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1.
Medicinal Herbs and Nutritional Supplements for Dementia Therapy: Potential Targets and Clinical Evidence.
Dorman, G, Flores, I, Gutiérrez, C, Castaño, RF, Aldecoa, M, Kim, L
CNS & neurological disorders drug targets. 2022;(1):26-51
Abstract
Spices and herbs have been used for medicinal purposes for centuries. Also, in the last decades, the use of different nutritional supplements has been implemented to treat all kinds of diseases, including those that present an alteration in cognitive functioning. Dementia is a clinical syndrome in which a person's mental and cognitive capacities gradually decline. As the disease progresses, the person's autonomy diminishes. As there is not an effective treatment to prevent progressive deterioration in many of these pathologies, nutritional interventions have been, and still are, one of the most widely explored therapeutic possibilities. In this review, we have discussed a great number of potentially interesting plants, nutritional derivatives, and probiotics for the treatment of dementia around the world. Their action mechanisms generally involve neuroprotective effects via anti-inflammatory, antioxidant, anti-apoptotic, b-amyloid, and tau anti-aggregate actions; brain blood flow improvement, and effects on synaptic cholinergic and dopaminergic neurotransmission, which may optimize cognitive performance in patients with cognitive impairment. As for their efficacy in patients with cognitive impairment and/or dementias, evidence is still scarce andthe outcomes are controversial. We consider that many of these substances have promising therapeutic properties. Therefore, the scientific community has to continue with a complete research focused on both identifying possible action mechanisms and carrying out clinical trials, preferably randomized, double-blind ones, with a greater number of patients, a long-term follow-up, dose standardization, and the use of current diagnostic criteria.
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2.
Gut microbiota in dementia. Critical review of novel findings and their potential application.
Łuc, M, Misiak, B, Pawłowski, M, Stańczykiewicz, B, Zabłocka, A, Szcześniak, D, Pałęga, A, Rymaszewska, J
Progress in neuro-psychopharmacology & biological psychiatry. 2021;:110039
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Abstract
There is a great deal of impetus for the comprehensive understanding of the complete pathological function, genetic information, and functional diversity of the gut microbiota that favors the development of dementia. It has been reported that patients with mild cognitive impairment and Alzheimer's disease present with several metabolic and immune-inflammatory alterations. The recently highlighted aspects of human health linked to cognitive decline include insulin-resistance, obesity, and chronic low-grade inflammation. Gut microbiota is known to produce neurotransmitters, such as GABA, acetylcholine, dopamine or serotonin, vitamins, intestinal toxins, and modulate nerve signaling - with emphasis on the vagus nerve. Additionally, gut dysbiosis results in impaired synthesis of signaling proteins affecting metabolic processes relevant to the development of Alzheimer's disease. Due to numerous links of gut microbiota to crucial metabolic and inflammatory pathways, attempts aimed at correcting the gut microflora composition may affect dementia pathology in a pleiotropic manner. Taking advantage of the metabolic effects of cold exposure on organisms by the introduction of whole-body cryostimulation in dementia patients could lead to alterations in gut microbiota and, therefore, decrease of an inflammatory response and insulin resistance, which remain one of the critical metabolic features of dementia. Further studies are needed in order to explore the potential application of recent findings and ways of achieving the desired goals.
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Enteral tube feeding for people with severe dementia.
