Week 6: Understanding Alzheimer’s Disease
Recording:
Miss the class? Would you like to hear the lecture again? In this short video, Dr. Minoo provides an excellent session explaining Alzheimer's Disease.
Understanding Alzheimer's Disease
You might have experienced not remembering why you are somewhere or what your purpose is to be there. Is it due to age-related forgetfulness, a distraction that detoured your brain while you were multi-tasking, or Alzheimer’s disease?
In this week’s lesson we will look at the burden of Alzheimer’s Disease in the United States. What is Alzheimer’s Disease? How does Alzheimer’s change the brain? What happens when a person has Alzheimer’s disease? We will also explore additional topics such as the stages of Alzheimer’s disease, signs of Alzheimer’s disease, when to see a doctor, Alzheimer’s risk factors and prevention, treatments for Alzheimer’s disease, and how to get help.
Video: A short video describing Alzheimer's Disease and some of the statistics surrounding Alzheimer's Disease
Burden of Alzheimer’s Disease in the United States
In 2023 an estimated 6.7 million Americans aged 65 and older are living with Alzheimer's dementia. Seventy-three percent are 75 or older. About 1 in 9 people (10.8%) aged 65 and older has Alzheimer’s dementia.
Figure 1 shows the number and ages of people 65 or older with Alzheimer’s dementia, 2023. The percentage of people with Alzheimer’s dementia increases with age: 26.7% of people aged 65 to 74, 37.9% of people aged 75 to 84, and 35.4% of people aged 85 and older have Alzheimer’s dementia.
Figure 2 shows that between 2020 and 2025 every state across the country (excluding the District of Columbia) will have experienced an increase of at least 6.7% in the number of people with Alzheimer's.
Figure 3 shows that by 2060, the number of people age 65 and older with Alzheimer’s dementia is projected to reach 13.8 million, barring the development of medical breakthroughs to prevent, slow or cure Alzheimer’s disease. (Alzheimer's & Dementia, 2023,1598-1695)
Alzheimer’s disease is one of the top 10 leading causes of death in the United States. It’s the 6th leading cause of death among US adults, and the 5th leading cause of death among adults aged 65 years or older. Death rates for Alzheimer’s disease are increasing, unlike heart disease and cancer death rates that are on the decline. Dementia, including Alzheimer’s disease, has been shown to be under-reported in death certificates and therefore the proportion of older people who die from Alzheimer’s may be considerably higher. (Centers for Disease Control and Prevention, 2020)
Figure 1: Incidence of Alzheimer's by age
https://www.alz.org/media/documents/alzheimers-facts-and-figures.pdf
Figure 2: Alzheimer's by State
https://www.alz.org/media/documents/alzheimers-facts-and-figures.pdf
Figure 3: Projections for the future
https://www.alz.org/media/documents/alzheimers-facts-and-figures.pdf
The Costs of Healthcare and Long-term Care for Individuals with Alzheimer’s in the U.S.
Total payments in 2023 (in 2023 dollars) for all individuals with Alzheimer’s or other dementias are estimated at $345 billion. Medicare and Medicaid are expected to cover $222 billion, or 64%, of the total health care and long-term care payments for people with Alzheimer’s or other dementias. Out of pocket spending is expected to be $87 billion, or 25% of total payments. This is not including the value of informal caregiving which is nearly $340 billion. (Alzheimer's & Dementia, 2023, 1598-1695)
Figure 4: Cost of caring for those with Alzheimer's or dementia
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13016
What is Alzheimer’s Disease?
