Preventing Alzheimer's disease within reach by 2025: Targeted‐risk‐AD‐prevention (TRAP) strategy

Abstract Delaying the onset of Alzheimer’s Disease by five years could save the U.S. ~$89 billion by 2030. Aerobic exercise and cognitive training are two promising interventions for AD prevention and the two together may have a synergistic cognitive effect than either alone. The purposes of this study were to develop an integrated virtual-reality cognitive training (VRCT) and cycling intervention known as exergame and test its feasibility in older adults with subjective cognitive decline (SCD). The VRCT included grocery shopping from a list, flower shopping from a list, dinnerware sorting, book sorting, and postage estimation. Twelve participants enrolled in the 1-month program (12 sessions) achieved 81.2% session adherence and 81.4% adherence to the exercise prescription. The exergame was well accepted by 75% of the participants and 100% were satisfied with the exergame quality and delivery. To conclude, exergame is a flexible intervention that is feasible for older adults with SCD.

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Antioxidant strategies for Alzheimer's disease

Proceedings of The Nutrition Society ◽

10.1079/pns2002146 ◽

2002 ◽

Vol 61 (2) ◽

pp. 191-202 ◽

Cited By ~ 110

Author(s):

Michael Grundman ◽

Patrick Delaney

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Vitamin E ◽

Oxidative Damage ◽

Functional Decline ◽

Antioxidant Properties ◽

Epidemiological Studies ◽

Clinical Value ◽

Antioxidant Defences ◽

Ad Prevention

Oxidative damage is present within the brains of patients with Alzheimer's disease (AD), and is observed within every class of biomolecule, including nucleic acids, proteins, lipids and carbohydrates. Oxidative injury may develop secondary to excessive oxidative stress resulting from β-amyloid-induced free radicals, mitochondrial abnormalities, inadequate energy supply, inflammation or altered antioxidant defences. Treatment with antioxidants is a promising approach for slowing disease progression to the extent that oxidative damage may be responsible for the cognitive and functional decline observed in AD. Although not a uniformly consistent observation, a number of epidemiological studies have found a link between antioxidant intake and a reduced incidence of dementia, AD and cognitive decline in elderly populations. In AD clinical trials molecules with antioxidant properties such as vitamin E andGinkgo bilobaextract have shown modest benefit. A clinical trial with vitamin E is currently ongoing to determine if it can delay progression to AD in individuals with mild cognitive impairment. Combinations of antioxidants might be of even greater potential benefit for AD, especially if the agents worked in different cellular compartments or had complementary activity (e.g. vitamins E, C and ubiquinone). Naturally-occurring compounds with antioxidant capacity are available and widely marketed (e.g. vitamin C, ubiquinone, lipoic acid, β-carotene, creatine, melatonin, curcumin) and synthetic compounds are under development by industry. Nevertheless, the clinical value of these agents for AD prevention and treatment is ambiguous, and will remain so until properly designed human trials have been performed.

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Forgot to Exercise? Exercise Derived Circulating Myokines in Alzheimer's Disease: A Perspective

Frontiers in Neurology ◽

10.3389/fneur.2021.649452 ◽

2021 ◽

Vol 12 ◽

Author(s):

Rajesh Gupta ◽

Rizwan Khan ◽

Constanza J. Cortes

Keyword(s):

