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"Real-world" eligibility for aducanumab depends on clinical setting and patients' journey.
Padovani, A, Caratozzolo, S, Rozzini, L, Pilotto, A, Benussi, A, Tedeschi, G
Journal of the American Geriatrics Society. 2022;(2):626-628
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Abstract
See related editorial by Lundebjerg et al.
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Direct Modulation of the Gut Microbiota as a Therapeutic Approach for Alzheimer's Disease.
Wang, Y, Dykes, GA
CNS & neurological disorders drug targets. 2022;(1):14-25
Abstract
Alzheimer's disease is a neurodegenerative disease characterized by a progressive decline in memory and cognitive functions. It is a multifactorial disease involving a wide range of pathological factors that are not fully understood. As supported by a growing amount of evidence in recent years, gut microbiota plays an important role in the pathogenesis of Alzheimer's disease through the brain-gut-microbiota axis. This suggests that direct modulation of the gut microbiota can be a potential therapeutic target for Alzheimer's disease. This review summarizes recent research findings on the modulation of the gut microbiota by probiotic therapies and faecal microbiota transplantation for controlling the pathologies of Alzheimer's disease. Current limitations and future research directions of this field are also discussed.
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Dietary Nutrients and Prevention of Alzheimer's Disease.
Chauhan, PS, Yadav, D, Arukha, AP
CNS & neurological disorders drug targets. 2022;(3):217-227
Abstract
Alzheimer's disease is an irrevocable, progressive brain disorder that gradually destroys memory and cognitive skills. One of the extensively studied methods of preventing Alzheimer's disease (AD) progression is by providing a nutritional diet. Several reports have shown that intake of nutritional elements as huperzine A, ursolic acid, vitamins etc., can directly influence pathogenesis of AD. Surprisingly, the occurrence of metabolic disorders due to an unhealthy diet has been known to be a major environmental cause of AD. It has been noted that AD severity can be controlled by supplementing dietary supplements containing huge amounts of health-promoting ingredients. These elements promote cell health, regeneration, and the anti-aging process that specifically interrupt the pathogenic pathways in AD development. Fortunately, incorporating changes in the nutritional content is inexpensive, easy, acceptable, safe, effective, and in most cases, free from major adverse events. Many nutritional phytoconstituents such as flavonoids, alkaloids, and terpenoids are still being evaluated in the hope of identifying a successful therapy for AD. This review discusses the therapeutical potential of several key nutrients that have been researched for treating AD treatment and the method of their neuroprotective intervention.
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The Efficacy and Safety of Alzheimer's Disease Therapies: An Updated Umbrella Review.
Fan, F, Liu, H, Shi, X, Ai, Y, Liu, Q, Cheng, Y
Journal of Alzheimer's disease : JAD. 2022;(3):1195-1204
Abstract
BACKGROUND Evidence summaries for efficacy and safety of frequently employed treatments of Alzheimer's disease (AD) are sparse. OBJECTIVE We aimed to perform an updated umbrella review to identify an efficacious and safe treatment for AD patients. METHODS We conducted a search for meta-analyses and systematic reviews on the Embase, PubMed, The Cochrane Library, and Web of Science to address this knowledge gap. We examined the cognitive functions, behavioral symptoms, global clinical assessment, and Activities of Daily Living as efficacy endpoints, and the incidence of adverse events as safety profiles. RESULTS Sixteen eligible papers including 149 studies were included in the umbrella review. The results showed that AChE inhibitors (donepezil, galantamine, rivastigmine, Huperzine A), Ginkgo biloba, and cerebrolysin appear to be beneficial for cognitive, global performances, and activities of daily living in patients with AD. Furthermore, anti-Aβ agents are unlikely to have an important effect on slowing cognitive or functional impairment in mild to moderate AD. CONCLUSION Our study demonstrated that AChE inhibitors, Ginkgo biloba, and cerebrolysin are the optimum cognitive and activities of daily living medication for patients with AD.
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Methylxanthines Induce a Change in the AD/Neurodegeneration-Linked Lipid Profile in Neuroblastoma Cells.
