alzheimer's disease research essays

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Seven recent papers amplify advances in Alzheimer’s research

Alzheimer's Disease Biomarkers Dementias Neuroscience

AMP AD uses an open-science research model that makes all data and methods rapidly available to the research community at large through the data sharing infrastructure, the AD Knowledge Portal. Since the Portal’s launch in 2015, more than 3,000 researchers world wide from the academic, biotech, and pharmaceutical industry sectors have used the data resources for research on Alzheimer’s and related dementias.

Alzheimer’s is a complex disease, and as it slowly develops, many normal biological processes in the brain and the body go awry, from inflammation, to blood vessels damage and neuronal death. Seven recent AMP AD reports showcase research advances related to the discovery of new drug candidate targets, identification of molecular subtypes of the disease, and new potential biomarkers that can serve as the basis for a precision medicine approach to therapy development.

Identifying ATP6VA1 gene as a candidate target for treatment: Researchers at the Icahn School of Medicine at Mount Sinai in New York generated several types of molecular data from 364 brain donors at different stages of Alzheimer’s. Using network modeling, a way to show data and its relationships, the team identified large sets of genes associated with the disease. Among the thousands of molecular changes associated with Alzheimer’s, the expression of a set of neuronal genes (neuronal network) was the most disrupted. Their analyses identified ATP6VA1 as a master regulator gene of this neuronal network and demonstrated that increasing its expression genetically, or by using a pharmacologic agent, led to improving neuronal function in cultured cells and in flies. These findings were published in Neuron and pave the way for new drug discovery efforts targeting ATP6VA1 .

Finding and validating VGF gene as key regulator of Alzheimer’s: Another AMP AD study led by researchers at Icahn School of Medicine identified the VGF gene and protein as having a key role in protecting the brain against Alzheimer’s. This discovery was made possible by combining computational analyses that integrate large human Alzheimer’s molecular datasets, clinical features of Alzheimer’s, DNA variation, and data on gene- and protein expression with experimental studies in mouse models. The findings provide a new target for researchers seeking to develop drugs to treat or prevent Alzheimer’s. The report of the discovery of this gene as a key driver and its validation in mouse studies was published in Nature Communications .

Identifying different types of microglia associated with Alzheimer’s: An AMP AD research team at Columbia University conducted a study that measured the expression of genes in individual microglial cells purified from human brain samples obtained at autopsy and during neurosurgical procedures. This single cell profiling technology identified several molecular subtypes of microglia based on the pattern of gene expression. Follow-up validation studies in post mortem brain tissue showed that this microglia subtype was less abundant in Alzheimer's brains compared to control brains. These results, published in Nature Communications , will help design larger, more specific studies of the role of microglia subtypes in Alzheimer’s.

Using data to unfold and predict disease process: An AMP AD team led by researchers at Sage Bionetworks in Seattle used innovative computational approaches to make predictions about the sequence of molecular changes that lead to Alzheimer’s. The team used RNA sequencing data collected from a large collection of post-mortem tissue from Alzheimer’s and control brains. This modeling method, called the manifold learning method, predicted early-stage disease processes, such as RNA-splicing, mitochondrial function, and protein transport. Additionally, the method predicted several distinct molecular subtypes of late-onset Alzheimer’s. These predictions speak to the complex nature of the disease and the need to verify these observations in longitudinal studies where molecular signatures can be linked to different clinical features of the disease. These findings were published in Nature Communications .

Network modeling identifies molecular subtypes of Alzheimer’s: Using a large collection of human brain samples from different studies, a team led by researchers at Icahn School of Medicine also analyzed RNA sequencing data and identified three major molecular subtypes of Alzheimer’s. The subtypes, which are independent of age and disease stage, and are replicated across multiple brain regions, show how different combinations of biological pathways lead to brain degeneration. With further research and validation in larger groups, these molecular subtypes may help reveal how Alzheimer’s progresses and potential ways to slow or stop it. Their findings were published in Science Advances .

Identifying new biomarkers in spinal fluid: AMP AD researchers at Emory University identified groups of proteins (protein panels) associated with Alzheimer’s that could be identified in both brain and spinal fluid. These overlapping protein panels detected in the spinal fluid reflected changes in multiple biological process in the brain. The researchers found this by measuring 3,500 proteins in spinal fluid, and 12,000 proteins in a collection of postmortem brain samples, from patients with Alzheimer’s and cognitively normal study participants. The study also showed that these changes in the protein expression pattern were specific for Alzheimer’s. This work lays the foundation for the discovery of new fluid biomarkers for Alzheimer’s. These findings were published in Science Advances .

Investigating how being female may increase risk of Alzheimer’s: Duke University researchers and members of the Alzheimer’s Disease Metabolomic Consortium (ADMC) participating in the AMP AD program, analyzed the changes in the levels of 180 metabolites in the blood from more than 1,500 people who took part in the NIA-supported Alzheimer’s Disease Neuroimaging Initiative . The researchers reported that there are differences in a subset of blood metabolites associated with Alzheimer's based on sex and ApoE4 status. ApoE4 is the strongest Alzheimer's risk factor gene. Women with Alzheimer’s who carry the ApoE4 gene have a distinct metabolic pattern in blood. These metabolic changes suggest that females have a greater impairment of brain energy production than males. Dissecting metabolic differences in Alzheimer’s can identify specific pathways within specific patient subgroups and guide the way to personalized medicine.

The data and methods from the above studies are available and can be accessed by researchers across the world through the AD Knowledge Portal . The portal is the data repository for the AMP AD Target Discovery Program, and other NIA-supported team-science programs operating under open-science principles. Now in its sixth year, AMP AD is demonstrating the power of open science to enable the scientific community to investigate difficult scientific questions and jumpstart new drug discovery projects.

The AMP AD research teams are funded by NIA grants U01AG046152, U01AG046170, U01AG046139, U01AG046161, R01AG046171, R01AG046174, U19AG010483, U01AG042791, U01AG061357, U01AG061359, U01AG061835, and U24AG061340.

The studies outlined here were also supported by the following NIA grants (in order of appearance):

• ATP6VA1: NIA grants U01AG046170, RF1AG054014, RF1AG057440, R01AG057907, U01AG052411, R01AG062355, U01AG058635, and R01AG068030
• VGF: NIA grants U01AG046170, R01AG046170, RF1AG054014, RF1AG057440, R01AG057907, R01AG055501, U01AG046161, P50AG025688, 5R01AG053960, and 5R01AG062355
• Microglia: NIA grants U01AG046152, R01AG036836, R01AG048015, and RF1AG057473
• Disease process: NIA grants U54AG054345, RF1AG057443, P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984, U01AG46152, P50AG016574, R01AG032990, U01AG046139, R01AG018023, U01AG006576, U01AG006786, R01 AG025711, R01AG017216, and R01AG003949
• Subtypes: U01AG046170, RF1AG054014, RF1AG057440, R01AG057907, U01AG052411, R01AG062355, U01AG058635, R01AG068030, P30AG10161, R01AG15819, R01AG17917, R01AG30146, R01AG36836, U01AG32984, U01AG46152, U01AG52411, K01AG062683, and U01AG058635
• Spinal fluid biomarkers: NIA grants R01AG053960, R01AG057911, R01AG061800, RF1AG057471, RF1AG057470, R01AG061800, R01AG057911, R01AG057339, U01AG046161, and U01AG061357
• Female risk: NIA grants U01AG024904, P30AG10161, R01AG15819, R01AG17917, U01AG46152, U01AG61356, R01AG059093, R01AG046171, RF1AG051550, and U01AG024904, RF1AG058942, R01AG057452, R03AG054936, and RF1AG061872

These AMP AD activities relate to NIH’s AD+ADRD Research Implementation Milestone 2.A , “Create new research programs that use data-driven, systems-based approaches to integrate the study of fundamental biology of aging with neurobiology of aging and research on neurodegeneration, AD and AD-related dementias to better understand the mechanism(s) of vulnerability and resilience in AD across all levels of biologic complexity (from cellular to population level) and to gain a deeper understanding of the complex biology and integrative physiology of healthy and pathologic brain aging;” Milestone 9.B , "Accelerate the development of the next generation CNS imaging ligands and biofluid molecular signatures targeting a variety of disease processes (neuroinflammation, bioenergetic/metabolic compromise, oxidative stress, synaptic pathology) that can be used as research tools or developed into diagnostic, prognostic, theragnostic or target engagement biomarkers;" and Milestone 9.F , “Initiate studies to develop minimally invasive biomarkers for detection of cerebral amyloidosis, AD and AD-related dementias pathophysiology.”

