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Vitamin and mineral supplementation for preventing dementia or delaying cognitive decline in people with mild cognitive impairment.
McCleery, J, Abraham, RP, Denton, DA, Rutjes, AW, Chong, LY, Al-Assaf, AS, Griffith, DJ, Rafeeq, S, Yaman, H, Malik, MA, et al
The Cochrane database of systematic reviews. 2018;(11):CD011905
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Abstract
BACKGROUND Vitamins and minerals have many functions in the nervous system which are important for brain health. It has been suggested that various different vitamin and mineral supplements might be useful in maintaining cognitive function and delaying the onset of dementia. In this review, we sought to examine the evidence for this in people who already had mild cognitive impairment (MCI). OBJECTIVES To evaluate the effects of vitamin and mineral supplementation on cognitive function and the incidence of dementia in people with mild cognitive impairment. SEARCH METHODS We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's (CDCIG) specialised register, as well as MEDLINE, Embase, PsycINFO, CENTRAL, CINAHL, LILACs, Web of Science Core Collection, ClinicalTrials.gov, and the WHO Portal/ICTRP, from inception to 25 January 2018. SELECTION CRITERIA We included randomised or quasi-randomised, placebo-controlled trials which evaluated orally administered vitamin or mineral supplements in participants with a diagnosis of mild cognitive impairment and which assessed the incidence of dementia or cognitive outcomes, or both. We were interested in studies applicable to the general population of older people and therefore excluded studies in which participants had severe vitamin or mineral deficiencies. DATA COLLECTION AND ANALYSIS We sought data on our primary outcomes of dementia incidence and overall cognitive function and on secondary outcomes of episodic memory, executive function, speed of processing, quality of life, functional performance, clinical global impression, adverse events, and mortality. We conducted data collection and analysis according to standard Cochrane systematic review methods. We assessed the risk of bias of included studies using the Cochrane 'Risk of bias' assessment tool. We grouped vitamins and minerals according to their putative mechanism of action and, where we considered it to be clinically appropriate, we pooled data using random-effects methods. We used GRADE methods to assess the overall quality of evidence for each comparison and outcome. MAIN RESULTS We included five trials with 879 participants which investigated B vitamin supplements. In four trials, the intervention was a combination of vitamins B6, B12, and folic acid; in one, it was folic acid only. Doses varied. We considered there to be some risks of performance and attrition bias and of selective outcome reporting among these trials. Our primary efficacy outcomes were the incidence of dementia and scores on measures of overall cognitive function. None of the trials reported the incidence of dementia and the evidence on overall cognitive function was of very low-quality. There was probably little or no effect of B vitamins taken for six to 24 months on episodic memory, executive function, speed of processing, or quality of life. The evidence on our other secondary clinical outcomes, including harms, was very sparse or very low-quality. There was evidence from one study that there may be a slower rate of brain atrophy over two years in participants taking B vitamins. The same study reported subgroup analyses based on the level of serum homocysteine (tHcy) at baseline and found evidence that B vitamins may improve episodic memory in those with tHcy above the median at baseline.We included one trial (n = 516) of vitamin E supplementation. Vitamin E was given as 1000 IU of alpha-tocopherol twice daily. We considered this trial to be at risk of attrition and selective reporting bias. There was probably no effect of vitamin E on the probability of progression from MCI to Alzheimer's dementia over three years (HR 1.02; 95% CI 0.74 to 1.41; n = 516; 1 study, moderate-quality evidence). There was also no evidence of an effect at intermediate time points. The available data did not allow us to conduct analyses, but the authors reported no significant effect of three years of supplementation with vitamin E on overall cognitive function, episodic memory, speed of processing, clinical global impression, functional performance, adverse events, or mortality (five deaths in each group). We considered this to be low-quality evidence.We included one trial (n = 256) of combined vitamin E and vitamin C supplementation and one trial (n = 26) of supplementation with chromium picolinate. In both cases, there was a single eligible cognitive outcome, but we considered the evidence to be very low-quality and so could not be sure of any effects. AUTHORS' CONCLUSIONS The evidence on vitamin and mineral supplements as treatments for MCI is very limited. Three years of treatment with high-dose vitamin E probably does not reduce the risk of progression to dementia, but we have no data on this outcome for other supplements. Only B vitamins have been assessed in more than one RCT. There is no evidence for beneficial effects on cognition of supplementation with B vitamins for six to 24 months. Evidence from a single study of a reduced rate of brain atrophy in participants taking vitamin B and a beneficial effect of vitamin B on episodic memory in those with higher tHcy at baseline warrants attempted replication.
