Alzheimer's Disease

Alzheimer's Disease: Overview

Alzheimer's disease is the most common form of senile dementia.  The causes are not yet known, and up to now there is no effective treatment.  Patients with Alzheimer's disease deteriorate very gradually, so the disease is often not detected in its early stages.

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Incidence; Causes and Development; Contributing Risk Factors

By the year 2001, over 4 million living Americans had been diagnosed with Alzheimer's disease and, barring scientific progress, about 14 million will have it by the middle of this century.  In 2017 Alzheimer's was the sixth leading cause of death in the United States.

As the disease develops, two key structural changes are often observed in the brain:

  1. The build-up of senile plaques, consisting mostly of amyloid beta protein
  2. The development of neurofibrillary tangles, composed of phosphorylated tau protein
A senile plaque and neurofibrillary tangle
As senile plaques (left) and neurofibrillary tangles (right) build up, the brain atrophies (shrinks) and ceases proper function

The end result is that neurons in certain brain regions disconnect from each other and eventually die, causing memory loss.  As these processes continue, the brain shrinks and loses function.

Increased free radical activity (oxidative stress) appears to fuel Alzheimer's pathology – acting simultaneously as a mediator, product, and trigger for this "clogging" process and its related neural damage.

Scientists are increasingly finding that it is a combination of many interrelated factors that seems to strongly influence a person's genetic predisposition to develop this devastating degenerative condition.  The top two risk factors of the disease – age and genetics – are unfortunately beyond our control.

Moderate alcohol consumption may reduce the risk.  One study found that those drinking under one or two drinks per day had a roughly 50% lower risk of developing the disease, while people drinking more than one or two drinks had a 30% lower risk than non-drinkers.  Although a protective effect may be had by consuming alcohol, the advice to drink is still premature.  Some people are consuming a modest level of alcohol each day as a preventative measure against heart disease and this study appears to confirm that benefit.

Signs and Symptoms

An older woman with dementia looking at herself in the mirror
As Alzheimer's progresses, each person will cope, react, and adapt differently to the changes that dementia brings

The Alzheimer's Association publishes a list of 10 signs indicative of dementia.  Note that most of us suffer from some of these issues occasionally, so the list is referring to signs that either did not exist previously, or which have become significantly more noticeable:

  • Progressive memory loss that disrupts daily life is the classic feature of Alzheimer's Disease.  At first, only short-term memory is affected, making the patient appear simply forgetful.  Long-term memory survives much longer, but eventually becomes fragmented to the point where the patient does not even know their own name.
  • Decline in cognitive abilities: challenges in planning, solving problems, making decisions
  • Difficulty completing familiar tasks; "forgetting how to do things".  Problems with basic motor skills such as walking, dressing or eating develop, not caused by weakness or paralysis.  In the later stages of the disease, the patient may forget how to chew or sit up in bed.
  • Confusion with time, places, and people
  • Trouble understanding visual images and spatial relationships
  • New problems with communication; difficulties with language: reading, writing, speaking, understanding speech, finding the right words.  In many cases, all language abilities are lost and the patient eventually becomes mute.
  • Misplacing things
  • Decreased or poor judgment, leading to accidents for example
  • Withdrawal from work or social activities.  Poor short-term memory limits a person's ability to function in work and social settings.
  • Changes in mood and personality.  This is often what convinces friends and family that something is wrong.  Apathy, depression, losing interest in previously enjoyable activities, withdrawal, irritability, extreme reactions to minor problems, and unexplained hostility are common examples.

For some reason, problems often worsen late in late afternoon or evening.

Interestingly, the inability to smell peppermint – one of the easiest smells to distinguish – is strongly linked to dementia.  A study published in September of 2017 in the Journal of the American Geriatrics Society and carried out at the University of Chicago Medical Center, tested 3,000 people aged 57 to 85 on their ability to distinguish 5 different smells (peppermint, fish, orange, rose and leather).  Here were the results:

  • 78% correctly named 4 or 5 of the scents
  • 14% correctly named 3
  • 5% correctly named 2
  • 2% could only name one
  • 1% could not name any

Following up 5 years later, almost 100% of the test subjects who were unable to name any of the smells had been diagnosed with dementia, and nearly 80% of those who could only name one or two smells had dementia.

