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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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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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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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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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Tackling challenges in care of Alzheimer's disease and other dementias amid the COVID-19 pandemic, now and in the future.
Mok, VCT, Pendlebury, S, Wong, A, Alladi, S, Au, L, Bath, PM, Biessels, GJ, Chen, C, Cordonnier, C, Dichgans, M, et al
Alzheimer's & dementia : the journal of the Alzheimer's Association. 2020;(11):1571-1581
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Abstract
We have provided an overview on the profound impact of COVID-19 upon older people with Alzheimer's disease and other dementias and the challenges encountered in our management of dementia in different health-care settings, including hospital, out-patient, care homes, and the community during the COVID-19 pandemic. We have also proposed a conceptual framework and practical suggestions for health-care providers in tackling these challenges, which can also apply to the care of older people in general, with or without other neurological diseases, such as stroke or parkinsonism. We believe this review will provide strategic directions and set standards for health-care leaders in dementia, including governmental bodies around the world in coordinating emergency response plans for protecting and caring for older people with dementia amid the COIVD-19 outbreak, which is likely to continue at varying severity in different regions around the world in the medium term.
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Dietary interventions in mild cognitive impairment and dementia.
Vlachos, GS, Scarmeas, N
Dialogues in clinical neuroscience. 2019;(1):69-82
Abstract
Dietary intervention is an enticing approach in the fight against cognitive impairment. Nutritional supplements and dietetic counseling are relatively easy and benign interventions, but research has not yet yielded irrefutable evidence as to their clinical utility. Heterogeneity in the results of available clinical studies, as well as methodological and practical issues, does not allow replication and generalization of findings. The paper at hand reviews only randomized clinical trials of single nutrients, multi-nutrient formulations and dietary counseling in mild cognitive impairment and dementia of the Alzheimer's type focusing on both cognitive and functional outcomes. Thus far, folate, vitamin E, Ω-3 fatty acids, and certain multi-nutrient formulations have shown some preliminary promising results; larger, well-designed trials are needed to confirm these findings before nutritional elements can be incorporated in recommended clinical guidelines.
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Dietary Protein and Amino Acid Intake: Links to the Maintenance of Cognitive Health.
Glenn, JM, Madero, EN, Bott, NT
Nutrients. 2019;(6)
Abstract
With the rapid growth in the aging population, there has been a subsequent increase in the rates of Alzheimer's disease and related dementias (ADRD). To combat these increases in ADRD, scientists and clinicians have begun to place an increased emphasis on preventative methods to ameliorate disease rates, with a primary focus area on dietary intake. Protein/amino acid intake is a burgeoning area of research as it relates to the prevention of ADRD, and consumption is directly related to a number of disease-related risk factors as such low-muscle mass, sleep, stress, depression, and anxiety. As a result, the role that protein/amino acid intake plays in affecting modifiable risk factors for cognitive decline has provided a robust area for scientific exploration; however, this research is still speculative and specific mechanisms have to be proven. The purpose of this review is to describe the current understanding of protein and amino acids and the preventative roles they play with regard to ADRD, while providing future recommendations for this body of research. Additionally, we will discuss the current recommendations for protein intake and how much protein older adults should consume in order to properly manage their long-term risk for cognitive decline.
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A scoping review of behaviour change theories in adults without dementia to adapt and develop the 'PHYT in dementia', a model promoting physical activity in people with dementia.
Di Lorito, C, Pollock, K, Harwood, R, das Nair, R, Logan, P, Goldberg, S, Booth, V, Vedhara, K, Van Der Wardt, V
Maturitas. 2019;:101-113
Abstract
INTRODUCTION Research has established that exercise and physical activity can improve executive functioning, independence and quality of life in people with dementia. A dedicated theory explaining behaviour change in relation to physical activity in people with dementia does not exist. We aimed to develop a theoretical model which can be used to inform effective interventions to promote physical activity in people with dementia. METHODS There were five phases: 1. A search of the literature to identify theories which have been used to explain behaviour change in relation to physical activity in adult populations without a diagnosis of dementia; 2. Description of the theories (and sub-theories) and their main constructs; 3. Synthesis of the constructs; 4. Adaptation of the constructs to dementia; 5. Development and explanation of a model for physical activity in people with dementia (the 'PHYT in dementia'). RESULTS We identified nine theories used to explain behaviour change in relation to physical activity in adult populations without a diagnosis of dementia. Through our synthesis, we identified nine umbrella constructs. We integrated three more dementia-relevant constructs and developed the 'PHYT in dementia'. The model was explained by providing a practical example of its application. DISCUSSION Based on a scoping review of behaviour change theories in adults without dementia and following adaptation of the constructs from these theories to dementia, we derived a new theoretical model, the 'PHYT in dementia', which includes both individual-level and environment-level constructs. The model needs to be tested empirically, which our research team will do in the process evaluation of the Promoting Activity, Independence and Stability in Early Dementia and Mild Cognitive Impairment (PrAISED 2) study. Results from field-testing will inform refinement of the model.
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Antibody-LGI 1 autoimmune encephalitis manifesting as rapidly progressive dementia and hyponatremia: a case report and literature review.
Li, X, Yuan, J, Liu, L, Hu, W
BMC neurology. 2019;(1):19
Abstract
BACKGROUND Anti leucine-rich glioma inactivated 1 (LGI1) encephalitis is a rare autoimmune encephalitis (AE), characterized by acute or subacute cognitive impairment, faciobrachial dystonic seizures, psychiatric disturbances and hyponatremia. Antibody-LGI 1 autoimmune encephalitis (anti-LGI1 AE) has increasingly been recognized as a primary autoimmune disorder with favorable prognosis and response to treatment. CASE PRESENTATION Herein, we reported a male patient presenting as rapidly progressive dementia and hyponatremia. He had antibodies targeting LGI1 both in the cerebrospinal fluid and serum, which demonstrated the diagnosis of typical anti-LGI1 AE. The scores of Mini-Mental State Examination and Montreal Cognitive Assessment were 19/30 and 15/30, respectively. Cranial magnetic resonance images indicated hyperintensities in bilateral hippocampus. The findings of brain arterial spin labeling and Fluorine-18-fluorodeoxyglucose positron emission tomography showed no abnormal perfusion/metabolism. After the combined treatment of intravenous immunoglobulin and glucocorticoid, the patient's clinical symptoms improved obviously. CONCLUSIONS This case raises the awareness that a rapid progressive dementia with predominant memory deficits could be induced by immunoreactions against LGI1. The better recognition will be great importance for the early diagnosis, essential treatment, even a better prognosis.