Alzheimer’s Disease & Dementia

Introduction

Dementia : Dementia is an overall term used to describe a group of symptoms that impact memory, performance of daily activities, and communication abilities.
Dementia is a syndrome, not a disease – usually of a chronic or progressive nature – that leads to the deterioration in cognitive function (i.e. the ability to process thought) beyond what might be expected from the usual consequences of biological ageing. It affects memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgement. However, consciousness is not affected. 
Alzheimer’s Disease: Alzheimer’s disease is the most common type of dementia.
Alzheimer’s disease gets worse with time and affects memory, language, and thought. Although symptoms of the two conditions may overlap, distinguishing them is important for management and treatment.

What should I know about Dementia and Alzheimer’s Disease?

As baby boomers age and the senior population swells, more people than ever before are faced with the impact of aging on the brain. Loss of memory and thinking ability is one of aging’s most tragic consequences. Without memory, we lose our sense of identity and relationship to the world around us. A haunting song about aging recorded by Simon and Garfunkel in the 1960s ends with the words: “Preserve your memories, they’re all that’s left you.” How sad that so many people spend their final years with few memories left intact.

Senile dementia is the medical term for senility, the gradual loss of mental function that so often occurs with aging. Alzheimer’s disease, the most common form of senile dementia, accounts for more than 60 percent of the cognitive function disorders in the aging population. Alzheimer’s disease is a progressive condition that results in a slow deterioration of memory, reasoning, and behavior. The loss of intellectual function interferes with daily life, and after a disease course that may last many years, eventually results in death. Death is usually due to factors such as malnutrition, complications of the immune system such as pneumonia or infection, injury, and even choking. (1)

Alzheimer’s is a debilitating disease that causes severe degeneration of brain tissue. Plaque deposits accumulate in the spaces between brain cells. The cells themselves form twisted, spaghetti-like masses called “neurofibrillary tangles.” Why these changes happen in the brains of some people but not others remains a matter of speculation. Scientists are unsure as to which of these abnormalities occurs first, the plaque or the tangles. What triggers them in the first place is not known for certain.

One leading theory involves a protein called “amyloid” that builds up on the surface of brain cells in Alzheimer’s sufferers. An especially sticky form of amyloid protein fills up the plaque deposits observed in Alzheimer’s disease. As the amyloid laden plaque deposits grow, they trigger an inflammatory immune reaction that begins to destroy the surrounding brain neurons. (2) Amyloid synthesis is controlled by an enzyme called “secretase.” Researchers are now developing a class of drugs called secretase inhibitors that may be able to inhibit excess production of amyloid in people with Alzheimer’s disease. (3)

Another theory centers around a protein called “tau” which functions as structural support for brain cells. Like all neurons, brain cells contain long fibers neatly arranged in bundles that look a bit like cable wire. These fibers contain tiny, tube-like structures called microtubules. Chemical changes cause tau to alter it shape, resulting in distortion of the microtubules. As the microtubules twist and tangle up, the surrounding cells begin to shrink and die, forming the useless “neurofibrillary tangles” which are the distinctive characteristic of Alzhheimer’s disease. (4)

Another hallmark of Alheimer’s is a decline in production of the neurotransmitter acetylcholine, which regulates many memory-related functions. (5) Heredity may also play a role in some cases. (6)

Past research has implicated aluminum toxicity in the brain as a possible cause of Alzheimer’s disease, but this remains unproven. Animals exposed to aluminum develop both symptoms and brain lesions that resemble those found in patients with Alzheimer’s disease. (7) Exactly how aluminum may contribute to the disease has not been determined. Aluminum may cause inflammation in the brain by triggering the formation of cell-damaging molecules called “free radicals.” There is evidence that aluminum may be a nerve toxin. (8)

In its beginning stages, Alzheimer’s can be a difficult disease to spot; the changes in memory and behavior are barely noticeable at first. The disease may worsen within the first several years or take as long as twenty to progress. Average survival time after diagnosis is generally four to eight years. Memory loss gradually worsens, along with a decline in ability to perform routine daily tasks. Late stage Alzheimer’s sufferers experience increasing disorientation, impaired judgment, personality changes, difficulty in learning, and a loss of language skills. As yet, there is no cure for Alzheimer’s disease.

