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Alzheimer’s disease (AD) is named after Dr. Alois Alzheimer, who in 1906 noticed changes in the brain tissue of a woman who had died of an unusual mental illness. Her symptoms included memory loss, language problems, and unpredictable behavior. Following her death, he examined her brain and found many abnormal clumps (amyloid plaques) and tangled bundles of fibers (neurofibrillary, or tau, tangles).
These plaques and tau tangles in the brain are some of the main physical features of AD. Another feature is the loss of connections between neurons that transmit messages between different parts of the brain and from the brain to muscles and organs of the body (NIA, 2023a).
Alzheimer’s disease is one of a group of disorders called dementias, which are brain failures characterized by progressive cognitive and behavioral changes.
Research the most common forms of dementia:
- Alzheimer’s disease
- Vascular dementia
- Multi-infarct dementia
- Subcortical vascular dementia
- Stroke-related dementia
- Frontotemporal dementia (Pick’s disease)
- Mixed dementia (a combination of two or more types)
Other rarer conditions that can result in dementia include:
- Atypical Alzheimer’s disease
- Cadasil (a rare inherited form of vascular disease)
- Corticobasal syndrome (CBS)
- Creutzfeldt-Jakob disease (CJD)
- HIV-associated neurocognitive disorder (HAND)
- Huntington’s disease
- Normal pressure hydrocephalus (NPH)
- Progressive supranuclear palsy (PSP)
(Alzheimer’s Society, 2024a)
Alzheimer’s disease results from a complex pattern of abnormal changes, develops slowly, and gradually worsens. The course of Alzheimer’s and the rate of decline vary from person to person. Alzheimer’s disease can be present for many years before there are clinical signs and symptoms of the disease. On average, a person with Alzheimer’s lives for four to eight years after diagnosis. However, some may live for as many as 20 years.
Alzheimer’s disease is reported as the sixth leading cause of death in the United States. However, studies have found that it is underreported as an underlying cause of death. It is the only cause among the top 10 that cannot be prevented or cured. However, currently some treatments can help manage symptoms and slow disease progression for a period of time (Alzheimer’s Association, 2024a).
Historical Perspective
“Senile dementia”—the loss of memory and other intellectual faculties that occurs in older adults—was recognized in the time of Hippocrates. In the centuries that followed, this condition was thought to be simply a result of old age, commonly called hardening of the arteries.
Diseases of old age, however, were considered unimportant until the second half of the 19th century. Prior to this period, people in the United States lived an average of 50 years and few reached the age of greatest risk for Alzheimer’s disease. For this reason, the disease was considered rare, and there was little scientific interest in it.
This changed as the average lifespan increased and Alzheimer’s became more common in people aged 70 and older. During this period of time, advancements in medicine and the ability to look inside the brain gave the medical community the realization that diseases could be the cause of this deterioration.
| 1906 | German psychiatrist Alois Alzheimer first described the pathology of the disease after using staining techniques to identify amyloid plaques and neurofibrillary tangles in the brain associated with the symptoms of senile dementia. |
| 1910 | The disease was labeled Alzheimer’s disease by Emil Kraepelin. |
| 1931 | After the invention of the electron microscope, it became possible to conduct further study of the brain by viewing actual brain cells, opening the door to research into many areas of brain disorders, including Alzheimer’s disease. |
| 1968 | The Lawton Instrumental Activities of Daily Living Scale was developed to measure cognitive function at baseline and to identify improvement or deterioration over time. |
| 1976 | Alzheimer’s disease was recognized as the most common form of dementia. |
| 1980 | The Alzheimer’s Association was founded. |
| 1983 | National Alzheimer’s Disease Month was declared. |
| 1984 | Beta-amyloid was identified as forming Alzheimer’s disease’s characteristic plaques, which cause reduced neurologic function. A nationwide infrastructure for Alzheimer’s research was established by the National Institute on Aging. |
| 1986 | Tau protein was identified as forming Alzheimer’s disease’s characteristic neurofibrillary tangles. |
| 1987 | The first Alzheimer’s drug trial (tacrine) was begun. The first deterministic Alzheimer’s gene, amyloid precursor protein (APP), was discovered. |