Alzheimer’S Disease ◽

Skeletal Muscle ◽

Alzheimer's Disease ◽

Expression Profiles ◽

Metabolic Stress ◽

Bioactive Molecules ◽

Neuroprotective Effects ◽

Metabolic Remodeling ◽

Therapeutic Tools ◽

Ad Prevention

Regular exercise plays an essential role in maintaining healthy neurocognitive function and central nervous system (CNS) immuno-metabolism in the aging CNS. Physical activity decreases the risk of developing Alzheimer's Disease (AD), is associated with better AD prognosis, and positively affects cognitive function in AD patients. Skeletal muscle is an important secretory organ, communicating proteotoxic and metabolic stress to distant tissues, including the CNS, through the secretion of bioactive molecules collectively known as myokines. Skeletal muscle undergoes significant physical and metabolic remodeling during exercise, including alterations in myokine expression profiles. This suggests that changes in myokine and myometabolite secretion may underlie the well-documented benefits of exercise in AD. However, to date, very few studies have focused on specific alterations in skeletal muscle-originating secreted factors and their potential neuroprotective effects in AD. In this review, we discuss exercise therapy for AD prevention and intervention, and propose the use of circulating myokines as novel therapeutic tools for modifying AD progression.

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Alzheimer’s Disease: From Amyloid to Autoimmune Hypothesis

The Neuroscientist ◽

10.1177/1073858420908189 ◽

2020 ◽

Vol 26 (5-6) ◽

pp. 455-470

Author(s):

Yuri I. Arshavsky

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Immune System ◽

Pyramidal Neurons ◽

Adaptive Immune System ◽

Memory Formation ◽

Autoimmune Response ◽

Prevention And Treatment ◽

Ad Prevention ◽

Clinical Verification

Although Alzheimer’s disease (AD) was described over a century ago, there are no effective approaches to its prevention and treatment. Such a slow progress is explained, at least in part, by our incomplete understanding of the mechanisms underlying the pathogenesis of AD. Here, I champion a hypothesis whereby AD is initiated on a disruption of the blood-brain barrier (BBB) caused by either genetic or non-genetic risk factors. The BBB disruption leads to an autoimmune response against pyramidal neurons located in the allo- and neocortical structures involved in memory formation and storage. The response caused by the adaptive immune system is not strong enough to directly kill neurons but may be sufficient to make them selectively vulnerable to neurofibrillary pathology. This hypothesis is based on the recent data showing that memory formation is associated with epigenetic chromatin modifications and, therefore, may be accompanied by expression of memory-specific proteins recognized by the immune system as “non-self” antigens. The autoimmune hypothesis is testable, and I discuss potential ways for its experimental and clinical verification. If confirmed, this hypothesis can radically change therapeutic approaches to AD prevention and treatment.

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On the personal utility of Alzheimer’s disease-related biomarker testing in the research context

Journal of Medical Ethics ◽

10.1136/medethics-2018-104772 ◽

2018 ◽

Vol 44 (12) ◽

pp. 830-834 ◽

Cited By ~ 5

Author(s):

Eline M Bunnik ◽

Edo Richard ◽

Richard Milne ◽

Maartje H N Schermer

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Information Provision ◽

Research Participants ◽

Personal Utility ◽

Prevention Studies ◽

Biomarker Testing ◽

Asymptomatic Individuals ◽

Ad Prevention ◽

Explicit Request

Many healthy volunteers choose to take part in Alzheimer’s disease (AD) prevention studies because they want to know whether they will develop dementia—and what they can do to reduce their risk—and are therefore interested in learning the results of AD biomarker tests. Proponents of AD biomarker disclosure often refer to the personal utility of AD biomarkers, claiming that research participants will be able to use AD biomarker information for personal purposes, such as planning ahead or making important life decisions. In this paper, the claim that AD biomarkers have personal utility for asymptomatic individuals is critically assessed. It demonstrates that in the absence of clinical validity, AD biomarkers cannot have personal utility and do not serve research participants’ autonomy. Over the next few years, many research groups will be confronted with participants’ preferences to learn the results of AD biomarker tests. When researchers choose to make results available upon explicit request, they should ensure adequate information provision and education, notably on the uncertain clinical significance of AD biomarker information. Routine disclosure of AD biomarkers to cognitively unimpaired individuals in research settings cannot be justified with an appeal to the personal utility of AD biomarker information.

