Antioxidant strategies for Alzheimer's disease

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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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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Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer’s Disease: The Role of Antioxidants in Prevention and Treatment

Antioxidants ◽

10.3390/antiox10091439 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1439 ◽

Cited By ~ 1

Author(s):

Gabriela Juszczyk ◽

Joanna Mikulska ◽

Kamila Kasperek ◽

Diana Pietrzak ◽

Weronika Mrozek ◽

...

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Vitamin E ◽

Chronic Stress ◽

Antioxidant Properties ◽

Stress Oxidative ◽

The Relationship ◽

The Brain

There is a growing body of scientific research showing the link between depression and dementia in Alzheimer’s disease (AD). The chronic stress contributes to the formation of oxidative stress in the parts of the brain involved in the development of depression and AD. The scientific literature reports the significant role of antioxidants, which are highly effective in treating these diseases. In this review, we have summarized the relationship between chronic stress, oxidative stress, and the changes in the brain they cause occurring in the brain. Among all the compounds showing antioxidant properties, the most promising results in AD treatment were observed for Vitamin E, coenzyme Q10 (CoQ10), melatonin, polyphenols, curcumin, and selenium. In case of depression treatment, the greatest potential was observed in curcumin, zinc, selenium, vitamin E, and saffron.

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Neuroprotective Effects of Fluoxetine on Molecular Markers of Circadian Rhythm, Cognitive Deficits, Oxidative Damage, and Biomarkers of Alzheimer’s Disease-Like Pathology Induced under Chronic Constant Light Regime in Wistar Rats

ACS Chemical Neuroscience ◽

10.1021/acschemneuro.1c00238 ◽

2021 ◽

Author(s):

Ashish Sharma ◽

Ashu Mohammad ◽

Adesh K. Saini ◽

Rohit Goyal

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Circadian Rhythm ◽

Molecular Markers ◽

Oxidative Damage ◽

Cognitive Deficits ◽

Wistar Rats ◽

Light Regime ◽

Constant Light ◽

Neuroprotective Effects

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Remote monitoring technologies in Alzheimer’s disease: design of the RADAR-AD study

Alzheimer s Research & Therapy ◽

10.1186/s13195-021-00825-4 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Marijn Muurling ◽

◽

Casper de Boer ◽

Rouba Kozak ◽

Dorota Religa ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Remote Monitoring ◽

Rating Scales ◽

Functional Decline ◽

Cognitive Domain ◽

Subjective Rating ◽

Functional Domain ◽

Smartphone Applications ◽

Monitoring Technologies

Abstract Background Functional decline in Alzheimer’s disease (AD) is typically measured using single-time point subjective rating scales, which rely on direct observation or (caregiver) recall. Remote monitoring technologies (RMTs), such as smartphone applications, wearables, and home-based sensors, can change these periodic subjective assessments to more frequent, or even continuous, objective monitoring. The aim of the RADAR-AD study is to assess the accuracy and validity of RMTs in measuring functional decline in a real-world environment across preclinical-to-moderate stages of AD compared to standard clinical rating scales. Methods This study includes three tiers. For the main study, we will include participants (n = 220) with preclinical AD, prodromal AD, mild-to-moderate AD, and healthy controls, classified by MMSE and CDR score, from clinical sites equally distributed over 13 European countries. Participants will undergo extensive neuropsychological testing and physical examination. The RMT assessments, performed over an 8-week period, include walk tests, financial management tasks, an augmented reality game, two activity trackers, and two smartphone applications installed on the participants’ phone. In the first sub-study, fixed sensors will be installed in the homes of a representative sub-sample of 40 participants. In the second sub-study, 10 participants will stay in a smart home for 1 week. The primary outcome of this study is the difference in functional domain profiles assessed using RMTs between the four study groups. The four participant groups will be compared for each RMT outcome measure separately. Each RMT outcome will be compared to a standard clinical test which measures the same functional or cognitive domain. Finally, multivariate prediction models will be developed. Data collection and privacy are important aspects of the project, which will be managed using the RADAR-base data platform running on specifically designed biomedical research computing infrastructure. Results First results are expected to be disseminated in 2022. Conclusion Our study is well placed to evaluate the clinical utility of RMT assessments. Leveraging modern-day technology may deliver new and improved methods for accurately monitoring functional decline in all stages of AD. It is greatly anticipated that these methods could lead to objective and real-life functional endpoints with increased sensitivity to pharmacological agent signal detection.

