User:Amylaid/Alzheimer disease in African American individuals

Alzheimer's disease in African Americans is becoming a rising topic of interest in Alzheimer's care, support, and scientific research, as African Americans are disproportionately affected by Alzheimer's. There has been increasing research on the racial disparities in Alzheimer's disease recently, as there are clear disparities between racial groups. Specifically, both the prevalence and incidence of Alzheimer's in African Americans are higher than the overall average. However, because of the lack of representation in clinical trials, there is still a gap in the current understanding of Alzheimer's and how it affects African Americans. Genetic factors could explain why the prevalence of Alzheimer's is higher in African Americans. The lower quality and accessibility of education could also be a risk factor. Furthermore, the costly care services put a huge financial burden on the families impacted, which could result in lack of quality care and early diagnosis.

Alzheimer's disease
Alzheimer's disease (AD) is a progressive, irreversible neurodegenerative disease and it is the leading cause of dementia. According to the National Institute on Aging (NIA), Alzheimer's disease is characterized by the intracellular aggregation of Neurofibrillary tangle (NFT), consisted of hyper-phosphorylated Tau protein, and extracellular accumulation of Amyloid beta. Symptoms of Alzheimer's include memory loss, cognitive decline, increased anxiety or aggression, and ultimately fatal.

Prevalence and Incidence
Approximately 5.8 million Americans over the age of 65 have Alzheimer's dementia in 2020, which is approximately 1 in 10 people in that age group, and eighty percent are over the age of 75. The risk increases with age, with 32% of people over the age of 85 living with Alzheimer's dementia.

The number of Alzheimer's patients will increase rapidly in the coming years, as the Baby Boom generation has begun to reach the age of 65 and above, and the population of Americans over the age of 65 is projected to grow to 88 million by 2050. Many studies have found that African Americans are about twice as likely to have Alzheimer's disease as Caucasians, and the prevalence of Alzheimer's in African Americans is higher than any other racial groups. In fact, 21.3% of African Americans over the age of 70 have Alzheimer's, a much higher prevalence comparing to the national average. The risk of dementia (not limited to Alzheimer's) among relatives of African Americans who have Alzheimer's is 43.7%, suggesting a strong role of genetic in disease onset. The incidence of Alzheimer's in African Americans is also the highest out of all racial groups. The age-adjusted incidence rate per 1,000 person per year is 26.6 for African Americans, comparing to the overall average 21.7.

Neuroinflammation
Neuroinflammation has been suggested to play a prominent role in the pathogenesis of Alzheimer's after the discovery of increased levels of inflammatory markers in Alzheimer's patients and the identification of Alzheimer's risk genes associated with innate immune functions such as TREM2 and CD33. While the exact mechanism is still not conclusive, one leading hypothesis is that it exacerbates Amyloid-beta and tau pathologies. PET scanning also showed increased microglia activation (inflammation) in the brains of AD patients. Microglia acts as the macrophage for the Central nervous system (CNS), and its main functions include maintenance of neuronal networks and injury repairs.

There is an increased level of inflammation markers, such as IL-1β, MIG, TRAIL, and FADD, in the brains of African Americans compared to Caucasians. Furthermore, the NLPR3 inflammasome that is thought to be critically involved in Alzheimer's has increased activation in African Americans. There is also evidence that shows a stronger association between the level of IL-8, an inflammation marker, and cognitive performance in African Americans than Caucasians.

Cognitive decline/Mild cognitive impairment
Cognitive decline is a hallmark of Alzheimer's disease. Because Alzheimer's involves neuropathological changes in the cortex and hippocampus, AD patients often show deficits in learning, memory, and language, and the precise nature and severity of the cognitive decline also reflects disease progression.

