Alzheimer’s Disease is relevant among most of the world’s population today. It is a disease that effects the cognitive function, memory, and language in an individual’s daily life. Now Alzheimer’s Disease has no cure, is untreatable, and the most significant cause is not really known. Also, traditional methods of diagnosing and care are not that efficient. Researchers have been driven to making a connection between the composition of the microbiota inside the gastrointestinal tract and cognitive decline. It is stated that these microorganisms are causing an effect outside of their organ systems, specifically the central nervous system, and by altering the composition it can possibly reduce the neuroinflammatory properties. Another suggestion researchers have put forth is that exercise and probiotic supplementation can have a beneficial impact on cognitive decline. By introducing additional good bacteria into the body as well as maintaining the body system at a healthy state it can prolong the cognitive aging process. Researchers are also attempting to provide the public with better methods and radiotracers for brain imaging to be able to diagnose Alzheimer’s Disease at an earlier stage. If these more advanced protein radiotracers and diagnosis tests can detect the disease earlier than it can be detected now, then it will give physicians a better chance of confronting the disease with the patient. Possible future implications include advancing diagnosis methods and formulating newer medications to delay the neurological aging process. It can even be thought to bring about the studies of looking for an Alzheimer’s Disease cure.
Alzheimer’s Disease is a neurodegenerative disease that affects millions of individuals every year. Currently, Alzheimer’s Disease is the most common type of neurodegenerative disease, in comparison to Parkinson’s and Huntington’s Diseases (Alzheimer’s Association, 2018). It is the most common cause of Dementia, the underlying group of symptoms that are exhibited with the disease. Alzheimer’s Disease specifically affects the neurons in the brain. It is when an individual’s brain accumulates a high amount of beta-amyloid proteins and the neurons begin to degenerate or ultimately become destroyed (Alzheimer’s Association, 2018). While age and genetic mutation seem to be the most common risk factors for Alzheimer’s Disease, it may seem to be that women are more susceptible to being diagnosed with it due to their longevity (Alzheimer’s Association, 2018). Professionals seem to think that there might be ways to prevent or even treat Alzheimer’s Disease due to its link to other organ systems in the human body. In addition to the brain’s natural aging process, scientists believe that there is a connection between the body’s gut microbiome and mental capability. Since the gut is home to billions of microorganisms, it is possible they can have a role in the progress of disease outside of the gastrointestinal tract (Abraham et al., 2019). This association can lead to therapeutic methods or even prevention through healthier lifestyle choices. Probiotic supplementation may also prove beneficial due to a leaky gut having influence on inflammatory response and neuromodulatory mechanisms (Leblhuber et al., 2018). Given that the number of individuals effected by this disease is growing exponentially being able to detect it at an early stage of its development can aid in the treatment of its symptoms. Unlike current imaging techniques, diagnosing this disease early with new radiotracers can aid with tracking its progression and evaluate the effectiveness of therapeutic drug options (Harada et al, 2016). In this review, I will be discussing the correlation between nutritional habits, therapeutic methods, and early detection for Alzheimer’s Disease.
