Myths and Facts: Alzheimer’s Disease

It’s an alarming statistic: 5.3 million Americans have Alzheimer’s disease (AD).¹ But, that statistic belies reality: It’s estimated that only one in four Americans with AD has been diagnosed.² It is a disease that develops in someone every 67 seconds. And, the figure rises each year, with an expected 7.1 million people with AD by 2025 — a 40 percent increase. As the numbers rise, so do the costs. In 2015, AD and other dementias cost the nation $226 billion. That number in 2050 is expected to rise to $1.1 trillion.¹

The sixth-leading cause of death in the U.S., AD affects twice the number of women as men and more African-Americans and Hispanics, even though there are more non-Hispanic whites living with the disease than any other racial or ethnic groups.¹ Sadly, how AD develops and how it impacts those living with it is clouded by many misconceptions about the disease, which stands in the way of helping those affected.

Separating Myth from Fact

MYTH: AD and dementia are the same disease.

FACT: While the terms “Alzheimer’s” and “dementia” are often used interchangeably, they are very different. Dementia is an umbrella term for a group of symptoms that result in trouble with learning and memory.3 And, dementia is caused by many things, including AD (as many as 50 percent to 70 percent of all dementia cases are caused by AD), Huntington’s disease, Parkinson’s disease and Creuzfeldt-Jakob disease. Some forms of dementia are temporary or they can be reversed, but with AD, that is not the case.⁴

MYTH: Memory loss is AD.

FACT: AD is much more than memory loss. Some memory loss is a normal part of aging. But, memory loss can also be caused by many other things such as medication side effects, vitamin deficiencies and other types of dementia.⁵

With AD, damage to the brain starts a decade or more before memory and other cognitive problems become evident, when people seem to be symptom-free. But, during this time, toxic changes are taking place in the brain. Abnormal deposits of proteins form amyloid plaques and tau tangles throughout the brain, and once-healthy neurons stop functioning, lose connections with other neurons and die. The damage initially appears to take place in the hippocampus, the part of the brain essential in forming memories, which can be one of the first signs of AD. But as more neurons die, additional parts of the brain are affected, and by the final stage of AD, damage is widespread, and brain tissue has shrunk significantly.⁶ The Alzheimer’s Association has identified 10 early signs and symptoms of AD: 1) memory loss, 2) challenges in planning or solving problems, 3) difficulty with completing familiar tasks, 4) confusion with time or place, 5) trouble understanding visual images and spatial relationships, 6) new problems with words in speaking or writing, 7) misplacing things and losing the ability to retrace steps, 8) decreased or poor judgment, 9) withdrawal from work or social activities and 10) changes in mood and personality.⁷

MYTH: All older adults develop AD.

FACT: While most people who develop AD are over age 65, AD isn’t a normal part of aging. And, although a person’s risk of developing AD doubles every five years after 65, nearly half of 85-year-olds don’t have the disease.³

MYTH: Only seniors develop AD.

FACT: AD does most commonly occur in older adults, yet it can also affect people in their 30s, 40s and 50s. Approximately 90 percent of AD cases are called late-onset, meaning they occur after age 65. But, one in 10 cases occurs before age 65, known as early-onset AD.⁸

MYTH: AD is hereditary.

FACT: Less than 5 percent of all cases of AD are “familial Alzheimer’s,” a type that runs in families,3 but genes do play a role. Indeed, several genes associated with late-onset and early-onset AD have been identified in recent years.

In late-onset AD, the most common gene is apolipoprotein E (APOE), which has three common forms: APOE e2 is the least common and appears to reduce the risk of AD; APOE e4 is more common and appears to increase the risk of AD; and APOE e3 is the most common and doesn’t seem to affect the risk of AD. The APOE gene can be inherited from both the mother and father. Inheriting at least one APOE e4 gene increases risk of developing AD. With two APOE e4 genes, the risk is even higher. Yet, not everyone who has one or two APOE e4 genes develops AD. What’s more, the disease develops in people with no APOE e4 gene. In addition, with continuing research into the genetics of AD, five other genes have been identified. Some variations of SORL1 on chromosome 11 appear to be associated with AD. The CLU gene, which helps to regulate the clearance of amyloid-beta from the brain, suggests an imbalance that is central to the development of AD. A deficiency of the protein in the CR1 gene may contribute to chronic inflammation in the brain, which is a possible factor in the development of AD. The PICALM gene is linked to the communication process between the brain and nerve cells, suggesting the proper functioning of this gene is necessary. And, rare variants in the recently identified TREM2 gene, which regulates the brain’s response to inflammation, are associated with an increased risk of AD.