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Adiponectin: The Potential Regulator and Therapeutic Target of Obesity and Alzheimer’s Disease

International Journal of Molecular Sciences ◽

10.3390/ijms21176419 ◽

2020 ◽

Vol 21 (17) ◽

pp. 6419

Author(s):

Jong Youl Kim ◽

Sumit Barua ◽

Ye Jun Jeong ◽

Jong Eun Lee

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Underlying Mechanism ◽

Mechanistic Studies ◽

Beneficial Effects ◽

Adipose Tissue Dysfunction ◽

Insulin Receptor Signaling ◽

Receptor Signaling Pathway ◽

Ad Prevention ◽

Safe Approach

Animal and human mechanistic studies have consistently shown an association between obesity and Alzheimer’s disease (AD). AD, a degenerative brain disease, is the most common cause of dementia and is characterized by the presence of extracellular amyloid beta (Aβ) plaques and intracellular neurofibrillary tangles disposition. Some studies have recently demonstrated that Aβ and tau cannot fully explain the pathophysiological development of AD and that metabolic disease factors, such as insulin, adiponectin, and antioxidants, are important for the sporadic onset of nongenetic AD. Obesity prevention and treatment can be an efficacious and safe approach to AD prevention. Adiponectin is a benign adipokine that sensitizes the insulin receptor signaling pathway and suppresses inflammation. It has been shown to be inversely correlated with adipose tissue dysfunction and may enhance the risk of AD because a range of neuroprotection adiponectin mechanisms is related to AD pathology alleviation. In this study, we summarize the recent progress that addresses the beneficial effects and potential mechanisms of adiponectin in AD. Furthermore, we review recent studies on the diverse medications of adiponectin that could possibly be related to AD treatment, with a focus on their association with adiponectin. A better understanding of the neuroprotection roles of adiponectin will help clarify the precise underlying mechanism of AD development and progression.

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Nutrients in the Prevention of Alzheimer’s Disease

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/9874159 ◽

2019 ◽

Vol 2019 ◽

pp. 1-20 ◽

Cited By ~ 13

Author(s):

Anna Laura Cremonini ◽

Irene Caffa ◽

Michele Cea ◽

Alessio Nencioni ◽

Patrizio Odetti ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Dietary Patterns ◽

Synergistic Effects ◽

Antioxidant Properties ◽

Hippocampal Neurogenesis ◽

Intermittent Fasting ◽

Human Beings ◽

The Mediterranean ◽

Ad Prevention

Alzheimer’s disease (AD) is a disease caused by the complex interaction of multiple mechanisms, some of which are still not fully understood. To date, pharmacological treatments and supplementation of individual nutrients have been poorly effective in terms of the prevention and treatment of AD, while alternative strategies based on multimodal approaches (diet, exercise, and cognitive training) seem to be more promising. In this context, the focus on dietary patterns rather than on single food components could be more useful in preventing or counteracting the pathological processes typical of AD, thanks to the potential synergistic effects of various nutrients (neuronutrients). The aim of this narrative review is to summarize the currently existing preclinical and clinical evidence regarding the Mediterranean diet (MeDi), the Dietary Approaches to Stop Hypertension (DASH) diet, and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which are three dietary patterns with well-known anti-inflammatory and antioxidant properties. Recently, they have been related to brain protection and AD prevention, perhaps thanks to their high content of neuroprotective bioactive compounds. Similarly, intermittent fasting (IF) or calorie restriction (CR) is emerging as interesting approaches that seem to promote hippocampal neurogenesis, activate adaptive stress response systems, and enhance neuronal plasticity, thus leading to motor and cognitive improvements in animal models of AD and hopefully also in human beings.

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Sleep disturbance: an emerging opportunity for Alzheimer's disease prevention?