Alzheimer’s Disease is a degenerative disease that effects the cognitive abilities in individuals. Throughout the progression of this disease the brain goes through the process of decaying. It is possible for outside environmental factors to contribute to this decaying; however, hereditary, age, and genetics are the biggest contributors to contracting this disease (Alzheimer’s Association, 2018). Out of those three risk factors, age has the most impact on determining the development of Alzheimer’s Disease. It seems to be more prevalent in the elderly in comparison to middle-aged adults. Most of the individuals who have been diagnosed with this disease tend to be 65 or older (Alzheimer’s Association, 2018). As the individuals age past that specific threshold, the percentage of neurological degeneration begins to increase even more. An individual’s family history does need to be considered as well. Even though it is not a needed for an individual to develop this disease, it is more likely for someone to be diagnosed with it if they have a first-degree relative with the disease (Alzheimer’s Association, 2018). An individual’s hereditary can play a crucial role in mapping out the genes passed down from parent to offspring. The last major risk factor, genetics, can provide the most obvious sign of Alzheimer’s Disease which is the accumulation of excess cholesterol in the bloodstream and/or proteins in the brain (Alzheimer’s Association, 2018). Specifically, the APOE gene is what provides this symptom. There are three forms of this APOE gene: e2, e3, and e4. Depending on which specific combination the offspring receives from each parent can determine the chances of the offspring contracting Alzheimer’s Disease and at what stage of their life. Inheriting two copies of the APOE-e4 gene increases the risk the most which is 8-12-fold (Alzheimer’s Association, 2018). Unfortunately, these are not the only risk factor that can contribute to Alzheimer’s Disease diagnoses. A wide variety of contributions can make an effect such as: cardiovascular disease, healthy lifestyle choices, cognitive training, or even sex. Studies show that females have a higher chance of contracting Alzheimer’s Disease than men because they tend to live longer (Alzheimer’s Association, 2018).
Alzheimer’s Disease can make itself known through a variety of signs and symptoms. The most common cause of dementia is Alzheimer’s Disease. The difference between the two is that dementia is a group of symptoms while Alzheimer’s is the underlying disease. Dementia can manifest itself as cognitive and problem-solving issues as well as having difficulty with memory (Alzheimer’s Association, 2018). Most individuals diagnosed with Alzheimer’s Disease have neuropsychiatric symptoms, or NPS. NPS is when the patient exhibits certain behaviors along the lines of apathy, agitation, and psychosis which can have a major effect on daily life (Eikelboom et al., 2019). In the mild, or early stages, of Alzheimer’s Disease individuals can still go about their daily lives independently but might need some help with certain tasks to ensure safety and effectiveness. On the other hand, as the disease progresses during the later stages daily life becomes a struggle. This is when the individual will be needing assistance with activities such as taking a bath, eating, getting dressed, or even using the restroom. In the most severe stages, the patient is bed-bound and can no longer help themselves. This can leave a significant impact on the patient’s physical health since it can increase their chances of getting blood clots, problematic infections, or even have difficulties swallowing food (Alzheimer’s Association, 2018). Overall, diagnosing Alzheimer’s Disease can be quite tedious since there is not one way to do so. Doctors can determine if an individual has dementia; however, it is difficult to find out why (Alzheimer’s Association, 2018). Since there is no single way to diagnose it, doctors perform a serious of tests to come to a conclusive evaluation. Among these tests are: obtaining a medical and family history, asking a family member for evaluations of the patient, cognitive and neurological tests, and blood tests and brain imaging to see for high counts of beta-amyloid (Alzheimer’s Association, 2018). An accumulation of amyloid-B and tau proteins are presymptomatic changes that lead to Alzheimer’s Disease as well as cortical thinning (Preische et al., 2019).
Diet and Nutrition
The well-being of the neurovascular system plays a significant role with cognitive capability. Researchers have shown through their studies that microorganisms located inside the gut can regulate the neurovascular integrity (Ma et al., 2018). Specifically, it was tested on mice if a ketogenic diet, KD, intervention can alter the microorganisms in the GI tract to improve neurovascular functions. After a 16-week trial, it showed that with the assistance of KD there was an increase in function of CBF transports on the blood brain barrier, which helps clear the abundant amounts of amyloid-beta in the brain. This was linked with the increased count of good gut microbiota and diminished the bad pro-inflammatory ones (Ma et al., 2018). Thus, it was proven that a ketogenic diet intervention can heighten neurovascular functions while improving gut microbiota and, in the end, reduce the risk of contracting Alzheimer’s Disease (Ma et al., 2018).