Janitschke, D, Lauer, AA, Bachmann, CM, Winkler, J, Griebsch, LV, Pilz, SM, Theiss, EL, Grimm, HS, Hartmann, T, Grimm, MOW
International journal of molecular sciences. 2022;(4)
Abstract
Alzheimer's disease (AD) is characterized by an increased plaque burden and tangle accumulation in the brain accompanied by extensive lipid alterations. Methylxanthines (MTXs) are alkaloids frequently consumed by dietary intake known to interfere with the molecular mechanisms leading to AD. Besides the fact that MTX consumption is associated with changes in triglycerides and cholesterol in serum and liver, little is known about the effect of MTXs on other lipid classes, which raises the question of whether MTX can alter lipids in a way that may be relevant in AD. Here we have analyzed naturally occurring MTXs caffeine, theobromine, theophylline, and the synthetic MTXs pentoxifylline and propentofylline also used as drugs in different neuroblastoma cell lines. Our results show that lipid alterations are not limited to triglycerides and cholesterol in the liver and serum, but also include changes in sphingomyelins, ceramides, phosphatidylcholine, and plasmalogens in neuroblastoma cells. These changes comprise alterations known to be beneficial, but also adverse effects regarding AD were observed. Our results give an additional perspective of the complex link between MTX and AD, and suggest combining MTX with a lipid-altering diet compensating the adverse effects of MTX rather than using MTX alone to prevent or treat AD.
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Trace concentrations, heavy implications: Influences of biometals on major brain pathologies of Alzheimer's disease.
Lippi, SLP, Neely, CLC, Amaya, AL
The international journal of biochemistry & cell biology. 2022;:106136
Abstract
Alzheimer's disease (AD) is a neurodegenerative condition that involves accumulation of toxic protein species, notably amyloid-β (Aβ)plaques and neurofibrillary tau tangles that are associated with cognitive decline. These proteins can bind metal ions, ultimately affecting their structure and function. In this review, we discuss key biometals such as zinc, copper, and iron that interact with protein species involved in AD, mainly Aβ, tau, and the late-onset AD risk factor Apolipoprotein E (APOE). These metals interact with Aβ and tau proteins, affecting their aggregation and toxicity. The allele variants of APOE also have different interactions with these metals, affecting APOE protein expression and aggregation of AD protein species.
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The link between nutrition and Alzheimer's disease: from prevention to treatment.
Martins, LB, Malheiros Silveira, AL, Teixeira, AL
Neurodegenerative disease management. 2021;(2):155-166
Abstract
Alzheimer's disease (AD) is the most common cause of dementia. To date, there is no effective pharmacological strategy to slow or stop disease progression. In this context, multiple alternative therapeutic strategies have been investigated for AD. This review addresses the potential role of nutrition interventions in AD prevention and treatment. Nutritional strategies for AD have been based on four pillars: maintaining a healthy weight (i.e., prevention and/or treatment of obesity, especially in midlife and prevention of weight loss in the later stages of AD); correction of nutritional deficiencies; adequate consumption of micronutrients (vitamins and minerals), especially those implicated in the pathways of AD pathophysiology; and microbiota modulation.
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Gut Microbiota and Alzheimer's Disease: Pathophysiology and Therapeutic Perspectives.
Li, Y, Wang, R, Li, Q, Wang, YJ, Guo, J
Journal of Alzheimer's disease : JAD. 2021;(3):963-976
Abstract
Alzheimer's disease (AD) is the most common cause of dementia in the elderly and is characterized by a progressive decline in cognitive function. Amyloid-β protein accumulation is believed to be the key pathological hallmark of AD. Increasing evidence has shown that the gut microbiota has a role in brain function and host behaviors. The gut microbiota regulates the bidirectional interactions between the gut and brain through neural, endocrine, and immune pathways. With increasing age, the gut microbiota diversity decreases, and the dominant bacteria change, which is closely related to systemic inflammation and health status. Dysbiosis of the gut microbiota is related to cognitive impairment and neurodegenerative diseases. The purpose of this review is to discuss the impacts of the gut microbiota on brain function and the development of AD. It is a feasible target for therapeutic invention. Modulating the composition of the gut microbiota through diet, physical activity or probiotic/prebiotic supplements can provide new prevention and treatment options for AD.