Davies, N, Barrado-Martín, Y, Vickerstaff, V, Rait, G, Fukui, A, Candy, B, Smith, CH, Manthorpe, J, Moore, KJ, Sampson, EL
The Cochrane database of systematic reviews. 2021;(8):CD013503
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Abstract
BACKGROUND The balance of benefits and harms associated with enteral tube feeding for people with severe dementia is not clear. An increasing number of guidelines highlight the lack of evidenced benefit and potential risks of enteral tube feeding. In some areas of the world, the use of enteral tube feeding is decreasing, and in other areas it is increasing. OBJECTIVES To assess the effectiveness and safety of enteral tube feeding for people with severe dementia who develop problems with eating and swallowing or who have reduced food and fluid intake. SEARCH METHODS We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE, Embase, four other databases and two trials registers on 14 April 2021. SELECTION CRITERIA We included randomised controlled trials (RCTs), or controlled non-randomised studies. Our population of interest was adults of any age with a diagnosis of primary degenerative dementia of any cause, with severe cognitive and functional impairment, and poor nutritional intake. Eligible studies evaluated the effectiveness and complications of enteral tube feeding via a nasogastric or gastrostomy tube, or via jejunal post-pyloric feeding, in comparison with standard care or enhanced standard care, such as an intervention to promote oral intake. Our primary outcomes were survival time, quality of life, and pressure ulcers. DATA COLLECTION AND ANALYSIS Three review authors screened citations and two review authors assessed full texts of potentially eligible studies against inclusion criteria. One review author extracted data, which were then checked independently by a second review author. We used the 'Risk Of Bias In Non-randomised Studies of Interventions' (ROBINS-I) tool to assess the risk of bias in the included studies. Risk of confounding was assessed against a pre-agreed list of key potential confounding variables. Our primary outcomes were survival time, quality of life, and pressure ulcers. Results were not suitable for meta-analysis, so we presented them narratively. We presented results separately for studies of percutaneous endoscopic gastrostomy (PEG) feeding, nasogastric tube feeding and studies using mixed or unspecified enteral tube feeding methods. We used GRADE methods to assess the overall certainty of the evidence related to each outcome for each study. MAIN RESULTS We found no eligible RCTs. We included fourteen controlled, non-randomised studies. All the included studies compared outcomes between groups of people who had been assigned to enteral tube feeding or oral feeding by prior decision of a healthcare professional. Some studies controlled for a range of confounding factors, but there were high or very high risks of bias due to confounding in all studies, and high or critical risks of selection bias in some studies. Four studies with 36,816 participants assessed the effect of PEG feeding on survival time. None found any evidence of effects on survival time (low-certainty evidence). Three of four studies using mixed or unspecified enteral tube feeding methods in 310 participants (227 enteral tube feeding, 83 no enteral tube feeding) found them to be associated with longer survival time. The fourth study (1386 participants: 135 enteral tube feeding, 1251 no enteral tube feeding) found no evidence of an effect. The certainty of this body of evidence is very low. One study of PEG feeding (4421 participants: 1585 PEG, 2836 no enteral tube feeding) found PEG feeding increased the risk of pressure ulcers (moderate-certainty evidence). Two of three studies reported an increase in the number of pressure ulcers in those receiving mixed or unspecified enteral tube feeding (234 participants: 88 enteral tube feeding, 146 no enteral tube feeding). The third study found no effect (very-low certainty evidence). Two studies of nasogastric tube feeding did not report data on survival time or pressure ulcers. None of the included studies assessed quality of life. Only one study, using mixed methods of enteral tube feeding, reported on pain and comfort, finding no difference between groups. In the same study, a higher proportion of carers reported very heavy burden in the enteral tube feeding group compared to no enteral tube feeding. Two studies assessed the effect of nasogastric tube feeding on mortality (236 participants: 144 nasogastric group, 92 no enteral tube feeding). One study of 67 participants (14 nasogastric, 53 no enteral tube feeding) found nasogastric feeding was associated with increased mortality risk. The second study found no difference in mortality between groups. The certainty of this evidence is very low. Results on mortality for those using PEG or mixed methods of enteral tube feeding were mixed and the certainty of evidence was very low. There was some evidence from two studies for enteral tube feeding improving nutritional parameters, but this was very low-certainty evidence. Five studies reported a variety of harm-related outcomes with inconsistent results. The balance of evidence suggested increased risk of pneumonia with enteral tube feeding. None of the included studies assessed behavioural and psychological symptoms of dementia. AUTHORS' CONCLUSIONS We found no evidence that tube feeding improves survival; improves quality of life; reduces pain; reduces mortality; decreases behavioural and psychological symptoms of dementia; leads to better nourishment; improves family or carer outcomes such as depression, anxiety, carer burden, or satisfaction with care; and no indication of harm. We found some evidence that there is a clinically significant risk of pressure ulcers from enteral tube feeding. Future research should focus on better reporting and matching of control and intervention groups, and clearly defined interventions, measuring all the outcomes referred to here.