References:

Wang M, et al. Transformative network modeling of multi-omics data reveals detailed circuits, key regulators, and potential therapeutics for Alzheimer's disease . Neuron . 2021;109(2):257-272.e14. doi:10.1016/j.neuron.2020.11.002.

Beckmann ND, et al. Multiscale causal networks identify VGF as a key regulator of Alzheimer's disease . Nature Communications. 2020;11(1): 3942. doi:10.1038/s41467-020-17405-z.

Olah M, et al. Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer's disease . Nature Communications . 2020;11(1):6129. doi:10.1038/s41467-020-19737-2.

Mukherjee S, et al. Molecular estimation of neurodegeneration pseudotime in older brains . Nature Communications . 2020;11(1):5781. doi:10.1038/s41467-020-19622-y.

Neff RA, et al. Molecular subtyping of Alzheimer’s disease using RNA sequencing data reveals novel mechanisms and targets . Science Advances . 2021;7(2):eabb5398. doi: 10.1126/sciadv.abb5398.

Higginbotham L, et al. Integrated proteomics reveals brain-based cerebrospinal fluid biomarkers in asymptomatic and symptomatic Alzheimer's disease . Science Advances . 2020;6(43):eaaz9360. doi:10.1126/sciadv.aaz9360.

Arnold M, et al. Sex and APOE ε4 genotype modify the Alzheimer's disease serum metabolome . Nature Communications . 2020;11(1): 1148. doi:10.1038/s41467-020-14959-w.

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The interrelationships of CSF sTREM2, AD pathology, minimal depressive symptoms, and cognition in non-demented adults

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Dementia with Lewy bodies and gait neural basis: a cross-sectional study

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129 Alzheimer’s Disease Essay Topics & Examples

If you’re writing about patients with memory loss or dementia care and treatment, this article will be of use. Our team has prepared Alzheimer’s disease essay examples and topics below.

🏆 Best Alzheimer’s Disease Essay Examples & Topics

💡 most interesting alzheimer’s disease topics to write about, 📌 simple & easy alzheimer’s disease research topics, 👍 good research topics about alzheimer’s disease, ❓ research questions about alzheimer’s disease.

• The Case Study of Patient With Late-Stage Alzheimer’s Disease In the majority of cases of Alzheimer’s, it has been shown that patients are unable to make decisions on their own and are also unable to communicate their assent verbally.
• The Alzheimer’s Association Dementia Care Practice Therefore, achieving the philosophy and recommendations of the association is a shared responsibility between doctors, patients, and caregivers. Ultimately, CAPD tests the functionalities of the patient ranging from the psychomotor activities, perceptions, awareness, and orientations, […]
• Dementia, Alzheimer, and Delirium in an Elderly Woman Additionally, she struggles with identifying the appropriate words to use in dialogue and changes the topic. Timing: While in the middle of conversations and public places like supermarkets.
• Alzheimer’s Disease Diagnosis and Intervention The accumulation of plaques and tangles in the brain is a hallmark of the disease, resulting in the death of neurons and a decline in mental capacity.
• Alzheimer’s Disease: Assessment and Intervention The caregiver is recommended to install safety locks and alarms on all doors and windows to prevent the patient from leaving the apartment without supervision.
• Management of a Patient With Alzheimer’s: Case Study The correlation between this issue and the probability of the emergence of AD in elderly citizens is proved by the scholars who examined the impact of the quality of air on a person’s health.
• Bilinguals’ Cognitive-Linguistic Abilities and Alzheimer’s Disease This irregularity is reflected in the preserved linguistic abilities, including code-switching and semantic fluency, and the declined functions in translation, picture naming, and phonemic fluency, calling for improved therapy and testing practices.
• Managing Dementia and Alzheimer’s Disease The PICOT question is “In the care of Alzheimer’s and dementia patients, does integrated community-based care as compared to being in a long-term care facility improve outcome throughout the remainder of their lives”.
• Pathophysiology of Alzheimer’s Disease The study will discuss the pathophysiology of Alzheimer’s disease, such as risk factors, cellular involvement, genetic influences, and the interventions of the available therapy’s pharmacological Interventions.
• Alzheimer’s Disease: Definition, Stages, Diagnosis Alzheimer’s disease is the most common type of dementia, and it is a condition in which the brain stops appropriately performing its functions.
• Fall Risk Assessment of Alzheimer’s Patient The nurse answers questions about the old lady helps fill the Stay Independent brochure and assists the observing physician in carrying the various clinical tests on the patient.
• Alzheimer’s Disease in an Iranian Patient The patient in the company of his son returns to the clinic after four weeks. Since the patient shows no side effects of the disease and an increase in Exelon to 6 mg orally BID […]
• Mr. Akkad and Alzheimer’s Disease: Case Study The onset of the symptoms is reported to have been within the past two years, but the situation has begun to deteriorate, prompting Mr.
• Alzheimer’s Disease: History, Mechanisms and Treatment Nevertheless, researchers state that the development of Alzheimer’s is impacted by the formation of protein plaques and tangles in the brain.
• Alzheimer’s Disease: Causes and Treatment AD is associated with different changes, both cognitive and behavioral. A patient can observe some or all of them depending on the development of the disease.
• Frontotemporal Dementia vs. Alzheimer’s Disease in a Patient Moreover, Alzheimer’s disease affects hypertrophies in the hippocampus as the initial part is involved in the brain’s memory areas and spatial orientation.
• Alzheimer’s Disease: Diagnostic and Treatment Alzheimer’s disease is a progressive degenerative disorder that causes a deterioration of mental and cognitive abilities.
• The Effect of Music on People With Alzheimer’s Disease The evidence suggests that one of the most prominent effects of music on patients with Alzheimer’s disease is autobiographical memory preservation alongside the stimulation of both sympathetic and parasympathetic nervous systems.
• Community Health: Alzheimer’s Disease The community nurse’s role is to develop and participate in primary, secondary, and tertiary preventive strategies and to provide a wide range of nursing care services while maintaining the health and wellbeing of individuals with […]
• Challenges of Living With Alzheimer Disease The medications make the condition of the patient better during the first stages of the disease. During the middle stage of the disease, the symptoms worsen.
• The Burden of Alzheimer’s Disease Assessing the appropriateness and effectiveness of reducing the cost of providing care for patients with Alzheimer remains a major issue that needs to be addressed.
• Chronic Care For Alzheimer’s Disease The application of the Chronic Care Model, in its turn, will serve as the foundation for building the patient’s awareness about their condition, thus, improving the patient’s quality of life and creating the environment, in […]
• Synopsis of Research Studies of Individuals Afflicted by Mild Alzheimer’s Disease The research questions in the articles were tailored along the various physical activities that can assist patients affected by Alzheimer Disease.
• Alzheimer’s Disease and Naturopathic Medicine The main feature of AD is the aggregation of -amyloid. However, application of natural therapies to prohibit the process of the pathways can slow the progress of AD.
• Brain Reduction and Presence of Alzheimer’s Disease The purpose of the study was to examine the correlation between brain reduction and the presence of Alzheimer’s disease. The researchers wanted to examine the nature of such changes in elderly individuals at low risk […]
• Alzheimer Related Morbidity and Death Among New Yorkers Generally, Alzheimer disease is a form of dementia, which inflicts a loss of memory, thinking and behavior. The proportion of ethnic and racial diversity in the US is increasing.
• Environmental Interview on a Patient With Alzheimer Disease In the 1980s, delusions and hallucinations were added as signs of the disease. Researches in the 1960’s show a link between cognitive reduction and the number of ailments in the brain.
• Alzheimer’s Disease Article and Clinical Trial This study shows that environmental hazards, in this case lead, increase the risk of developing Alzheimer’s disease and that the development period is crucial for determining future vulnerability to neurodegeneration and Alzheimer’s disease.
• Alzheimer’s Disease: Regarding Physiology However, one clear aspect of the development of this disease arises from a very complex chain of activities taking place in the brain over a long period of time.
• Mapping the Neurofibrillary Degeneration From Alzheimer’s Disease Patient This is an analytic review of the studies elaborating on the relationship of hyperphosphorylated tau proteins to the development of Alzheimer’s disease and focusing on the antigen capture ELISA specific for p-tau proteins.
• Role of Alzheimer’s Disease Advanced in Our Understanding of the Aging Process Aging on the hand can be defined as the accumulation of different harmful changes in the tissues and cells that raises the possibility of disease and death.
• Depression and Alzheimer’s Disease Moretti et al have studied the relationship between depression and Alzheimer’s disease and explored whether depression is a symptom of AD or comorbidity.
• Alzheimer’s Disease: Medical Analysis Such gene-associated markers have been characterized, in particular the apolipoprotein E gene, which was linked to chromosome# 19, and was responsible for accumulation of A by way of binding to this protein.
• Diabetic Teaching Plan for Alzheimer’s Patient He knows the purposes and some of the steps and needs to be taught again to regain his independence in monitoring his blood glucose level.
• Comparing Alzheimer’s Disease and Parkinson’s Disease There are many superficial similarities between Alzheimer’s disease and Parkinson’s disease primarily in some symptoms and age-group of persons afflicted by these two diseases.
• The Effects of Alzheimer’s Disease on Family Members The disease develops gradually and is said to be a disease of the old because it relates to the inability to remember.
• Alzheimer’s Disease in Science Daily News Article The news article accurately reports the focus of the study in the diagnosis of AD. Hence, the news article accurately presents that the diagnostic method is important in the diagnosis and prognosis of AD among […]
• Dancing and Risk of Alzheimer’s Disease Despite the fact that there is no effective treatment for Alzheimer’s disease, scientists discovered that dancing could help reduce the severity of the disorder as this activity involves simultaneous brain functioning, which helps to affect […]
• Alzheimer’s Disease Prevalence and Prevention The estimated global prevalence of Alzheimer’s disease is 50 million and is projected to triple by 2050 due to growth in the older generation. According to Alzheimer’s Association, AD is the fifth-ranking killer of persons […]
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• Heart Disease and Alzheimer’s in Adult Women Education and Employment History: The patient reported she is a college graduate and has a master’s degree in Victorian Literature. The patient is currently working full-time as a Literature professor at UC Berkeley, in a […]
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• The Contingent Valuation Method in Health Care: An Economic Evaluation of Alzheimer’s Disease
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• What Is the Main Cause of Alzheimer’s Disease?
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• What Foods Cause Alzheimer’s Disease?
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• Do Alzheimer’s Disease Patients Feel Pain?
• What Is the Best Treatment for Alzheimer’s Disease?
• How Long Do Alzheimer’s Disease Patients Live?
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• What Are the Final Stages of Alzheimer’s Disease Before Death?
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• How Do You Know When an Alzheimer’s Disease Patient Is Dying?
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• Disease Questions
• Disorders Ideas
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• Caregiver Topics
• Health Promotion Research Topics
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• Published: 13 May 2021