Mutations in three genes that cause early-onset AD have also been identified: amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). Mutations in these genes cause excessive amounts of the toxic amyloid-beta peptide protein, which cause tau protein malfunctions and the formation of neurofibrillary tangles that cause the brain cells to die.⁹

Most recently, a team of scientists discovered an immune system gene associated with higher rates of amyloid plaque buildup in the brains of AD patients and older adults at risk for the disease. Using positron emission tomography (PET) imaging in nearly 500 individuals, researchers assessed the levels of brain amyloid deposits at an initial visit and again two years later. Subsequently, a genome-wide analysis was conducted to identify genetic variants associated with the rate of plaque accumulation during the two-year window. As predicted, APOE e4 was found to be associated with higher rates of plaque buildup. But what was surprising is the finding that IL1RAP, which codes for the key immune signaling factor interleukin-1 receptor accessory protein, showed an independent and even stronger influence on amyloid accumulation. They also found that the amyloid-associated IL1RAP variant was associated with a lower level of microglial activity as measured by PET scans, greater atrophy of the temporal cortex (a region of the brain involved with memory), faster cognitive decline and greater likelihood among study participants of progression from mild cognitive impairment to AD.¹⁰

MYTH: AD can be caused by flu shots, depression, aluminum, silver fillings and aspartame.

FACT: The truth is that experts don’t really know what causes AD. It’s likely a mixture of genes, environmental factors and lifestyle. And, some research suggests it might be related to health conditions such as heart disease, high blood pressure and diabetes.¹¹

Depression can easily be mistaken for a cause of AD since it often occurs with symptom onset, and the changes in abilities brought on by AD cause fear.⁸

The theory that flu shots cause AD is due to the small amount of mercury in thimerosal, the preservative that is still contained in some flu vaccines. But, several studies debunk that theory and show that flu shots and other vaccines actually reduce the risk of AD and lead to overall better health.⁵ One study conducted in 2001 with 4,392 participants showed that there was a decreased risk of developing AD for those who had received influenza immunizations, as well as for those who received vaccinations for diphtheria or tetanus (which were grouped together in the research) or poliomyelitis (polio). While it didn’t actually show that the flu vaccine was what caused a lower risk of AD, it did indicate that those who received the vaccine were less likely to develop AD, and those who didn’t were more likely to develop AD. In addition, a study published in the Journal of the American Medical Association in 2004 showed that annual flu shots for older adults were associated with a reduced risk of death from all causes.¹²

Mercury is also at the root of the theory that silver dental fillings increase the risk of AD. Silver fillings are made of an amalgam mixture that typically contains about 50 percent mercury, 35 percent silver and 15 percent tin. But, once again, studies show no relationship to AD. The most recent study was conducted in 2003, which found no connection between mercury-containing dental fillings and Alzheimer’s or other neurological diseases.

Lastly, in May 2006, the U.S. Food and Drug Administration (FDA) reported that of the more than 100 laboratory and clinical studies conducted to determine if aspartame causes memory loss, none had presented any scientific evidence of it.⁵

MYTH: AD can be prevented.

FACT: It’s really not yet known what can prevent AD, and there is certainly no single treatment to prevent it. It has been purported that taking supplements can help inhibit AD, but studies conducted on vitamins E, B and C, ginkgo biloba, folate and selenium have been inconclusive.¹³

Many things, however, can be done to protect the brain such as building brain power by learning new skills, exercising daily and maintaining a busy social life.³ The National Institute on Aging (NIA) and other public and private agencies have conducted observational and animal studies associated with changes in AD risk. In recent years, these studies have suggested there may be a connection between high levels of blood cholesterol and the development of AD. On the flip side, some studies have shown that statins, the most commonly prescribed cholesterol-lowering drugs, may reduce the risk of dementia (although other studies have found no relationship). Yet, other studies have found that high levels of the amino acid homocysteine, which are known to increase heart disease risk, are associated with an increased risk of developing AD. Studies in mice have shown that the amino acid can make neurons stop working and die. A current NIA-funded study is investigating whether reducing homocysteine levels with folic acid and vitamins B6 and B12 supplements will slow the rate of cognitive decline in older adults with AD. But only future clinical trials will reveal whether any of these factors can help to prevent AD. And, those factors may vary from individual to individual, especially if a person has a risk factor gene.¹⁴

MYTH: There is a test for AD.

