The Role of Ethnicity, Environmental Factors, and Music Therapy in Alzheimer's Disease

Introduction

In 2023, the average world life expectancy has reached 73.16 years which is 0.24% more than that in 2022 (Macrotrends LLC,2023). As this number continues to grow, the likelihood of elderly people developing Alzheimer’s disease (AD) – a progressive loss of memory, thinking, and decision-making abilities that disturb the ability to carry out everyday activities – increases substantially. The study of the absolute 10-year risk of Alzheimer’s disease in 3017 women and men, who were apolipoprotein epsilon 4 (APOE4) carriers, showed 7% and 6% at age 60-69 years, 16% and 12% at age 70-79 years, 24 % and 19% at age 80 years, respectively. (Katrine L. Rasmussen,2018). 6.7 million Americans are suffering from different stages of AD and this number is predicted to rise in the upcoming years (Alzheimer’s Association, 2023). Many previous studies have been conducted to examine various causes of AD such as beta-amyloid plaques, neurofibrillary tangles, oxidative damage, and genetics, but there is still a huge gap considering the effects of environmental and cultural factors, education level, and nutrient intake. Scientists believe that AD is the result of a combination of genetic, lifestyle, and environmental factors. Specific genetic changes account for less than 1% of cases, which almost guarantee a person will develop the disease (Mayo Clinic,2023). The fact that ethnicity and culture have a huge impact on our genetics and our vulnerability to Alzheimer's is being neglected by many people and even in some cases by specialists to predict the occurrence of the disorder or explain its vital causes. In this research paper, I will elaborate on why ethnicity and cultural traits are essential in Alzheimer’s studies and treatment, and how they can help invoke people to save themselves from detrimental consequences of it. In addition, I will demonstrate why music therapy is one of the best approaches for treating AD.

Background information about AD and its development.

Dementia is a condition characterized by progressive or persistent loss of mechanical functioning, impairment of abstract thinking and memory, and abrupt changes in behavior and attitude. While dementia is a general term for different diseases, Alzheimer’s is a specific type of dementia. AD development is mostly associated with beta-amyloid plaques, which develop between neurons, and neurofibrillary tangles, which develop inside neurons.

Beta-amyloid plaque

In the typical brain the gene for amyloid precursor protein(APP) is located in chromosome 21 and encodes a transmembrane protein. The amyloid precursor protein is cleaved by gamma-secretase and beta-secretase to form the amyloid beta peptide. But mutations in the APP gene or secretases cause the build-up of “sticky” beta-amyloid into plaques.

Neurofibrillary tangles

In healthy neurons, tau binds to and stabilizes microtubules (components of the cytoskeleton). However, in AD, tau detaches from microtubules and sticks to other tau proteins. Eventually, this accumulation turns into tangles which harms the synaptic communication between neurons and causes neurons to shrink.

What are APOE and APOE 4?

APOE is an apolipoprotein that is involved in the metabolism of fat, and cholesterol in mammals and has a key role in lipid metabolism in the brain. In other words, it helps to clean excess amounts of fat from our brain to create a balance. APOE 4 is an allele often considered a risk factor for Alzheimer’s disease. As the life expectancy of many people is increasing year by year APOE 4 is becoming a threatening factor among elderly people.

The role of ethnicity in Alzheimer’s disease.