The Alzheimer's Association defines Mild cognitive impairment (MCI) as "early stage of memory loss or other cognitive ability loss, such as language or visual/spatial perception, in individuals who maintain the ability to independently perform most activities of daily living". For Alzheimer's. MCI can be an indicator of disease onset in early stages if the other hallmarks are also present. There are two types of MCI: Amnestic MCI which primarily affects the memory and Nonamnestic MCI which affects thinking skills other than the memory. The incidence of MCI is higher in African American populations as compared with White populations. However, risk factors of AD, such as diabetes and cardiovascular diseases, are not associated with an increased risk of MCI development in African Americans. The rate of cognitive decline in MCI also appears to be faster in African Americans. Specifically, majority of African American patients with MCI are considered nonamnestic, particularly in language and executive function. Therefore, diagnosis of nonamnestic MCI among African Americans could lead to early interventions to delay further cognitive decline.

Biomarkers
Biomarker is a measurable indicator of a disease state and status of the body. It is helpful in disease diagnosis, tracking progression, and monitoring the response to treatment. Developing reliable biomarkers is an important part of Alzheimer's research because an early, correct clinical diagnosis would allow physicians to initiate treatment with symptomatic and disease-modifying drugs. Biomarkers alone can't diagnose if a person might have Alzheimer's, as they are only part of the assessment, however they can help physicians and researchers identify potential risk factors, detect early brain changes, and track the response to drugs and other non-pharmacological interventions.

Brain Imagining
Positron emission tomography, or PET, is a brain technique that uses a small amount of radioactive substance, called a tracer, to measure energy use or a specific molecule in different brain regions. By selecting different tracers, physicians and researchers can measure different biomarkers associated with Alzheimer's disease.

Amyloid PET measures the abnormal deposits of Amyloid-beta. Higher levels of amyloid-beta is associated with presence of Amyloid plaques, one of the hallmarks of Alzheimer's disease.

Tau PET detects the abnormal accumulation of tau protein, which is also a hallmark of Alzheimer's disease. It is not commonly used in medical practice to diagnose patients, but it is still useful in research settings to test potential treatments.

CSF biomarkers
The Cerebrospinal fluid surrounds the brain and spinal cord to provide protection, supply nutrients, and help maintain the integrity of the Blood–brain barrier. Doctors can access CSF through a Lumbar puncture, commonly known as the spinal tab, to diagnose Alzheimer's or other types of dementia. The mostly widely used CSF biomarkers for Alzheimer's are amyloid-beta 42 (the major component of amyloid plaques), total tau (T-tau), and phosphorylated tau (the major component of tau tangles).

Risk factors
Alzheimer's disease is a complex condition where there isn't a single cause. However, some risk factors have been identified. While some factors such as age and heredity can't be changed, there are environmental factors that can be modify to influence disease onset and progression.

Genetics
There are two categories of genes influencing where a person will develop Alzheimer's: a risk gene, which only increase the risk of developing Alzheimer's but do not guarantee that it will happen, and a deterministic gene that actually causes Alzheimer's. Luckily, less than 1% of Alzheimer's cases are caused by deterministic genes.

APOE e4
The Apolipoprotein E (APOE) is a protein involved in fat transportation in the bloodstream such as cholesterol. It comes in three different forms, or Allele s, e2, e3, and e4. Each person carries two APOE alleles, one from each biological parent, resulting in six possible pairs: e2/e2, e2/e3, e2/e4, e3/e3, e3/e4, e4/e4. APOE-e4 is the strongest risk gene that has been discovered, as inheriting one copy of the e4 allele increases the risk of developing Alzheimer's about three times. It is also associated with increased Amyloid Beta accumulation and early disease onset.

According to Alzheimer's Association, a non-profit organization for the research and support of Alzheimer's disease, close to 40% of African Americans have at least one e4 allele, while only 26% of European Americans do. It has been shown that having one or two copies of the e4 allele significantly increases the risk for developing Alzheimer's and cognitive impairment.