Alzheimer’s Disease is the degeneration of a large number of brain cells, which causes problems with memory, thinking, reasoning, decision making, and changes in behavior and personality. It slowly gets worse over time until losing independence in personal daily activities. (Breijyeh & Karaman, 2020, 5789)
Alzheimer’s Disease is the main cause of dementia. The term “dementia” is an “umbrella” term for the symptoms that affect mental cognitive tasks. There are many types of dementia, and Alzheimer's disease accounts for 60%-80% of dementia cases. But Alzheimer's Disease and related dementias are not a normal part of aging. (What Is Dementia? Symptoms, Causes & Treatment | Alz.org, 2024)
Video: This short video describes the difference between Alzheimer's Disease and dementia
How Alzheimer’s Disease Changes the Brain
Alzheimer's disease is a result of complex changes in the brain that start years before symptoms appear and lead to the loss of brain cells and their connections. (Alzheimer's.gov, 2024) Alzheimer's disease is characterized by an accumulation of abnormal neuritic plaques and neurofibrillary tangles in the cerebral cortex. (Kumar et al., 2024)
Plaques and tangles lead to nerve cell death and tissue loss throughout the brain. Over time, the brain shrinks dramatically, affecting nearly all its functions. (What Is Alzheimer's Disease? Symptoms & Causes | Alz.org, 2024)
Figure 5 shows the physiological structure of the brain and neurons in (a) healthy brain and (b) Alzheimer’s disease (AD) brain. (Breijyeh & Karaman, 2020, 5798)
Figure 5: Physiology of the brain in a healthy brain and one with Alzheimer's Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/7764106/bin/molecules-25-05789-g001.jpg
More about plaques:
Plaques form when protein pieces called beta-amyloid clump together. Beta-amyloid comes from a larger protein found in the fatty membrane surrounding nerve cells.
Beta-amyloid is chemically "sticky" and gradually builds up into plaques. The most damaging form of beta-amyloid may be groups of a few pieces rather than the plaques themselves. The small clumps may block cell-to-cell signaling at synapses. They may also activate immune system cells that trigger inflammation and devour disabled cells.
Figure 6 shows the plaques in the brain.
Figure 6: Plaques
https://www.alz.org/media/braintour/plaques-3.jpg
More about Tangles:
Tangles destroy a vital cell transport system made of proteins. In areas where tangles are forming nutrients and other essential supplies can no longer move through the cells, which eventually die.
Progression through the brain:
Plaques and tangles tend to spread through the cortex in a predictable pattern as Alzheimer's disease progresses. The rate of progression varies greatly. On average, a person with Alzheimer's lives four to eight years after diagnosis, but can live as long as 20 years, depending on other factors. The course of the disease depends in part on age at diagnosis and whether a person has other health conditions. (Progression Through The Brain | Alz.org, 2024)
Video: How Alzheimer's changes the brain
Video: A little longer, but an excellent overview of dementia and Alzheimer's and how they affect the brain
The Stages of Alzheimer’s Disease
Alzheimer’s is a progressive disease that usually worsens over time. Because of this, there is an Alzheimer’s disease continuum with 3 main phases. (Figure 7) In this section we review these phases and the symptoms associated with each phase.
Figure 7: Progression of disease
https://alz-journals.onlinelibrary.wiley.com/cms/asset/c23ca5e8-12f1-4351-a931-20d4cfd03da4/alz12068-fig-0001-m.jpg
1. Preclinical or the pre-symptomatic stage, which can last for several years or more. This stage is characterized by mild memory loss and early pathological changes in cortex and hippocampus, with no functional impairment in the daily activities and absence of clinical signs and symptoms of AD. (Breijyeh & Karaman, 2020, 5798) In this stage, a person or people around him/her won't notice any changes. (Mayo Clinic, 2023) But Alzheimer's biomarkers indicate brain changes which include abnormal levels of beta-amyloid on positron emission tomography (PET) scans and in analysis of cerebrospinal fluid (CSF), changes in tau protein in CSF and plasma, and decreased metabolism of glucose as shown on PET scans. When the early changes of Alzheimer's disease occur, the brain compensates for them, enabling individuals to continue to function normally. (Alzheimer's & Dementia, 2023,1598-16950)
Image: Biomarkers of Alzheimer's disease (https://lions-talk-science.org/2022/04/05/predicting-alzheimers-disease-the-rise-of-novel-biomarkers/)
2. Mild cognitive impairment due to Alzheimer's disease. This stage is characterized by biomarker evidence of Alzheimer's brain changes and mild symptoms such as problems with memory, language and thinking. These cognitive problems may be noticeable to the individual, family members and friends, but not to others. These changes aren't significant enough to interfere with individuals’ ability to carry out everyday activities. Not everyone with mild cognitive impairment has Alzheimer's disease. Systematic reviews showed that 15% of people with MCI due to Alzheimer's disease develop dementia after two years, about one-third develop dementia within five years. (Alzheimer's & Dementia, 2023,1598-1695)
Image: Progression, and comparison between MCI and Dementia (https://mind.uci.edu/dementia/mild-cognitive-impairment/
