Do "Brain-Training" Programs Work? Simons, Daniel J.; Boot, Walter R.; Charness, Neil ...
Psychological science in the public interest,
10/2016, Letnik:
17, Številka:
3
Journal Article
In 2014, two groups of scientists published open letters on the efficacy of brain-training interventions, or "brain games," for improving cognition. The first letter, a consensus statement from an ...international group of more than 70 scientists, claimed that brain games do not provide a scientifically grounded way to improve cognitive functioning or to stave off cognitive decline. Several months later, an international group of 133 scientists and practitioners countered that the literature is replete with demonstrations of the benefits of brain training for a wide variety of cognitive and everyday activities. How could two teams of scientists examine the same literature and come to conflicting "consensus" views about the effectiveness of brain training? In part, the disagreement might result from different standards used when evaluating the evidence. To date, the field has lacked a comprehensive review of the brain-training literature, one that examines both the quantity and the quality of the evidence according to a well-defined set of best practices. This article provides such a review, focusing exclusively on the use of cognitive tasks or games as a means to enhance performance on other tasks. We specify and justify a set of best practices for such brain-training interventions and then use those standards to evaluate all of the published peer-reviewed intervention studies cited on the websites of leading brain-training companies listed on Cognitive Training Data (www.cognitivetrainingdata.org), the site hosting the open letter from brain-training proponents. These citations presumably represent the evidence that best supports the claims of effectiveness. Based on this examination, we find extensive evidence that brain-training interventions improve performance on the trained tasks, less evidence that such interventions improve performance on closely related tasks, and little evidence that training enhances performance on distantly related tasks or that training improves everyday cognitive performance. We also find that many of the published intervention studies had major shortcomings in design or analysis that preclude definitive conclusions about the efficacy of training, and that none of the cited studies conformed to all of the best practices we identify as essential to drawing clear conclusions about the benefits of brain training for everyday activities. We conclude with detailed recommendations for scientists, funding agencies, and policymakers that, if adopted, would lead to better evidence regarding the efficacy of brain-training interventions.
A hexanucleotide GGGGCC repeat expansion in the noncoding region of the C9ORF72 gene is the most common genetic abnormality in familial and sporadic amyotrophic lateral sclerosis (ALS) and ...frontotemporal dementia (FTD). The function of the C9ORF72 protein is unknown, as is the mechanism by which the repeat expansion could cause disease. Induced pluripotent stem cell (iPSC)-differentiated neurons from C9ORF72 ALS patients revealed disease-specific (1) intranuclear GGGGCCexp RNA foci, (2) dysregulated gene expression, (3) sequestration of GGGGCCexp RNA binding protein ADARB2, and (4) susceptibility to excitotoxicity. These pathological and pathogenic characteristics were confirmed in ALS brain and were mitigated with antisense oligonucleotide (ASO) therapeutics to the C9ORF72 transcript or repeat expansion despite the presence of repeat-associated non-ATG translation (RAN) products. These data indicate a toxic RNA gain-of-function mechanism as a cause of C9ORF72 ALS and provide candidate antisense therapeutics and candidate human pharmacodynamic markers for therapy.
•iPSC neurons mirror dysregulated gene expression in C9ORF72 brain•Aggregated RNA binding proteins contribute to toxicity•C9ORF72 iPSC neurons are highly susceptible to excitotoxicity.•Pathology and toxicity is abrogated with antisense to C9ORF72 expansion
Donnelly et al. provide evidence for RNA toxicity, through the use of induced pluripotent cells, as the cause of amyotrophic lateral sclerosis and frontotemporal dementia in patients with mutation in the C9ORF72 gene and a cellular rescue using antisense oligonucleotide therapy.