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4.
Primary Prevention of Dementia: An Ethical Review.
Horstkötter, D, Deckers, K, Köhler, S
Journal of Alzheimer's disease : JAD. 2021;(2):467-476
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Abstract
Dementia poses important medical and societal challenges, and of all health risks people face in life, dementia is one of the most feared. Recent research indicates that up to about 40% of all cases of dementia might be preventable. A series of environmental, social, and medical risk-factors have been identified that should be targeted from midlife onwards when people are still cognitively healthy. At first glance, this seems not merely advisable, but even imperative. However, these new developments trigger a series of new ethical questions and concerns which have hardly been addressed to date. Pro-active ethical reflection, however, is crucial to ensure that the interests and well-being of those affected, ultimately all of us, are adequately respected. This is the goal of the current contribution. Against the background of a concrete case in primary dementia prevention, it provides a systematic overview of the current ethical literature and sketches an ethical research agenda. First, possible benefits of increased well-being must be balanced with the burdens of being engaged in particularly long-term interventions for which it is unclear whether they will ever pay out on a personal level. Second, while knowledge about one's options to maintain brain health might empower people, it might also undermine autonomy, put high social pressure on people, medicalize healthy adults, and stigmatize those who still develop dementia. Third, while synergistic effects might occur, the ideals of dementia prevention might also conflict with other health and non-health related values people hold in life.
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Is Weight Loss More Severe in Older People with Dementia?
Tjahyo, AS, Gandy, J, Porter, J, Henry, CJ
Journal of Alzheimer's disease : JAD. 2021;(1):57-73
Abstract
Weight loss, a hallmark feature of dementia, is associated with higher mortality in older people. However, there is a lack of consensus in the literature as to whether the weight loss commonly observed in older people with dementia results from reduced energy intake and/or increased energy expenditure. Understanding the cause of energy imbalance in older people with dementia would allow more targeted interventions to avoid detrimental health effects in this vulnerable group. In this paper, we review studies that have considered weight change, energy intake, and energy expenditure in older people with and without dementia. We critically assess the studies' methodology and outline the various factors which may decrease and increase energy intake and expenditure respectively in older people with and without dementia. Current available literature does not support the view that there is a lower energy intake and/or a higher energy expenditure in older people with dementia when compared to those without dementia. The need for more high-quality studies is also highlighted in order to shed more light towards this issue which continues to elude researchers and clinicians alike.
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Ginger, a Possible Candidate for the Treatment of Dementias?
Schepici, G, Contestabile, V, Valeri, A, Mazzon, E
Molecules (Basel, Switzerland). 2021;(18)
Abstract
As the human life expectancy increases, age-linked diseases have become more and more frequent. The worldwide increment of dementia cases demands medical solutions, but the current available drugs do not meet all the expectations. Recently the attention of the scientific community was attracted by natural compounds, used in ancient medicine, known for their beneficial effects and high tolerability. This review is focused on Ginger (Zingiber officinale) and explore its properties against Alzheimer's Disease and Vascular Dementia, two of the most common and devastating forms of dementia. This work resumes the beneficial effects of Ginger compounds, tested in computational in vitro and in vivo models of Alzheimer's Disease and Vascular Dementia, along with some human tests. All these evidences suggest a potential role of the compounds of ginger not only in the treatment of the disease, but also in its prevention.
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Optogenetic stimulation of serotonin nuclei retrieve the lost memory in Alzheimer's disease.