Diagnosis and Tests

Early detection of Alzheimer's is vital because the best treatments are only effective in the early stages.  According to the Alzheimer's Association, there is no single means of definitively identifying and diagnosing the disease so it comes down to recognizing warning signs and performing various tests, which are often expensive.

Unfortunately, Alzheimer's Disease is rarely diagnosed in its early stages, even when patients complain of memory problems.  Various additional factors often delay proper diagnosis:

  • Symptoms are not taken seriously by either patients or their families
  • Symptoms are confused with normal signs of aging
  • Symptoms develop so slowly that they go unnoticed
  • The patient may wish to hide their problems from others; they deny there is a problem and refuse to see a doctor

The build-up of plaque, consisting mostly of beta-amyloid peptides, generally starts 10 to 15 years before symptoms of Alzheimer's Disease start to appear.  In 2017, researchers developed a blood test that can detect the amyloid beta build-up in the brain, suggesting a rapid and inexpensive way to identify those at high risk of developing the disease in the future.

During the diagnostic process, the physician will want to know about the patient's medical history, any recent illnesses, changes in mental abilities, mood, behavior, or physical abilities, medications being taken, and illness in other family members.  This information is needed in order to determine whether imaging studies (CT scan or MRI) are necessary in order to look for changes in the brain.

By testing muscle strength, coordination, reflexes, hearing, vision, smell, taste, touch, eye movement, and eye pupil reaction to light, the diagnostician can determine the health of specific areas of the brain.

Because many other disorders cause dementia-like changes, these need to be ruled out through various tests.  These include heart failure, liver disease, kidney failure, thyroid disorders, respiratory diseases, vitamin B12 deficiency, and sexually-transmitted disease such as syphilis or AIDS.

Comparing a brain with Alzheimer's disease to a normal brain
Brain of an Alzheimer's patient (left) showing shrinkage, narrower brain folds, wider gaps compared to a normal brain (right)

A neurologic examination will determine mental status and help diagnose dementia or delirium.  Mental exercises are also part of the process.

A brain scan (CT or MRI) is normally part of the evaluation.  Aside from ruling out problems such as stroke, tumor, hemorrhage or hydrocephalus, they also show any signs of brain shrinkage typical of Alzheimer's Disease and other forms of dementia.

Recent developments in medical technology are able to more accurately diagnose the disease by, for example, using a chemical tracer that binds specifically to amyloid deposits in the brain, allowing them to show up clearly on the PET (Positron Emission Tomography) scans.  It is hoped that doctors will soon be able to diagnose the disease even before symptoms appear.

Treatment and Prevention

A very important factor in the treatment of Alzheimer's is keeping active, both physically and mentally.  Walking, tai chi, swimming, reading, playing games and socializing with others are all excellent ways to keep active.  In China, old people who are surrounded by a loving family and have grandchildren around have better mental function than those who live alone.  This is not saying that one has to live in a crowded house with an extended family to be healthy, but that having a hobby and keeping some excitement in your life is recommend.

Although a relationship between a stressful lifestyle, a low level of education and a lack of stimulation has been raised through some studies, experts say such links are not yet definitive but deserving of further study.  Despite the unproven associations, fostering a healthier, less stressful lifestyle is always a good idea.

Tacrine is a synthetic drug that has been used successfully with Alzheimer's patients.  Studies indicate that Alzheimer's patients have a deficiency of the neurotransmitter acetylcholine (ACh) in particular areas of the brain.  Tacrine works by blocking the enzyme that breaks down ACh, which means that more ACh is available in the brain.

Vaccinations have shown protective and reversal effects.  Although promising, it is still unknown if one will be successfully developed for human use.

Signs, symptoms & indicators of Alzheimer's Disease:

Symptoms - Head - Mouth/Oral

Gradual/rapid decline in speaking ability

Difficulty speaking is a common symptom of Alzheimer's Disease and is often made worse by patients being unable to remember simple words or concentrate on what they are saying.

(Much) reduced sense of taste

Alzheimer's disease may lead to a decreased sense of taste.

Symptoms - Head - Nose

(Much) reduced sense of smell

Reduction of the sense of smell has been identified as an early sign of Alzheimer's disease since the 1970s.

