Myths & Facts: Alzheimer’s Disease

It’s an alarming statistic: An estimated 5.8 million Americans age 65 and older were living with Alzheimer’s disease (AD) in 2020, and 80 percent are age 75 or older. Indeed, one in 10 people age 65 and older (10 percent) has AD. It affects almost twice as many women as men. Older African-Americans are about twice as likely to have AD or other dementias as older whites. And, older Hispanics are about one and one-half times as likely to have AD or other dementias as older whites. Also, with the number of older Americans growing rapidly, so too will the number of new and existing cases.¹

The sixth-leading cause of death in the U.S., 61 percent of those with AD are expected to die before age 80 compared with 30 percent of people without AD — a rate twice as high. And, it is a costly disease. In 2020, AD and other dementias cost the nation $305 billion, including $206 billion in Medicare and Medicaid payments. By 2050, AD is projected to cost more than $1.1 trillion (in 2020 dollars). This is more than four-fold increases both in government spending under Medicare and Medicaid and in out-of-pocket spending.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 describes a group of symptoms affecting memory, thinking and social abilities severely enough to interfere with daily life.² AD is only one form of dementia and the most common type, but it accounts for only 60 percent to 80 percent of all dementia cases.³ And, dementia is caused by many things, including AD (it is the most common cause of dementia), Huntington’s disease, Parkinson’s disease and Creutzfeldt-Jakob disease. Some forms of dementia are temporary or they can be reversed, but with AD and some other forms of dementia, that is not the case.²

Myth: Memory loss is AD.

Fact: AD is much more than memory loss. AD causes brain cells to malfunction and ultimately die. When this happens, an individual may forget the name of a longtime friend or what roads to take to return to a home they’ve lived in for decades.⁴ 

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.⁵

The Alzheimer’s Association has identified 10 early signs and symptoms of AD: 1) memory loss that disrupts daily life, 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.⁶

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. And, AD can start young. Symptoms in those with younger-onset AD, which is a rare inherited form, can start between 30 years old and 50 years old.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, it is estimated 5 percent to 6 percent of people with AD develop symptoms before age 65. So, if 5.8 million Americans have AD, around 285,000 to 342,000 people have the early-onset form of the disease.⁷

Myth: AD is hereditary.

Fact: Less than 5 percent of all cases of AD are “familial Alzheimer’s,” a type that runs in families, but if a person has a parent or sibling with AD, he or she will have a higher chance of getting it.³ 

However, genes have been shown to 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, seven other genes have been identified. These include:

• ABCA7, whose exact role isn’t clear, but the gene seems to be linked to a greater risk of AD, and it appears to be linked to the gene’s role in how the body uses cholesterol;

• CLU, which helps regulate the clearance of amyloid-beta (central to the development of AD) from the brain;

• CR1, which may contribute to chronic inflammation in the brain due to a deficiency of the protein this gene produces;

• PICALM, which is linked to the process by which brain nerve cells (neurons) communicate with each other;

• PLD3 that has recently been linked to a significantly increased risk of AD, although not much is known about this gene;

• TREM2, which is involved in the regulation of the brain’s response to inflammation; and

• SORL1 variants on chromosome 11, which appear to be associated with AD.

It should be noted that all of these genes are risk factors, not direct causes, for developing AD. Not everyone who has one of these genes will develop the disease.⁸

Mutations in three genes that cause early-onset AD have also been identified: amyloid precursor protein (APP) on chromosome 21, presenilin 1 (PSEN1) on chromosome 14 and presenilin 2 (PSEN2) on chromosome 1. Mutations in these genes result in the production of abnormal proteins associated with the disease. Each of these mutations plays a role in the breakdown of APP that generates harmful forms of amyloid plaques, a hallmark of AD. However, APP’s precise function is not yet fully understood. If a child’s biological mother or father carries a genetic mutation for one of these three genes, that child has a 50/50 chance of inheriting that mutation, resulting in a very strong probability of developing early-onset AD.