Alzheimer disease

• David S. Knopman   ORCID: orcid.org/0000-0002-6544-066X 1 ,
• Helene Amieva 2 ,
• Ronald C. Petersen 1 ,
• Gäel Chételat 3 ,
• David M. Holtzman 4 ,
• Bradley T. Hyman   ORCID: orcid.org/0000-0002-7959-9401 5 ,
• Ralph A. Nixon 6 , 7 &
• David T. Jones   ORCID: orcid.org/0000-0002-4807-9833 1  

Nature Reviews Disease Primers volume  7 , Article number:  33 ( 2021 ) Cite this article

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• Alzheimer's disease
• Diagnostic markers
• Translational research

Alzheimer disease (AD) is biologically defined by the presence of β-amyloid-containing plaques and tau-containing neurofibrillary tangles. AD is a genetic and sporadic neurodegenerative disease that causes an amnestic cognitive impairment in its prototypical presentation and non-amnestic cognitive impairment in its less common variants. AD is a common cause of cognitive impairment acquired in midlife and late-life but its clinical impact is modified by other neurodegenerative and cerebrovascular conditions. This Primer conceives of AD biology as the brain disorder that results from a complex interplay of loss of synaptic homeostasis and dysfunction in the highly interrelated endosomal/lysosomal clearance pathways in which the precursors, aggregated species and post-translationally modified products of Aβ and tau play important roles. Therapeutic endeavours are still struggling to find targets within this framework that substantially change the clinical course in persons with AD.

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Acknowledgements

The authors acknowledge research support from NIH (D.S.K. and R.C.P, P30 AG062677 and U01 AG006786; B.T.H., P30AG062421; R.A.N. P01 AG017617 and R01 AG062376).

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Department of Neurology, Mayo Clinic, Rochester, MN, USA

David S. Knopman, Ronald C. Petersen & David T. Jones

Inserm U1219 Bordeaux Population Health Center, University of Bordeaux, Bordeaux, France

Helene Amieva

Normandie Univ, UNICAEN, INSERM, U1237, PhIND “Physiopathology and Imaging of Neurological Disorders”, Institut Blood and Brain @ Caen-Normandie, Cyceron, Caen, France

Gäel Chételat

Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA

David M. Holtzman

Department of Neurology, Massachusetts General Hospital, Boston, MA, USA

Bradley T. Hyman

Departments of Psychiatry and Cell Biology, New York University Langone Medical Center, New York University, New York, NY, USA

Ralph A. Nixon

NYU Neuroscience Institute, New York University Langone Medical Center, New York University, New York, NY, USA

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Introduction (D.S.K.); Epidemiology (H.A.); Mechanisms/pathophysiology (D.T.J., R.A.N., B.T.H. and D.M.H.); Diagnosis, screening and prevention (G.C., R.C.P. and D.S.K.); Management (R.C.P. and D.S.K.); Quality of life (D.S.K.); Outlook (D.S.K.); Overview of Primer (D.S.K.).

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Correspondence to David S. Knopman .

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Competing interests.

D.S.K. served on a Data Safety Monitoring Board for the DIAN study. He serves on a Data Safety Monitoring Board for a tau therapeutic for Biogen but receives no personal compensation. He is a site investigator in a Biogen aducanumab trial. He is an investigator in a clinical trial sponsored by Lilly Pharmaceuticals and the University of Southern California. He serves as a consultant for Samus Therapeutics, Third Rock, Roche and Alzeca Biosciences but receives no personal compensation. He receives research support from the NIH. G.C. serves on the Scientific Advisory Board of the Fondation Vaincre Alzheimer but receives no personal compensation. She receives personal fees from Fondation d’entreprise MMA des Entrepreneurs du Futur and from Fondation Alzheimer as she serves in the Operational Committee. She receives research support from European Union Horizon 2020 research and innovation programme (grant agreement number 667696), Inserm, Fondation d’entreprise MMA des Entrepreneurs du Futur, Fondation Alzheimer, Programme Hospitalier de Recherche Clinique, Région Normandie, Association France Alzheimer et maladies apparentées and Fondation Vaincre Alzheimer. R.C.P. is a consultant for Biogen, Inc., Roche, Inc., Merck, Inc., Genentech Inc. and Eisai, Inc., has given educational lectures for GE Healthcare, receives publishing royalties from Mild Cognitive Impairment (Oxford University Press, 2003), UpToDate, and receives research support from the NIH. B.T.H. has a family member who works at Novartis and owns stock in Novartis; he serves on the SAB of Dewpoint and owns stock. He serves on a scientific advisory board or is a consultant for Biogen, Novartis, Cell Signalling, the US Dept of Justice, Takeda, Vigil, W20 group and Seer. His laboratory is supported by sponsored research agreements with Abbvie, F Prim, and research grants from the National Institutes of Health, Cure Alzheimer’s Fund, Tau Consortium, Brightfocus and the JPB Foundation. H.A. serves on the Scientific Advisory Board of the Observatoire des Mémoires but receives no personal compensation. She receives research support from Spoelberch Foundation, Association France Alzheimer et maladies apparentées, the Regional Health Agency of Aquitaine and National Research Agency. D.M.H. reports being a Co-founder for C2N Diagnostics LLC and participating in scientific advisory boards/consulting for Genentech, C2N Diagnostics, Denali, Merck and Idorsia. He is an inventor on patents licensed by Washington University to C2N Diagnostics on the therapeutic use of anti-tau antibodies (this anti-tau antibody programme is licensed to Abbvie) and to Eli Lilly on the therapeutic use of an anti-amyloid-β antibody. His laboratory receives research grants from the National Institutes of Health, Cure Alzheimer’s Fund, Tau Consortium, the JPB Foundation, Good Ventures, Centene, BrightFocus and C2N Diagnostics. All other authors declare no competing interests.