Symptoms - Metabolic

Moderate/major/very great unexplained weight loss

Weight loss can be a predictor of developing Alzheimer's Disease and allow for earlier intervention.  The accumulation of the peptide amyloid-beta inside the brain disrupts the body's weight-regulating mechanism, leading to accelerated weight loss years before an actual Alzheimer's diagnosis. [Journal of Neuroscience 2 July 2014, 34 (27) 9096-9106]

Symptoms - Mind - General

Counter-indicators

Conditions that suggest Alzheimer's Disease:

Aging

Parkinson's Disease

A study published in 2003 in The Archives of Neurology found that people who rapidly develop symptoms of Parkinson's disease may be up to 8 times as likely to develop Alzheimer's disease.  The study found that the physical symptoms of Parkinson's disease are linked to a decline in mental functioning as seen in Alzheimer's disease.  About 15% of Parkinson's disease victims eventually develop Alzheimer's disease, and another 15% develop other forms of dementia.

Dental / Oral

Dry Mouth

Alzheimer's patients may have a diminished thirst signal so they don't feel thirsty and drink water when they are dehydrated.  In addition, dry mouth is very common among seniors and those with Alzheimer's may not tell anyone that they are thirsty due to reduced mental functioning.

Mental

Senile Dementia

Alzheimer's Disease is the most common cause of dementia, being responsible for 60-80% of cases.  All people with Alzheimer's disease have problems with memory loss, disorientation and thinking ability.

Symptoms - Mind - General

Risk factors for Alzheimer's Disease:

Autoimmune

Diabetes Type I

According to the "Rotterdam Study" reported in the journal Neurology, diabetes mellitus may not only damage the function of the eyes, limbs, kidneys, and heart – it may also impair the function of the brain and hasten the process of senile dementia.

The Rotterdam Study is a large, ongoing prospective analysis which tracked dysglycemia and dementia in over 6,000 individuals over age 55.  The researchers found that diabetes mellitus nearly doubles the risk of developing both vascular dementia and Alzheimer's disease.  Diagnosis of diabetes was based on World Health Organization criteria using a glucose tolerance test.

A related editorial called Alzheimer's a possible "brain-type diabetes".  Besides damaging important blood vessel networks and increasing the risk of small "silent" strokes deep inside the brain, dysglycemia may be directly involved in the development of the neurofibrillary tangles, the clumping of nerves and fiber tissue inside the brain characteristic of Alzheimer's.

The researchers noted that advanced glycation end products (AGE), proteins damaged by chronically high blood sugar levels, are commonly found inside these tangles.  "In brains of AD patients the receptor for AGE appears overexpressed," they noted.  "Activation of this receptor leads to increased oxidative stress that may result in cellular damage."

Diabetes also disrupts insulin signaling to other cells in the body.  This altered signaling may increase the activity of a neuronal enzyme that stimulates phosphorylated tau proteins to build up, a key trigger mechanism cited as one of the earliest signs of Alzheimer's.

NOTE: This study strongly suggests the important potential role of glycation products and insulin response, not just glucose levels, in causing degenerative disease.

Diet

Excess Salt Consumption

August 25th, 2011: A study published in the journal Neurobiology of Aging has found that elderly people who have salt-rich diets and exercise little suffer quicker mental decline.  Just over a teaspoon (7.7gm) of salt a day can dull the mind and raise the risk of Alzheimer's, the study suggests.

The team from the University of Toronto tracked salt consumption and physical activity of 1,262 healthy men and women aged between 67 and 84 over a three-year period.  They also assessed the mental health of the participants at the start of the study and once a year for the duration.

The good news is that sedentary older adults showed no cognitive decline over the three years if they had low sodium intake.

Environment / Toxicity

Heavy Metal Toxicity

Because Alzheimer's patients often exhibit increased concentration of heavy metals in their blood and brain, toxic exposure is believed to play an important role.

Mercury Toxicity (Amalgam Illness)

Because Alzheimer's patients often exhibit increased concentration of heavy metals such as mercury in their blood and brain, toxic exposure is believed to play an important role.  The areas of the brain that mercury favors are those involved with memory (amygdala and hippocampus).  It is not just aluminum that is implicated in Alzheimer's.