Other genetic components have also been found to be associated with early-onset AD, and studies are ongoing to identify additional genetic risk variants.

In addition, Down syndrome increases the risk of developing early-onset AD, and many people with Down syndrome develop AD as they get older, with symptoms appearing in their 50s or 60s. It is believed this is because people with Down syndrome are born with an extra copy of chromosome 21, which carries the APP gene.⁹

Myth: AD can be caused by influenza (flu) shots, depression, aluminum, silver fillings and aspartame.

Fact: The truth is 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.¹⁰ 

New research reported at the Alzheimer’s Association International Conference in 2020 found risk factors for AD may be apparent as early as the teens and 20s, although many of these risk factors are disproportionately apparent in African-Americans. 

In the Study of Health Aging in African Americans that included more than 714 African-Americans, researchers found high blood pressure, diabetes or two or more heart health risk factors in adolescence, young adulthood or midlife was associated with statistically significantly worse late-life cognition. And these differences persisted after accounting for age, gender, years since risk factors were measured and education. 

Another study found a correlation between body mass index (BMI) and higher late-life dementia risk. Scientists analyzed 5,104 older adults from two studies, including 2,909 from the Cardiovascular Health Study (CHS) and 2,195 from the Health, Aging and Body Composition study (Health ABC), 18 percent of whom were black and 56 percent of whom were women. Using pooled data from four established cohorts spanning the adult life course, including the two cohorts under the study, scientists estimated BMI beginning at age 20 for all older adults of CHS and Health ABC. For women, dementia risk increased with higher early adulthood BMI. Compared to women with normal BMI in early adulthood, dementia risk was 1.8 times higher among those who were overweight, and 2.5 times higher among those who were obese. Analyses were adjusted for midlife and late-life BMI. They found no association between midlife BMI and dementia risk among women. For men, dementia risk was 2.5 times higher among those who were obese in early adulthood, 1.5 times higher among those who were overweight in midlife and 2.0 times higher among those who were obese in midlife in models also adjusted for late-life BMI. For both women and men, dementia risk decreased with higher late-life BMI.

In another study that followed a diverse group of more than 2,400 people for up to 21 years, higher-quality early-life education was associated with better language and memory performance and lower risk of late-life dementia. However, results were somewhat different between blacks and whites and men and women. The study included 2,446 black and white men and women age 65 and older enrolled in the Washington Heights/Inwood Columbia Aging Project who attended elementary school in the United States. A school quality variable based on historical measures included mandatory school enrollment age, minimum dropout age, school-term length, student-teacher ratio and student attendance. Those who attended school in states with lower-quality education had more rapid decline in memory and language as an older adult. Black women and men and white women who attended schools in states with higher-quality education were less likely to develop dementia. According to the scientists, the results were explained, in part, because people who attend higher-quality schools end up getting more years of education.¹¹

The theory that flu shots cause AD may stem from statements by Hugh Fudenberg, MD, claiming the flu shot increases the risk of AD because of the small amount of mercury in thimerosal, the preservative that is still contained in some flu vaccines. However, there has been no peer-reviewed research that supports this allegation, and Dr. Fudenberg’s medical license was revoked in 1995. In fact, several studies debunk that theory and show flu shots and other vaccines actually reduce the risk of AD and lead to overall better health. One study conducted in 2001 with 4,392 participants showed 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 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 annual flu shots for older adults were associated with a reduced risk of death from all causes.¹² 