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Uric Acid and Cognitive Function in Older Individuals.
Tana, C, Ticinesi, A, Prati, B, Nouvenne, A, Meschi, T
Nutrients. 2018;(8)
Abstract
Hyperuricemia has been recognized as an independent cardiovascular risk factor in epidemiological studies. However, uric acid can also exert beneficial functions due to its antioxidant properties, which may be particularly relevant in the context of neurodegenerative diseases. In this paper, we critically revise the evidence on the relationship between serum uric acid levels and cognitive function in older individuals, focusing on the etiology of cognitive impairment (Alzheimer's disease, Parkinson's dementia, and vascular dementia) and on the interactive connections between uric acid, dementia, and diet. Despite high heterogeneity in the existing studies, due to different characteristics of studied populations and methods of cognitive dysfunction assessment, we conclude that serum uric acid may modulate cognitive function in a different way according to the etiology of dementia. Current studies indeed demonstrate that uric acid may exert neuroprotective actions in Alzheimer's disease and Parkinson's dementia, with hypouricemia representing a risk factor for a quicker disease progression and a possible marker of malnutrition. Conversely, high serum uric acid may negatively influence the disease course in vascular dementia. Further studies are needed to clarify the physio-pathological role of uric acid in different dementia types, and its clinical-prognostic significance.
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Diet, nutrition and the ageing brain: current evidence and new directions.
Moore, K, Hughes, CF, Ward, M, Hoey, L, McNulty, H
The Proceedings of the Nutrition Society. 2018;(2):152-163
Abstract
Globally populations are ageing. By 2050, it is estimated that there will be two billion people aged 60 years or over, of which 131 million are projected to be affected by dementia, while depression is predicted to be the second leading cause of disability worldwide by 2020. Preventing or delaying the onset of these disorders should therefore be a public health priority. There is some evidence linking certain dietary patterns, particularly the Mediterranean diet, with a reduced risk of dementia and depression. Specific dietary components have also been investigated in relation to brain health, with emerging evidence supporting protective roles for n-3 PUFA, polyphenols, vitamin D and B-vitamins. At this time, the totality of evidence is strongest in support of a role for folate and the metabolically related B-vitamins (vitamin B12, vitamin B6 and riboflavin) in slowing the progression of cognitive decline and possibly reducing the risk of depression in ageing. Future studies incorporating new technologies, such as MRI and magnetoencephalography, offer much promise in identifying effective nutrition interventions that could reduce the risk of cognitive and mental disorders. This review will explore the ageing brain and the emerging evidence linking diet and specific nutrients with cognitive function and depression in ageing, with the potential to develop strategies that could improve quality of life in our ageing population.
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The Association between Social Engagement, Loneliness, and Risk of Dementia: A Systematic Review and Meta-Analysis.
Penninkilampi, R, Casey, AN, Singh, MF, Brodaty, H
Journal of Alzheimer's disease : JAD. 2018;(4):1619-1633
Abstract
It has been reported that social engagement may be associated with dementia risk. We searched PubMed, EMBASE, PsycINFO, CINAHL, LILACS, Biomed Central, Scopus, and Web of Science from January 2012 - May 2017, supplemented by extraction from previous reviews. We included cohort and case-control studies examining the association between social engagement or loneliness and dementia risk, pooling data using a random-effects model. Registered: PROSPERO (CRD42017067074). We included 31 cohort and 2 case-control studies comprising 2,370,452 participants. Poor social engagement indices were associated with increased dementia risk, including having a poor social network (RR = 1.59, 95% CI 1.31-1.96; I2 = 0.00%) and poor social support (RR = 1.28, 95% CI 1.01-1.62; I2 = 55.51%). In long-term studies (≥10 years), good social engagement was modestly protective (RR = 0.88, 95% CI 0.80-0.96; I2 = 0.00%). Loneliness was non-significantly associated with increased risk (RR = 1.38, 95% CI 0.98-1.94; I2 = 45.32). Our findings encourage interventions targeting social isolation and disengagement for dementia prevention.