In today’s world population obesity has risen significantly as well as metabolic disorders (Solas et al., 2017). Specifically, cardiovascular and type 2 diabetes have this increase in frequency. Research has shown that there is a specific link between obesity and Alzheimer’s Disease. Even though the reasons behind this are currently unknown, there are some suggestions that it could be due to the gut-brain axis or even the central inflammation process (Solas et al., 2017). Studies have shown that the activation of the inflammatory system in metabolic disease can spread to the brain tissues which in turn causes Alzheimer’s Disease. This specific inflammation can be influenced by changes in the microorganisms in the GI tract (Solas et al., 2017). Research has concluded that unbalanced diets, or even obesity, can have an impact on cognitive dysfunction or age-related disorders (Solas et al., 2017). This ties in with the inflammation happening at the peripheral nervous system. This inflammation then travels into the central nervous system where the brain is located and causes dysfunction of the synapses or begins atrophy of the brain (Solas et al., 2017). It might not be clear what initiates the inflammation at the peripheral level; however, this does give a better understanding of how microorganisms in the GI tract can affect an individual’s neurological state (Solas et al., 2017).
Research has concluded that there seems to be a bidirectional communication between the intestines and the brain, referring to it as the gut-microbiota-brain axis (Lombardi et al., 2018). With studies pointing out how an altered microbiome and neuroinflammatory diseases go hand in hand, it is still unclear in most cases if it is due to one another. It has been pointed out and proven that an individual’s diet contributes to the type of microorganisms in the GI tract and in turn the immune system (Lombardi et al., 2018). Several studies identify changes in these microorganisms in neuroimmune diseases; however, they cannot point out just yet if it causes the disease itself or is a result of it (Lombardi et al., 2018). Theses observations and results can lead to many new methods of approaching a disease in the near future. It can lead to the possibility of altering gut microorganism as a treatment option for neuroimmune and neuroinflammatory diseases (Lombardi et al., 2018).
Studies performed on mice have repeatedly shown how changes in the gut has contributed to deposits of amyloid-beta in the brain; however, it does not say much about how it associates with humans (Vogt et al., 2017). In this study, a fecal test was performed on healthy patients and patients diagnosed with Alzheimer’s Disease. The results of this study showed that in patients diagnosed with Alzheimer’s Disease the microorganisms in the gut have a decreased diversity compared to healthy patients (Vogt et al., 2017). Differences were found in the quantity of a wide range of bacteria. To be specific, there was a decrease in Firmicutes, increase in Bacteroidetes, and decrease in Bifidobacterium in Alzheimer’s patients (Vogt et al., 2017). The findings of this study prove that in addition to other neurodegenerative disease, Alzheimer’s Disease is associated with alterations to the gut microbiota.
Furthermore, another potential determining factor of the gut microbiota composition could be bile acids. It seems that bile acids are altered and deregulated in Alzheimer’s Disease (MahmoudianDehkordi et al., 2018). Bile acids are produced by the liver specifically and metabolized by the gut microorganisms when clearing cholesterol (MahmoudianDehkordi et al., 2018). In this study, bile acid serums were tested from a few groups of participants: healthy individuals, early mild cognitive impairment individuals, late mild cognitive impairment individuals, and Alzheimer’s Disease individuals. Serum ratios were compared to cognition, diagnosis, and genetic variants (MahmoudianDehkordi et al., 2018). Test results showed that in Alzheimer’s patients there was a significant decrease in serum concentration compared to the healthy test participants. The Alzheimer’s Disease patients also showed an increase in bacteria produced in the bile acids. This conclusion confirmed the significant role of the gut-liver-brain axis in the progression of Alzheimer’s Disease (MahmoudianDehkordi et al., 2018).
At this moment in time Alzheimer’s Disease does not seem to be treatable. There may be way to prolong the aging process; however, there is no definitive way to treat the symptoms. Recently, scientists have suggested that exercise and probiotic supplementation can help slow down the neurodegenerative progress (Abraham et al., 2019). In this study, researchers tested genetically modified mice that carry the Alzheimer’s Disease gene. This were tested on whether exercise training, probiotic supplementation, or a combination of both had better cognitive abilities compared to untreated Alzheimer’s Disease mice (Abraham et al., 2019). After the treatment was completed the different groups of mice were subjected to a series of maze and obstacle tests to determine their cognitive abilities. In the end, the results showed that the group with the combined exercise and probiotic treatments significantly out-performed the other three groups (Abraham et al., 2019). Thus, the combination treatment proved to help decrease the abundant amount of amyloid-beta in the central nervous system and reduce the neuroinflammatory properties (Abraham et al., 2019).
