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1.
Differential effects of cognitive training modules in healthy aging and mild cognitive impairment: A comprehensive meta-analysis of randomized controlled trials.
Basak, C, Qin, S, O'Connell, MA
Psychology and aging. 2020;(2):220-249
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Abstract
This meta-analysis was designed to compare the effectiveness of 2 cognitive training modules, single-component training, which targets 1 specific cognitive ability, versus multicomponent training, which trains multiple cognitive abilities, on both trained abilities (near transfer) and untrained abilities (far transfer) in older adults. The meta-analysis also assessed whether individual differences in mental status interacted with the extent of transfer. Eligible randomized controlled trials (215 training studies) examined the immediate effects of cognitive training in either healthy aging (HA) or mild cognitive impairment (MCI). Results yielded an overall net-gain effect size (g) for the cognitive training of 0.28 (p < .001). These effects were similar across mental status and training modules, and were significant for both near (g = 0.37) and far (g = 0.22) transfer. Although all training modules yielded significant near transfer, only a few yielded significant far transfer. Single-component training of executive functions was most effective on near and far transfer, with processing speed training improving everyday functioning. All modules of multicomponent training (specific and nonspecific) yielded significant near and far transfer, including everyday functioning. Training effects on cognition were moderated by educational attainment and number of cognitive outcomes, but only in HA. These findings suggest that, in older adults, all modules of multicomponent training are more effective in engendering near and far transfer, including everyday functioning, when compared with single-component training modules. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
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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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Adherence to Mediterranean diet and risk of developing cognitive disorders: An updated systematic review and meta-analysis of prospective cohort studies.
Wu, L, Sun, D
Scientific reports. 2017;:41317
Abstract
Recent articles have presented inconsistent findings on the impact of Mediterranean diet in the occurrence of cognitive disorders; therefore, we performed an updated systematic review and meta-analysis to evaluate the potential association and dose-response pattern with accumulating evidence. We searched the PubMed and the Embase for the records relevant to this topic. A generic inverse-variance method was used to pool the outcome data for continuous variable, and categories of high vs. low, median vs. low of Mediterranean diet score with a random-effects model. Generalized least-squares trend estimation model was used to estimate the potential dose-response patterns of Mediterranean diet score on incident cognitive disorders. We identified 9 cohort studies involving 34,168 participants. Compared with the lowest category, the pooled analysis showed that the highest Mediterranean diet score was inversely associated with the developing of cognitive disorders, and the pooled RR (95% CI) was 0.79 (0.70, 0.90). Mediterranean diet score of the median category was not significantly associated with cognitive disorders. Dose-response analysis indicated a trend of an approximately linear relationship of the Mediterranean diet score with the incident risk of cognitive disorders. Further studies of randomized controlled trials are warranted to confirm the observed association in different populations.
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Administration of lidocaine to prevent cognitive deficit in patients undergoing coronary artery bypass grafting and valve plasty: a systematic review and meta-analysis.
Gholipour Baradari, A, Habibi, MR, Habibi, V, Nouraei, SM
Expert review of clinical pharmacology. 2017;(2):179-185
Abstract
The administration of lidocaine to maintain cognitive function following coronary artery bypass grafting (CABG) and valve plasty is a controversial concept in terms of its effectiveness. We performed a systematic review to determine the effectiveness of treatment with lidocaine in preventing the occurrence of cognitive deficit after cardiac surgery. Area covered: To review the current literature on the subject, we searched the PubMed database and the Cochrane Library database (up to May 2015) and compiled a list of retrieved articles. Our final review includes only randomized controlled trials (RCTs) that compared lidocaine to a control (placebo) following CABG and valve plasty. Statistical analysis of the odds ratio (OR) and corresponding 95% confidence interval (CI) were used to determine the overall effectiveness of lidocaine for the prevention of cognitive deficit with both procedures. The Mantel-Haenszel method was used to pool data of the outcomes of cognitive deficit occurrence into fixed-effect model meta-analyses. Five RCTs were included in this study, with a total of 688 patients. Perioperative administration of lidocaine in patients undergoing cardiac surgery reduced occurrence of cognitive deficit (OR 0.583 [95% CI 0.438-0.777]; Z = -3.680; P = 0.00; I2 = 52%). No significant difference in the early occurrence of cognitive deficit was revealed in patients after cardiac surgery (OR 0.909 [95% CI 0.600-1.376]; Z = -0.451; P = 0.652; I2 = 11%). Expert commentary: Cognitive deficit associated with cardiac surgery is a common postoperative event. Lidocaine is contributed to a significantly reduced occurrence of cognitive deficit. Cognitive deficit management is recommended.