Intracellular pathogens and danger signals trigger the formation of inflammasomes, which activate inflammatory caspases and induce pyroptosis. The anthrax lethal factor metalloprotease and ...small-molecule DPP8/9 inhibitors both activate the NLRP1B inflammasome, but the molecular mechanism of NLRP1B activation is unknown. In this study, we used genome-wide CRISPR-Cas9 knockout screens to identify genes required for NLRP1B-mediated pyroptosis. We discovered that lethal factor induces cell death via the N-end rule proteasomal degradation pathway. Lethal factor directly cleaves NLRP1B, inducing the N-end rule-mediated degradation of the NLRP1B N terminus and freeing the NLRP1B C terminus to activate caspase-1. DPP8/9 inhibitors also induce proteasomal degradation of the NLRP1B N terminus but not via the N-end rule pathway. Thus, N-terminal degradation is the common activation mechanism of this innate immune sensor.
Prior research has reported disparities in environmental exposures in the United States, but, to our knowledge, no nationwide studies have assessed inequality in noise pollution.
We aimed to
) assess ...racial/ethnic and socioeconomic inequalities in noise pollution in the contiguous United States; and
) consider the modifying role of metropolitan level racial residential segregation.
We used a geospatial sound model to estimate census block group–level median (L
) nighttime and daytime noise exposure and 90th percentile (L
) daytime noise exposure. Block group variables from the 2006–2010 American Community Survey (ACS) included race/ethnicity, education, income, poverty, unemployment, homeownership, and linguistic isolation. We estimated associations using polynomial terms in spatial error models adjusted for total population and population density. We also evaluated the relationship between race/ethnicity and noise, stratified by levels of metropolitan area racial residential segregation, classified using a multigroup dissimilarity index.
Generally, estimated nighttime and daytime noise levels were higher for census block groups with higher proportions of nonwhite and lower-socioeconomic status (SES) residents. For example, estimated nighttime noise levels in urban block groups with 75% vs. 0% black residents were 46.3 A-weighted decibels (dBA) interquartile range (IQR): 44.3–47.8 dBA and 42.3 dBA (IQR: 40.4–45.5 dBA), respectively. In urban block groups with 50% vs. 0% of residents living below poverty, estimated nighttime noise levels were 46.9 dBA (IQR: 44.7–48.5 dBA) and 44.0 dBA (IQR: 42.2–45.5 dBA), respectively. Block groups with the highest metropolitan area segregation had the highest estimated noise exposures, regardless of racial composition. Results were generally consistent between urban and suburban/rural census block groups, and for daytime and nighttime noise and robust to different spatial weight and neighbor definitions.
We found evidence of racial/ethnic and socioeconomic differences in model-based estimates of noise exposure throughout the United States. Additional research is needed to determine if differences in noise exposure may contribute to health disparities in the United States. https://doi.org/10.1289/EHP898
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Recent studies have begun to reveal critical roles for the brain’s professional phagocytes, microglia, and their receptors in the control of neurotoxic amyloid beta (Aβ) and myelin debris ...accumulation in neurodegenerative disease. However, the critical intracellular molecules that orchestrate neuroprotective functions of microglia remain poorly understood. In our studies, we find that targeted deletion of SYK in microglia leads to exacerbated Aβ deposition, aggravated neuropathology, and cognitive defects in the 5xFAD mouse model of Alzheimer’s disease (AD). Disruption of SYK signaling in this AD model was further shown to impede the development of disease-associated microglia (DAM), alter AKT/GSK3β-signaling, and restrict Aβ phagocytosis by microglia. Conversely, receptor-mediated activation of SYK limits Aβ load. We also found that SYK critically regulates microglial phagocytosis and DAM acquisition in demyelinating disease. Collectively, these results broaden our understanding of the key innate immune signaling molecules that instruct beneficial microglial functions in response to neurotoxic material.
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•Disruption of microglial SYK signaling exacerbates disease in models of AD and MS•Microglial proliferation and association with Aβ plaques is coordinated by SYK•SYK is a pivotal regulator of microglial activation and AKT/GSK3β-signaling•Phagocytic clearance of neurotoxic material by microglia is dependent on SYK
SYK is a central intracellular regulator of microglial activation and phagocytosis that is deployed to limit Aβ pathology and demyelinating disease.