3. Dementia due to Alzheimer's disease, which is broken down into mild, moderate and severe dementia.
● The mild or early stage of AD where a person may function independently. He or she may still drive, work and be part of social activities. Handling finances and paying bills may be especially challenging, and they may need more time to complete common daily tasks. Symptoms may not be widely apparent at this stage, but family and close friends may take notice and a doctor would be able to identify symptoms using certain diagnostic tools. (Alzheimer's & Dementia, 2023,1598-1695)
● Moderate or middle stage of AD, in which the disease spreads to cerebral cortex areas that results in an increased memory loss with trouble recognizing family and friends, a loss of impulse control, and difficulty in reading, writing, and speaking. Individuals are more likely to become confused, and find it harder to complete multi step tasks such as bathing and dressing. They may become incontinent at times, and they may start having personality and behavioral changes, including suspiciousness and agitation. They may also begin to have problems recognizing loved ones. The person with Alzheimer's will require a greater level of care. During this stage caregivers may want to consider respite care or an adult day center so they can have a temporary break from caregiving while the person living with Alzheimer’s continues to receive care in a safe environment. (Alzheimer's & Dementia, 2023,1598-1695)
● Severe or late stage of AD, which involves the spread of the disease to the entire cortex area with a severe accumulation of neuritic plaques and neurofibrillary tangles, resulting in a progressive functional and cognitive impairment where the individuals lose the ability to respond to their environment, to carry on a conversation and, eventually, to control movement. They may still say words or phrases, but communicating becomes difficult. (Breijyeh & Karaman, 2020, 5798) Because of damage to areas of the brain involved in movement, individuals become bed-bound. Being bed-bound makes them vulnerable to physical complications including blood clots, skin infections and sepsis, which triggers body-wide inflammation that can result in organ failure. Damage to areas of the brain that control swallowing makes it difficult to eat and drink. This can result in individuals swallowing food into the trachea (windpipe) instead of the esophagus (food pipe). Because of this, food particles may be deposited in the lungs and cause lung infection. This type of infection is called aspiration pneumonia, and it is a contributing cause of death among many individuals with Alzheimer's. During this stage, caregivers may want to use support services, such as hospice care, which focus on providing comfort and dignity at the end of life. Hospice can be of great benefit to people in the final stages of Alzheimer’s and other dementias and their families. (Alzheimer's & Dementia, 2023, 1598-1695)
Video: A look at Alzheimer's and dementia from someone experiencing it
Video: What is a dementia friendly environment? This short video demonstrates how you can assist with someone experiencing dementia.
Warning Signs
While normal aging can affect cognitive and memory performance, Alzheimer’s is not a part of the normal aging process. Alzheimer's causes a slow decline in memory, thinking and reasoning skills. There are 10 warning signs and symptoms which can tell you the differences between normal age-related cognitive changes and the cognitive changes of Alzheimer's disease.
● Memory loss that disrupts daily life
● Challenges in planning or solving problems
● Difficulty completing familiar tasks
● Confusion with time or place
● Trouble understanding visual images and spatial relationships
● New problems with words in speaking or writing
● Misplacing things and losing the ability to retrace steps
● Decreased or poor judgment
● Withdrawal from work or social activities
● Changes in mood, personality and behavior
If you notice any of them, don't ignore them. Schedule an appointment with your doctor. See Figure 8 (below) for warning signs of dementia.