Most recently, two new studies show the flu and pneumonia vaccines lessen the risk of developing AD in the future. The first study examined a large American health record data set of more than 9,000 patients over age 60 years and found having one flu vaccination was associated with a 17 percent reduction in AD. Further, those vaccinated more than once over the years saw an additional 13 percent reduction in incidence. The protective association appeared to be strongest for those who received their first vaccine at a younger age, for example at age 60 years versus 70 years. The second study, which examined the associations between pneumococcal vaccine with and without an accompanying flu shot and the risk of AD, analyzed more than 5,000 people over 65 years who were participating in the Cardiovascular Health Study, a long-term government-funded look at risk factors for cardiovascular disease. Some participants had a known genetic risk factor for AD: the rs2075650 G allele in the TOMM40 gene, which has also been linked to a higher risk for lifetime depression. The researchers found that getting a pneumococcal vaccine between the ages of 65 years and 75 years reduced risk of developing AD by 25 percent to 30 percent after adjusting for sex, race, birth cohort, education, smoking and genetic risk factors. However, the largest reduction in the risk of AD — up to 40 percent — was seen among people vaccinated against pneumonia who didn’t have the risk gene.¹³ 

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 and published in the New England Journal of Medicine, which found no connection between mercury-containing dental fillings and AD 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.⁴

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.¹⁴

Many things, however, can be done to protect the brain. A committee of experts from the National Academies of Sciences, Engineering and Medicine (NASEM) conducted a recent review of research that looked at the evidence on ways to prevent or delay AD or age-related cognitive decline and found “encouraging but inconclusive” evidence for three types of interventions: increased physical activity, blood pressure control for people with high blood pressure (hypertension) and cognitive training. While there isn’t adequate research to recommend exercise as a way to prevent AD, years of observational studies show people who exercise have a lower risk of cognitive decline than those who don’t. Exercise has also been associated with fewer AD plaques and tangles in the brain and better performance on certain cognitive tests. Many studies show a connection between high blood pressure, cerebrovascular disease and dementia, and there are many clinical trials underway to determine whether this is true. For instance, one large clinical trial called Systolic Blood Pressure Intervention Trial-Memory Cognition in Decreased Hypertension found lowering systolic blood pressure to less than 120 mmHg compared to a target of less than 140 mmHg didn’t significantly reduce the risk of dementia. However, the multiyear study did show intensive blood pressure lowering significantly reduced the risk of mild cognitive impairment (MCI), a common precursor of AD. Finally, there is evidence that computer-based cognitive training may help delay or slow age-related cognitive decline. However, there is no evidence it can prevent or delay AD’s-related cognitive impairment.¹⁵

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. An MRI can be used to rule out other conditions and to assess whether there is shrinkage in brain regions implicated in AD. A CT 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. In special circumstances, such as rapidly progressive dementia or very early-onset dementia, other tests may be used to measure abnormal beta-amyloid or tau in the cerebrospinal fluid.¹⁶

Unfortunately, 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.17 In fact, AD can develop 20-plus years before memory loss.³ AD can also be overdiagnosed because it mimics other conditions such as transient ischemic attack,  depression, vascular dementia, Creutzfeldt-Jacob disease, bovine spongiform encephalopathy, brain tumor, hydrocephalus or advanced syphilis or AIDS.¹⁷

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. Research investigating new tests include:¹⁸

• A biomarker test that can indicate the presence of two proteins, beta-amyloid and tau, which are found in the brains of people with AD and that can measure the fluid that surrounds the brain and spinal cord (cerebrospinal fluid), which is examined for evidence of abnormal development of beta-amyloid proteins that form plaques, and tau proteins that form tangles. 

• Brain imaging (neuroimaging) such as MRI and PET scans used with radiotracers (charged particles that “light up” when a person has dementia).

• Cognitive assessment technology that can detect cognitive changes and may be useful in the early diagnosis of AD.

• Loss of odor identification tests (olfactory impairment), which can indicate a decline in mild cognitive impairment and progression from MCI to AD. 

Recently, two new studies have shown blood levels of a specific form of phosphorylated tau effectively identify AD, which could lead to a highly accurate diagnostic blood test with the potential to predict AD up to 20 years before disease onset. In the first study, researchers looked at whether CSF levels of tau phosphorylated at threonine 217 (p-tau217) could be a blood-based biomarker of AD using mass spectrometry to measure tau in blood samples from participants of previous AD studies, including a discovery cohort of 32 individuals and a validation cohort of 92 individuals. Low blood concentrations of tau meant the protein had to be purified and concentrated 800-fold to enable its detection with mass spectrometry, an approach that enabled reliable measurement of p-tau181 and p-tau217. They found blood levels of p-tau181 and p-tau217 correlated well with CSF levels, despite a lack of correlation between total tau levels in the two compartments. Blood levels of both tau isoforms were higher among AB-positive individuals than among AB-negative people, but the magnitude of change was greater for p-tau217.