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Knopman, D.S., Amieva, H., Petersen, R.C. et al. Alzheimer disease. Nat Rev Dis Primers 7 , 33 (2021). https://doi.org/10.1038/s41572-021-00269-y

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DOI : https://doi.org/10.1038/s41572-021-00269-y

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• An Introduction to Alzheimer’s Disease: What is it?

By: Adrianna Fusco

Introduction: Alzheimer’s disease, something we hear about online, in commercials, on news stations, and in many other parts of life. However, we are never told much about Alzheimer’s disease other than the devastating impacts it has. What is Alzheimer’s disease? What are the symptoms or signs to look out for? How does it progress? What causes it? How can it be prevented?

What is it? Alzheimer’s disease is a form of dementia, which is just an umbrella term used to describe loss of memory, language, problem solving, and other thinking abilities. More specifically, Alzheimer’s diseaseis a progressive, neurodegenerative disease that is categorized by a loss of memory, along with basic life skills like eating, bathing, talking, etc.

Symptoms: Common symptoms include: memory loss, paranoia, depression, anger, aggression, anxiety, apathy, loneliness, and psychosis. These symptoms vary from person to person.

Progress: As mentioned above, Alzheimer’s disease is a progressive disease. This means that it develops and gets worse over time. In the first stages of Alzheimer’s disease, there is usually very mild memory loss or problems with thinking abilities. The person may have a hard time remembering where they placed something or have a hard time recalling the right word to say. However, they still are independent, meaning they can still take care of themselves and do things like driving.

During the middle stages of Alzheimer’s disease, the cognitive processes get worse. Now the person may not be able to remember their personal history, like their address or phone number. They also may have a hard time recalling memories or remembering something from their past. The person is no longer able to take care of themselves because in this stage, they tend to forget where they are and often have a hard time using the bathroom or getting dressed appropriately for the day. An example of this is the person wearing shorts in the winter. Along with the cognitive changes, the person may begin to feel sad, lonely, anxious, and paranoid. The symptoms vary from person to person.

When the person hits stage 2, they will need a caregiver to assist them with their tasks and the caregiving will increase as the disease progresses. However, it’s important to help them without trying to do everything for them. They are still adults and they want to be treated as such, so it’s important to still let them have at least some control over their life. Whether that’s letting them do simply chores, like folding clothes, or doing activities, like arts and crafts. This will help provide a sense of normalcy.

The final stage of Alzheimer’s disease is when people begin to lose sense and control of the environment around them. By this point, the cognitive abilities of the individual have tremendously decreased. They can no longer speak in long formulated sentences, instead they speak in short fragments or words. They have trouble completing everyday tasks like walking, sitting, eating, and drinking. This means that they require around the clock assistance to make sure that they are remembering to eat and to help them eat. In general, the assistance is meant to make sure the person is safe and is living to their best ability. At this point, the individuals are very susceptible to infections. When the symptoms and daily conditions get really bad, usually, families turn to hospice care, so that the patient is comfortable at the end of their life. Hospice care also provides emotional support to loved ones, which is vital. Losing a loved one can cause serious emotional and mental strain, so that support is important.

The cause of Alzheimer’s disease is still being researched, but researchers have identified what they believe to be the main culprits of the disease: plaques and tangles. 

Plaques are deposits of amyloid beta that forms between nerve cells that blocks the signals and stops the right materials from being sent to the nerve for survival. In a healthy brain, amyloid beta is used to help support neural repair and growth. However, in Alzheimer’s disease, there is an overproduction of this amyloid beta protein that disturbs these cells and eventually causes the death of the cells. The death of the old cells causes the loss of old memories and information. The blocking of nerve cells can stop the production of new connections, which means short term memories are not being accurately encoded in the brain to become long term memories. 

Tangles are made up of twisted tau that builds up between cells. In a healthy brain, tau is used to help support neural strength and is important in keeping stability in the cells. However, a build up leads to the cells not being able to receive signals and the supplies it needs to function (i.e. energy). These lead to death of the cells, leading to loss of information and life skills.

There is also a biomarker known as APOE-4, that is thought to predispose people to Alzheimer’s disease. This gene along with some environmental stressors could affect whether someone gets the disease and the progression of it. However, a lot of research is still being conducted on this topic and we are constantly rerouting what we know, as new information is found.

Alzheimer’s disease is a terrible disease that claims the lives of a lot of people every year. It’s important to know the signs and to check up with your doctor when anything seems unusual. Alzheimer’s disease and dementia are not a normal part of aging, so see your doctor if you notice any issues with your memory. The earlier the disease is detected, the better it can be treated.

Stay tuned for more blog posts about Alzheimer’s disease, including a look into the mental health of caregivers, prevention, treatment, and more! We also will be writing posts about interviews with doctors, as well as posts about brain health!

Thank you for reading!

References: 

“Alzheimer’s Caregivers: 8 Tips for People Caring for a Loved One With Alzheimer’s Disease or Dementia: Caregivers.” 30Seconds Health , 

30seconds.com/health/tip/14389/Alzheimers-Caregivers-8-Tips-for-People-Caring-for-a-Loved-One-With -Alzheimers-Disease-or-Dementia. 

Mayeux, Richard, et al. “Treatment of Alzheimer’s Disease: NEJM.” Edited by Alastair J.J. Wood, New England Journal of Medicine , 16 Mar. 2000, www.nejm.org/doi/pdf/10.1056/NEJM199911253412207. 

NHS Choices, NHS, 10 May 2018, 

www.nhs.uk/conditions/alzheimers-disease/causes/#:~:text=Alzheimer’s%20disease%20is%20thought%2 0to,form%20tangles%20within%20brain%20cells. 

Porsteinsson, Anton P., et al. “Neuropsychiatric Symptoms in Dementia: A Cause or Consequence?” American Journal of Psychiatry , American Psychiatric Association Publishing, 30 Apr. 2015, ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.15030277#:~:text=The%20term%20neuropsychiatric %20symptoms%20describes%20heterogeneous%20behavioral%20or,agitation%2C%20anxiety%2C%20 apathy%2C%20depression%2C%20psychosis%2C%20and%20sleep%20disturbance. 

“Stages of Alzheimer’s.” Alzheimer’s Disease and Dementia , www.alz.org/alzheimers-dementia/stages. 

“What Is Alzheimer’s?” Alzheimer’s Disease and Dementia , 

www.alz.org/alzheimers-dementia/what-is-alzheimers.

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• v.134(18); 2021 Sep 20

Current Alzheimer disease research highlights: evidence for novel risk factors

Willa d. brenowitz.