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Protocol for a pragmatic randomised controlled trial of Body Brain Life-General Practice and a Lifestyle Modification Programme to decrease dementia risk exposure in a primary care setting.
Kim, S, McMaster, M, Torres, S, Cox, KL, Lautenschlager, N, Rebok, GW, Pond, D, D'Este, C, McRae, I, Cherbuin, N, et al
BMJ open. 2018;(3):e019329
Abstract
INTRODUCTION It has been estimated that a 10%-25% reduction in seven key risk factors could potentially prevent 1.1-3.0 million Alzheimer's disease cases globally. In addition, as dementia is preceded by more subtle cognitive deficits which have substantial social and economic impact, effective preventative interventions would likely have more extensive benefits. The current study evaluates in primary care a multidomain risk-reduction intervention targeting adults with high risk of developing dementia. METHODS AND ANALYSIS A randomised controlled trial (RCT) is being conducted to evaluate three intervention programmes using a pragmatic approach suitable to the clinic: (1) a 12-week online and face-to-face dementia risk-reduction intervention (Body Brain Life-General Practice (BBL-GP)); (2) a 6-week face-to-face group lifestyle modification programme (LMP); and (3) a 12-week email-only programme providing general health information. We aim to recruit 240 participants, aged 18 and over, to undergo a comprehensive cognitive and physical assessment at baseline and follow-ups (postintervention, 18, 36 and 62 weeks). The primary outcome is dementia risk measured with the modified version of the Australian National University-Alzheimer's Disease Risk Index Short Form. Secondary outcomes are cognitive function measured with Trails A and B, and the Digit Symbol Modalities Test; physical activity with moderate-vigorous physical activity and the International Physical Activity Questionnaire; depression with the Centre for Epidemiological Studies Depression; cost evaluation with the 12-item Short Form Health Survey, Framingham Coronary Heart Disease Risk Score and Australian Type 2 Diabetes Risk Assessment Tool; diet quality with the Australian Recommended Food Score; and sleep quality with the Pittsburgh Sleep Quality Index. ETHICS AND DISSEMINATION This RCT is a novel pragmatic intervention applied in a primary care setting to reduce the dementia risk exposure in adults at high risk. If successful, BBL-GP and LMP will provide a versatile, evidence-based package that can be easily and quickly rolled out to other primary care settings and which can be scaled up at relatively low cost compared with other strategies involving intensive interventions. TRIAL REGISTRATION NUMBER ACTRN12616000868482.
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Which interventions work for dementia family carers?: an updated systematic review of randomized controlled trials of carer interventions.
Kishita, N, Hammond, L, Dietrich, CM, Mioshi, E
International psychogeriatrics. 2018;(11):1679-1696
Abstract
UNLABELLED ABSTRACTObjective:The aim of this study was to update the literature on interventions for carers of people with dementia published between 2006 and 2016 and evaluate the efficacy of psychoeducational programs and psychotherapeutic interventions on key mental health outcomes (depression, anxiety, burden, and quality of life). METHODS A meta-analysis was carried out of randomized controlled trials of carer interventions using MEDLINE, PsycINFO, Scopus, and Cochrane Central Register of Controlled Trials. RESULTS The majority of studies were conducted in Western and Southern Europe or the United States and recruited carers of people with Alzheimer's disease or dementia grouped as a whole. The most commonly used outcome measures were depression and burden across studies. The updated evidence suggested that psychoeducation-skill building interventions delivered face-to-face can better impact on burden. Psychotherapeutic interventions underpinned by Cognitive Behavior Therapy (CBT) models demonstrated strong empirical support for treating anxiety and depression and these effects were not affected by the mode of delivery (i.e. face-to-face vs. technology). A modern CBT approach, Acceptance and Commitment Therapy (ACT), seemed to be particularly beneficial for carers experiencing high levels of anxiety. CONCLUSIONS Future research needs to explore the efficacy of interventions on multiple clinical outcomes and which combination of interventions (components) would have the most significant effects when using CBT. The generalization of treatment effects in different countries and carers of different types of dementia also need to be addressed. More research is needed to test the efficacy of modern forms of CBT, such as ACT.