Rates of dementia

World Health Organization, 2021

Worldwide, around 55 million people have dementia, with over 60% living in low- and middle-income countries. As the proportion of older people in the population is increasing in nearly every country, this number is expected to rise to 78 million in 2030, and 139 million in 2050. There are nearly 10 million new cases every year. Alzheimer’s disease is the most common form of dementia and may contribute to 60-70% of cases.

Statistic

Alzheimer’s Research Trust, 2005.

  • Worldwide, there is a new case of dementia every seven seconds.
    More than 24.3 million people are currently estimated to have dementia, and 4.6 million new cases are diagnosed each year.
    60 percent of people with dementia live in developing countries.
    Rate of dementia is expected to double between 2001 and 2040 in developed nations, it is forecast to increase by more than 300 percent in India and China.
  • WHO estimates the number of anaemic people worldwide to be a staggering two billion and that approximately 50% of all anaemia can be attributed to iron deficiency.

Alzheimer’s Disease Foundation (Malaysia), 2007.

  • Estimated that there are currently about 50,000 people with Alzheimer’s Disease in Malaysia.

Alzheimer’s Association Statistical Update, 2005.

  • Approximately 4.5 million Americans have Alzheimer’s disease. The number of Americans with Alzheimer’s has more than doubled since 1980.
  • 14 million Americans will have Alzheimer’s disease by the middle of this century unless a cure or prevention is found.
  • One in 10 persons over 65 and nearly half of those over 85 have Alzheimer’s disease.
  • Alzheimer’s disease costs the U.S. at least $100 billion a year.
  • A person with Alzheimer’s disease will live an average of eight years.

Signs and Symptoms

As the disease progresses, these symptoms begin to occur with increasing frequency. In the earlier stages of the disease, people with these conditions may forget how to do simple tasks, such as brushing their teeth or combing their hair. 

During the more advanced phases, logical and rational thinking processes decline and they begin to have problems speaking, understanding, reading, or writing. People with advanced dementia or Alzheimer’s disease may become anxious or aggressive, or wander away from home. Eventually, patients may require total nursing care.

Dementia affects each person differently, depending upon the underlying causes, other health conditions, and the person’s cognitive functioning before becoming ill. The signs and symptoms linked to dementia can be described into three stages.

Mild symptoms (early onset/stage)

The early stage of dementia is often overlooked because the onset is gradual. Common symptoms may include:

  • Confusion and forgetfulness
  • Getting lost in familiar surroundings
  • Losing track/disoriented of time

Intermediate symptoms (intermediate onset/stage)

As dementia progresses to the middle stage, the signs and symptoms become clearer and may include:

  • Forgetful of recent events and people’s names 
  • Difficulty in performing normal daily activities, such as brushing teeth, bathing, combing hair, and feeding,  being confused at home/familiar place or needing help with personal care
  • Increased anxiety and agitation
  • Disturbed sleep patterns
  • Wandering and pacing
  • Repeated questioning
  • Increased difficulty with name and face recognition of family and friends.

Severe symptoms (late onset/stage)

The late stage of dementia is when a sufferer nears a total dependence and inactivity. Memory disturbances are serious and the physical signs and symptoms become more obvious and may include:

  • Unaware of time and place
  • Difficulty in recognising relatives and friends 
  • Difficulty in walking
  • Loss of speech, writing skills and comprehension
  • Behavioural changes that may escalates 
  • Aggression
  • Loss of bladder and bowel control
  • Require full-time care or increasing need for assisted self-care

Treatment Options

Conventional

In the early stages of Alzheimer’s disease, a class of drugs called “ACE” inhibitors” can be used to reverse memory loss and improve mental function. ACE inhibitors are only effective for about 3 years after the disease has been clinically diagnosed, and they do not halt or slow the neurological deterioration. Although all ACE inhibitors work about as well, some have more side effects than others. (9)