Looking back to the relationship between gut microorganisms and the central nervous system, treatment of those gut bacteria can prove to be beneficial in treating the overall Alzheimer’s Disease. Researchers in this study tested twenty patients with Alzheimer’s Disease before and after a four-week probiotic supplementation schedule. The test included biomarkers of immune activation, gut inflammation markers, and composition of gut microorganisms in fecal specimens (Leblhuber et al., 2018). After the four-week treatment the test concluded that there was a noteworthy decay of fecal zonulin concentrations while there was a growth in Faecalibacterium prausnitzii (Leblhuber et al., 2018). These results illustrate how Alzheimer’s patients that are given a multispecies probiotic supplementation had an increase in diversity of microorganisms in the GI tract. This diverse composition proves beneficial with potential activation of neurological and immunologic processes (Leblhuber et al., 2018). Even though it may sound like all positive results, further studies are recommended by the researchers to figure out consequences of over-supplementation.
Even though there is a lot of correlation with systems outside of the central nervous systems with the brain, there are still some specific factors inside the brain that seem to lead to Alzheimer’s Disease. Meningeal lymphatic vessels inside the brain oversee the draining of macromolecules from the central nervous system (Da Mesquita et al., 2018). Basically, their role is waste removal of abundant proteins. In this study, researchers tested whether impaired meningeal lymphatic vessels had an impact on cognitive function in mice. The test was conducted on three groups of mice and one of the groups was injected with Visudyne with photoconversion, a meningeal lymphatic vessel damaging drug (Da Mesquita et al., 2018). In comparison to the other two controlled groups, the group injected with this specific drug had a significant meningeal lymphatic vessel dysfunction. These mice were no longer able to remove that abundant amount of amyloid-beta from the meninges and caused the cognitive impairment Alzheimer’s Disease promotes. In the end, the results show that this meningeal lymphatic function might be a site for potential therapeutic treatment to prevent or delay the aging process in neurological disease like Alzheimer’s (Da Mesquita et al., 2018).
Even though researchers are searching for methods of treatment through how our body’s organ systems interact with each other, there seems to be a natural occurring product that proves beneficial in the treatment of Alzheimer’s. Bryostatin 1 is an extremely rare marine product that has the potential to eradicate HIV/AIDS, play an intricate part in cancer immunotherapy, and even treat Alzheimer’s Disease (Wender et al., 2017). Since it is such a limited and uncommon natural product, scientists are attempting to synthesize it in clinical studies. This particular study shows that attempts made by scientists to synthesize Bryostatin 1 is revealing a wider range of possible alternate treatment products (Wender et al., 2017). These alternative synthetically accessible products seem to be more effective and better endured by cells in tests (Wender et al., 2017).
With most of the population’s focus centered on treatment methods, another important aspect of disease control is early detection. Early detection of Alzheimer’s Disease can prove crucial by being able to focus on the symptoms as soon as possible. Most cognitive assessments rely on decades old methods which are questionable on their early detection efficacy (Loewenstein et al., 2018). Early detection can prove crucial in prevention before the neurodegeneration spreads throughout the brain. In this study it is shown that controlled learning and assessing the performance of an individual’s memory capacity can be the most effective route in comparison to uncontrolled learning paradigms (Loewenstein et al., 2018). Examples of these memory tests are those that use memory binding, proactive interference, and retroactive interference (Loewenstein et al., 2018). These tests give the opportunity for the individual to be their own standard. Their initial performance is used as the control and is compare with additional trials (Loewenstein et al., 2018).