Figure 8: Warning signs of dementia
https://www.alzint.org/u/updated-warning-signs-graphic_english_pdf.pdf
Early Diagnosis
If you are worried about your own memory, or that of someone close to you, it’s important to consider seeking help and receive an early and accurate diagnosis. Additionally receiving a timely diagnosis of Alzheimer’s dementia will enable you to:
● Gain access to information, resources, and support for yourself and those close to you
● Demystify and destigmatize your condition
● Maximize your quality of life
● Benefit from support and available drug and nondrug therapies that may improve your condition
● Plan for the future explain to your family, friends, and colleagues what has changed in your life and how they can help you (Alzheimer's Disease International, 2024)
To diagnose Alzheimer’s, physicians may use a) medical history, b) cognitive functional and behavioral tests, c) depression screen and mood test, d) brain imaging (MRI/CT) to rule out other conditions that may cause symptoms similar to Alzheimer's such as brain tumor or stroke, e) cerebral spinal fluid (CSF) tests to detect beta-amyloid and tau markers in CSF, which can be predictive of amyloid changes in the brain. (Medical Tests for Diagnosing Alzheimer's & Dementia | Alz.org, 2024) Figure 9 shows that as the disease progresses, many brain areas and their functions become impaired, culminating in severe memory loss and metabolic derangements, both of which affect autonomy. Despite the lack of bona fide biomarkers to date, earlier detection will ensure that treatments reach individuals in a timely manner. (Frozza et al., 2018)
Figure 9: Progression of disease
https://www.frontiersin.org/files/Articles/334515/fnins-12-00037-HTML/image_m/fnins-12-00037-g001.jpg
Risk factors and prevention
Age- The most important risk factor in AD is aging. It’s called late onset that starts after 65 years. Younger individuals rarely (9%) have this disease before age 65, that is called young onset dementia.
Family history- Individuals with a family history of dementia are more likely to develop it themselves.
Infections- Chronic infections to the central nervous system (CNS) can cause an accumulation of Amyloid beta protein (Aβ plaques) and Neurofibrillary Tangles (NFTs) therefore, they are included among the risk factors in AD.
Figure 10: Family History
https://www.alz.org/media/HomeOffice/Inline%20Image/is-Alzheimers-genetic.jpg
Air Pollution- The air pollution is characterized by modifying the nature of the atmosphere through the introduction of chemical, physical, or biological pollutants. It is associated with respiratory and cardiovascular diseases and recently, its association with AD was documented. Six air pollutants have been defined by National Ambient Air Quality Standards (NAAQSs) in the USA as a threat to human health, including ozone (O3), nitrogen oxides (NOx), carbon monoxide (CO), particulate matter (PM), sulfur dioxide (SO2), and lead.
Metals- Toxicological metals which do not possess any biological function such as Lead, Aluminum, and Cadmium are shown to increase risk of Alzheimer’s. (Breijyeh & Karaman, 2020, 5789)
Head injury- Head injuries can increase the risk of developing Alzheimer’s.
Medical factors- Diabetes, cardiovascular disease, high cholesterol, high blood pressure, obesity, and smoking are associated with increased risk of AD.
Additional risk factors include depression, social isolation, low educational attainment, and cognitive inactivity.
Age and family history are all non-modifiable risk factors. However, studies show that people can reduce their risk of cognitive decline and dementia by maintaining healthy blood pressure, cholesterol and blood sugar levels, being physically active, not smoking, avoiding harmful use of alcohol, controlling their weight, and eating more nutrient-rich whole foods in a healthy diet. (World Health Organization, 2023)
Figure 11 shows Alzheimer’s risk factors
Figure 12 shows the components of lifestyle medicine. Lifestyle medicine focuses on six pillars of a healthy lifestyle: nutrition, exercise, stress management, social support, sleep, and avoiding risky behaviors, such as smoking tobacco. Adherence to the six pillars is expected to reduce the risk of Alzheimer’s disease.
Figure 13 shows the influence of diet and dietary components in dementia. Eating more nutrient-rich whole foods in a healthy diet reduces the risk of dementia. Eating more ultra-processed foods in a Western diet increases the risk of dementia.
