermittently, because of the fear doctors projected based on the problems with body builders, and men with prostate cancer. As I researched more and more, I learned the healthy truth about hormones, and later began total Hormone Replacement Therapy.

As time passed, more and more patients arrived with similar issues that I had, and many with sexual dysfunction. Hormone supplementation was working miracles. I treated friends for free, and eventually learned the art of balancing female hormones. Many relationships were revitalized as the couples individually found their “mojo” again. Romance once again arose in couples that were ready to give it up, because they thought the chemistry was gone.

I have now been doing this work for years and continue to attend different seminars around the country to learn as much new research as possible. The field of age management medicine, as it is called by some is growing so quickly. Us baby boomers expect the best out of life, and demand the best quality of life, which is greatly enhanced by hormone supplementation. My goal in life is to remain young and loving, not only on the inside, but also physically, mentally, emotionally, and spiritually. My children are my finest teachers.