Brain imaging is a particularly effective step towards diagnosing Alzheimer’s Disease. In order to take a PET image of an individual’s brain a radiotracer is needed to bind to specific parts of the brain as well as contrast at a high intensity. The traditional radiotracer of choice is called F-THK5117. In this study, researchers tested a new novel tau PET tracer called F-THK5351 (Harada et al., 2016). This radiotracer binds to specific tau protein fibrils and proved to have a higher binding rate in these test trials than traditional methods. The Alzheimer’s patients treated in this study not only showed a faster binding rate to proteins but also a significantly higher intensity image of the brain proteins (Harada et al., 2016).
Researchers are improving their methods of early diagnosis of Alzheimer’s Disease, coming up with different ways to easily detect the symptoms. These improved methods of choice are faster than traditional ways to detect and diagnose a patient. In this study, researchers proposed a new method system to classify patients with Alzheimer’s Disease and mild cognitive impairment through 3D magnetic resonance imaging (Zhang et al., 2015). 3D MRI’s were taken and pre-processed for each of the 180 subjects in the test. They were then processed several times again with specific wavelet transforms to extract wavelet coefficients from the image (Zhang et al., 2015). After the processing steps were completed, the images were then analyzed to test the specific accuracy on all the classifiers used to process the images, three individual classifiers and three multiclass methods (Zhang et al., 2015). In the end, the researchers were able to state that WTA-KSVM + PSOTVAC was the best classifier and significantly outperformed the entire experimental group for the best accuracy (Zhang et al., 2015).
Furthermore, in this study researchers planned on testing the detection of Alzheimer’s Disease in its early stages by using magnetic resonance elastography. MRE is noninvasive tool that is used to measure certain characteristics of tissues in vivo (Munder et al., 2018). Researchers in this study used female mice that carried the Alzheimer’s Disease gene and applied the MRE at different stages of the disease early on in its progression. The results showed that by detecting alterations in the diversity, density, and mobility of the cell types in the hippocampus with the MRE, Alzheimer’s Disease can be determined at an early stage (Munder et al., 2018). The MRE being delicate enough to detect these changes is crucial.
In this last study, researchers attempted to make a connection between retinal imaging and diagnosing Alzheimer’s Disease. Retinal imaging for diagnosing can prove to be a noninvasive form of Alzheimer’s detection as well as an earlier specific form (Koronyo et al., 2017). Individuals that exhibit traditional symptoms of Alzheimer’s Disease will also show high amounts of amyloid-B protein inside their retinas. These researchers took a group of normal individuals and compared retina images to those of Alzheimer’s patients. The results showed that in the retinal images, Alzheimer’s patients exhibited retinal amyloid index scores 2.1 times higher (Koronyo et al., 2017). This states that Individuals with Alzheimer’s Disease have an abundant amount of protein deposits inside their retinas. In turn, this study brought to light a more feasible and less invasive way to detect these amyloid-B deposits in patients which can lead to a more practical way to diagnose Alzheimer’s Disease (Koronyo et al., 2017).
Alzheimer’s Disease is the most common neurodegenerative brain disorder that effects millions of individuals worldwide each year. Prevention methods are constantly sought after since Alzheimer’s Disease is still an untreatable disease. In this review, Alzheimer’s Disease was discussed in terms of its link with diet habits, the possibility of new therapeutic methods, and improved forms of early detection. In particular, researchers are identifying the correlation between nutritional habits and the gut microbiota composition causing an effect in cognitive abilities. Researchers are also finding out that probiotic supplementation and a regulated exercise regimen can prove to be a sufficient therapeutic method to reduce the neuroinflammatory process. Finally, these researchers are identifying new radiotracers that have a better ability of binding with amyloid-B proteins in the brain which can lead to a better method of early detection of the underlying disease. With these new findings brought to light it can advance the diagnosis methods used today as well as bring the possibility of delaying the neurological aging process through new medications. We can hope that this can propel new studies into an Alzheimer’s Disease cure somewhere in the near future.
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