Family History

Alzheimer's in family members

By age 80, people with Alzheimer's disease in both parents had a 54% risk, 1.5 times the risk of Alzheimer's in people with just one affected parent, and 5 times the risk of people with two unaffected parents.

Hormones

Low Male Testosterone Level

Baltimore Longitudinal Study showed a strong correlation between low testosterone levels and dementia, as well as increased risk of Alzheimer's disease.

Inflammation

Chronic Inflammation

Research published in the Journal of Neuroinflammation in July, 2012 has shown that chronic inflammation can leave the brain vulnerable to developing Alzheimer's.

Lab Values

Elevated Homocysteine Levels

People with elevated levels of homocysteine have nearly double the risk of developing Alzheimer's disease, according to a report from researchers at Boston University.  The findings, which come from the long-running Framingham Study, are the first to tie homocysteine levels measured several years before with later diagnosis of Alzheimer's and other dementias.  The report, which appeared in the New England Journal of Medicine, provides some of the most compelling evidence yet of an association between high plasma homocysteine and eventual significant memory loss.

High Total Cholesterol

It is thought that the connection between high cholesterol and Alzheimer's disease exists in a protein called beta-amyloid, a sticky substance that builds up in the brains of Alzheimer's patients leading to nerve cell damage and loss of cognitive function.  Accumulation of the protein is believed to be related to higher cholesterol levels.

Lifestyle

Low aerobic exercise level

Keeping an active mind and body has been shown to reduce slightly the risk of developing the disease.

Counter-indicators
(Very) good aerobic exercise level

Keeping an active mind and body has been shown to reduce slightly the risk of developing the disease.

Organ Health

Diabetes Type II

According to the Rotterdam Study of 6,370 subjects over age 55, diabetes mellitus may not only damage the function of the eye, limbs, kidneys, and heart – it also appears to impair the function of the brain and hasten the process of senile dementia. [Neurology. 1999 Dec 10;53(9): pp.1937-42]

The researchers found that diabetes mellitus nearly doubles the risk of developing both vascular dementia and Alzheimer's disease.  Diagnosis of diabetes was based on World Health Organization criteria using a glucose tolerance test.

A related editorial called Alzheimer's a possible "brain-type diabetes".  Besides damaging important blood vessel networks and increasing the risk of small "silent" strokes deep inside the brain, dysglycemia may be directly involved in the development of the neurofibrillary tangles, the clumping of nerves and fiber tissue inside the brain characteristic of Alzheimer's.

The researchers noted that advanced glycation end products (AGE), proteins damaged by chronically high blood sugar levels, are commonly found inside these tangles.  "In brains of AD patients the receptor for AGE appears overexpressed," they noted.  "Activation of this receptor leads to increased oxidative stress that may result in cellular damage."

Diabetes also disrupts insulin signaling to other cells in the body.  This altered signaling may increase the activity of a neuronal enzyme that stimulates phosphorylated tau proteins to build up, a key trigger mechanism cited as one of the earliest signs of Alzheimer's.

NOTE: This study strongly suggests the important potential role of glycation products and insulin response, not just glucose levels, in the etiology of degenerative disease.

Supplements, Medications, Drugs

Counter-indicators
Using NSAIDs or history of NSAID use

Research has shown that regularly taking NSAIDs reduces the risk of developing Alzheimer's Disease.

Frequent/regular aspirin use

People who regularly take aspirin or other non-steroidal anti-inflammatory drugs (NSAIDs) have a reduced risk of developing Alzheimer's Disease.

Symptoms - Food - Beverages

Counter-indicators
(High) green tea consumption

Research suggests that drinking green tea may halt brain diseases such as Alzheimer's, Parkinson's and Huntington's.  A chemical found in green tea (EGCG), combined with another chemical DAPH-12, combine to prevent and destroy amyloids, which play key roles in the development of these disorders.

Symptoms - Food - Intake

Counter-indicators
High/moderate/low cold water fish consumption

Researchers from the University of Pittsburgh announced in August, 2012 that eating fish regularly appears to boost the size and health of the brain's neurons, and that people who eat grilled or baked fish (but not fried or dried fish) at least once a week are up to five times less likely to develop Alzheimer's Disease than those who do not consume fish.

However, the most effective ways to reduce risk of developing dementia are eating a healthy diet including fruit and vegetables, taking regular exercise, and giving up smoking.