Ethnicity is a term that refers to the social and cultural characteristics, backgrounds, or experiences shared by a group of people. It connects both cultural and genetic characteristics and explains the predisposed behaviors of different people. Ethnicity is integral in Alzheimer’s studies as it can explain the reasons for dementia development scientifically and culturally. There is an existing disparity in the prevalence, treatment, incidence, and mortality of the disease across ethnic groups. Previous studies suggest that African Americans are about two times more likely to have AD than Europeans and Hispanics are 1.5 times more likely to develop AD than Europeans. (Alzheimer’s Association,2014). Several studies in states like Texas, New York, Mississippi, etc. demonstrated higher rates of dementia among African Americans and Hispanics than among Europeans and Asians (Harwood & Ownby,2000). AD and other types of dementia are the product of both cultural and biological factors. Disparities in the incidence and prevalence of AD can be explained by ethnoracial differences in biological factors such as genetics and cardiovascular disorders. Meanwhile, diagnosis and treatment are affected by race-specific cultural factors. Differences in perceptions, cognition, lack of adequate access to medical care, and issues of trust between minority groups and the establishment are the constituents of cultural factors that affect AD prevalence and development in different ethnic groups (Chin, Alexander L. et al, 2011). Even the same gene can act differently in different ethnic groups due to several environmental or other factors. For example, the HANDLS (Healthy Aging in Neighborhoods of Diversity across the Lifespan) study in Baltimore depicted an adverse association between APOE4 dosage and cognitive decline among Europeans, whereas, among African American women,APOE4 dosage had a potential protective effect on the ability to keep an attention over time, slower decline on a test of attention. ( May A. Beydoun et al.,2021). As ethnicity plays a pivotal role in AD development and distribution all across the world, it is essential to conduct further investigations to scrutinize its possible effects on people’s brains, cognition, and attitudes.

Genetics.

Alzheimer’s disease has a dichotomous pattern One pattern is rare mutations in APP, presenilin 1 (PSEN1), and PSEN2 which lead to early-onset familial AD and the other one is gene polymorphisms, such as APOE2 and APOE4, which can influence the susceptibility of the later-onset AD (Rudolph E. Tanzi,2012). This research paper highlights how genetics plays a role in disparities in AD prevalence among different ethnoracial groups. Apolipoprotein alleles are expressed in three forms - APOE2, APOE3, and APOE4. APOE 4 is considered the most vital genetic risk factor for Alzheimer’s disease, while APOE3 is neutral, and APOE2 is protective. Utilizing embryonic stem (ES) ) cell-derived human neurons, it was reported that APOE is secreted by glial cells, which protect the brain from different infections and debris. Glial cells also stimulate amyloid-beta production with an APOE4>APOE3>APOE2 potency rank order. APOE 4 is the apolipoprotein allele that is adaptive for declining mortality under circumstances of high infection and shorter life expectancy. Since the modern healthcare system transitioned humans into less-infectious environments and longer life spans, APOE4 raised the risk of age-related diseases, particularly affecting arteries and the brain. The prevalence of the APOE4 allele has a wide range of 3-41% globally (Hussein N. Yassine & Caleb E. Finch,2020). The frequency of APOE4 was higher in African Americans compared to Europeans and Hispanics. In New York City studies, a strong relationship between APOE 4 homozygosity and AD among Hispanics, African Americans, and Europeans was found. Although, there was an association between AD and ApoE 4 heterozygosity in Hispanics and Europeans, an inverse association was found among African Americans. APOE2 genotypes were linked with reduced risk in Europeans, but no such association existed in Hispanics and African Americans (Maestre G. et al, 1996). This variability in the function of APOE alleles among various ethnic groups cannot be explained by age differences, but only by environmental and cultural factors. Another example can be represented by Cherokee Native Americans. A study of Native Americans inhabiting Oklahoma found that as a genetic degree of ancestry increased, the frequency of AD decreased. Elders with more than fifty percent genetic Cherokee ancestry were less likely to be in the AD group than the other control group (Rosenberg et al.,1996). Hendrie and his colleagues from the Indiana University School of Medicine and the University of Ibadan began investigating the epidemiology of dementia among African Americans inhabiting Indianapolis and Nigerians in Ibadan. Age-related prevalence for dementia and AD among Nigerian elders in Ibadan was significantly lower than rates of dementia and AD among African Americans (Hendrie et al.,2001). Even though APOE3 is considered a neutral and common type of APOE allele, its intensity of association with AD varies in different ethnic groups. Therefore, a meta-analysis of the Chinese people was carried out. The meta-analysis included 166 eligible studies from Chinese and English databases, enrolling 23396 patients with AD and 25568 healthy controls. The frequency of the APOE4 allele in AD was higher than that in healthy controls while the frequencies of ApoE2 and APOE3 in AD were lower than those in healthy controls. The results provided support for the protective effect of the APOE3/APOE3 genotype against AD development. In sum, the APOE3 allele had a protective effect against sporadic AD in the Chinese population studied. (Qian Chen et al., 2022) Down syndrome has a direct connection with AD development. About 40-80% of people with this syndrome develop Alzheimer’s disease in their 50s and 60s. The cause of this linkage is explained by chromosome 21 in both conditions( Down syndrome and AD). Individuals with Down syndrome have an extra copy of chromosome 21, predisposing them to developing AD. The reason for this connection can be explained by the location APP( one of the main factors of early-onset of). Because APP is also found in chromosome 21. One more chromosome for housing APP, more chance of developing AD (Ahmad Salehi et al., 2019). All these studies show that Alzheimer's disease is not only linked by genetics among various ethnic groups, but also other factors can cause the variability of the functions of the same alleles among ethnic groups.