International Psychogeriatrics ◽

10.1017/s1041610216002131 ◽

2016 ◽

Vol 29 (4) ◽

pp. 529-531 ◽

Cited By ~ 17

Author(s):

Adam P. Spira ◽

Rebecca F. Gottesman

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Decline ◽

Sleep Disturbances ◽

Sleep Disordered Breathing ◽

Later Life ◽

Optimal Timing ◽

Modifiable Risk Factors ◽

Dementia Prevalence ◽

Ad Prevention

As the older segment of our population grows, cognitive decline and dementia will increase in prevalence, with Alzheimer's disease (AD) as the cause in most cases. Until a cure exists, prevention through the identification and manipulation of modifiable risk factors for dementia, in general, or AD, in particular, will be our only means of reducing dementia prevalence or delaying its onset. Furthermore, it is likely that eventual treatments for AD, when available, will depend on the ability to identify individuals at greatest risk for developing AD. Sleep disturbances are common in later life – roughly half of older adults experience regular insomnia (Ohayon, 2002) and about as many have some degree of sleep-disordered breathing (SDB) (Ancoli-Israel et al., 1991) – and accumulating evidence suggests they may contribute to cognitive decline, at least in part, by promoting the development of AD pathology (Spira et al., 2014). Because they are treatable, sleep disturbances are an important potential target for ongoing study in AD prevention. Moreover, understanding the mechanisms underlying an effect of sleep on subsequent cognitive decline and AD would allow for better identification of opportunities and optimal timing for treatment of sleep disorders, and ultimately perhaps, AD prevention.

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Differential Expression of mRNAs in the Brain Tissues of Patients with Alzheimer’s Disease Based on GEO Expression Profile and Its Clinical Significance

BioMed Research International ◽

10.1155/2019/8179145 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Guowei Ma ◽

Mingyan Liu ◽

Ke Du ◽

Xin Zhong ◽

Shiqiang Gong ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Differential Expression ◽

Brain Tissue ◽

Peripheral Blood ◽

Bioinformatics Analysis ◽

Venn Diagram ◽

Ad Prevention ◽

The Brain ◽

Brain Tissues

Background. Early diagnosis of Alzheimer’s disease (AD) is an urgent point for AD prevention and treatment. The biomarkers of AD still remain indefinite. Based on the bioinformatics analysis of mRNA differential expressions in the brain tissues and the peripheral blood samples of Alzheimer’s disease (AD) patients, we investigated the target mRNAs that could be used as an AD biomarker and developed a new effective, practical clinical examination program. Methods. We compared the AD peripheral blood mononuclear cells (PBMCs) expression dataset (GEO accession GSE4226 and GSE18309) with AD brain tissue expression datasets (GEO accessions GSE1297 and GSE5281) from GEO in the present study. The GEO gene database was used to download the appropriate gene expression profiles to analyze the differential mRNA expressions between brain tissue and blood of AD patients and normal elderly. The Venn diagram was used to screen out the differential expression of mRNAs between the brain tissue and blood. The protein-protein interaction network map (PPI) was used to view the correlation between the possible genes. GO (gene ontology) and KEGG (Kyoto Gene and Genomic Encyclopedia) were used for gene enrichment analysis to determine the major affected genes and the function or pathway. Results. Bioinformatics analysis revealed that there were differentially expressed genes in peripheral blood and hippocampus of AD patients. There were 4958 differential mRNAs in GSE18309, 577 differential mRNAs in GSE4226 in AD PBMCs sample, 7464 differential mRNAs in GSE5281, and 317 differential mRNAs in GSE129 in AD brain tissues, when comparing between AD patients and healthy elderly. Two mRNAs of RAB7A and ITGB1 coexpressed in hippocampus and peripheral blood were screened. Furthermore, functions of differential genes were enriched by the PPI network map, GO, and KEGG analysis, and finally the chemotaxis, adhesion, and inflammatory reactions were found out, respectively. Conclusions. ITGB1 and RAB7A mRNA expressions were both changed in hippocampus and PBMCs, highly suggested being used as an AD biomarker with AD. Also, according to the results of this analysis, it is indicated that we can test the blood routine of the elderly for 2-3 years at a frequency of 6 months or one year. When a patient continuously detects the inflammatory manifestations, it is indicated as a potentially high-risk AD patient for AD prevention.

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