Symptoms - Glandular

Under 4/4-6/7-9/Over 9 years at 120-180 blood sugar

According to the "Rotterdam Study" reported in the journal Neurology, diabetes mellitus may not only damage the function of the eyes, limbs, kidneys, and heart – it may also impair the function of the brain and hasten the process of senile dementia.

The Rotterdam Study is a large, ongoing prospective analysis which tracked dysglycemia and dementia in over 6,000 individuals over age 55.  The researchers found that diabetes mellitus nearly doubles the risk of developing both vascular dementia and Alzheimer's disease.

A related editorial called Alzheimer's a possible "brain-type diabetes."  Besides damaging important blood vessel networks and increasing the risk of small "silent" strokes deep inside the brain, dysglycemia may be directly involved in the development of the neurofibrillary tangles, the clumping of nerves and fiber tissue inside the brain characteristic of Alzheimer's.

The researchers noted that advanced glycation end products (AGE), proteins damaged by chronically high blood sugar levels, are commonly found inside these tangles.  "In brains of AD patients the receptor for AGE appears overexpressed," they noted.  "Activation of this receptor leads to increased oxidative stress that may result in cellular damage."

Diabetes also disrupts insulin-signaling to other cells in the body.  This altered signaling may increase the activity of a neuronal enzyme that stimulates phosphorylated tau proteins to build up, a key trigger mechanism cited as one of the earliest signs of Alzheimer's.

Symptoms - Mind - General

(Serious) past head injury

Besides age and genetics, most experts agree the evidence is conclusive enough to name serious head injury as a strong risk factor for the disease.  Inflammation in the brain can lead to the death of cells which contributes to the disease.

Not keeping mind active

Staying mentally active/stimulated appears to reduce the risk.

Counter-indicators
Keeping mind active

Staying mentally active/stimulated appears to reduce the risk.

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Alzheimer's Disease could instead be:

Circulation

Infections

Lyme Disease

Spirochetes, such as those found in Lyme disease, may be one of the causes of Alzheimer's disease and may also be the source of beta amyloid deposited in the brains of such infected patients.

Reproductive

STD Syphilis

See the link between syphilis and schizophrenia.

Recommendations for Alzheimer's Disease:

Botanical / Herbal

Chlorella

A study showed that among 50 people with Alzheimer's, aged 70-90, taking 6gm daily of chlorella for 6 months, 68% experienced either a stabilization or improvement in cognitive functions.

Ginkgo Biloba

Patients with mild to moderate Alzheimer's-type dementia have shown statistically significant improvement with Ginkgo use.  One effect of Ginkgo extract is that of promoting vasodilation and blood flow, thus providing a therapeutic effect on cognitive disorders and high blood pressure.  In Germany, doctors are enthusiastic about the benefits of ginkgo.  A combination of ginkgo and ginseng called Gincosan is claimed to produce very good results in elderly patients.

Chinese Medicine

Acupuncture

The Chinese consider acupuncture to be an effective therapy for Alzheimer's disease.  There is solid evidence that acupuncture increases certain neurotransmitters in the brain and can actually stimulate nerve regeneration.  Increased serotonin levels probably explain why acupuncture is so effective in controlling pain and managing stress.  Acupuncture also promotes blood circulation to the brain and improves memory and concentration so there is good reason for people who have Alzheimer's, or who are at risk for developing it, to try acupuncture.

Diet

Aspartame (Nutrasweet) Avoidance

Aspartame use has been reported to trigger symptoms of Alzheimer's disease.

Drug

NSAIDs

At least twenty studies suggest that Ibuprofen and other NSAIDs – common non-prescription drugs – may slow or prevent the onset of Alzheimer's disease by as much as 60%.  Researchers say it also opens up a new way to think about how Ibuprofen protects the brain.

"We've shown that a drug that's available, that's been in use for 30 to 40 years, and for which we know the side-effect profiles... can reduce both the inflammatory response to amyloid and the amyloid itself", says study leader Gregory M. Cole of the University of California in Los Angeles.

Note that NSAIDs can cause serious stomach problems, including bleeding.  Investigators therefore hesitate to recommend widespread use of the drugs until they can develop safer versions.