Importance of environmental and cultural factors.

Culture is defined as the set of learned traditions, customs, beliefs, and ways of living shared by members of a particular society. The ways of thinking, behaving, and feeling have three components: the internal representation, the behavioral dimensions, and cultural elements which are parts of the culture. The ways of feeling and thinking, values, knowledge, attitudes, and beliefs are represented by our internal representation and it is subjective. How our behavior and attitude change in various contexts and conditions and how we relate with other people is demonstrated by our behavioral dimensions. Cultural elements include symbolic objects that represent abstract concepts. While conducting ethnoracial-based AD studies, many researchers neglect cultural background – linguistic, country of origin– which can lead to contradictory results. It is important to note that ethnicity is not only described by genetics, but also by societies. Therefore, differences in cognitive performances and disparities in AD development among Europeans, Asians, and African Americans are likely attributable to cultural differences. Ethnicity is a broad category, and it cannot be limited by only racial and genetic variabilities; ethnicity also includes elements such as language, society, culture, nationality, common ancestry, and environment.

Neuropsychological assessments test for the presence and characterization of cognitive impairment in AD and other dementias. Though, tests of cognitive abilities are susceptible to the impact of culture ( Roselli M et al, 2003). The observation focusing on distinctions in the attentional patterns among Westerners and East Asians showed that East Asians concentrated on contextual characteristics of objects and relationships to their environment more than Westerners. The alteration in the object’s environment negatively affected East Asians’ accuracy in their responses, whereas change had no significant effect on the Westerner’ ability to identify objects. This result explains the idea that Westerners think more autonomously, while Easterners think more interdependently and how the modification in the environment can affect East Asians’ cognitive development. For example, the age-standardized test of Japanese-American men in Hawaii showed an increased prevalence of AD at 7.6 percent among Japanese-American men, which was similar to that of European populations and more than Japanese men living in Japan (4-6 percent). It is suggested that environmental and cultural exposures associated with migration from Japan to America affected the development of AD in Japanese immigrants (White L, et al,1996).