Nutritional Supplementation

Choline
Alzheimer’s disease primarily affects “cholinergic” neurons in the cerebral cortex of the brain. Activity of these neurons is largely governed by the neurotransmitter “acetylcholine.” Animal studies suggest cholinergic neurons control learning and memory. In Alzheimer’s, the enzyme that produces acetylcholine becomes defective, resulting in a shortage of this neurotransmitter. In theory, supplying the body with nutritional sources of choline such as lecithin might be helpful for Alzheimer’s sufferers. Clinical trials using supplements of choline and phosphatidylcholine extracted from soy lecithin have been disappointing, however. (10) , (11)

Phosphatidylserine
Phosphatidylserine is a “phospholipid” derived from lecithin that has proved mildly effective in early Alzheimer’s disease and dementia. Phospholipids are fat-like, phosphorus-containing substances that form the structural framework of cell membranes. Brain cell membranes are especially rich in phosphatidylserine. Acting like a “master switch” for membrane functions, PS coordinates various enzymes and proteins that allow brain cells to communicate. (12)

In one trial, 51 people with early stage Alzheimer’s took either 300 mg of phosphatidylserine or a placebo (dummy pill) daily for 12 weeks. PS had a mild therapeutic effect, improving several measures of mental function. (13)

In another trial, patients suffering from senile dementia were given phosphatidylserine for 60 days. At the end of the study, the PS-treated patients showed improvements in memory and mental ability, and these gains continued for some time after they discontinued taking it. (14)

In a 6-month study giving PS to Alzheimer’s patients, results seen after 8 and 16 weeks faded toward the end of the treatment period. These results seem to suggest phosphatidylserine provides mainly short-term benefits that disappear as the disease worsens. (15)

Acetyl-L-Carnitine (ALC)
Acetyl-L-Carnitine is an amino acid that plays a key role in the metabolism of fats. Produced in the body from the dietary amino acids lysine and methionine, carnitine facilitates the conversion of fat into cellular energy and removes the metabolic waste products that accumulate during fat metabolism. L-carnitine and its cousin, acetyl-L-carnitine, have shown usefulness in the treatment of Alzheimer’s disease and dementia. (16)

Acetyl-L-carnitine is another nutritional precursor for acetylcholine, making it potentially beneficial for people with acetylcholine deficiencies. Animal studies indicate that acetyl-L-carnitine also promotes energy production in cells and reverses age-related changes in cellular membranes.

Recent studies suggest that malfunctions in cellular energy production contribute to brain cell damage in Alzheimer’s disease. Acetyl-L-carnitine, by protecting the cellular energy-generating machinery, may help slow the degeneration of brain cells. (17)

Vitamin E
Evidence suggests that free radicals–unstable molecules that disrupt cell membranes—contribute to cellular degeneration in Alzheimer’s disease. Amyloid, the protein mentioned earlier that occurs abundantly in the brains of Alzheimer’s disease patients, inflicts free radical damage on brain cells. Vitamin E is one of the major dietary antioxidants, which are nutrients that neutralize free radicals. In animals, vitamin E has successfully prevented the free radical injury caused by amyloid and delayed memory loss.

In one clinical trial, a group of individuals with moderately advanced Alzheimer disease took 2000 IU vitamin E daily. The results indicated that vitamin E might slow mental and psychological decline and help the Alzheimer’s sufferer function well enough to delay placement in a nursing home. (18) , (19)

A long-term study that followed 633 individuals aged 65 for an average of 4.3 years suggests that vitamin E may lower the risk of developing Alzheimer disease. (20) In this group, 27 individuals were taking high doses of supplemental vitamin E, and none developed Alzheimer’s.

Vitamin C
Low blood levels of vitamin C have been seen in people with Alzheimer’s. Vitamin C levels were lowest in those with the greatest declines in mental function. These low vitamin C measurements were not connected to the dietary intake of vitamin. This implicates free radicals in the cell damage that occurs in Alzheimer’s since free radicals use up the body’s vitamin C supplies. (21)

In the long-term research study mentioned earlier that found no Alzheimer’s cases among vitamin E users, none of 23 subjects taking vitamin C developed the disease. (22)