Certain NSAIDs work by decreasing the levels of amyloid-beta 42 rather than by inhibiting cyclooxygenase, as was once proposed.  Advil (Ibuprofen) is the most effective, requiring as little as 800mg per day to reduce the risk of Alzheimer's without serious side-effects.  Other NSAIDs require much higher doses to achieve this benefit, while aspirin, Naproxen and celecoxib (Celebrex) were found ineffective.

Laboratory Testing

Test for Hormones

Make sure estrogen and testosterone levels are normal.

Test for Heavy Metals

Avoid mercury, and detoxify if levels are found elevated.  See discussion of Melatonin for details.

Supplements

Phosphytidalserine

Although not a cure, placebo-controlled and double-blind studies involving patients with early Alzheimer's disease have shown mild benefits from 300mg per day of PS supplementation when used for three to twelve weeks.  In one double-blind study, the improvement on standardized tests of mental functioning averaged approximately 15%. [Fünfgeld EW, Baggen M, Nedwidek P, et al. Double-blind study with phosphatidylserine (PS) in Parkinsonian patients with senile dementia of Alzheimer's type (SDAT). Prog Clin Biol Res 1989;317:1235-46]  Continued improvement has been reported up to three months beyond the end of the supplementation period.

Note, however, that PS probably only slows the rate of deterioration rather than halting the progression altogether.  For example, in a six-month trial, benefits began to fade after the fourth month.

Vitamins

Vitamin E

Ensure sufficient antioxidant intake.  A study of more than 5,000 men and women found that people who consumed very high amounts of dark green, yellow, and red vegetables appear to reduce their risk of dementia by about 25%.  Several studies have shown that vitamin E, an anti-oxidant, can slow progression of Alzheimer's.

Preventive measures against Alzheimer's Disease:

Diet

Processed Foods Avoidance

Keep your weight down, and keep simple sugars and refined carbohydrates to a minimum.  Researchers have found that diabetes mellitus (for which these are risk factors) nearly doubles the risk of developing both vascular dementia and Alzheimer's disease.

Habits

Aluminum Consumption Avoidance

Alzheimer's Disease has been linked to a number of risk factors, including exposure to aluminum.  A study in France found that drinking water with high aluminum concentrations may indeed increase the risk of developing Alzheimer's and dementia.  High sources of aluminum in the diet include: aluminum cooking utensils, aluminum-containing antacids, and tap water (which may have aluminum sulfate added to remove particulate and organic matter). [American Journal of Epidemiology 2000;152: pp.59-66.]

The researchers determined that a concentration of aluminum in drinking water above 0.1mg/liter may be a risk factor for dementia and Alzheimer's disease.  2,698 individuals were followed for an 8-year period to identify new cases of probable Alzheimer's or other dementing illness.  The sample was divided into 75 drinking water areas, with surveys conducted to determine concentrations of aluminum, calcium, and fluorine in each water supply.  The study authors point out that their findings support those of several other studies linking aluminum to Alzheimer's, but add that "this result needs to be confirmed using a higher number of exposed subjects."

One of our doctors comments: This is another reason to make sure that you limit your water intake to filtered or bottled.  Aluminum is certainly an issue, but probably not as significant as chlorine exposure.  Unless you have well water you will also need a filter for your shower as most of us will absorb for more toxins from bathing or showering than we ever will from drinking tap water.

Aerobic Exercise

Stay physically active.  Patients with Alzheimer's disease have been found to have had lower levels of physical activity earlier in life.  Those who exercised regularly throughout life were less likely to contract the disease than those who were inactive.  Doctors caution that exercise does not guarantee immunity.

Hormone

Estrogen Replacement

Estrogen replacement therapy may help reduce the risk of developing Alzheimer's disease or delay its occurrence, but it does not help once disease is established.

One reason for the confusion is the use of synthetic estrogens: natural estrogens should exert a protective effect.  One study found that the risk of Alzheimer's disease and related dementia for women who had used estrogen was found to be about one third below that of women who had never used estrogen.  The risk also decreased with increasing dosage and duration of estrogen therapy.  The lowest risk was observed in long-term users taking high doses.

Suggestions that the decline in estrogen levels in women at menopause might somehow make them more vulnerable to the disease have prompted interest in the hormone as a possible treatment and research has suggested that women who take estrogen are less likely to develop Alzheimer's.