| 1993 | The first Alzheimer’s disease risk factor gene was identified, called APOE4. The first Alzheimer’s drug, tacrine (Cognex), was approved by the U.S. Food and Drug Administration (FDA). |
| 1994 | President Reagan announced he had been diagnosed with Alzheimer’s disease. The first World Alzheimer’s Day was held. |
| 1996 | FDA approved donepezil (Aricept), a cholinesterase inhibitor, for treating Alzheimer’s-type dementia. |
| 1999 | Report published showing that injecting transgenic “Alzheimer’s” mice with beta-amyloid prevents the animals from developing plaques and other Alzheimer’s-like brain changes. |
| 2000 | FDA approved rivastigmine (Exelon), a cholinesterase inhibitor, for treating all stages of Alzheimer’s disease. |
| 2001 | FDA approved galantamine (Razadyne), a cholinesterase inhibitor, for treating mild to moderate Alzheimer’s disease. |
| 2003 | FDA approved memantine, an N-methyl-D-aspartate (NMDA) antagonist that reduces certain types of brain activity by binding to NMDA receptors and blocking the activity of glutamate, which in Alzheimer’s disease can overstimulate nerve cells and kill them. |
| 2004 | A new imaging agent known as Pittsburgh Compound B (PiB) was produced to be used with positron emission tomography for early detection of Alzheimer’s. Alzheimer’s Disease Neuroimaging Initiative was begun to share research data worldwide. |
| 2009 | An effort was begun to standardized biomarkers for Alzheimer’s disease. |
| 2011 | Alzheimer’s disease advanced to become the sixth leading cause of death in the United States and the fifth leading cause of death for persons over the age of 65. Canadian scientists used a technique known as deep brain stimulation (applying electricity to regions of the brain) to reverse Alzheimer’s disease-related memory loss. Annual assessment for cognitive impairment for all Medicare recipients was implemented as part of an annual wellness visit. President Obama signed the National Alzheimer’s Project Act into law, a framework for a national strategic plan. |
| 2012 | Scientists at University College London discovered that specific antibodies that block the function of a related protein (Dkk1) are able to completely suppress the toxic effect of beta-amyloid on synapses. The first major clinical trial for prevention of Alzheimer’s disease was begun. |
| 2013 | International Genomics of Alzheimer’s Project researchers identified new genetic risk factors for Alzheimer’s disease. |
| 2014 | FDA approved donepezil combined with memantine (Namzaric) for treatment of moderate to severe Alzheimer’s disease. Rates of death caused by Alzheimer’s disease were found to be much higher than reported on death certificates. |
| 2015 | A UCLA study identified three distinct subtypes of Alzheimer’s disease: inflammatory, noninflammatory, and cortical (associated with significant zinc deficiency). Research began to determine if they have different underlying causes and respond differentially to potential treatments. |
| 2017 | An historic $400 million increase for federal Alzheimer’s disease research funding was signed into law, bringing annual funding to $1.4 billion. |
| 2018 | Dementia Care Practice Recommendations were developed to help professional care providers deliver optimal quality, person-centered care. |
| 2021 | Aducanumab (Aduhelm), the first therapy to address the underlying biology of Alzheimer’s disease, received accelerated approval by the FDA for limited use. |
| 2023 | Lecanemab (Leqembi), which addresses the underlying biology of AD, was approved for treatment of early AD. Donanemab (Kisunla) was approved; it removes beta-amyloid from the brain. |
| 2024 | Aducanumab (Aduhelm) was discontinued by its manufacturer, Biogen. |
| (Alzheimer’s Association, 2024b) | |
Scientists continue the search for answers regarding causes, diagnoses, and treatments for Alzheimer’s disease, but developing new treatments for Alzheimer’s disease has proven difficult. Some challenges in developing new treatments include:
- Most drugs fail during testing.
- Brains are almost impenetrable and are protected by the blood-brain barrier.
- Treating a symptom isn’t treating a disease.
- There is inadequate funding for Alzheimer’s research.
- Scientists aren’t sure what causes Alzheimer’s disease.
(Brookshire, 2024)
SCOPE OF THE DISEASE
Alzheimer’s Disease Worldwide
Every three seconds someone in the world develops dementia, and every year there are nearly 10 million new cases. Worldwide, more than 55 million people are living with Alzheimer’s and other dementias, over 60% of whom are in low- and middle-income countries.
That number is expected to increase in 2030 to 78 million and in 2050 to 139 million. Dementia is one of the major causes of disability and dependency among older people globally. Dementia is currently the seventh leading cause of death, and 65% of dementia-related deaths are in women (WHO, 2024).