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Learning Deficits Accompanied by Microglial Proliferation After the Long-Term Post-Injection of Alzheimer’s Disease Brain Extract in Mouse Brains

Journal of Alzheimer s Disease ◽

10.3233/jad-201002 ◽

2021 ◽

Vol 79 (4) ◽

pp. 1701-1711

Author(s):

Tetsuo Hayashi ◽

Shotaro Shimonaka ◽

Montasir Elahi ◽

Shin-Ei Matsumoto ◽

Koichi Ishiguro ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Mouse Brain ◽

Functional Decline ◽

Brain Regions ◽

Insoluble Fraction ◽

Brain Extract ◽

Post Injection ◽

Learning Deficits

Background: Human tauopathy brain injections into the mouse brain induce the development of tau aggregates, which spread to functionally connected brain regions; however, the features of this neurotoxicity remain unclear. One reason may be short observational periods because previous studies mostly used mutated-tau transgenic mice and needed to complete the study before these mice developed neurofibrillary tangles. Objective: To examine whether long-term incubation of Alzheimer’s disease (AD) brain in the mouse brain cause functional decline. Methods: We herein used Tg601 mice, which overexpress wild-type human tau, and non-transgenic littermates (NTg) and injected an insoluble fraction of the AD brain into the unilateral hippocampus. Results: After a long-term (17–19 months) post-injection, mice exhibited learning deficits detected by the Barnes maze test. Aggregated tau pathology in the bilateral hippocampus was more prominent in Tg601 mice than in NTg mice. No significant changes were observed in the number of Neu-N positive cells or astrocytes in the hippocampus, whereas that of Iba-I-positive microglia increased after the AD brain injection. Conclusion: These results potentially implicate tau propagation in functional decline and indicate that long-term changes in non-mutated tau mice may reflect human pathological conditions.

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The Associations of Plasma/Serum Carotenoids with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Journal of Alzheimer s Disease ◽

10.3233/jad-210384 ◽

2021 ◽

pp. 1-12

Author(s):

Mingyue Qu ◽

Hanxu Shi ◽

Kai Wang ◽

Xinggang Wang ◽

Nan Yu ◽

...

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Meta Analysis ◽

Scoring Systems ◽

Serum Levels ◽

Epidemiological Studies ◽

Pooled Analysis ◽

Protective Effects ◽

Mean Differences

Background: Multiple lines of evidence indicate protective effects of carotenoids in Alzheimer’s disease (AD). However, previous epidemiological studies reported inconsistent results regarding the associations between carotenoids levels and the risk of AD. Objective: Our study aims to evaluate the associations of six major members of carotenoids with the occurrence of AD by conducting a systematic review and meta-analysis. Methods: Following PRISMA guidelines, a comprehensive literature search of PubMed, Web of Science, Ebsco, and PsycINFO databases was conducted, and the quality of each included studies was evaluated by a validated scoring systems. Standardized mean differences (SMD) with 95%confidence intervals (CI) were determined by using a random effects model. Heterogeneity was evaluated by I2 statistics. Publication bias was detected using funnel plots and Egger’s test. Results: Sixteen studies, with 10,633 participants were included. Pooled analysis showed significantly lower plasma/serum levels of lutein (SMD = –0.86, 95%CI: –1.67 to –0.05, p = 0.04) and zeaxanthin (SMD = –0.59; 95%CI: –1.12 to –0.06, p = 0.03) in patients with AD versus cognitively intact controls, while α-carotene (SMD = 0.21, 95%CI: –0.68 to 0.26, p = 0.39), β-carotene (SMD = 0.04, 95%CI: –0.57 to 0.65, p = 0.9), lycopene (SMD = –0.12, 95%CI: –0.96 to 0.72, p = 0.78), and β-cryptoxanthin (SMD = –0.09, 95%CI: –0.83 to 0.65, p = 0.81) did not achieve significant differences. Conclusion: Of six major members of carotenoids, only lutein and zeaxanthin concentrations in plasma/serum were inversely related to the risk of AD. More high-quality longitudinal studies are needed to verify these findings.

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Developing an Exergame Intervention to Prevent Alzheimer’s Disease

Innovation in Aging ◽

10.1093/geroni/igaa057.3117 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 849-849

Author(s):

Fang Yu ◽

Dereck Salisbury ◽

Tom Plocher

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cognitive Training ◽

Exercise Prescription ◽

Subjective Cognitive Decline ◽

Grocery Shopping ◽

Cognitive Effect ◽

Ad Prevention ◽

The U.S

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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