Interestingly, APOE e4 seems to have different effects on African Americans compared to other racial groups. APOE e4 homozygosity (having two e4 alleles) is highly associated with AD in African Americans. However, the results are inconsistent for heterozygotic e4 carrier, suggesting that APOE e4 might have less predictive impact on Alzheimer's onset and progression in African Americans. Additional APOE e4 allele is associated with a faster decline on memory test among Whites only, not African Americans. Compared with individuals with no APOE E4 allele, the relative risk (RR) of AD associated with one or more alleles of APOE e4 is significantly increased among whites (RR=2.5) but not African Americans (RR=1.0). Furthermore, in the presence of an APOE e4 allele, the cumulative risk of AD to age 90 years is similar for both Whites and African Americans. However, in the absence of the APOE e4 allele, the cumulative risk of AD was 4 times higher for African Americans (RR=4.4), suggesting that the presence of an APOE e4 allele is a much stronger determinant of AD risk in Whites than African Americans. Despite the inconclusive role of APOE e4 in African Americans, it has been associated with an increased risk of late onset AD in African American population nonetheless. Therefore, more research is needed to better understand the role of APOE and its alleles in Alzheimer's onset and progression.

APP
The Amyloid-beta precursor protein (APP) is a transmembrane protein whose proteolysis produces the amyloid-beta peptides. Several rare mutations on APP cause Familial Alzheimer's disease (FAD) in only a few hundred extended families worldwide. Mutations on APP cause early-onset Alzheimer's in which symptoms start developing in a person's early 40s, and it accounts for less than 1% of all Alzheimer's cases.

APP is cleaved first by β-secretase and then γ-secretase to produce amyloid-beta peptide. Most of the APP mutations cluster near the β-secretase and γ-secretase cleaving sites, and generally increase total Aβ levels and/or the Aβ42/Aβ40 ratio. Aβ42 is the more toxic form of amyloid beta, so an increased Aβ42/Aβ40 ratio is a sign of disease progression.

PS-1 and PS-2
Presenilin 1 (PS1) and Presenilin 2 (PS2) are the cleaving enzymes in the γ-secretase complex. There are close to 200 mutations on PS1 and PS2 combined that cause early-onset Alzheimer's disease, and they predominantly alter the amino acids in their transmembrane domains. These mutations increase the production of the less soluble, more toxic Aβ42.

ABCA7
ABCA7 is a member of the high conserved family of ATP-binding cassette (ABC) transporter, which uses energy from ATP hydrolysis to transfer molecules across cell membranes toward the outside. The ABCA7 gene is among the top 10 risk genes for Alzheimers, and the association is the strongest for African Americans, whose risk for AD has an effect size approaching that of APOE. Furthermore, deleterious ABCA7 alleles could cause protein loss-of function, and these loss-of-function mutations increase risk of Alzheimer's by 80% in African Americans.

The mechanism of ABCA7's role in Alzheimer's pathogenesis remains unknown. A leading hypothesis is that ABCA7 regulates APP processing and Aβ clearance.

Comorbidity
Although age and heredity are risk factors that can't be changed, there are some risk factors that could be influenced through lifestyle changes and making wellness choices to effectively manage other health conditions. There are a wide range of comorbid diseases that are associated with Alzheimer's.

Cardiovascular diseases, such as stroke, Atrial Fibrillation, and Coronary Heart Disease, have been recognized as closely related to the development of AD at both clinical and pathological levels. In additional, risk factors for cardiovascular diseases themselves, such as obesity, is also associated with an increased risk for Alzheimer's. African Americans are at a high risk of developing cardiovascular diseases. In 2018, they were 30% more likely to die from a cardiovascular disease than non-Hispanic whites. Cardiovascular diseases can be managed and countered through exercise. Regular exercise can reduce the risk of developing Alzheimer's by 45%. Exercise also has a greater positive effect in cognitive function in Alzheimer's patients who are APOE e4 carriers compared to non-carriers. Conversely, APOE e4 carriers with a sedentary lifestyle show a greater amyloid-beta deposition compared to non-carriers.