In the second study, the value of p-tau217 as a blood biomarker was independently identified. The study involved samples from three different cohorts: one in which pathology had been determined post-mortem; one in which patients with dementia and other neurological disease were classified as AB-positive or AB-negative; and one comprising cognitively impaired and unimpaired carriers of a PSEN1 mutation that is known to cause AD. Across the three cohorts, measurement of p-tau217 enabled individuals with a diagnosis of AD to be distinguished from those with other neurodegenerative diseases, and allowed the identification of individuals with pathologically defined AD. The findings of the two studies suggest p-tau217 levels could form the basis of a diagnostic, and possibly even predictive, blood test for AD.¹⁹

Myth: AD can be treated.

Fact: Currently, there is no treatment to indefinitely delay or stop the progression of AD. However, there are two types of drugs approved by the U.S. Food and Drug Administration (FDA) that treat the symptoms of AD — temporarily helping memory and thinking problems. However, these medications do not treat the underlying causes of the disease or slow its progression.20 The first type of drugs are cholinesterase inhibitors, and they include donepezil (Aricept), galantamine (Razadyne) and rivastigmine (Exelon), all of which curb the breakdown of a chemical in the brain called acetylcholine, which is important for memory and learning. They may slow down how fast symptoms get worse for about half of people who take them, and the effect lasts for a limited time, on average six to 12 months. The second type is memantine (Namenda), which treats moderate-to-severe AD. It works by changing the amount of a brain chemical called glutamate, which plays a role in learning and memory. Brain cells in people with AD give off too much glutamate, and Namenda keeps the levels of that chemical in check. Also available is Namzaric, which is a mix of Namenda and Aricept, that is best for people with moderate to severe AD who already take the two drugs separately.^20,21

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), beta-secretase (the enzyme that makes it possible for beta-amyloid to form), tau protein (the chief component of tangles), inflammation (another key AD brain abnormality) and 5-HT2A receptor (found on some brain cells that can lock in chemicals called neurotransmitters).²¹ 

There are also several clinical trials underway by the Alzheimer’s Association:²¹

• The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease study is examining the effectiveness of solanezumab, a drug targeting beta-amyloid, in 1,169 symptom-free volunteers whose PET scans show abnormally high levels of beta-amyloid in the brain. This drug could possibly prevent cognitive decline in individuals at increased risk of developing AD. The estimated completion date for the study is July 2022.

• The Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) hopes to slow or stop the development of AD in individuals who have mutations on three genes known to cause a rare form of AD that accounts for less than 1 percent of cases. Currently being tested are two drugs, gantenerumab and solanezumab, that are designed to help remove excess beta-amyloid in the brain. The study is expected to conclude in March 2021.

• The Alzheimer’s Prevention Initiative (API) includes both the Autosomal Dominant Alzheimer’s Disease (ADAD) trial and the Generation Study. Like DIAN-TU, the API tests therapies in people who have a gene mutation that causes AD but who have not yet developed symptoms. The ADAD trial is studying the effects of crenezumab, an immune-based therapy that delivers antibodies against beta-amyloid in an effort to reduce the negative cognitive effects of excess beta-amyloid. The Generation Study includes cognitively healthy older adults who are at high risk of developing AD based on their age and having two copies of the AD risk gene APOE-e4. The study is expected to conclude in February 2022.

