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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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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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Visual Impairment, Eye Diseases, and Dementia Risk: A Systematic Review and Meta-Analysis.
Kuźma, E, Littlejohns, TJ, Khawaja, AP, Llewellyn, DJ, Ukoumunne, OC, Thiem, U
Journal of Alzheimer's disease : JAD. 2021;(3):1073-1087
Abstract
BACKGROUND Visual impairment and eye diseases have been associated with dementia, though with mixed findings and often in cross-sectional studies. OBJECTIVE To identify prospective studies investigating associations between visual impairment or common eye diseases and risk of all-cause dementia or key dementia subtypes. METHODS We searched Medline, PsycINFO, and Embase from inception to January 2020. We also conducted backward and forward citation searches of included studies and set up alerts to identify studies published after the search date. Random-effects meta-analysis was used to combine adjusted estimates across studies. RESULTS Thirty studies met our eligibility criteria. For visual impairment, pooled estimates indicated an increased risk of all-cause dementia (37,705 participants, 3,415 cases, risk ratio [RR] = 1.38, 95% confidence interval [CI]: 1.19-1.59, I2 = 28.6%). Pooled estimates also suggested an increased dementia risk associated with cataract (6,659 participants, 1,312 cases, hazard ratio [HR] = 1.17, 95% CI: 1.00-1.38, I2 = 0.0%) and diabetic retinopathy (43,658 participants, 7,060 cases, HR = 1.34, 95% CI: 1.11-1.61, I2 = 63.9%), respectively. There was no evidence of an association between glaucoma (175,357 participants, 44,144 cases, HR = 0.97, 95% CI: 0.90-1.04, I2 = 51.5%) or age-related macular degeneration (7,800,692 participants, > 2,559 cases, HR = 1.15, 95% CI: 0.88-1.50, I2 = 91.0%) and risk of dementia, respectively. CONCLUSION As visual impairment, cataract, and diabetic retinopathy are associated with an increased likelihood of developing dementia, early diagnosis may help identify those at risk of dementia. Given most causes of visual impairment are treatable or preventable, the potential for dementia prevention warrants further investigation.
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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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Studies test lifestyle changes to avert dementia.
Leslie, M
Science (New York, N.Y.). 2021;(6545):891-892
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Association of Angiotensin II-Stimulating Antihypertensive Use and Dementia Risk: Post Hoc Analysis of the PreDIVA Trial.
van Dalen, JW, Marcum, ZA, Gray, SL, Barthold, D, Moll van Charante, EP, van Gool, WA, Crane, PK, Larson, EB, Richard, E
Neurology. 2021;(1):e67-e80
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Abstract
OBJECTIVE To assess whether angiotensin II-stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin I receptor blockers) convey a lower risk of incident dementia compared to angiotensin II-inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, β-blockers, and nondihydropyridine calcium channel blockers), in accordance with the "angiotensin hypothesis." METHODS We performed Cox regression analyses of incident dementia (or mortality as competing risk) during 6-8 years of follow-up in a population sample of 1,909 community-dwelling individuals (54% women) without dementia, aged 70-78 (mean 74.5 ± 2.5) years. RESULTS After a median of 6.7 years of follow-up, dementia status was available for 1,870 (98%) and mortality for 1,904 (>99%) participants. Dementia incidence was 5.6% (27/480) in angiotensin II-stimulating, 8.2% (59/721) in angiotensin II-inhibiting, and 6.9% (46/669) in both antihypertensive type users. Adjusted for dementia risk factors including blood pressure and medical history, angiotensin II-stimulating antihypertensive users had a 45% lower incident dementia rate (hazard ratio [HR], 0.55; 95% CI, 0.34-0.89) without excess mortality (HR, 0.86; 95% CI, 0.64-1.16), and individuals using both types had a nonsignificant 20% lower dementia rate (HR, 0.80; 95% CI,0.53-1.20) without excess mortality (HR, 0.97; 95% CI, 0.76-1.24), compared to angiotensin II-inhibiting antihypertensive users. Results were consistent for subgroups based on diabetes and stroke history, but may be specific for individuals without a history of cardiovascular disease. CONCLUSIONS Users of angiotensin II-stimulating antihypertensives had lower dementia rates compared to angiotensin II-inhibiting antihypertensive users, supporting the angiotensin hypothesis. Confounding by indication must be examined further, although subanalyses suggest this did not influence results. If replicated, dementia prevention could become a compelling indication for older individuals receiving antihypertensive treatment.