Multiple factors affect a person's mental health and increase vulnerability to Alzheimer’s disease. These include diet, lifestyle, air quality, exposure to magnetic fields, noise, and cardiovascular or chronic diseases. Each of these factors has a profound effect on the function and development of the brain. The first factor is a diet which is important for delivering necessary chemicals, and components to our nervous system to develop and function properly. Possibly, eating a certain diet affects biological mechanisms, such as inflammation and oxidative damage, that cause Alzheimer’s disease. Moreover, diet indirectly affects other AD risk factors, including diabetes, obesity, and heart disease. A diet that shows a shred of promising evidence is the Mediterranean diet, which consists of vegetables, fruits, legumes, fish, grains, and other seafood, low amounts of red meat, eggs, and sweets, and unsaturated fats like olive oils.The MIND(Mediterranean–DASH Intervention for Neurodegenerative Delay ) diet was seen to lower high blood pressure, a risk factor for Alzheimer’s disease(Cristiana Sara,2020). Still, many scientists are arguing why the Mediterranean diet may help the brain. Perhaps, its ability to improve cardiovascular health can in turn reduce the risk of dementia. An analysis of diet and other factors found that, after an average of 4.5 years, people who had a diet close to the MIND diet had a 53 % reduced rate of Alzheimer’s disease compared to those who did not follow the diet (Martha Clare Morris et al., 2015). The study carried out at the New York University School of Medicine among 116 cognitively healthy participants showed that those who followed a Mediterranean diet had thicker cortical brain regions than those who did not. Cortical brain regions shrink in patients with Alzheimer’s. Therefore, having thicker regions can mean cognitive benefit(Lisa Mosconi et al.,2018). Despite this evidence, scientists are persisting in looking for clues and other facts to support the importance of diet in cognitive development and health. Dr. Martha Morris and her colleagues from Rush University conducted a prospective study of 960 participants aged 58-99 years, who completed a food frequency questionnaire and had cognitive assessments for over 4.7 years. The researchers concluded that consumption of green leafy vegetables like spinach, kale, and lettuce was associated with a slower cognitive decline (Martha Clare Morris et al.,2017). Vitamin D has numerous effects for stimulating macrophages to clear amyloid plaques, reducing amyloid-induced cytotoxicity as well as cerebrovascular function (Littlejohns TJ. et al.,2014). In a study of salt’s effect on the brain, mice were fed with a high-salt diet containing 16 times more sodium chloride than that typically found in their food. This slowed the blood flow in the brain and was accompanied by dementia-like symptoms. Researchers concluded that consuming higher amounts of salt increased tau levels (Costantino Iadecola et al.,2018).

Multiple air pollutants are associated with ascended Alzheimer’s and dementia risk, such as ozone, nitrogen oxides, and tobacco smokes. A prospective study of the association between ozone, particular matter, and AD in Taiwan showed a negative effect of these air pollutants as the risk of AD incident rose by two to threefold (Jung CR et al.,2015). Toxic metals could also be the source of AD for many people. For instance, a case-control study of 129 people in Canada found that an excess number of people with Alzheimer’s dementia resided in areas with higher than average lead concentrations (Emard JF et al.,1994). In Sweden, there was a study of 4.7 million people investigating the relationship between the risk ratio of AD and residential field exposure to power lines. As the span of years increased the risk ratio of Alzheimer’s disease development increased correspondingly. This study suggests a relationship between magnetic/electrical fields and onset of AD. Findings showed that people living in the vicinity of power lines for over 15 years had doubled levels of AD mortality(Anke Huss et al.,2009). It is proposed that electric and magnetic fields can affect the brain in a variety of mechanisms– such as oxidative stress, apoptosis, and so on. In addition, there are other factors also that can underlie AD, including pesticides (Dandan Yan et al.,2016), copper (Roshni Patel et al.,2021), and traumatic brain injuries (Corinna Van Den Heuvel et al., 2007).

There are also assumptions that education level can act as a possible protective effect against AD. Higher education is thought to delay the onset of Alzheimer’s disease by improving cognitive reserve. Cognitive reserve is the ability to remain functionally resilient in the presence of AD. People with higher education levels show AD symptoms later than those with less education. Examining 24 potential Alzheimer’s disease risk factors showed that higher education attainment was significantly linked with declined risk of developing AD (Larsson SC. et al.,2017). If it is continued, many other factors can be emphasized to affect AD development and susceptibility as our organism and brain are connected with our environment, culture, and ethnicity.

Did drug treatments succeed solely? The promising non-pharmaceutical treatments.