A systematic review and meta-analysis done in 2020 showed that the prevalence of dementia was higher in Europe and North America than in South America, Asia, and Africa. China has surpassed all other countries to become the nation with the highest number of dementia patients.
Currently more than 15 million people ages 60 and above in China have dementia, accounting for a quarter of all dementia patients worldwide. Of this number, 9.83 million have Alzheimer’s disease. The disease is now affecting people in China at a younger age, with 21.4% being below the age of 60. AD and other dementias have become an increasingly serious public and social problem (Lv et al., 2023; Global Times, 2023).
A recent study reveals that two small Indigenous groups in the Bolivian Amazon have among the lowest rates of dementia in the world, at around 1% in people ages 60 and older (Miller, 2022).
Alzheimer’s Disease in the United States
It is estimated that as many as 6.9 million Americans aged 65 and older have Alzheimer’s disease. As the size of the U.S. population ages 65 and older continues to grow, so too will the number and proportion of Americans with AD and other dementias.
By 2050, the number of people age 65 and older with Alzheimer’s may reach a projected 12.7 million unless there is a medical breakthrough to prevent or cure the disease (Alzheimer’s Association, 2024a).
The states with the highest prevalence of Alzheimer’s disease are in the east and southeast regions, with the highest in Maryland (12.9%), New York (12.7%), and Mississippi (12.5%). States with the highest number of people with AD were California, Florida, and Texas. Among larger counties, those with the highest prevalence of AD were Miami-Dade County in Florida, Baltimore City in Maryland, and Bronx County in New York (Alzheimer’s Association, 2024c).
BY AGE
Following is the distribution of Alzheimer’s by age in the United States:
- 65–74 years: 26.4%
- 75–84 years: 38.6%
- 85+ years: 35.4%
(Statista, 2024a)
BY SEX
Almost two thirds of Americans with AD are women. Of the 6.9 million people ages 65 and older with AD, 4.2 million are women (11%) and 2.7 million (9%) are men. The main reason for this is that women live longer than men and older age is the biggest risk factor for this disease. Studies have been unclear whether those of female sex are more likely to develop dementia than those of male sex (Alzheimer’s Association, 2024a). (See also “Sex” under “Etiology and Risk Factors of Alzheimer’s Disease” later in this course.)
BY RACE/ETHNICITY
African Americans are about two times more likely than White people to have Alzheimer’s and other dementias but only 34% more likely to have a diagnosis. They are also more likely to be diagnosed in later stages. Hispanics are about one and one half times more likely than White people to have Alzheimer’s and other dementias but only 18% more likely to have a diagnosis (Alzheimer’s Association, 2024d).
As many as 1 in 3 Native American older adults will develop Alzheimer’s or some other form of dementia. Between 2020 and 2060, the number of American Indian/Alaska Native individuals age 65 and older living with dementia is projected to increase fourfold. More than one third of Native Americans say they do not expect to live long enough to develop Alzheimer’s, and more than half (53%) believe that significant memory or cognitive losses are a normal part of aging (Alzheimer’s Association, 2024e).
BY EDUCATION LEVEL
Research has found a high educational level to be associated with a 30% lower risk of Alzheimer’s compared with a low educational level. Combining genetic risk and education categories, individuals with a low genetic risk and a high educational level had a more than 90% lower risk of AD compared to those with a high genetic risk and low educational level (Li et al., 2023).
MORBIDITY AND MORTALITY
Before a person with Alzheimer’s dies, they live through years of morbidity as the disease progresses.
Between 2019 and 2020, the total number of deaths from Alzheimer’s disease increased 10.5%, with COVID-19 being a significant contributor. In 2022, AD was the seventh-leading cause of death in the United States, with more than 120,000 deaths and an age-adjusted mortality rate of 28.9 per 100,000 people. This was a nearly 7% decline from 2021, when deaths from AD had more than doubled between 2000 and that year. Among Americans ages 65 and older, AD is the fifth-leading cause of death (Alzheimer’s Association, 2023a).
Alzheimer’s disease is associated with excess comorbidity, including hypertension, diabetes (types 1 and 2), cardiovascular disease, and depression. There is evidence that risk factors common to comorbidities and AD, such as chronic inflammation, can place individuals with comorbidities at increased risk of developing AD. The interplay between comorbidities and development and progression of AD, however, remains incompletely understood (Lanctôt et al., 2023).
Source Alzheimer’s Disease and Dementia CEU | Wild Iris Medical Education
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