1 Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA

2 Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

3 Institute of Neurology, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China

4 Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu, Sichuan, China

Claire T. McEvoy

5 Centre for Public Health, Queen's University Belfast, Belfast, UK

6 Global Brain Health Institute, University of California, San Francisco, San Francisco, CA, USA

Kristine Yaffe

7 Department of Neurology, University of California, San Francisco, CA, USA.

Wei-Dong Le

Alzheimer disease (AD) is the most common type of dementia characterized by the progressive cognitive and social decline. Clinical drug targets have heavily focused on the amyloid hypothesis, with amyloid beta (Aβ), and tau proteins as key pathophysiologic markers of AD. However, no effective treatment has been developed so far, which prompts researchers to focus on other aspects of AD beyond Aβ, and tau proteins. Additionally, there is a mounting epidemiologic evidence that various environmental factors influence the development of dementia and that dementia etiology is likely heterogenous. In the past decades, new risk factors or potential etiologies have been widely studied. Here, we review several novel epidemiologic and clinical research developments that focus on sleep, hypoxia, diet, gut microbiota, and hearing impairment and their links to AD published in recent years. At the frontiers of AD research, these findings and updates could be worthy of further attention.

Introduction

As one of the most common neurodegenerative diseases and causes of dementia, Alzheimer disease (AD) is a critical topic for biomedical research. The main clinical manifestation of AD is the progressive decline of cognitive function and activities of daily living, and the pivotal pathological features of AD are amyloid beta (Aβ) deposition, neurofibrillary tangles, neuroinflammation, synaptic degeneration, and neuronal loss. [ 1 ] While research on AD has been ongoing for >100 years, our understanding of AD is also constantly enriched by the new research directions. However, there are still no effective treatments to delay, halt, or even reverse the process of AD.

In the past few decades, researchers have gradually shifted their attention from treatments to the early diagnosis and prevention of AD. [ 2 ] There is an interest in identifying the novel risk factors for AD as well as the novel biomarkers to help detect AD before the symptom onset. Several potential risk factors for AD have been studied extensively, including cardiovascular disease (CVD), diabetes, obesity, low education, social isolation, and depression. [ 3 ] However, recent epidemiologic and clinical studies are expanding our understanding of potential AD markers and risk factors to other health behaviors and conditions, such as sleep, diet, and hearing loss. For example, sleep disturbance has a complex association with AD and may be either a preclinical biomarker or potential modifiable risk factor for AD. In particular, hypoxia, often caused by severe obstructive sleep apnea syndrome (OSAS), significantly promotes the development of AD, inspiring the attempts to treat AD using the hyperbaric oxygen treatment (HBOT). [ 4 ] Dietary patterns are associated with cognition in older adults, and the Mediterranean-style diet (MD) is associated with reduced risk of AD. Gut microbiota may be an intriguing potential mediator between diet and AD. [ 5 ] Also, hearing impairment which is often ignored in clinical practice has strong associations with the risk of AD.

Here, we review the latest developments and especially the epidemiological evidence on sleep, hypoxia, diet, gut microbiota, and hearing impairment in the research field of AD published in recent years. These topics are receiving increasing research interest and may point to novel areas for intervention in the treatment and prevention of AD. As the frontiers of AD research, these findings and updates could be worthy of further attention.

Recent Progress in the Research of AD

In this section, we will review and summarize the recent progress in the research of AD focusing on five novel potential risk factors or early disease indicators such as sleep, hypoxia, diet, gut microbiota, and hearing impairment. As these factors are relatively novel, this review focuses on the epidemiologic evidence with some discussion of potential mechanisms as well as areas for future research.

Sleep and AD

One of the most exciting recent highlights in Alzheimer research is the bi-directional relationship between sleep disturbances and the risk of AD. Patients with AD frequently experience sleep disturbances, including insomnia, abnormal sleep duration, poor nighttime sleep quality, excessive daytime sleepiness, and disrupted circadian rhythms. [ 6 ] These sleep problems subsequently reduce patient quality of life and increase the risk for premature institutionalization.

Importantly, growing evidence from the epidemiological studies has suggested that 50% to 80% increased risk of dementia is associated with sleep disturbances, including insomnia, sleep-disordered breathing (SDB), disrupted circadian rhythms, and sleep-related movement disorders. [ 7 – 12 ] Excessive daytime napping has also been associated with an increased risk of cognitive impairment in older men, although the underlying mechanisms are less clear. [ 13 ] Several studies have found a U-shaped association between sleep duration and risk of dementia, [ 14 , 15 ] indicating the effects of both short and long sleep duration on cognitive aging. Furthermore, one recent study discovered 23 macro- and micro-physiological architecture metrics of sleep, including rapid eye movement sleep duration, features of the electroencephalography power spectra derived from multivariate analysis, and spindle and slow oscillation morphology and coupling, which were all strongly linked with cognitive performance in older adults. [ 16 ] Sleep disturbances are increasingly recognized as a preclinical marker or potential modifiable risk factor for AD.

Over the past decade, emerging evidence from animal and human studies has begun to uncover the nature of the association between sleep disturbances and AD. Since the earlier animal studies that identified a close link between sleep-wake cycle and the pathogenesis of AD, [ 17 , 18 ] a growing body of research has suggested sleep deprivation as both a result and trigger of Aβ, the hallmark pathological feature of AD. [ 19 ] Prospective analysis also showed that baseline measures of non-rapid eye movement (NREM) sleep slow-wave activity and sleep quality are sensitive in predicting longitudinal trajectory of Aβ deposition in healthy older adults, indicating the role of sleep as a useful biomarker for forecasting Aβ pathological progression before the clinical cognitive impairment. [ 20 ] Furthermore, sleep–wake cycle was found to regulate brain interstitial fluid (ISF) tau, and chronic sleep deprivation might increase ISF and cerebrospinal fluid (CSF) tau as well as tau pathology spreading. [ 21 ] It was also suggested that SDB might lead to increased tau levels over time in those with normal cognition or mild cognitive impairment (MCI). [ 22 ] Interestingly, one recent study found a coherent pattern of electrophysiological, hemodynamic, and CSF oscillations during human NREM sleep, suggesting a link in the neurophysiology of sleep and waste clearance in the brain. [ 23 ]

In addition to the use of neuroimaging and biomarkers, recent studies are also starting to use novel statistical approaches, such as Mendelian randomization (MR), to overcome the limitations of observational epidemiological studies and to reveal the causal relationship between sleep and AD. For instance, using the MR approach, it was found that higher genetic risk for AD might predict shorter sleep duration, suggesting that short sleep duration could be part of the AD disease process and thus serve as an early marker for AD. [ 24 ] Meanwhile, another MR study showed no causal effect of self-reported or accelerometer-measured sleep traits on AD risk. Given the growing evidence that indicates a bi-directional relationship between sleep disturbances and AD, emerging studies are underway to examine the use of sleep interventions in the prevention and treatment of AD. One recent review summarized the effects of several sleep interventions that have been studied in patients with MCI or mild dementia, including Cognitive Behavioral Therapy-Insomnia (CBT-I), a structured limbs exercise program, aromatherapy, phase locked loop acoustic stimulation, transcranial stimulation, suvorexant, melatonin, donepezil, galantamine, rivastigmine, tetrahydroaminoacridine, and Continuous Positive Airway Pressure (CPAP) and concluded that CBT-I, melatonin, suvorexant, and CPAP for OSA hold the most promises. [ 25 ] Since medications might further impair cognition, non-pharmacological interventions are of particular interest for older adults who are at high risk for dementia. Cordone et al [ 26 ] highlighted several promising techniques to enhance NREM sleep oscillations that have solid scientific basis for preventing or slowing down AD pathology but remain to be tested in clinical settings.