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Body, Brain, Life for Cognitive Decline (BBL-CD): protocol for a multidomain dementia risk reduction randomized controlled trial for subjective cognitive decline and mild cognitive impairment.
McMaster, M, Kim, S, Clare, L, Torres, SJ, D'Este, C, Anstey, KJ
Clinical interventions in aging. 2018;:2397-2406
Abstract
BACKGROUND With no cure for dementia and the number of people living with the condition predicted to rapidly rise, there is an urgent need for dementia risk reduction and prevention interventions. Modifiable lifestyle risk factors have been identified as playing a major role in the development of dementia; hence, interventions addressing these risk factors represent a significant opportunity to reduce the number of people developing dementia. Relatively few interventions have been trialed in older participants with cognitive decline (secondary prevention). OBJECTIVES This study evaluates the efficacy and feasibility of a multidomain lifestyle risk reduction intervention for people with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). METHODS This study is an 8-week, two-arm, single-blind, randomized controlled trial (RCT) of a lifestyle modification program to reduce dementia risk. The active control group receives the following four online educational modules: dementia literacy and lifestyle risk, Mediterranean diet (MeDi), cognitive engagement and physical activity. The intervention group also completes the same educational modules but receives additional practical components including sessions with a dietitian, online brain training and sessions with an exercise physiologist to assist with lifestyle modification. RESULTS Primary outcome measures are cognition (The Alzheimer's Disease Assessment Scale-Cognitive-Plus [ADAS-Cog-Plus]) and a composite lifestyle risk factor score for Alzheimer's disease (Australian National University - Alzheimer's Disease Risk Index [ANU-ADRI]). Secondary outcome measures are motivation to change lifestyle (Motivation to Change Lifestyle and Health Behaviour for Dementia Risk Reduction [MCLHB-DRR]) and health-related quality of life (36-item Short Form Health Survey [SF-36]). Feasibility will be determined through adherence to diet (Mediterranean Diet Adherence Screener [MEDAS] and Australian Recommended Food Score [ARFS]), cognitive engagement (BrainHQ-derived statistics) and physical activity interventions (physical activity calendars). Outcomes are measured at baseline, immediately post-intervention and at 3- and 6-month follow-up by researchers blind to group allocation. DISCUSSION If successful and feasible, secondary prevention lifestyle interventions could provide a targeted, cost-effective way to reduce the number of people with cognitive decline going on to develop Alzheimer's disease (AD) and other dementias.
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Ginkgo biloba extract EGb 761® alleviates neurosensory symptoms in patients with dementia: a meta-analysis of treatment effects on tinnitus and dizziness in randomized, placebo-controlled trials.
Spiegel, R, Kalla, R, Mantokoudis, G, Maire, R, Mueller, H, Hoerr, R, Ihl, R
Clinical interventions in aging. 2018;:1121-1127
Abstract
BACKGROUND Tinnitus and dizziness are frequent in old age and often seen as concomitant symptoms in patients with dementia. In earlier clinical trials, Ginkgo biloba extract EGb 761® was found to alleviate tinnitus and dizziness in elderly patients. Consequently, a meta-analysis was conducted to evaluate the effects of EGb 761® at a daily dose of 240 mg on tinnitus and dizziness associated with dementia. METHODS Randomized, placebo-controlled clinical trials of G. biloba extract EGb 761® identified by a systematic database search were included in a meta-analysis if they met all of the following selection criteria: 1) diagnosis of dementia according to generally accepted criteria, 2) treatment period of at least 20 weeks, 3) outcome measures covering at least two of the three conventional domains of assessment, 4) presence and severity of dizziness and tinnitus were assessed, and 5) assessment was done before and after randomized treatment. RESULTS Five trials that met the inclusion criteria were included in the meta-analysis. The risk of bias was judged as low, with Jadad scores of 3 and 5. In all trials, 11-point box scales were used to assess the severity of tinnitus and dizziness. Overall, EGb 761® was superior to placebo, with weighted mean differences for change from baseline, calculated in meta-analyses using random effects models, of -1.06 (95% CI: -1.77, -0.36) for tinnitus (p = 0.003) and -0.77 (95% CI: -1.44, -0.09) for dizziness (p = 0.03). CONCLUSION Our findings support the notion that EGb 761® is also effective in alleviating concomitant neurosensory symptoms in patients with dementia.