Type 2 diabetes (T2D) is a well-established risk factor for Alzheimer's, and T2D patients also have a higher risk of developing Alzheimer's and Vascular dementia. Although the exact cause of this association is unclear, alterations in insulin, glucose, and amyloid metabolism may underlie the association between both diseases. Finally, there is a 1.25-1.9 fold increase for cognitive impairment in patients with T2D. In 2018, African Americans were twice as likely as non-Hispanic whites to die from diabetes, and African American adults are 60% more likely than non-Hispanic whites to be diagnosed with diabetes by a physician. There is also a greater prevalence of risk factors related to diabetes among African Americans, contributing to the higher burden of diabetes and higher risk of AD.

Treatments
There is no cure for Alzheimer's, but there are drugs approved by the Food and Drug Administration (FDA) to manage disease progression. Treatments can be divided into either symptomatic drugs, meaning that they only affect the symptoms and not the underlying cause, or disease-modifying drugs, meaning that they could change the disease progression overtime.

Education
People with more years of education have a lower risk of developing Alzheimer's in a year-dependent manner. insert citation With each additional year of formal education, the odds of developing Alzheimer's is decreased by 12%. A lot several or various instead? of factors may contribute to this. For example, having a fulfilling and stimulating job allows the brain to make more flexible and efficient use of cognitive networks, which are the networks of neuron-to-neuron connections known as "cognitive reserve". Building cognitive reserve also enables a person to continue carrying out day-to-day and more complex cognitive tasks despite brain damages, such as beta-amyloid and tau accumulation. And finally, a person with more education is more likely to recognize signs of Alzheimer's symptoms when they first appear and consult a physician, resulting in better prevention in disease progression and better quality of life. I think you cold talk about prevention more later on and maybe include examples of programs that are working towards mediating this disparity

A report from the United States Census Bureau indicated that around 38% of Americans have a Bachelor's degree. The number is significantly lower for African Americans, as only 25% of African Americans have at least a college degree. Furthermore, the quality of education, instead of quantity, could also contribute to difference in risks. In a 2012 study, Wechsler Test of Adult Reading was used to assess the individuals' intellectual functioning and therefore an estimate of quality of education. African Americans scored significantly lower than their White Non-Hispanic counterparts, matched for with age, sex, and years of formal education, in many different areas such as memory, attention, and language. However, when adjusted for reading level, the previously observed differences were attenuated, suggesting that the quality of education needs to be taken into account when assessing cognitive impairment in Alzheimer's patients.

Clinical Trials
For a new drug to be approved by the Food and Drug Administration, it has to first go through a clinical trial in both healthy subjects and patients. Clinical trial is important because it can determine if a new treatment is safe and efficacious to be distributed to patients.

African Americans are disproportionally underrepresented in clinical trials. Clinical trials volunteers are mostly, sometimes exclusively, consisted of White male. In fact, African American patients account for just 5% of clinical trial participants in the United States. This could create gaps in scientists' understanding of disease conditions, risk factors, and treatment options, especially for a disease like Alzheimer's that impacts African Americans at a higher rate. More African Americans should be included in clinical trials for Alzheimer's treatment, so scientists and physicians could better development treatments and care plans for African American population.

A long history of discrimination from medical professionals could be the reason why there is a high level of mistrust of clinical trial in African Americans. 62% of African Americans believe that medical research is biased against people of color. Therefore, it is important to improve the Diversity and Inclusion of clinical trials and encourage African Americans to volunteer for clinical trials.

Cost of Care Services
According to a 2019 data, among Alzheimer's and other dementia patients, African Americans have the highest total payments per person per year of $28,633, while White Non-Hispanics have the lowest payments of $21,174. This difference is observed in every type of care services, with the biggest different in Hospital Care where the payments are almost $4,000 more per person per year for African Americans ($9,566 vs. $5,683). The difference could be due to more co-morbidities or late-stage diagnosis, which could lead to the worsening of disease. This presents a challenge for the family and physician for African American Alzheimer's patients, since the median household for African Americans is the lowest among the racial groups at $45,870.

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