FACT: There is no test that can definitively diagnose AD. The only conclusive diagnosis of AD is at death, when microscopic examination of the brain reveals the characteristic plaques and tangles. However, to distinguish AD from other causes of memory loss, physicians rely on personal and medical history, blood tests, neurological tests and some imaging tests. The physical exam is used to determine overall neurological health by testing reflexes, muscle tone and strength, the ability to get up from a chair and walk across a room, sense of sight and hearing, coordination and balance. Blood tests help to rule out other causes of memory loss and confusion such as thyroid disorders or vitamin deficiencies. Neurophysical testing may include a brief mental status test or a more extensive assessment of thinking and memory. Magnetic resonance imaging can be used to rule out other conditions and to assess whether there is shrinkage in brain regions implicated in AD. Computerized tomography is used to rule out tumors, strokes and head injuries. And, a PET scan can show which parts of the brain aren’t functioning well, with new techniques able to detect the levels of plaques and tangles in the brain.¹⁵

Researchers are also working to develop new diagnostic tools to help diagnose AD, including additional approaches to brain imaging, more sensitive tests of mental abilities and measurement of key proteins or protein patterns in blood or spinal fluid.¹⁵ Better testing is needed since a diagnosis of AD can be delayed or missed because it is often associated with the normal aging process, and early symptoms develop gradually.¹⁶ In fact, AD can develop 20-plus years before memory loss.³ AD can also be over-diagnosed because it mimics other conditions such as transient ischemic attack, depression, vascular dementia, Creutzfeldt-Jacob disease, brain tumor, hydrocephalus and other problems.¹⁶

This is why early detection is a key focus of research today. The earlier AD can be identified, the better the effectiveness of existing medications. At the University of Alberta, Canada, a student has developed a potential new test that uses a form of protein analysis called liquid chromatography-mass spectrometry to analyze saliva samples to determine what substances are predominant in the saliva of AD patients. Results suggest that higher levels of certain substances present in the blood of AD patients can predict “worse episodic memory performance” and “slower speed in processing information.”

Other areas of research include sampling cerebrospinal fluid, which offers protection to the brain and spinal cord. And, PET scan technology has made it possible to isolate tau tangles in the brain to help understand how advanced a person’s disease may be. The scan can also be used to track inflammation, whose role in AD is still being investigated, as well as microglial cells, the brain’s immune cells, to get a better picture of brain health.¹⁷

MYTH: AD can be treated.

FACT: Currently, there is no treatment to indefinitely delay or stop the progression of AD. However, FDA has approved five medications that may help slow the progression of AD temporarily, but they work in only one in three people for a period of six months to a year.⁵ These drugs, which include donepezil (Aricept), galantamine (Razadyne), memantine (Namenda), rivastigmine (Exelon) and tacrine (Cognex), help with thinking, memory, language skills and some behavioral problems.¹¹

Because of the progress in understanding healthy brain function and what goes wrong in AD, there are some promising targets for next-generation drug therapies under investigation. These include trials for drugs targeting beta-amyloid (the chief component of plaques), tau protein (the chief component of tangles), inflammation (another key AD brain abnormality) and insulin resistance (the way brain cells process insulin may be linked to AD). There are also clinical trials in progress for brain imaging studies and testing of blood or spinal fluid to reveal AD biomarkers.

For individuals with rare genetic mutations, the Alzheimer’s Prevention Initiative (API) in Antioquia, Colombia, South America, is investigating the world’s largest family in which a gene for familial AD (also known as autosomal-dominant AD) has been identified. API’s first clinical studies will test therapies targeting beta-amyloid in family members who are known to have the AD-causing gene but who have not yet experienced symptoms.18

Several studies investigating the possibility of treating AD with intravenous immune globulin (IVIG) have shown mixed results. Both preclinical and clinical studies have shown that “IVIG has anti-amyloid and immune modulatory properties relevant to treating neurodegenerative disorders.” In early stage AD clinical trials, IVIG reduced cognitive decline and increased brain glucose metabolism. Unfortunately, IVIG failed to meet primary outcome objectives in the Phase III clinical trial in mild to moderate AD. However, positive cognitive signals were observed in pre-planned subgroup analyses among APOE e4 carriers and moderately impaired AD patients. In these patients, biomarker studies revealed dose-dependent increases in plasma and cerebrospinal fluid immunoglobulins and decreases in beta amyloid-42 levels.¹⁹