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Cognitive Frailty: A Systematic Review of Epidemiological and Neurobiological Evidence of an Age-Related Clinical Condition.
Panza, F, Solfrizzi, V, Barulli, MR, Santamato, A, Seripa, D, Pilotto, A, Logroscino, G
Rejuvenation research. 2015;(5):389-412
Abstract
Advancing age is the focus of recent studies on familial and sporadic Alzheimer's disease (AD), suggesting a prolonged pre-clinical phase several decades before the onset of dementia symptoms. Influencing some age-related conditions, such as frailty, may have an impact on the prevention of late-life cognitive disorders. Frailty reflects a nonspecific state of vulnerability and a multi-system physiological change with increased risk for adverse health outcomes in older age. In this systematic review, frailty indexes based on a deficit accumulation model were associated with late life cognitive impairment and decline, incident dementia, and AD. Physical frailty constructs were associated with late-life cognitive impairment and decline, incident AD and mild cognitive impairment, vascular dementia, non-AD dementias, and AD pathology in older persons with and without dementia, thus also proposing cognitive frailty as a new clinical condition with co-existing physical frailty and cognitive impairment in non-demented older subjects. Considering both physical frailty and cognitive impairment as a single complex phenotype may be central in the prevention of dementia and its subtypes with secondary preventive trials on cognitive frail older subjects. The mechanisms underlying the cognitive-frailty link are multi-factorial, and vascular, inflammatory, nutritional, and metabolic influences may be of major relevance. There is a critical need for randomized controlled trials of intervention investigating the role of nutrition and/or physical exercise on cognitive frail subjects with the progression to dementia as primary outcome. These preventive trials and larger longitudinal population-based studies targeting cognitive outcomes could be useful in further understanding the cognitive-frailty interplay in older age.
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Suicidal behaviour and memory: A systematic review and meta-analysis.
Richard-Devantoy, S, Berlim, MT, Jollant, F
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry. 2015;(8):544-66
Abstract
OBJECTIVES Suicidal behaviour results from a complex interplay between stressful events and vulnerability factors, including cognitive deficits. It is not yet clear if memory impairment is part of this specific vulnerability. Therefore, the objective of this study was to examine the association between memory deficits and vulnerability to suicidal acts. METHODS A literature review was performed using Medline, Embase, and PsycInfo databases. Twenty-four studies (including 2,595 participants) met the selection criteria. Four different types of memory (i.e., working memory, short- and long-term memory, and autobiographical memory) were assessed in at least three different studies. RESULTS Autobiographical memory was significantly less specific and more general in patients with a history of suicide attempt relative to those without such a history (Hedges' g = 0.8 and 0.9, respectively). Long-term memory and working memory were both more impaired in suicide attempters than in patient and healthy controls. Only short-term memory did not differentiate suicide attempters from patient controls. CONCLUSIONS Memory may play a significant role in the risk of suicidal acts, perhaps by preventing these individuals from using past experiences to solve current problems and to envision the future, and by altering inhibitory processes. More studies are necessary to better clarify these relationships.
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Pharmacological interventions for cognitive decline in people with Down syndrome.