Traumatic brain injury (TBI) is a leading global cause of death and disability. Here we demonstrate in an experimental mouse model of TBI that mild forms of brain trauma cause severe deficits in ...meningeal lymphatic drainage that begin within hours and last out to at least one month post-injury. To investigate a mechanism underlying impaired lymphatic function in TBI, we examined how increased intracranial pressure (ICP) influences the meningeal lymphatics. We demonstrate that increased ICP can contribute to meningeal lymphatic dysfunction. Moreover, we show that pre-existing lymphatic dysfunction before TBI leads to increased neuroinflammation and negative cognitive outcomes. Finally, we report that rejuvenation of meningeal lymphatic drainage function in aged mice can ameliorate TBI-induced gliosis. These findings provide insights into both the causes and consequences of meningeal lymphatic dysfunction in TBI and suggest that therapeutics targeting the meningeal lymphatic system may offer strategies to treat TBI.
Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota ...transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients.
A multicenter retrospective series was performed on the use of FMT in IC patients with CDI that was recurrent, refractory, or severe. We aimed to describe rates of CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item questionnaire soliciting demographic and pre- and post-FMT data was completed for 99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such as death or hospitalization within 12 weeks of FMT, (iii) infection within 12 weeks of FMT, and (iv) AEs (related and unrelated) to FMT.
Cases included adult (75) and pediatric (5) patients treated with FMT for recurrent (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean follow-up period between FMT and data collection was 11 months (range 3-46 months). Reasons for IC included: HIV/AIDS (3), solid organ transplant (19), oncologic condition (7), immunosuppressive therapy for inflammatory bowel disease (IBD; 36), and other medical conditions/medications (15). The CDI cure rate after a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI. Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during sedation for FMT administered via colonoscopy; the other was unrelated to FMT. None suffered infections definitely related to FMT, but two patients developed unrelated infections and five had self-limited diarrheal illness in which no causal organism was identified. One patient had a superficial mucosal tear caused by the colonoscopy performed for the FMT, and three patients reported mild, self-limited abdominal discomfort post FMT. Five (14% of IBD patients) experienced disease flare post FMT. Three ulcerative colitis (UC) patients underwent colectomy related to course of UC >100 days after FMT.
This series demonstrates the effective use of FMT for CDI in IC patients with few SAEs or related AEs. Importantly, there were no related infectious complications in these high-risk patients.
IMPORTANCE: Frailty is an important risk factor for postoperative mortality. Whether the association between frailty and mortality is consistent across all surgical specialties, especially those ...predominantly performing lower stress procedures, remains unknown. OBJECTIVE: To examine the association between frailty and postoperative mortality across surgical specialties. DESIGN, SETTING, AND PARTICIPANTS: A cohort study was conducted across 9 noncardiac specialties in hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and Veterans Affairs Surgical Quality Improvement Program (VASQIP) from January 1, 2010, through December 31, 2014, using multivariable logistic regression to evaluate the association between frailty and postoperative mortality. Data analysis was conducted from September 15, 2019, to April 30, 2020. Patients 18 years or older undergoing noncardiac procedures were included. EXPOSURES: Risk Analysis Index measuring preoperative frailty categorized patients as robust (Risk Analysis Index ≤20), normal (21-29), frail (30-39), or very frail (≥40). Operative Stress Score (OSS) categorized procedures as low (1-2), moderate (3), and high (4-5) stress. Specialties were categorized by case-mix as predominantly low intensity (>75% OSS 1-2), moderate intensity (50%-75%), or high intensity (<50%). MAIN OUTCOMES AND MEASURES: Thirty-day (both measures) and 180-day (VASQIP only) postoperative mortality. RESULTS: Of the patients evaluated in NSQIP (n = 2 339 031), 1 309 795 were women (56.0%) and mean (SD) age was 56.49 (16.4) years. Of the patients evaluated in VASQIP (n = 426 578), 395 761 (92.78%) were men and mean (SD) age was 61.1 (12.9) years. Overall, 30-day mortality was 1.2% in NSQIP and 1.0% in VASQIP, and 180-day mortality in VASQIP was 3.4%. Frailty and OSS distributions differed substantially across the 9 specialties. Patterns of 30-day mortality for frail and very frail patients were similar in NSQIP and VASQIP for low-, moderate-, and high-intensity specialties. Frailty was a consistent, independent risk factor for 30- and 180-day mortality across all specialties. For example, in NSQIP, for plastic surgery, a low-intensity specialty, the odds of 30-day mortality in very frail (adjusted odds ratio aOR, 27.99; 95% CI, 14.67-53.39) and frail (aOR, 5.1; 95% CI, 3.03-8.58) patients were statistically significantly higher than for normal patients. This was also true in neurosurgery, a moderate-intensity specialty, for very frail (aOR, 9.8; 95% CI, 7.68-12.50) and frail (aOR, 4.18; 95% CI, 3.58-4.89) patients and in vascular surgery, a high-intensity specialty, for very frail (aOR, 10.85; 95% CI, 9.83-11.96) and frail (aOR, 3.42; 95% CI, 3.19-3.67) patients. CONCLUSIONS AND RELEVANCE: In this study, frailty was associated with postoperative mortality across all noncardiac surgical specialties regardless of case-mix. Preoperative frailty assessment could be implemented across all specialties to facilitate risk stratification and shared decision-making.
Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes that burn energy and generate heat; this is a potential anti-diabesity therapy. However, the potential ...to form cold-induced beige adipocytes declines with age. This creates a clinical roadblock to potential therapeutic use in older individuals, who constitute a large percentage of the obesity epidemic. Here we show that aging murine and human beige progenitor cells display a cellular aging, senescence-like phenotype that accounts for their age-dependent failure. Activating the senescence pathway, either genetically or pharmacologically, in young beige progenitors induces premature cellular senescence and blocks their potential to form cold-induced beige adipocytes. Conversely, genetically or pharmacologically reversing cellular aging by targeting the p38/MAPK-p16Ink4a pathway in aged mouse or human beige progenitor cells rejuvenates cold-induced beiging. This in turn increases glucose sensitivity. Collectively, these data indicate that anti-aging or senescence modalities could be a strategy to induce beiging, thereby improving metabolic health in aging humans.
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•Cellular aging of beige progenitors prevents cold-induced beiging in older mammals•Inducing premature aging in young beige progenitors is sufficient to block beiging•Genetically reversing beige progenitor senescence rejuvenates beiging•Pharmacologically targeting aging rejuvenates progenitors and beiging potential
Cold temperatures induce progenitor cells within white adipose tissue to form beige adipocytes, but this process fails during aging. Berry et al. show that beige progenitors undergo an age-associated, senescence-like phenotype that accounts for this age-dependent beiging failure. Targeting the p38/Ink4a-Arf pathway rejuvenates beige progenitors and restores beiging potential.
Thiamine is an essential micronutrient that plays a key role in energy metabolism. Many populations worldwide may be at risk of clinical or subclinical thiamine deficiencies, due to famine, reliance ...on staple crops with low thiamine content, or food preparation practices, such as milling grains and washing milled rice. Clinical manifestations of thiamine deficiency are variable; this, along with the lack of a readily accessible and widely agreed upon biomarker of thiamine status, complicates efforts to diagnose thiamine deficiency and assess its global prevalence. Strategies to identify regions at risk of thiamine deficiency through proxy measures, such as analysis of food balance sheet data and month‐specific infant mortality rates, may be valuable for understanding the scope of thiamine deficiency. Urgent public health responses are warranted in high‐risk regions, considering the contribution of thiamine deficiency to infant mortality and research suggesting that even subclinical thiamine deficiency in childhood may have lifelong neurodevelopmental consequences. Food fortification and maternal and/or infant thiamine supplementation have proven effective in raising thiamine status and reducing the incidence of infantile beriberi in regions where thiamine deficiency is prevalent, but trial data are limited. Efforts to determine culturally and environmentally appropriate food vehicles for thiamine fortification are ongoing.
This paper describes the current state of thiamine research and the significance of thiamine deficiency in low‐ and middle‐income countries from public health and clinical perspectives. The map shows countries where the estimated per capita availability of thiamine in the national food supply (as per food balance sheets) is below the recommended nutrient intake for men (in turquoise), and countries where rice or wheat flour fortification are in place to address low thiamine availability (in yellow).
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