However, a new study found that once the mind-robbing disease sets in, the female hormone offers no benefit.  A year of estrogen did nothing to slow the progression of the disease or improve mental functioning in 120 older women with mild to moderate Alzheimer's.  Overall, the results of this study do not support the role of estrogen in the treatment.

In another study, women aged 60 and older were given either a low estrogen dose, a high dose or a placebo every day for a year.  Instead of showing any improvement, those taking estrogen in fact fared worse than the placebo group in a rating of dementia. [JAMA February 23, 1999 283: pp.1007-1015]

[One of our doctors comments: I am really surprised that this study did not receive more widespread news coverage.  When the drug companies had the initial studies published suggesting that estrogen will help protect against Alzheimer's it was all over the news.  I was immediately confronted by many patients who felt my recommendation to avoid estrogens was unwise.  Now the evidence is in that estrogen does NOT help Alzheimer's but actually worsens it.  I am delighted that JAMA continues to take a leadership role in publishing these landmark articles which refute the drug companies' position.  Unfortunately, the conventional media still appears to be sold out – hence the lack of notification of the results of this study.

There are times when estrogen is necessary.  I believe if phytoestrogens are unable to stop the hot flashes then it would be wise to use small amounts of estrogens to stop them.  Waking up every night with hot flashes is a surefire prescription for depression and increased risk of disease.  Thus in this case the estrogen is the lesser of two evils.  It should be used for the shortest time possible and always with the intent of weaning oneself off of it.]

Testosterone

The popular image of this sex hormone is primarily as a muscle-building machismo-inducing substance that "pumps men up", yet clinical research is uncovering important roles for testosterone in many other diverse areas of health and physiology, including the brain.  New evidence suggests that testosterone may enhance memory function and protect against the development of Alzheimer's disease.

Neuroscientists from Rockefeller University and Weill Medical College of Cornell University recently discovered that when neural cells from the brains of rats are exposed to testosterone, the cells don't produce as much Amyloid beta-peptide (AB-peptide).  The accumulation of AB-peptide can cause plaque deposits to form in the brain.  These deposits are believed to play a major role in the development of Alzheimer's disease.

Testosterone in addition appears to improve certain cognitive abilities in men, such as verbal and spatial memory function.  Levels of bioavailable testosterone are especially important, researchers emphasized, because these levels decline most rapidly as men and women age.

Since high levels of testosterone have been linked with prostate cancer in men and endometriosis in women, however, they urged caution when using replacement therapy, carefully weighing the risks and benefits for each patient.

Increasing levels of adrenal hormones such as cortisol, which rise in response to stress and aging, may also play an important role in Alzheimer's.  High levels of these hormones can damage the hippocampus region in the brain, causing
learning impairment and memory loss.  Testosterone, however, shows the potential to reverse some of this damage.

Melatonin

Melatonin, a powerful antioxidant and heavy-metal-chelating agent, has been shown to protect against heavy metal exposure which is in turn implicated in Alzheimer's Disease.  Ensuring normal melatonin levels therefore has a protective effect.

After exposing nerve cells to inorganic mercury, neurobiologists observed a toxic reaction that reduced cellular levels of the antioxidant glutathione by 30%, triggered the release of plaque-forming β-amyloid peptides, and spurred the hyperphosphorylation of tau-protein – all pivotal mechanisms in the development and progression of Alzheimer's.

However, they found that if the cells were first incubated with melatonin – a powerful antioxidant and heavy-metal-chelating agent – they were protected from these damaging effects.  In fact, despite being exposed to toxic doses of mercury, the cells treated with melatonin often showed metabolic status comparable to that of mercury-free cells.

These results provide strong experimental evidence that mercury toxicity may be involved in Alzheimer's development and that melatonin shows a marked potential to neutralize this toxic-induced pathology, by boosting antioxidant defense and binding to heavy metals.