Livingstone, N, Hanratty, J, McShane, R, Macdonald, G
The Cochrane database of systematic reviews. 2015;(10):CD011546
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Abstract
BACKGROUND People with Down syndrome are vulnerable to developing dementia at an earlier age than the general population. Alzheimer's disease and cognitive decline in people with Down syndrome can place a significant burden on both the person with Down syndrome and their family and carers. Various pharmacological interventions, including donepezil, galantamine, memantine and rivastigmine, appear to have some effect in treating cognitive decline in people without Down syndrome, but their effectiveness for those with Down syndrome remains unclear. OBJECTIVES To assess the effectiveness of anti-dementia pharmacological interventions and nutritional supplements for treating cognitive decline in people with Down syndrome. SEARCH METHODS In January 2015, we searched CENTRAL, ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), Ovid MEDLINE, Embase, PsycINFO, seven other databases, and two trials registers. In addition, we checked the references of relevant reviews and studies and contacted study authors, other researchers and relevant drug manufacturers to identify additional studies. SELECTION CRITERIA Randomised controlled trials (RCTs) of anti-dementia pharmacological interventions or nutritional supplements for adults (aged 18 years and older) with Down syndrome, in which treatment was administered and compared with either placebo or no treatment. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the risk of bias of included trials and extracted the relevant data. Review authors contacted study authors to obtain missing information where necessary. MAIN RESULTS Only nine studies (427 participants) met the inclusion criteria for this review. Four of these (192 participants) assessed the effectiveness of donepezil, two (139 participants) assessed memantine, one (21 participants) assessed simvastatin, one study (35 participants) assessed antioxidants, and one study (40 participants) assessed acetyl-L-carnitine.Five studies focused on adults aged 45 to 55 years, while the remaining four studies focused on adults aged 20 to 29 years. Seven studies were conducted in either the USA or UK, one between Norway and the UK, and one in Japan. Follow-up periods in studies ranged from four weeks to two years. The reviewers judged all included studies to be at low or unclear risk of bias.Analyses indicate that for participants who received donepezil, scores in measures of cognitive functioning (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) -0.27 to 1.13) and measures of behaviour (SMD 0.42, 95% CI -0.06 to 0.89) were similar to those who received placebo. However, participants who received donepezil were significantly more likely to experience an adverse event (odds ratio (OR) 0.32, 95% CI 0.16 to 0.62). The quality of this body of evidence was low. None of the included donepezil studies reported data for carer stress, institutional/home care, or death.For participants who received memantine, scores in measures of cognitive functioning (SMD 0.05, 95% CI -0.43 to 0.52), behaviour (SMD -0.17, 95% CI -0.46 to 0.11), and occurrence of adverse events (OR 0.45, 95% CI 0.18 to 1.17) were similar to those who received placebo. The quality of this body of evidence was low. None of the included memantine studies reported data for carer stress, institutional/home care, or death.Due to insufficient data, it was possible to provide a narrative account only of the outcomes for simvastatin, antioxidants, and acetyl-L-carnitine. Results from one pilot study suggest that participants who received simvastatin may have shown a slight improvement in cognitive measures. AUTHORS' CONCLUSIONS Due to the low quality of the body of evidence in this review, it is difficult to draw conclusions about the effectiveness of any pharmacological intervention for cognitive decline in people with Down syndrome.
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Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: a gradient of severity in cognitive impairments.
Leblond, CS, Nava, C, Polge, A, Gauthier, J, Huguet, G, Lumbroso, S, Giuliano, F, Stordeur, C, Depienne, C, Mouzat, K, et al
PLoS genetics. 2014;(9):e1004580
Abstract
SHANK genes code for scaffold proteins located at the post-synaptic density of glutamatergic synapses. In neurons, SHANK2 and SHANK3 have a positive effect on the induction and maturation of dendritic spines, whereas SHANK1 induces the enlargement of spine heads. Mutations in SHANK genes have been associated with autism spectrum disorders (ASD), but their prevalence and clinical relevance remain to be determined. Here, we performed a new screen and a meta-analysis of SHANK copy-number and coding-sequence variants in ASD. Copy-number variants were analyzed in 5,657 patients and 19,163 controls, coding-sequence variants were ascertained in 760 to 2,147 patients and 492 to 1,090 controls (depending on the gene), and, individuals carrying de novo or truncating SHANK mutations underwent an extensive clinical investigation. Copy-number variants and truncating mutations in SHANK genes were present in ∼1% of patients with ASD: mutations in SHANK1 were rare (0.04%) and present in males with normal IQ and autism; mutations in SHANK2 were present in 0.17% of patients with ASD and mild intellectual disability; mutations in SHANK3 were present in 0.69% of patients with ASD and up to 2.12% of the cases with moderate to profound intellectual disability. In summary, mutations of the SHANK genes were detected in the whole spectrum of autism with a gradient of severity in cognitive impairment. Given the rare frequency of SHANK1 and SHANK2 deleterious mutations, the clinical relevance of these genes remains to be ascertained. In contrast, the frequency and the penetrance of SHANK3 mutations in individuals with ASD and intellectual disability-more than 1 in 50-warrant its consideration for mutation screening in clinical practice.