There are several drug trials that are going on all over the world to find the best medication for Alzheimer’s treatment. Despite all efforts and many expensive clinical trials, no new drug has been approved for treatment of Alzheimer’s disease since 2003. More than 200 investigations have failed or have been stopped in the last decade. Several factors caused this situation, including late initiation of treatments during AD, inappropriate drug dosages, and mainly an inadequate comprehension of the complex pathophysiology of AD. Therefore, drug treatment may require combination treatments rather than monotherapy (Konstantina G. Giannopoulou et al.,2019). Drugs are only targeted to decrease certain symptoms of AD that are known currently for experts and each of them has their specific functions. These drugs are palliative rather than curative and cannot alter the outcome of the disease (David A. Casey et al., 2010). Apart from drug treatments experts introduced several non-pharmaceutical therapies for the betterment of patients to extend their lives. One of them is cognitive behavioral therapy that is useful in treating depression in the early stage of AD. Psychotherapy and psycho-educational interventions assist in coping with the maintenance of patient's health by talking and communicating with them. Behavioral Management Therapy is conducted to target challenging behavioral patterns(wandering, agitation, anxiety) in people with AD. Environmental approaches encourage creative solutions to the disease by targeting a person's surroundings. The ideal environment for the patient with AD should be non-stressful, constant, and familiar. Memory training can help a person maximize cognitive functioning and independence (Dementia Australia,n.d.). There is also one therapy that can encompass all aforementioned approaches. It is music therapy. Music therapy has positive effects in the domain of episodic and semantic memory retrieval ( El Haj et al., 2012). It is the best non-pharmacological intervention to reduce behavioral and psychological symptoms– depression and anxiety — in AD patients (Iosief Abraha et al.,2017). The brain areas involved in musical memory retrieval are the last to show atrophy in AD patients (Jacobsen JH et al.,2015). Importantly, music therapy can be bridge between dementia patients and their loved ones. According to “Musical Bridges to Memory” intervention, developed at Institute for Therapy through Art (ITA), when a live ensemble played music from patients’ youth this created an emotional connection between patients and their caregivers by allowing them to interact with each other via singing,dancing and playing simple musical instruments.In the intervention, the group of patients who were exposed to music were more socially engaged, had less distraction, less agitation and an elevated mood compared to patients who received daily care and programs(Emily Henderson,2022).

Why is music vital? Music therapy.

Music has been an inseparable part of cultures and ethnic groups for centuries, and it plays a significant role in people’s development. In the second trimester of pregnancy, fetuses start to hear music in the womb and begin to recognize their mothers’ blood flow, heartbeat, and breathing rate. These things soothe them and create a special connection between mother and infant ( Jessica Timmons, 2018). Music is an amazing tool that involves almost every region of the brain to function, to feel, hear, and create it. Many neurological diseases involve different changes in brain activity and result in cognitive decline, mood swings, and emotional instability. The first reference to using music as a therapy appeared in 1789 and in the early 1800s writings about the therapeutic importance of music were published in the form of two medical dissertations ( American Music Therapy Association archives, n.d.). Music therapy is a therapeutic approach that uses the naturally mood-lifting properties of music to assist people in improving their mental health and well-being. It may involve making music, writing songs, singing, dancing, listening to music, and discussing music. Music therapy is considered an active process when patients play a role in creating music, or a passive one that involves responding or listening to music. There are several types of music therapy, including analytical music therapy, Benzon music therapy, cognitive behavioral music therapy, community music therapy, Noroff-Robbins music therapy, and vocal psychotherapy (Steven Gans,2023). Analytical music therapy encourages patients to improvise music or create musical “ dialogue” through singing and playing different instruments to express their thoughts. Benzon music therapy combines concepts of psychoanalysis with making music. This therapy primarily focuses on finding a patient's own “musical sound identity”. Cognitive behavioral music therapy involves Cognitive Behavioral Therapy in combination with music. It is a structured process that comprises dancing, singing, listening to or making music to make changes in a patient's attitude. Community music therapy is a complex therapy. As the name suggests it requires a high level of engagement from each member of the community to socialize together through music. Noroff-Robbins music therapy involves playing an instrument while the therapist accompanies the process with other instruments. It encourages companionship, harmony, and improvisation. Vocal psychotherapy includes various vocal exercises, natural sounds, and breathing techniques to connect patients with their emotions and impulses and to create a sense of connection with themselves. The use of musical intervention in clinical settings is showing a growing body of evidence regarding singing, music listening, musical improvisation, and other musical activities, as well as more structured music therapy treatments. Since music engages several brain areas involved in emotion, cognition, motivation, and motor functions, musical interventions have been utilized to increase socialization and cognitive, neuromotor, and emotional functioning. Different approaches to music therapy are available referring to three principal domains: relational approaches, rehabilitative approaches, and music listening. Relational approaches refer to psychological models. Rehabilitative approaches, such as Neurologic Music Therapy, refer to neuroscientific models and use the potency of music stimuli to activate production regions in the human brain and perception, involving a series of therapeutic applications to sensory, motor, and cognitive dysfunctions. (Alfredo Raglio et al., 2015)