Figure 11: Risk factors
https://www.researchgate.net/profile/Mahendran-Sekar-2/publication/366445633/figure/fig1/AS:11431281108674742@1671565538251/Risk-factors-of-Alzheimers-Disease.png
Figure 12: Lifestyle
https://www.frontiersin.org/files/Articles/1213223/fnut-10-1213223-HTML/image_m/fnut-10-1213223-g001.jpg
Figure 13: Diet
https://www.frontiersin.org/files/Articles/1213223/fnut-10-1213223-HTML/image_m/fnut-10-1213223-g002.jpg
Americans and Their Physicians Are Not Talking About Cognitive Issues or a Medical Diagnosis
Many people do not discuss cognitive symptoms with their health care provider because they believe what they are experiencing is to be expected with getting older rather than a diagnosable medical condition. In the Special Report from 2019 Alzheimer’s Disease Facts and Figures, nearly all older adults surveyed (93%) reported that cognitive changes they experienced seemed like a part of normal aging and indicated that these changes were not severe. Physicians are not taking the initiative to talk with patients either. Nearly all primary care physicians (PCPs) report waiting for patients (97%) or family members (98%) to make them aware of symptoms or request an assessment.
A collective breakdown in communication about cognitive issues at any point in the patient journey is detrimental to care, especially in an era when treatments that alter the underlying biology of Alzheimer’s disease could change the course of the disease if started early enough. (Alzheimer's & Dementia, 2023, 1598-1695) (Figure 14).
Figure 14: Progression of cognition for patient
https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13016
Therefore, making an appointment for memory loss is crucial to early diagnosis. Alzheimer's Association recommends what to bring to a visit:
● A list of any changes in your health, including your mood, memory and behaviours. Make a note of any changes you’ve noticed since your last appointment. Be as specific as possible.
● A list of past and current medical problems. Tell your doctor if other family members had illnesses that caused memory problems.
● A list of current prescriptions and over-the-counter medications.
● A list of vitamins or supplements you’ve added to your medication regimen.
● A list of questions you want to ask.
● Be prepared to answer the doctor's questions honestly and to the best of your ability. (Visiting Your Doctor for Memory Loss | Alz.org, 2024)
Treatment
At this point, there are no known cures for Alzheimer’s disease or any other type of dementia. The U.S. Food and Drug Administration (FDA) has approved medications for Alzheimer's. These fall into two categories:
● Drugs that temporarily ease some symptoms of Alzheimer's disease.
● Drugs that change disease progression in people living with Alzheimer's. (Navigating Treatment Options | Alz.org, 2024)
There are also non-drug treatments for Alzheimer's disease. Non-drug treatments do not change the underlying biology of the disease. They are often used with the goals of maintaining or improving cognitive function, overall quality of life and engagement, and the ability to perform activities of daily living. Non-drug treatments include physical activity, memory and orientation exercises, and music and art based activities. (Alzheimer's & Dementia, 2023, 1598-1695)
Proactive Management of Dementia Due to Alzheimer's Disease
Proactive management of Alzheimer's and other dementias can improve the quality of life of affected individuals and their caregivers. Proactive management includes:
● Appropriate use of available treatment options.
● Effective management of coexisting conditions.
● Providing family caregivers with effective training in managing the day-to-day life of the care recipient.
● Coordination of care among physicians, other health care professionals and lay caregivers.
● Participation in activities that are meaningful to the individual with dementia and bring purpose to his or her life.
● Maintaining a sense of self identity and relationships with others.
● Having opportunities to connect with others living with dementia; support groups and supportive services are examples of such opportunities.
● Becoming educated about the disease.
● Planning for the future. (Alzheimer's & Dementia, 2023, 1598-1695)
Summary
Alzheimer's is the most common cause of dementia, a general term for memory loss and other cognitive abilities serious enough to interfere with daily life. The greatest known risk factor is older age. The majority of people with Alzheimer's are 65 and older, but it is not a normal part of aging. Alzheimer's is a progressive disease, where dementia symptoms gradually worsen over a number of years. In its early stages, memory loss is mild, but with late stage Alzheimer's, individuals lose the ability to carry on a conversation and respond to their environment. Seeking professional help when someone experiences the 10 warning signs helps to diagnose earlier and prevent the progression of the disease.
Next semester we will offer a course specifically focusing on all aspects of Alzheimer’s disease including Alzheimer’s caregivers, signs in each stage, more details on modifiable risk factors such as nutrition, and non-drug treatments including alternative therapies.