Overall, while it remains inconclusive whether sleep disturbances are early signs or risk factors for AD, recent research highlights the importance of sleep among older adults. Changes in sleep architecture and electroencephalogram might be considered as a valuable marker of AD before the onset of cognitive symptoms and help with the early detection of the disease. [ 27 ] Future research is needed to test whether sleep disturbances could be the risk factors for AD and to explore the use of sleep interventions in patients at high risk for AD. [ 25 ]

Hypoxia and AD

Hypoxia can be caused by CVD, hematological diseases, chronic kidney diseases (CKD), respiratory dysfunction, and environmental conditions, which could influence the central nervous system and induce neurodegeneration. [ 28 – 33 ] Acute hypoxia can be induced by stroke, while OSAS, capillary dysfunction, and CKD may lead to chronic hypoxia. Cognitive impairment may also occur in normal adults after hypoxia. [ 34 , 35 ]

Hypoxia is associated with AD. [ 28 – 33 ] Both acute and chronic hypoxia intervention in experimental animals can result in the aggravation of cognitive dysfunction and the AD-type pathological alterations including Aβ deposition, hyperphosphorylation of tau protein, synaptic degeneration, and neuronal loss. [ 36 ] Increasing evidence suggests that hypoxia facilitates the pathogenesis of AD through multiple pathways including increasing the production and accelerating the accumulation of Aβ, [ 36 ] decreasing the degradation of Aβ, [ 37 ] reducing the clearance of Aβ, [ 38 ] elevating the hyperphosphorylation of tau, [ 39 ] inhibiting the autophagic function, [ 40 ] aggravating neuroinflammation [ 41 ] and oxidation stress, [ 42 ] ruining the mitochondria function, [ 43 ] and causing the stress of endoplasmic reticulum. [ 44 ] As mentioned above, it is rational to propose that hypoxia is one of the essential factors contributing to the pathogenesis of AD.

Given that hypoxia contributes to the pathogenesis of AD, the development of prevention and treatment targeting hypoxia is promising. HBOT is a safe, effective, and routinely used medical procedure. Growing evidence suggests that HBOT can induce the neuroplasticity and improve the cognitive function in patients suffering from neurocognitive impairment due to stroke and brain injuries. [ 45 , 46 ] Moreover, HBOT cannot only improve cognitive functions and ameliorate the brain glucose metabolism in AD and amnestic MCI (aMCI) patients [ 4 , 47 ] but also induce significant senolytic effects including significantly increasing telomere length and clearance of senescent cells in the aging individuals. [ 48 ]

Besides, HBOT is capable of improving the cognitive behavioral performance, reducing Aβ burden and tau hyperphosphorylation, alleviating neuroinflammation by decreasing astrogliosis and microgliosis, reducing proinflammatory cytokines, and elevating phagocytic markers in mouse mole of AD. [ 49 ] More recently, HBOT was shown to be able to reduce Aβ accumulation and hippocampal neuritic atrophy, increase hippocampal neurogenesis, and profoundly improve the cognitive deficits through the upregulation of neurotrophic factors. [ 50 ] Moreover, HBOT has been proved to inhibit Aβ25–35-induced toxicity, oxidative stress, and neuronal apoptosis. [ 51 , 52 ] In addition, both the cognitive impairment and hippocampal damage can be attenuated by HBOT via NF-κB signaling pathway [ 53 ] or p38 mitogen-activated protein kinase (MAPK) in the animal model of AD. [ 54 ] However, there is still no research report on whether HBOT has the capacity of preventing or delaying the occurrence of AD in high-risk groups at an early stage. Besides, further experiments are still warranted because of the possibility of oxygen toxicity, even though HBOT itself seems to be beneficial to cognition.

Diet and AD

As poor diet contributes to several AD risk factors including obesity, hypertension, and diabetes, modifying the dietary behavior could be an effective public health strategy to protect against age-related neurodegeneration and AD in late life.

A growing body of evidence has linked several foods (eg, green vegetables, berries, fish, and olive oil), nutrients (eg, B-vitamins, vitamin E, and omega-3 fatty acids), and plant bioactives (eg, flavanoids) to reduce dementia risk. Consuming these nutrients and foods in combination as a dietary pattern is likely to exert greater synergistic effects on the physiological processes underlying neurodegeneration. The MD rich in antioxidants and flavonoids and characterized by high intake of fruits, vegetables, whole grains, olive oil, nuts, and legumes; moderate intake of fish, poultry, and alcohol, and low intake of red meat have proven cardiometabolic benefits [ 55 ] and remain the most frequently studied dietary pattern for neuroprotection during ageing. Evidence from prospective studies indicate beneficial associations among MD adherence, slower rate of cognitive decline, and reduced risk of cognitive impairment, in Western [ 56 , 57 ] and Asian [ 58 ] populations. However, findings have not been consistent likely because of the differences in populations studied, measures of MD and cognition, length of follow-up, and adjustment for important confounders such as cardiovascular morbidity and baseline cognitive function. To date, only a small number of studies have examined the relationship between diet and incident AD. [ 59 ] Among older cognitively healthy U.S. adults, those in the highest tertile of MD adherence had 40% to 54% reduced AD risk compared to those in the lowest MD tertile, but results have not been replicated in French or Swedish populations [ 59 ] making it difficult to draw firm conclusions.

The neuroprotective mechanisms of a healthy diet are not fully elucidated, but multiple antioxidants, anti-inflammatory, and vascular pathways are likely to be important. The MD improves vascular function and insulin resistance [ 55 , 60 ] that contribute to the cognitive decline and AD. Experimental and preclinical studies have shown that dietary antioxidants and flavonoids have a direct effect on the brain by inhibiting oxidative stress, cytokine production and pro-inflammatory cell signaling pathways, and suppressing neuroinflammatory processes implicated in AD. Emerging data suggest that diets rich in fruit, vegetables, whole grains, and fiber promote biodiversity of the gut microbiome and decreased pro-inflammatory gut-derived bacteria and toxins are shown to contribute to early neuroinflammatory changes, and AD pathology. [ 5 , 60 ] Evidence from observational studies report a link between greater MD adherence and favorable brain structures and functions that protect against neurodegeneration as well as less Aβ accumulation in AD-vulnerable regions of the brain. [ 61 ] Furthermore, dietary restriction [ 62 ] achieved by calorie restriction (30%–40%) or intermittent fasting may provide neuroprotection by attenuating neuroinflammation and insulin resistance and promoting synaptic plasticity and neurogenesis. [ 63 ] Beneficial effects of DR on AD pathology have been demonstrated in some [ 64 , 65 ] but not all [ 66 ] transgenic animal models, and it is not yet clear on how the findings translate to humans. [ 63 ]

The effect of diet on AD risk is not yet known; however, randomized controlled trial data evaluating the effect of diet on cognitive performance demonstrated less decline in global cognition, memory, and executive function in response to a MD >4 to 6 years [ 60 ] with no convincing benefit for shorter-term MD interventions (up to 12 months) [ 59 ] in cognitively healthy older adults, suggesting that several years of dietary exposure may be needed to detect changes in intermediate cognitive tests of AD risk in general populations.

Overall, accumulating data suggest a role for diet in AD prevention but larger adequately powered intervention and prospective studies in diverse populations with clinically relevant endpoints incorporating incident AD, MCI as well as sensitive neurocognitive tests and brain biomarkers associated with preclinical AD risk are required to understand the effect of diet on AD from the earliest to later stages of disease.

Gut microbiota and AD

Given the complex bidirectional communication system that exists between the gut and brain, there is a growing interest in the gut microbiome as a novel and potentially modifiable risk factor for cognitive impairment and AD. Gut dysbiosis has been implicated in the pathogenesis and progression of AD.