Herbal Supplementation

Ginkgo
In China, the medicinal use of Ginkgo leaf as a brain tonic dates back 4,000 years. Ginkgo biloba extract is the most frequently prescribed herbal medicine in Europe, and it ranks high on the list of America’s most popular herbal supplements. Ginkgo is also one of the world’s most extensively researched herbs, with more than 100 clinical studies to its credit. Virtually all of these clinical trials have used a standardized extract of Ginkgo biloba that contains a concentrated amount of substances in the leaf called “flavonglycosides” and “terpene lactones.” These active ingredients are flavonoid-like compounds that may enhance the health of the circulatory system. They neutralize free radicals, keep the blood from thickening, improve delivery of oxygen and nutrients to the brain, and strengthen blood vessel tissues. (23) There is evidence that Ginkgo improves function of the “cholinergic” neurons, the brains cells that suffer destruction in Alzheimer’s disease. (24)

This research shows that Ginkgo is a brain tonic: it increases brain circulation, improving memory and mental function. There is good evidence that Ginkgo may reverse the effects of aging on the brain, reduce senility, and perhaps delay the onset of Alzheimer’s disease. (25) , (26) , (27) , (28)

However not all the research supports these claims. In a study involving over 200 patients, a standardized ginkgo preparation (40mg three times a day) was compared to placebo. The gingko was reported safe and capable of stabilizing and improving mental and social functioning for up to a year. (29) Another trial involving over 200 patients, compared the same gingko preparation with placebo and reported no advantage with the gingko when used for 24 weeks. (30) A third trial compared 115 people over 60 years old using ginkgo to 115 people over 60 years old using placebo. The study evaluated these participants using 15 different tests for memory and learning. The results of this study showed no improvement in the tests for both the ginkgo and the placebo group. (31)

Huperzine A
Huperzine A is an extract from a club moss (Huperzia serrata) that has been used for centuries in Chinese folk medicine for conditions such as blood loss, fever, urinary troubles, and irregular menstruation. (32) Modern research, mostly done in China, has focused on huperzine’s potential benefits for improving in memory and learning ability.

Studies suggest huperzine A may benefit patients with Alzheimer’s disease and dementia. (33) Huperzine A inhibits an enzyme in the body that breaks down acetylcholine, as effectively as some drugs used for this purpose. (34) , (35) , (36) Acetylcholine is involved in memory and learning; inhibiting the enzyme that destroys it makes more of the neurotransmitter available to stimulate neurons. This casts huperzine A as a potentially valuable herbal extract in Alzheimer’s disease, where acetylcholine is in short supply. (37) , (38)

Animal studies have reported improvement in impaired learning and memory with huperzine A. (39) , (40) Several human studies have been done over the past few years in China and the United States. (41) , (42) , (43)

Vinpocetine
Vinpocetine is a synthetic product derived from vincamine, a substance found in the periwinkle plant. European physicians have used vinpocetine for more than 20 years to treat symptoms caused by poor brain circulation. (44) , (45) , (46) , (47)

An extensive amount of research has produced some fairly detailed information about how vinpocetine works. It improves circulation in the brain and helps the brain utilize oxygen more efficiently, protecting brain tissue against oxygen starvation. It acts a calcium channel blocker to help relax blood vessels in the brain and increase blood flow. Vinpocetine also has antioxidant properties that may help reduce damage to brain cells from free radicals. (48) , (49) , (50) , (51) , (52) , (53)

In several double-blind trials, vinpocetine has enhanced memory, learning, and mental performance in people suffering from mild-to-moderate dementia due to poor circulation. (54) , (55) , (56) In the only double-blind trial conducted to date testing vinpocetine’s effect on Alzheimer’s disease, no significant benefits were noted. (57)

Bacopa
Bacopa, or water hyssop, is a plant used since around the sixth century A.D. in the traditional Ayurvedic medical system of India as a brain and nerve tonic. The ancient Ayurvedics physicians called Bapoca “Brahmi,” reflecting the high value they placed on this herb. Bacopa has been traditionally used for epilepsy, mental illness, and to improve memory and mental capacities. (58) The herb’s active ingredients, a group of compounds called “bacosides,” have been shown to boost nerve impulse transmission and thereby strengthen memory, and mental function. Bacopa was found to increase learning ability in laboratory animals. (59) Clinically, bacopa has been reported to be a useful agent for improving learning and behavio behavior in children. In adults, bacopa has effectively reduced anxiety levels, improved memory and elevated mental performance. (60)

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