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Dementia is Associated With Poorer Quality of Care and Outcomes After Stroke: An Observational Study.
Callisaya, ML, Purvis, T, Lawler, K, Brodtmann, A, Cadilhac, DA, Kilkenny, MF
The journals of gerontology. Series A, Biological sciences and medical sciences. 2021;(5):851-858
Abstract
BACKGROUND To determine whether preexisting dementia is associated with poorer quality of care and outcomes after stroke in the acute hospital phase. METHOD This was a retrospective analysis of pooled data from the Australian Stroke Foundation national audit conducted in 2015 and 2017. Dementia status was obtained from the medical records. Processes of care to assess quality included: stroke unit care, time-dependent therapy, nursing/allied health assessments, and preparation for discharge. Outcomes included in-hospital complications, independence on discharge, and destination. Logistic regression was used to examine associations between dementia status and processes of care. Multilevel random effects logistic regression, with level defined as hospital, was used to examine associations between dementia status and outcomes. RESULTS There were 683/7,070 (9.7%) audited patients with dementia included. Patients with dementia were less likely to be treated in stroke units (58.3% vs 70.6%), receive thrombolysis if an ischemic stroke (5.8% vs 11.1%), have access within 48 hours to physiotherapy (56.4% vs 69.7%) or occupational therapy (46.8% vs 55.6%), see a dietitian if problems with nutrition (64.4% vs 75.9%), or have mood assessed (2.6% vs 12.3%). Patients with dementia were more likely to receive no rehabilitation (adjusted odds ratio 1.88, 95% confidence interval 1.25, 2.83) and be discharged to residential care (adjusted odds ratio 2.36, 95% confidence interval 1.50, 3.72). CONCLUSION People with dementia received poorer quality of care and had worse outcomes after stroke. Our findings raise questions regarding equity and the need for better understanding of why the quality of care differs after stroke for people with dementia.
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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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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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Associations of the Lifestyle for Brain Health Index With Structural Brain Changes and Cognition: Results From the Maastricht Study.
Heger, IS, Deckers, K, Schram, MT, Stehouwer, CDA, Dagnelie, PC, van der Kallen, CJH, Koster, A, Eussen, SJPM, Jansen, JFA, Verhey, FRJ, et al
Neurology. 2021;(13):e1300-e1312
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BACKGROUND AND OBJECTIVES Observational research has shown that a substantial proportion of all dementia cases worldwide are attributable to modifiable risk factors. Dementia risk scores might be useful to identify high-risk individuals and monitor treatment adherence. The objective of this study was to investigate whether a dementia risk score, the Lifestyle for Brain Health (LIBRA) index, is associated with MRI markers and cognitive functioning/impairment in the general population. METHODS Cross-sectional data were used from the observational population-based cohort of The Maastricht Study. The weighted compound score of LIBRA (including 12 dementia risk and protective factors, e.g., hypertension, physical inactivity) was calculated, with higher scores indicating higher dementia risk. Standardized volumes of white matter, gray matter, and CSF (as proxy for general brain atrophy), white matter hyperintensities, and presence of cerebral small vessel disease were derived from 3T MRI. Cognitive functioning was tested in 3 domains: memory, information processing speed, and executive function and attention. Values ≤1.5 SDs below the average were defined as cognitive impairment. Multiple regression analyses and structural equation modeling were used, adjusted for age, sex, education, intracranial volume, and type 2 diabetes. RESULTS Participants (n = 4,164; mean age 59 years; 49.7% men) with higher LIBRA scores (mean 1.19, range -2.7 to 9.2), denoting higher dementia risk, had higher volumes of white matter hyperintensities (β = 0.051, p = 0.002) and lower scores on information processing speed (β = -0.067, p = 0.001) and executive function and attention (β = -0.065, p = 0.004). Only in men, associations between LIBRA score and volumes of gray matter (β = -0.093, p < 0.001) and CSF (β = 0.104, p < 0.001) and memory (β = -0.054, p = 0.026) were found. White matter hyperintensities and CSF volume partly mediated the association between LIBRA score and cognition. DISCUSSION Higher health- and lifestyle-based dementia risk is associated with markers of general brain atrophy, cerebrovascular pathology, and worse cognition, suggesting that LIBRA meaningfully summarizes individual lifestyle-related brain health. Improving LIBRA factors on an individual level might improve population brain health. Sex differences in lifestyle-related pathology and cognition need to be further explored. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that higher LIBRA scores are significantly associated with lower scores in some cognitive domains and a higher risk of cognitive impairment.