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The effect of spermidine on memory performance in older adults at risk for dementia: A randomized controlled trial.
Wirth, M, Benson, G, Schwarz, C, Köbe, T, Grittner, U, Schmitz, D, Sigrist, SJ, Bohlken, J, Stekovic, S, Madeo, F, et al
Cortex; a journal devoted to the study of the nervous system and behavior. 2018;:181-188
Abstract
INTRODUCTION Nutritional intervention with the natural polyamine spermidine, an autophagy-enhancing agent, can prevent memory loss in aging model organisms. This is the first human study to evaluate the impact of spermidine supplementation on memory performance in older adults at risk for the development of Alzheimer's disease. METHODS Cognitively intact participants with subjective cognitive decline (n = 30, 60-80 years of age) were included in this three-months, randomized, placebo-controlled, double-blind Phase IIa pilot trial with a spermidine-rich plant extract supplement. Effects of intervention were assessed using the behavioral mnemonic similarity task, measured at baseline and post-intervention visits. Data analysis was focused on reporting and interpreting effectiveness based on effect sizes. RESULTS Memory performance was moderately enhanced in the spermidine group compared with placebo at the end of intervention [contrast mean = .17, 95% confidence interval (CI): -.01, .35, Cohen's d = .77, 95% CI: 0, 1.53]. Mnemonic discrimination ability improved in the spermidine-treated group with a medium effect size (mean difference = -.11, 95% CI: -.19, -.03, Cohen's d = .79, 95% CI: .01, 1.55). A similar effect was not found in the placebo-treated group (mean difference = .07, 95% CI: -.13, .27, Cohen's d = -.20, 95% CI: -.94, .54). DISCUSSION In this pilot trial, nutritional spermidine was associated with a positive impact on memory performance in older adults with subject cognitive decline. The beneficial effect might be mediated by stimulation of neuromodulatory actions in the memory system. A follow-up Phase IIb randomized controlled trial will help validate the therapeutic potential of spermidine supplementation and delineate possible neurophysiological mechanisms of action. TRIAL REGISTRATION Registered in ClinicalTrials.gov with the Identifier NCT02755246.
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Effect of dietary interventions in mild cognitive impairment: a systematic review.
McGrattan, AM, McEvoy, CT, McGuinness, B, McKinley, MC, Woodside, JV
The British journal of nutrition. 2018;(12):1388-1405
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Abstract
Diet has been investigated in relation to its ability to promote cognitive function. However, evidence is currently limited and has rarely been systematically reviewed, particularly in a mild cognitive impairment (MCI) population. This review examined the effect of diet on cognitive outcomes in MCI patients. A total of five databases were searched to find randomised controlled trial (RCT) studies, with diet as the main focus, in MCI participants. The primary outcome was incident dementia and/or Alzheimer's disease (AD) and secondary outcomes included cognitive function across different domains using validated neuropsychological tests. Sixteen studies met the inclusion criteria. There was a high degree of heterogeneity relating to the nature of the dietary intervention and cognitive outcomes measured, thus making study comparisons difficult. Supplementation with vitamin E (one study, n 516), ginkgo biloba (one study, n 482) or Fortasyn Connect (one study, n 311) had no significant effect on progression from MCI to dementia and/or AD. For cognitive function, the findings showed some improvements in performance, particularly in memory, with the most consistent results shown by B vitamins, including folic acid (one study, n 266), folic acid alone (one study, n 180), DHA and EPA (two studies, n 36 and n 86), DHA (one study, n 240) and flavonol supplementation (one study, n 90). The findings indicate that dietary factors may have a potential benefit for cognitive function in MCI patients. Further well-designed trials are needed, with standardised and robust measures of cognition to investigate the influence of diet on cognitive status.