References
Alzheimer's Association. (2024). How is Alzheimer's Diagnosed? Alzheimer's Association. Retrieved February 28, 2024, from https://www.alz.org/alzheimers-dementia/diagnosis
Alzheimer's Association. (2024). Questions for Your Doctor. Alzheimer's Association. Retrieved February 28, 2024, from https://www.alz.org/alzheimers-dementia/treatments/questions-for-your-doctor
Alzheimer's & Dementia. (2023, March 14). 2023 Alzheimer's disease facts and figures. Alzheimer's & Dementia, 19, 1598-1695. https://doi.org/10.1002/alz.13016
Alzheimer's Disease International. (2024). Importance of a timely diagnosis. Alzheimer's Disease International. Retrieved February 28, 2024, from https://www.alzint.org/about/symptoms-of-dementia/importance-of-early-diagnosis/
Alzheimer's.gov. (2024). What Is Alzheimer's Disease? Alzheimers.gov. Retrieved February 28, 2024, from https://www.alzheimers.gov/alzheimers-dementias/alzheimers-disease
Alzheimer's.org. (2024). How is Alzheimer's Diagnosed? Alzheimer's Association. Retrieved February 28, 2024, from https://www.alz.org/alzheimers-dementia/diagnosis
Breijyeh, Z., & Karaman, R. (2020, December 8). Comprehensive Review on Alzheimer’s Disease: Causes and Treatment. Molecules, 25(24), 5789. https://doi.org/10.3390/molecules25245789
Centers for Disease Control and Prevention. (2020, October 26). What is Alzheimer's Disease? | CDC. Centers for Disease Control and Prevention. Retrieved February 28, 2024, from https://www.cdc.gov/aging/aginginfo/alzheimers.htm
Frozza, R. L., Lourenco, M. V., & De Felice, F. G. (2018). Challenges for Alzheimer's Disease Therapy: Insights from Novel Mechanisms Beyond Memory Defects. Frontiers in Neuroscience, 12. https://doi.org/10.3389/fnins.2018.00037
Kumar, A., Sidhu, J., Goyal, A., & Tsao, J. W. (2024, January). Alzheimer Disease. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK499922/
Mayo Clinic. (2023, June 7). Alzheimer's stages: How the disease progresses. Mayo Clinic. Retrieved February 28, 2024, from https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-stages/art-20048448
Medical Tests for Diagnosing Alzheimer's & Dementia | alz.org. (2024). Alzheimer's Association. Retrieved February 28, 2024, from https://www.alz.org/alzheimers-dementia/diagnosis/medical_tests
Navigating Treatment Options | alz.org. (2024). Alzheimer's Association. Retrieved February 28, 2024, from https://www.alz.org/alzheimers-dementia/treatments/navigating-treatment-options
Progression Through The Brain | alz.org. (2024). Alzheimer's Association. Retrieved February 28, 2024, from https://www.alz.org/alzheimers-dementia/what-is-alzheimers/brain_tour_part_2
Visiting Your Doctor for Memory Loss Alz|org. (2024). Alzheimer's Association. Retrieved February 28, 2024, from https://www.alz.org/alzheimers-dementia/diagnosis/visiting-your-doctor
What is Alzheimer's Disease? Symptoms & Causes | alz.org. (2024). Alzheimer's Association. Retrieved February 28, 2024, from https://www.alz.org/alzheimers-dementia/what-is-alzheimers/brain_tour_part_2
What is Dementia? Symptoms, Causes & Treatment | alz.org. (2024). Alzheimer's Association. Retrieved February 28, 2024, from https://www.alz.org/alzheimers-dementia/what-is-dementia
World Health Organization. (2023, March 15). Dementia. World Health Organization. Retrieved February 28, 2024, from https://www.who.int/news-room/fact-sheets/detail/dementia/?gad_source=1&gclid=Cj0KCQiAxOauBhCaARIsAEbUSQQHo4PpPCy2AYwnE84QRVctuvAIBoaNTH5y5MhIRir-MnBmhBJzxP4aAurWEALw_wcB