“Music and the Brain” is one of the most popular courses in the Burnett Honors College which has been carried out by two professors at the University of Central Florida – neuroscientist Kiminobu Sugaya and world-renowned violinist Ayako Yonetani. This course explores how music impacts brain function and human behavior by reducing stress, symptoms of depression, and pain as well as improving motor and cognitive skills, neurogenesis( new neuron formation), and spatial-temporal learning. These professors show how people with neurodegenerative diseases such as Alzheimer’s positively respond to music. They explain how music positively impacts each region of the brain, including the hippocampus– the area of the brain that is responsible for making new memories, regulating emotional responses, helping us navigate, and the region that first starts dysfunction in AD. Yonetani says: “Music may increase neurogenesis in the hippocampus, allowing the production of new neurons and improving memory”.In addition, according to Sugaya, an Alzheimer’s patient, even if he does not recognize his wife, could still play the piano if he learned it when he was young because playing has been ingrained in muscle memory. Those memories in the cerebellum never fade out(Pegasus, University of Central Florida). Researchers from Turkiye experimented with 42 male Wistar Albino rats to examine how different genres of music at different decibels impact the oxidation state in the brain tissue and serum. As a result, high-decibel rock music created oxidative stress in cerebral tissue while low-decibel rock music and noise created oxidative stress in the cortex and cerebellum. These results suggest that both high and low-decibel slow music have positive impacts on oxidative stress. (Ülkühan Düzgün et al.,2022).As amyloid-beta plaques could be the result of oxidative stress, it is essential to note that not all types of music are suitable for music therapy and not all of them are beneficial for our brain. In recent years, music therapy has grown in popularity as a method of non-pharmacological treatment for AD patients. There is evidence to suggest that memory for music can remain intact, even though experiencing rapid cognitive decline like in AD (Cuddy et al., 2012). According to studies, music activates a broad network in the brain rather than a single “ music area”.Particularly, when listening to familiar music, musical memory retrieval involves areas both within and outside of the temporal lobes (which have a role in auditory, olfactory functions, and memory), including the parietal, which governs spatial recognition and relationship, and frontal regions. Therefore, music can be a promising approach for treating, and assuaging patients with different stages of AD and extending their lives.

Conclusion.

Day by day the number of Alzheimer’s patients is increasing due to several factors and many scientists, doctors, and neuroscientists are trying to come up with a clue to find the best method for treatment and rehabilitation. Ethnicity and culture are important targets of the research since they include several environmental, genetic factors and elements. But there is still a gap in this area that has not been explored yet. This research paper aims to raise awareness among the public to take care of their mental health and acknowledge the impact of their ancestral traits and origins. Everything we are exposed to influences our brain health and it is significant to know our limits and precautions. Our culture and ethnicity can be an answer to questions that have been challenging neuroscientists for a long time. For example, music has been part of human civilization for millennia, and it can be a great approach for avoiding and curing AD in the future by inventing new treatments with the aid of technology. By knowing our ancestral genetics, we can estimate the susceptibility of people to AD and create new solutions for this ongoing issue.

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