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Executive functions of sedentary elderly may benefit from walking: a systematic review and meta-analysis.
Scherder, E, Scherder, R, Verburgh, L, Königs, M, Blom, M, Kramer, AF, Eggermont, L
The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. 2014;(8):782-91
Abstract
OBJECTIVE The goal of the present meta-analysis was to address studies that examined the relationship between walking as one of the most prevalent types of leisure-time activity and executive function being a higher-order cognitive function essential for independent functioning. METHODS The following data sources were used: English-language publications in PubMed, EMBASE, PsycINFO, Cinahl, and Cochrane; the last search took place in January 2012. From these data sources, only randomized controlled trials including older people with (N = 3) and without (N = 5) cognitive impairment were selected. RESULTS Walking has been shown to improve set-shifting and inhibition in sedentary older persons without cognitive impairment (d = 0.36; 95% confidence interval: 0.16-0.55; z = 3.56; p <0.0001). In older persons with cognitive impairment, walking did not show improvements in executive functioning (d = 0.14; 95% confidence interval: -0.36-0.64; z = 0.35; p = 0.56). CONCLUSION This finding is clinically relevant because participation in a walking program may prevent or postpone a (further) decline in executive function in those who are sedentary.
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Interventions to reduce the number of falls among older adults with/without cognitive impairment: an exploratory meta-analysis.
Guo, JL, Tsai, YY, Liao, JY, Tu, HM, Huang, CM
International journal of geriatric psychiatry. 2014;(7):661-9
Abstract
OBJECTIVE This exploratory meta-analysis aimed to examine and compare the effective interventions to prevent falls among institutionalized/non-institutionalized older adults without cognitive impairment with interventions to prevent falls for older adults with cognitive impairment. DESIGN A database search identified 111 trials published between January 1992 and August 2012 that evaluated fall-prevention interventions among institutionalized/non-institutionalized older adults with and without cognitive impairment as measured by valid cognition scales. RESULTS Exercise alone intervention was similar effective on reducing the numbers of falls among older adults without cognitive impairment regardless of setting (non-institutionalized: OR = 0.783, 95% confidence interval (CI) = 0.656-0.936; p = 0.007 institutionalized: OR = 0.799, 95% CI = 0.646-0.988, p = 0.038). Vitamin D/calcium supplementation had a positive effect on the reduction of numbers of falls among non-institutionalized older adults without cognitive impairment (OR = 0.789, 95% CI = 0.631-0.985, p = 0.036), as did home visits and environment modification (OR = 0.751, 95% CI = 0.565-0.998, p = 0.048). Exercise alone, exercise-related multiple interventions, and multifactorial interventions were associated with positive outcomes among both institutionalized and non-institutionalized older adults with cognitive impairment, but studies are limited. CONCLUSIONS Single exercise interventions can significantly reduce numbers of falls among older adults with and without cognitive impairment in institutional or non-institutional settings. Vitamin D and calcium supplementation, home visits, and environment modification can reduce the risk of falls among older adults in non-institutional settings. Exercise-related multiple interventions and multifactorial interventions may only be effective for preventing falls in older adults with cognitive impairment.