Over the years, unfortunately, many studies that evaluated treatments for AD failed. But, in August, FDA gave priority review status to Biogen and its Japanese partner Eisai for the approval of aducanumab, a controversial investigational treatment for AD. While trials of the drug were discontinued in March 2019 because they were unlikely to meet their primary endpoints, the companies renewed plans in October 2019 to pursue regulatory approval of aducanumab based on positive results of a new analysis that showed a different outcome. The new analysis of the EMERGE study showed patients treated with a high dose (10 mg/kg) of aducanumab experienced a statistically significant reduction in clinical decline of AD. While a group of analysts believe FDA may not approve the drug, a decision is expected on March 7, 2021.²²

Myth: An AD diagnosis means life is over.

Fact: The progress of AD depends on the unique circumstances of each patient, and many people live years or even decades before the disease claims their lives. AD is commonly divided into three stages: 1) the mild stage in which the patient is able to live a mostly normal life, 2) the middle or moderate stage that requires more extensive care and 3) the late or severe stage that requires around-the-clock supervision and medical help. While life may never be the same after an AD diagnosis, it’s far from over.²³

Myth: AD isn’t fatal.

Fact: AD is the sixth-leading cause of death in the U.S., and the average life expectancy after diagnosis is 10 years.²⁴ In fact, AD has no survivors because it destroys brain cells and causes memory changes, erratic behaviors and loss of body functions. Sadly, it slowly and painfully takes away a person’s identity, ability to connect with others, think, eat, talk and walk.⁴

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

Fact: Eighty-three percent of caregivers are family members who don’t ask for help for many reasons such as pride, sense of obligation or love. In 2020, AD and other dementias will cost the nation $305 billion. Caregivers provided an estimated 18.6 billion hours of care valued at nearly $244 billion. In fact, of the total lifetime cost of caring for someone with dementia, 70 percent is borne by families either through out-of-pocket health and long-term care expenses or from the value of unpaid care. Caring for a person with AD takes a devastating toll, with twice as many caregivers of those with dementia suffering substantial emotional, financial and physical difficulties.¹

The reality is caregivers can’t do it alone. Federal and state programs offer many resources for caregivers that can be found at alz.org/help-support/caregiving. In addition, the Alzheimer’s Association has a 24/7 support line at (800) 272-3900, which can help caregivers find local support groups in their areas.²⁵

Dispelling the Myths Now

Developing treatments to slow or even cure AD is crucial. It is estimated by 2050 the number of people age 65 and older with AD may grow to a projected 13.8 million, and 50 percent of primary care physicians believe the medical profession is not ready for the growing numbers of people with it.¹ 

In recent years, both international and national efforts have recognized the public health importance of AD. The Alzheimer’s Association, working with and through the Alzheimer’s Impact Movement (AIM), is leading the way to increase research funding at the federal and state level. Their efforts have resulted in a more than six-fold increase in federal AD and dementia research funding since 2011, including a $350 million increase for AD research at the National Institutes of Health (NIH) in 2020. With this increase, along with previous research investments, NIH was expected to spend $2.8 billion on AD research in 2020. The association and AIM are also working to encourage investment by state and local governments. In 2019, they secured more than $100 million in state funding for dementia-specific care and support services, research, public health activities, home and community-based services and other areas to meet the needs of individuals and families living with dementia.²⁶

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. The goals of the project are to create and maintain an integrated national plan to overcome AD; coordinate AD research and services across all federal agencies; accelerate the development of treatments that would prevent, halt or reverse the course of AD; improve early diagnosis and coordination of care and treatment of AD; decrease disparities in AD for racial and ethnic minority populations that are at higher risk for AD; and coordinate with international bodies to fight AD globally.²⁷

In 2012, the World Health Organization (WHO) identified dementia as a public health priority. That same year, WHO and Alzheimer’s Disease International published a report titled “Dementia: A Public Health Priority” to raise awareness of dementia as a public health priority, articulate a public health approach and advocate for action at international and national levels.²⁸

Scientists have made remarkable progress in understanding AD, but there is much more to be accomplished. Through planning and research, it can only be hoped 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. 

Editor’s note: This article has been updated from the original published in the Winter 2016 edition of BioSupply Trends Quarterly.