While results of clinical trials to date don’t currently support the use of IVIG to treat AD, additional studies are being conducted. In October, researchers found that IVIG reduced brain atrophy and cognitive decline in patients in the early, pre-dementia phase of AD. The trial, administered from 2011 to 2013, included 50 patients aged 50 years to 84 years who were diagnosed with amnestic mild cognitive impairment due to AD. Participants were administered either IVIG or saline solutions every two weeks for a total of five infusions. Brain imaging was conducted at baseline, at 12 months and at 24 months. The images at 12 months for those who received IVIG showed less brain atrophy than those who were given the placebo. In addition, those who were treated with IVIG showed better cognitive testing results, and there were fewer conversions to dementia after 12 months. However, differences in the treatment groups faded by 24 months, which prompted the researchers to propose that annual infusions of IVIG may be necessary to sustain treatment effects. Additional research will be needed to prove this.²⁰

MYTH: AD symptoms are reversible.

FACT: AD is deterioration of the brain, and it can’t be reversed. In fact, no amount of effort such as physical activity or cognitive exercises will reverse AD. It is believed that those who think it is reversible may have known someone who was misdiagnosed with AD and then correctly treated for another condition such as thyroid problems, vitamin deficiency, depression and even medication. It’s also possible that people may misinterpret the advertising for AD disease medications, which provide a more subtle stabilization of symptoms rather than dramatic symptom relief.⁸

MYTH: An AD diagnosis means life is over.

FACT: Many people with AD can improve their quality of life and slow AD progression for years by eating a heart-healthy diet, exercising regularly, staying socially connected and doing things that challenge the brain.¹³ There are also other ways to improve daily life for those with AD. Keeping a routine helps because people with AD tend to prefer a familiar schedule and settings. Since crowds and noise can easily overwhelm people with AD, limiting the amount of sound and movement can help. Spending time on familiar tasks and hobbies can make them feel productive and happy. Caregivers can take some control of everyday choices to relieve the stress of making decisions. And, because people with AD can become more upset at night (called sundowning), caregivers can help by turning on more lights and showing concern by not dismissing fears.²¹

MYTH: AD isn’t fatal.

FACT: AD is the sixth-leading cause of death in the U.S., with most people living only eight to 10 years after diagnosis. It is a progressive disease that causes people to forget to drink and eat, have trouble swallowing, can lead to a severe shortage of nutrients, can cause breathing problems and can lead to pneumonia. AD is also associated with high-risk behavior such as wandering into dangerous situations.¹¹

MYTH: Caregivers don’t need help to care for their loved ones with AD.

FACT: Many caregivers, who are predominantly family members, don’t ask for help for many reasons such as pride, sense of obligation or love. In 2014, friends and family of people with AD and other dementias provided an estimated 17.9 billion hours of unpaid care, with an estimated value of $217.7 billion. Caring for a person with AD takes a devastating toll, with nearly 60 percent of caregivers rating their emotional stress as high or very high, and about 40 percent suffering from depression.¹

The reality is that caregivers can’t do it alone. In fact, studies show that those who get a break provide better care than those who do not.⁸ Federal and state programs offer many resources for caregivers that can be found at www.alzheimers.gov/caregiver_resources.html. In addition, the Alzheimer’s Association has a 24/7 support line at (800) 272-3900, and it can help caregivers find local support groups in their areas.

Dispelling the Myths Now

Developing treatments to slow or even cure AD is crucial. Without it, 28 million baby boomers will fall ill with AD by 2040, consuming 24 percent of Medicare spending, according to a report from the 2015 Alzheimer’s Association International Conference.¹⁷

In recent years, both international and national efforts have recognized the public health importance of AD. In 2011, President Obama enacted the National Alzheimer’s Project Act, which called for a National Advisory Council on Alzheimer’s Disease Research and resulted in the development of a national plan to address AD each year for the effective prevention and treatment of AD by 2025. In 2012, the World Health Organization identified dementia as a public health priority. And, to date, 40 states have developed plans to address AD.^22,23

Scientists have made remarkable progress in understanding AD in the last three decades, but there is much more to be accomplished. Through planning and research, it can only be hoped that we discover how AD can be prevented, treated and even cured. Until that happens, though, it’s important for those affected to know the signs of AD and where to get help.