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β-Lactolin Enhances Neural Activity, Indicated by Event-Related P300 Amplitude, in Healthy Adults: A Randomized Controlled Trial.
Kanatome, A, Ano, Y, Shinagawa, K, Ide, Y, Shibata, M, Umeda, S
Journal of Alzheimer's disease : JAD. 2021;(2):787-796
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Abstract
BACKGROUND Epidemiological studies have shown that dairy product consumption is beneficial for cognitive function in elderly individuals. β-lactolin is a Gly-Thr-Trp-Tyr lacto-tetrapeptide rich in fermented dairy products that improves memory retrieval, attention, and executive function in older adults with subjective cognitive decline and prevents the pathology of Alzheimer's disease in rodents. There has been no study on the effects of β-lactolin on neural activity in humans. OBJECTIVE We investigated the effects of β-lactolin on neural activity and cognitive function in healthy adults. METHODS In this randomized, double-blind, placebo-controlled study, 30 participants (45-64 years old) consumed β-lactolin or placebo for 6 weeks. Neural activity during auditory and language tasks was measured through 64-channel electroencephalography. Moreover, verbal fluency tests were performed at baseline and after 6 weeks. RESULTS The β-lactolin group had a significantly higher P300 amplitude at the Cp2 site (a part of the parietal lobe near the center of brain, p = 0.011), and C4 site (the area between the frontal and parietal lobe, p = 0.02) during the auditory tasks after 6 weeks than the placebo group. Thus, β-lactolin supplementation promoted neural activity in the parietal area, which increases concentration and attention during auditory cognitive tasks. Compared with the placebo group, the β-lactolin group also showed significant changes in the scores of verbal fluency test after 6 weeks (p = 0.033). CONCLUSION Our findings provide insight into the mechanisms underlying the effects of β-lactolin on attention in healthy adults.
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In vitro neuroprotective effects of farnesene sesquiterpene on alzheimer's disease model of differentiated neuroblastoma cell line.
Arslan, ME, Türkez, H, Mardinoğlu, A
The International journal of neuroscience. 2021;(8):745-754
Abstract
OBJECTIVE To investigate neuroprotective properties of the farnesene sesquiterpene on the experimental Alzheimer's disease model in vitro. METHODS Human neuroblastoma cell line (SHSY-5Y) was differentiated into neuron-like cells by using retinoic acid to constitute the in vitro Alzheimer's Disease model. β-amyloid 1-42 protein was applied to the transformed cells for 24 and 48 hours in a wide dose ranges (3.125-200 μM) to establish AD cytotoxicity. Then, farnesene was applied to cell cultures in a wide spectrum dose interval (1.625-100 μg/ml) to investigate neuroprotective effect against β-amyloid for 24 and 48 hours. 3-(4,5-dimethyl-thiazol-2-yl) 2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release tests were executed to determine cytotoxicity in the Alzheimer model. Nuclear DNA integrity of cells was examined under the fluorescent microscope using the Hoechst 33258 staining method. Furthermore, acetylcholinesterase (AChE) activity, total antioxidant capacity (TAC) and total oxidative status (TOS) levels were analyzed to understand the protection mechanism of the farnesene application on the cell culture model. Finally, flow cytometry analysis was used to find out the cell death mechanism after beta-amyloid and farnesene application to the cell culture. RESULTS Cell viability tests revealed significant neuroprotection against β-amyloid toxicity in both 24 and 48 hours and the Hoechst 33258 fluorescence staining method showed a significant decrease in necrotic deaths after farnesene application in the cell cultures. Finally, flow cytometry analysis put forth that farnesene could decrease necrotic cell death up to 3-fold resulted from beta-amyloid exposure. CONCLUSION According to the investigations, farnesene can potentially be a safe, anti-necrotic and neuroprotective agents against Alzheimer's disease.