Compared with the normal controls, the Bacteroidetes , Actinomyces , Ruminococcus , and Selenomonas in AD patients are significantly different. [ 67 ] The cognitively normal elderly do not have an AD-type pattern of gut microbiota compared with patients at the early stage of AD, [ 68 ] and specific gut microbiota, especially enriched Enterobacteriaceae , are associated with AD patients compared with aMCI and cognitively healthy controls, [ 69 ] indicating the potential of gut microbiota in the differential diagnosis of AD. Besides, the alteration of gut microbiota tends to occur several years before the onset of dementia, even at the early stage of MCI. [ 68 ] A cross-sectional study showed that an increase in Bacteroidetes in non-dementia patients is independently associated with the presence of MCI. [ 70 ] The abundance increase of Enterobacteriaceae , Akkermansia , Slackia , Christensenellaceae , and Erysipelotriaceae in MCI patients suggests that this special gut microbiota composition may indicate the presence of MCI. [ 71 ]

To investigate the causal relationship between gut microbiota and AD, a clinical study found that gamma-aminobutyric acid (GABA) and serotonin may play an important role in the gut microbiota–host interaction in AD patients. [ 72 ] A pilot study revealed the characteristics of the MCI-specific gut fungi (mycobiome) signatures and elucidated that the diet-regulated mycobiome are associated with AD markers and fungal–bacterial co-regulation networks in MCI patients. [ 73 ] A clinical study showed that Proteobacteria is positively correlated with Aβ42:Aβ40 ratio, but the fecal propionic acid and butyric acid are negatively correlated with Aβ42 level in MCI patients with the MD. [ 71 ] Intriguingly, the gut microbiota composition is strongly correlated with apolipoprotein E (ApoE) genotype. The relative abundance of different bacterial groups is significantly different under the influence of ApoE genotype, [ 74 ] which is also related to the specific gut microbiota composition of human and ApoE-targeted replacement mice, especially the Prevotellaceae and Ruminococcaceae and several butyrate-producing genera. [ 75 ] Moreover, the relative abundance of Prevotella and Ruminococcus in female ApoE4-familial Alzheimers disease (FAD) mice is higher than that of female ApoE3-FAD mice, whereas the relative abundance of Sutterella in male ApoE4-FAD mice is significantly higher than that of female ApoE3-FAD mice, implying a synergistic effect of ApoE and sex on gut microbiota of AD. [ 76 ]

The metabolites of gut microbiota are particularly critical in the mechanism of the gut–brain axis. Trimethylamine-n-oxide (TMAO), a kind of gut microbiota metabolites, can be found in human CSF. [ 77 ] It was suggested that the gut microbiota metabolites, such as lipopolysaccharide (LPS) and short chain fatty acids, could mediate the systemic inflammation and intracerebral amyloidosis through endothelial dysfunction. [ 78 ] A multicenter clinical study found that the serum concentration of primary bile acid (BA) is significantly decreased, whereas the concentrations of secondary BA, deoxycholic acid, and its conjugated form of glycine and taurine are increased in AD patients compared with cognitively normal elderly. [ 79 ] Moreover, it was found that the certain blood BA-related indicators are associated with CSF-Aβ, CSF-p-tau 181, CSF-t-tau, glucose metabolism, and brain atrophy in patients with MCI and AD, respectively. [ 80 ]

Additionally, there are also many studies exploring the effect and mechanism of different types of intervention on AD using gut microbiota as a potential mediator. High dose of Jatrorrhizine, [ 81 ] an essential component of coptidis rhizome, a Chinese traditional herb, is capable of improving the learning and memory ability, reducing Aβ deposition, and altering the abundance of certain gut microbiota composition such as Firmicutes and Bacteroidetes in APP/PS1 mice. [ 82 ] Besides, 27-hydroxycholesterol can aggravate AD-type pathological alterations, gut microbiota dysbiosis, and intestinal barrier dysfunction. [ 83 ] The fructooligosaccharides derived from Morinda officinalis improves the learning and memory abilities of rats by regulating the interaction between intestinal ecosystem and brain. [ 84 ] Xanthoceraside can alleviate the symptoms of AD by affecting the composition and endogenous metabolites of gut microbiota in rats. [ 85 ] GV-971, an oligosaccharide sodium, has the capacity of inhibiting gut microbiota dysbiosis and related phenylalanine/isoleucine accumulation, alleviating neuroinflammation, and reversing cognitive dysfunction. [ 86 ]

Environmental factors may also influence the pathogenesis of AD through gut microbiota. Long-term exposure to noise alters gut microbiota composition and accelerates age-related neurochemical and inflammatory regulation disorders, resulting in the aggravated AD-type pathological changes in the brain of senescence-accelerated prone mice. [ 87 ] Treatment of mid infrared light of peak wavelength 7.7 to 10 mm can attenuate the decline of learning and memory, reduce Aβ deposition, and alter the gut microbiota composition. [ 88 ]

Due to the importance of gut microbiota in the pathogenesis of AD, many studies assessed its potential therapeutic value. Clinical studies have found that supplement of multiple probiotics alters the gut microbiota composition and serum tryptophan metabolism in AD patients, [ 89 ] and promotes the mental plasticity and stress relief in healthy elderly. [ 90 ] A multicenter study published recently has also shown that the MD can alter the composition of the gut microbiota and improve cognitive function in older adults. [ 5 ]

In animal study, it revealed that the transplantation of feces from normal wild type mice to AD transgenic mice significantly reduces Aβ burden and tau pathology, attenuates the glial activation, learning and memory impairment, and abnormal expression of genes related to intestinal macrophage activity, and restores the circulating inflammatory monocytes and synaptic plasticity in AD mice. [ 91 , 92 ] The gut microbiota alteration can promote Aβ deposition by activating the MAPK signaling pathway and C/enhancer binding protein β (EBP)/asparagine endopeptidase (AEP) signaling pathway in the brain of AD transgenic mice. [ 93 , 94 ] In addition, the probiotics have the capacity of improving the maze navigation, restoring the long-term potential, and balancing the antioxidant/oxidative biomarkers in mice. [ 95 ] In detail, Lactobacillus plantarum inhibits the synthesis of TMAO and reduces the clusterin level. [ 96 ] Clostridium butyricum and its metabolites inhibit microglia-mediated neuroinflammation. [ 97 ] Bifidobacterium longum regulates NF-κB activation via inhibiting LPS production. [ 98 ] Of note, however, clinical studies have found that probiotics supplement does not significantly improve the cognitive and biochemical indicators in patients with severe AD. [ 99 ]

Unlike the intestinal probiotics, the effects of antibiotics on AD are more complicated. Antibiotics, such as streptozotocin, can promote the growth of proinflammatory gut microbiota sub-types in animals, leading to learning and memory impairment, as has been used to establish sporadic AD models. [ 100 ] Rifampicin and minocycline could decrease the levels of Aβ, glial activation, and inflammatory cytokines in the brain of AD mice. [ 101 , 102 ] Rapamycin not only reduces the level of Aβ and the activation of microglia but also decreases the phosphorylation of tau protein. [ 103 ] Nevertheless, despite some encouraging results in the animal studies, the clinical efficacy of antibiotics in patients with AD remains controversial so far.

Hearing impairment and AD

There is an emerging interest in the role of age-related hearing impairment on development of AD and other dementias. Hearing impairments can be caused by changes in the inner ear (eg, peripheral hearing) and/or dysfunction in auditory processing (eg, central hearing). Hearing impairments are common among older adults: affecting up to 40% of adults aged 65 and up to 90% of adults aged >90. [ 104 ] Hearing difficulty is commonly reported by patients with AD. [ 105 ] Observational studies have found a consistent association between hearing loss and risk of dementia and cognitive decline. [ 106 , 107 ] This work raises the question whether hearing loss may cause AD and dementia; however, alternative mechanisms could also explain this association. [ 108 ]

Hearing impairments may directly affect dementia risk through brain atrophy by impairing cognitive processing abilities or by increasing cognitive load. [ 108 ] In animal studies, noise-induced (peripheral) hearing loss is associated with increased neurodegeneration in the hippocampus, decreased neurogenesis, and poor memory function. [ 109 ] Hearing impairments may also affect “psychosocial wellbeing” including social engagement, mental health, and physical activity, [ 109 ] which could lead to increased dementia risk. [ 110 ] In epidemiologic studies, peripheral hearing loss measured by pure tone audiometry may offer some of the stronger evidence that hearing loss may cause dementia, since pure tones are less affected by AD-neurodegeneration than central hearing. [ 110 ] Peripheral hearing impairment has also been associated with decreased whole brain volumes, reduced temporal lobe or auditory cortex volumes, [ 111 , 112 ] or reduced hippocampal volume. [ 113 ] But there are conflicting results. [ 114 ]