Mineral

Zinc

Maintain adequate zinc status: Reduced levels of zinc are being linked to Alzheimer's disease.  In one study, 38 elements were evaluated by neutron activation and mass spectrometry in the post-mortem brain tissue of eleven Alzheimer's patients and six controls.  An increase was found in aluminum, silicon and calcium; a significant decrease was found in zinc and selenium.  The lower level of zinc in all areas of the tissue studied correlates with reports indicating low serum levels of zinc in other dementia studies. [Reduction of Zinc and Selenium in Brain Alzheimer's Disease: Corigan, et al., Trace Elements in Medicine, 91;8(1): pp.1-5]

Selenium

See the link between Alzheimer's Disease and Zinc.

Supplements

DHA (docosahexaenoic acid)

Over 1200 patients participated in an epidemiological study which showed that people with high DHA levels were 45% less likely to develop dementia than people with low DHA levels.  This suggests that proper DHA intake may reduce the risk of developing Alzheimer's.

Vitamins

Folic Acid

There is growing evidence suggesting that low blood folate levels can increase the risk of getting Alzheimer's.

In an ongoing study searching for new clues to the aging process, researchers took blood samples of nuns between the ages of 78-101 years old living in a convent in Mankato, Minnesota.  After 30 of the nuns died, researchers examined their brains for signs of atrophy and compared the results with previous blood nutrient levels.

In brain samples showing numerous Alzheimer's disease brain lesions, researchers found that significantly lower blood levels of folate corresponded with more severe atrophy of the neocortex, the region of the brain containing a rich supply of nerve cells.

Although the study was small, and did not attempt to prove a causal effect, it supports previous evidence linking defects in B-vitamin metabolism with age-related dementia and Alzheimer's.  "Optimal folate concentration may in fact be higher in old age or when diseases such as Alzheimer's are present," commented the researchers.

Low folate levels can trigger a build-up of the amino acid homocysteine, which has been linked to higher risk of Alzheimer's and accelerated atrophy of the medial temporal lobe in Alzheimer's patients.

"There seems little doubt now that there is an association between the evolution of certain brain diseases associated with cognitive decline in the elderly and vitamin deficiencies associated with hyperhomocysteinemia," a related editorial resounded.

Although the full extent to which B-vitamin metabolism influences the actual causal mechanisms of dementia is still not clear, "the potential therapeutic options [implicated by these discoveries] are exciting", the authors posited.

The nuns provided a unique population sample to study because they all had similar long-term diet and exercise habits.  Researchers found strong evidence of biochemical individuality among the group, despite their similar lifestyle and eating habits.  Blood nutrient levels varied widely, reflecting differences in "drug-nutrient and disease-nutrient interactions or differences in the intake, absorption, and metabolism of the nutrients."

NOTE: As this study suggests, even people with similar diets may show striking differences in nutrient metabolism related to various physiological functions.  Assessing each patient is the best way to gauge the effectiveness of nutrient intervention strategies.

References:

Snowdon DA, Tully CL, Smith CD, Riley KP, Markesbery WR.  Serum folate and the severity of the atrophy of the neocortex in Alzheimer disease: findings from the Nun Study.  Am J Clin Nutr 2000;71: pp.993-8.

Weir DG, Molloy AM.  Microvascular disease and dementia in the elderly: are they related to hyperhomocysteinemia?  Am J Clin Nutr 2000;71: pp.859-60.

Vitamin C (Ascorbic Acid)

Both vitamin E and vitamin C supplements reduced the incidence of Alzheimer's disease in a 1998 study.  This study followed 655 individuals over 65 years of age for an average of over 4 years.  The anticipated rate of Alzheimer's did not occur in those individuals taking larger amounts of either vitamin.  The lower levels of vitamin C and E found in some supplements did not provide this protection in this study.  A reasonable protective benefit could be expected with 400 IU of vitamin E or 500mg or more of vitamin C. [Alzheimer Dis. Assoc. Disord.1998:12(3): pp.121-126]

Vitamin B12 (Cobalamine)

Low levels of vitamin B12 have been linked to an increased risk Alzheimer's disease. [Neurology, May 2000]  It remains unclear as to whether B12 supplementation will reduce the risk.

Vitamin B-Complex

Optimize your B-complex status, especially folic acid and B12.  In one study, 76 Alzheimer's patients had lower blood levels of folic acid and vitamin B12 than 108 age-matched control subjects.  In addition, researchers found that Alzheimer's patients had higher blood levels of homocysteine, which is already implicated in atherosclerosis.  Folic acid and B12 supplementation is known to reduce homocysteine levels.

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