Bostancıklıoğlu, M
Journal of cellular physiology. 2020;(2):836-847
Abstract
How are memories stored and retrieved? It was one of the most discussed questions in the past century by neuroscientists. Leading studies of the period brought two different explanations to this question: The first statement considers memory as a physiological change in the brain and suggest that the retrieval of memory is only occurred by the same physiologic changes observed during the memory formation, while the second suggests that memory is a psychic mood stored in mind and the retrieval of memory is occurred by mystical energy fluctuations. Although the exact reason and the pathogenesis of Alzheimer's disease have not yet been fully understood, the approaches that centered the retrieval strategy of lost memory constitutes the basis of the treatment strategies in Alzheimer's disease today. The majority of treatment studies has based on the manipulation of the cholinergic system; however, although serotonin has mnemonic effects, its role in the pathogenesis of Alzheimer's disease has not been investigated as much as the cholinergic system. Here we show how serotonin affects the pathogenesis of Alzheimer's disease in a comprehensive perspective and we suggest that the optogenetics manipulation of serotonin nuclei retrieve the lost memory by closing the inward-rectifier potassium channel Kir2 on the memory engram cells. Also, we raise the possible effects of serotonin on the memory engram cells and the interactions between the amyloid-centric hypothesis of Alzheimer's disease and the memory engram hypothesis to explain the pathophysiology of memory loss in Alzheimer's disease.
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Preserving Cognition, Preventing Dementia.
Cleveland, ML
Clinics in geriatric medicine. 2020;(4):585-599
Abstract
Dementia incidence continues to rise in the United States and around the world. Although age is the single biggest risk factor for the development of dementia, it is not considered normal sequelae of aging. Although there has been little to no progress made in the past couple of decades in the treatment or cure of Alzheimer disease, there has been significant progress made in prevention. Single factors, such as hearing loss or cardiovascular risk factors, may increase the risk for cognitive decline. The opportunity to mitigate these risk factors provides an exciting new healthy aging approach to dementia prevention.
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Correlations between COVID-19 and burden of dementia: An ecological study and review of literature.
Azarpazhooh, MR, Amiri, A, Morovatdar, N, Steinwender, S, Rezaei Ardani, A, Yassi, N, Biller, J, Stranges, S, Tokazebani Belasi, M, Neya, SK, et al
Journal of the neurological sciences. 2020;:117013
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Abstract
INTRODUCTION Current evidence on the association between COVID-19 and dementia is sparse. This study aims to investigate the associations between COVID-19 caseload and the burden of dementia. METHODS We gathered data regarding burden of dementia (disability-adjusted life years [DALYs] per 100,000), life expectancy, and healthy life expectancy (HALE) from the Global Burden of Disease (GBD) 2017 study. We obtained COVID-19 data from Our World in Data database. We analyzed the association of COVID-19 cases and deaths with the burden of dementia using Spearman's rank correlation coefficient. RESULTS Globally, we found significant positive (p < .001) correlations between life expectancy (r = 0.60), HALE (r = 0.58), and dementia DALYs (r = 0.46) with COVID-19 caseloads. Likewise, we found similar correlations between life expectancy (r = 0.60), HALE (r = 0.58) and dementia DALYs (r = 0.54) with COVID-19 mortality. CONCLUSION Health policymakers should clarify a targeted model of disease surveillance in order to reduce the dual burden of dementia and COVID-19.
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Triad of impairment in older people with diabetes-reciprocal relations and clinical implications.
Abdelhafiz, AH, Davies, PC, Sinclair, AJ
Diabetes research and clinical practice. 2020;:108065
Abstract
Frailty is emerging as a new category complication of diabetes in older people. Clinically, frailty is still not well defined and mostly viewed as a decline in solely the physical domain. However, frailty is a multidimensional syndrome and the newly introduced concept of "triad of impairment" (physical, cognitive and emotional) may be a more representative of the broad nature of frailty. The components of the triad of impairment (TOI) commonly coexist and demonstrate a reciprocal relation. Diabetes in old age appears to increase the risk of the triad of impairment, which may eventually progress to disability. Therefore, older people with diabetes should be regularly assessed for the presence of these three key components. Adequate nutrition and regular resistance exercise training have been shown to have a positive impact on the long-term outcome in this population. However, the role of good glycaemic control and the use of current hypoglycaemic medications in reducing the incidence of this triad are less clear. Future research is needed to develop novel hypoglycaemic medications that not only focus on glycaemic control and cardiovascular safety but also on reducing the risk of the triad of impairment.