Hearing loss can often be corrected or mitigated, which could in turn also reduce dementia burden if hearing loss causes dementia. The Lancet commission on dementia prevention in 2020 suggested that treating hearing loss may reduce dementia burden by up to 8%. [ 110 ] However, this estimate is based on observational studies which may be biased. Evidence from several small clinical trials has been mixed; some studies are suggestive that treatment of hearing impairments may improve cognition in non-demented patients, [ 115 ] but this was not found in AD patients. [ 116 ] Although studies often include important confounders in statistical models, unmeasured or residual confounder may remain. Both hearing and cognitive impairments are strongly associated with age, tend to have a gradual onset, and may have shared etiologies, including neurodegeneration, vascular and metabolic diseases, and aging processes. [ 117 ] Some studies even question a biologic between hearing and cognition, as many cognitive tests rely on hearing and poor hearing may lead to more errors in hearing-based cognitive tests. [ 118 ]

Relatively few studies have examined associations between hearing and AD specifically; one study on dementia sub-types have found associations between hearing impairment and clinical AD but not vascular dementia. [ 119 ] One neuroimaging study found an association with pure tone and word recognition hearing loss and in vivo Aβ deposition, [ 120 ] while an autopsy study found an association between clinician rated hearing loss and tau neurofibrillary degeneration stage but not Aβ plaque frequency. [ 121 ] Higher genetic risk for AD also is associated with increased difficulty hearing in noise in older adults, suggesting a shared biologic pathway and that central hearing loss such as difficulty hearing in noise may be a preclinical marker for AD. [ 122 ] Neurodegeneration in AD affects anatomical structures including the auditory pathways: neuritic plaques and tangles have been found in auditory association cortex as well as subcortical auditory pathways, which includes the medial temporal lobe. Several studies find that central auditory processing dysfunction is strongly associated with AD and precedes dementia diagnosis. [ 123 ]

Older adults with hearing impairments are a higher risk for dementia and may be an important subgroup for referral for dementia evaluation. Treating hearing impairment may also help to prevent dementia; however, further research is needed to clarify the relationships between hearing impairments, AD, and dementia. Regardless, treatment for hearing impairments should be prioritized to improve quality of life of older adults with hearing loss.

Perspectives

There is no denying that the clinical treatment of AD is currently facing significant bottlenecks. The failure of many clinical trials suggests the importance of early diagnosis and prevention. Therefore, in recent years, researchers have been interested in thinking about AD from a broad perspective and in evaluating novel potential risk factors beyond those traditionally associated with AD such as CVD, diabetes, and education. These findings of the effects of oxygen metabolism, inflammation, and gut microbiota provide novel evidence that systemic effects may impact brain aging. Furthermore, our review highlights the potential importance of underappreciated health factors to healthy aging such as sleep, diet, and hearing. This new research adds further evidence to support a shift from amyloid focused drug targets to multi-domain interventions that may help prevent AD and slow cognitive decline.

However, there is still a lot of work to be done in these areas. In Table ​ Table1, 1 , we present main evidence for each topic in our review as well as list key next steps for research. In particular, studies are needed to clarify the causal directions of the association between these potential novel risk factors and AD and to understand the underlying mechanisms and how they are related to AD neuropathogenesis. The clinical application of the study of oxygen metabolism and AD, such as the attempt to treat AD with HBOT; development of new intestinal probiotics; the prevention and treatment effect of specific diet components on AD. As the future direction of AD research, these works will require more multidisciplinary collaboration and the use of innovative research methods.

Summary of current evidence and promising future research directions for novel factors related to AD.

AD: Alzheimer disease.

How to cite this article: Brenowitz WD, Xiang Y, McEvoy CT, Yang C, Yaffe K, Le WD, Leng Y. Current Alzheimer disease research highlights: evidence for novel risk factors. Chin Med J 2021;134:2150–2159. doi: 10.1097/CM9.0000000000001706

Willa D. Brenowitz and Yang Xiang contributed equally to the work.

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Essay Examples on Alzheimer's Disease

What makes a good alzheimer's disease essay topics.

When it comes to writing an essay on Alzheimer's Disease, choosing the right topic is crucial. An engaging and thought-provoking topic can make your essay stand out and leave a lasting impression on your readers. But What Makes a Good Alzheimer's Disease essay topic? Here are a few recommendations on how to brainstorm and choose an essay topic:

• Consider your interests and passions: Think about what aspects of Alzheimer's Disease you find most intriguing. Whether it's the latest research developments, caregiving challenges, or the impact on society, choosing a topic that aligns with your interests will make the writing process more enjoyable and the final product more engaging.
• Brainstorm ideas: Take some time to brainstorm potential essay topics. Consider the latest trends and developments in Alzheimer's Disease research, as well as the impact of the disease on individuals, families, and communities. You can also explore controversial issues or ethical dilemmas related to Alzheimer's Disease to spark ideas for your essay topic.
• Research potential topics: Once you have a list of potential essay topics, take the time to research each one. Consider the availability of credible sources, the depth of information on the topic, and its relevance to the current discourse on Alzheimer's Disease. This will help you narrow down your options and choose a topic that is well-supported and relevant.
• Choose a unique angle: Instead of rehashing common topics, try to approach Alzheimer's Disease from a unique angle. Consider how you can shed new light on a familiar topic or explore a lesser-known aspect of the disease. This will make your essay more compelling and help it stand out from the rest.

In summary, a good Alzheimer's Disease essay topic is one that aligns with your interests, is well-researched, and offers a unique perspective on the subject. By following these recommendations, you can ensure that your essay topic is engaging, thought-provoking, and well-supported.

Best Alzheimer's Disease Essay Topics

When it comes to choosing the best Alzheimer's Disease essay topics, it's important to think outside the box and choose topics that are not only relevant but also creative and thought-provoking. Here are some of the best Alzheimer's Disease essay topics that are sure to stand out:

• The Role of Genetics in Alzheimer's Disease
• The Impact of Alzheimer's Disease on Family Caregivers
• Treating Alzheimer's Disease: A Comprehensive Review
• Ethical Considerations in Alzheimer's Disease Research
• The Stigma of Alzheimer's Disease in Society
• The Link Between Alzheimer's Disease and Lifestyle Factors
• Innovative Approaches to Alzheimer's Disease Treatment
• Alzheimer Disease: Effects on Patients and Families
• Alzheimer's Disease in the Aging Population
• The Economic Burden of Alzheimer's Disease on Society
• The Intersection of Alzheimer's Disease and Mental Health
• The Future of Alzheimer's Disease Research and Treatment

These essay topics offer a fresh perspective on Alzheimer's Disease and are sure to capture the attention of your readers. By choosing a creative and thought-provoking topic, you can set your essay apart and make a lasting impression.

Alzheimer's Disease essay topics Prompts

Looking for some creative prompts to inspire your Alzheimer's Disease essay? Here are five engaging prompts to get you started:

• Imagine a world where Alzheimer's Disease is completely eradicated. How would this impact society, healthcare, and the lives of individuals and families affected by the disease?
• Write a personal reflection on your experience with Alzheimer's Disease, whether as a caregiver, a healthcare professional, or a researcher. What have you learned from this experience, and how has it shaped your perspective on the disease?
• Explore the ethical implications of using artificial intelligence and technology to diagnose and treat Alzheimer's Disease. What are the potential benefits and drawbacks of these advancements?
• Consider the impact of Alzheimer's Disease on different cultural and ethnic communities. How does cultural diversity influence the experience of the disease, as well as access to care and support?
• Imagine a day in the life of someone living with Alzheimer's Disease. What challenges do they face, and how do they navigate their daily routines and interactions with others?

These prompts are designed to spark creativity and encourage you to explore the complexities of Alzheimer's Disease from a fresh perspective. Whether you're writing an essay for a class assignment or for personal exploration, these prompts can help you delve into the many facets of Alzheimer's Disease and create a compelling and engaging essay.

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