Hypoalbuminemia Predicts Failure of Two-Stage Exchange for Chronic Periprosthetic Joint Infection of the Hip and Knee.

BACKGROUND: Nutritionally compromized patients, with preoperative serum albumin (SAB) < 3.5g/dL, are at higher risk for periprosthetic joint infection (PJI) in total joint arthroplasty. The relationship between nutritional and PJI treatment success is unknown. The purpose of this study was to examine the relationship between preresection nutrition and success after first-stage resection in planned two-stage exchange for PJI. METHODS: A retrospective review was performed on 418 patients who had first-stage resection of a planned two-stage exchange for chronic hip or knee PJI between 2014 and 2018. A total of 157 patients (58 hips and 99 knees) were included who completed first stage, had available preop SAB and had a 2-year follow-up. Failure was defined as persistent infection or repeat surgery for infection after resection. Demographic and surgical data were abstracted and analyzed. RESULTS: Among knee patients with preop SAB >3.5 g/dL, the failure rate was 32% (15 of 47) versus a 48% (25 of 40) failure rate when SAB <3.5 g/dL (P = .10). Similarly, the failure rate among hip patients with preop SAB >3.5 g/dL versus 12.5% (3 of 24) versus 44% (15 of 34) for hip patients with SAB <3.5 g/dL (P = .01). Multivariable regression results indicated that patients with SAB< 3.5 g/dL (P = .0143) and Musculoskeletal Infection Society host type C (P = .0316) were at an increased risk of failure. CONCLUSION: Low preoperative SAB and Musculoskeletal Infection Societyhost type-C are independent risk factors for failure following first-stage resection in planned two-stage exchange for PJI. Efforts to nutritionally optimize PJI patients, when possible, may improve the outcome of two-stage exchange.

Nutrition Module design in Maintain Your Brain: an internet-based randomised controlled trial to prevent cognitive decline and dementia.

The Maintain Your Brain (MYB) trial is one of the largest internet-delivered multidomain randomised controlled trial designed to target modifiable risk factors for dementia. It comprises four intervention modules: physical activity, nutrition, mental health and cognitive training. This paper explains the MYB Nutrition Module, which is a fully online intervention promoting the adoption of the 'traditional' Mediterranean Diet (MedDiet) pattern for those participants reporting dietary intake that does not indicate adherence to a Mediterranean-type cuisine or those who have chronic diseases/risk factors for dementia known to benefit from this type of diet. Participants who were eligible for the Nutrition Module were assigned to one of the three diet streams: Main, Malnutrition and Alcohol group, according to their medical history and adherence to the MedDiet at baseline. A short dietary questionnaire was administered weekly during the first 10 weeks and then monthly during the 3-year follow-up to monitor whether participants adopted or maintained the MedDiet pattern during the intervention. As the Nutrition Module is a fully online intervention, resources that promoted self-efficacy, self-management and process of change were important elements to be included in the module development. The Nutrition Module is unique in that it is able to individualise the dietary advice according to both the medical and dietary history of each participant; the results from this unique intervention will contribute substantively to the evidence that links the Mediterranean-type diet with cognitive function and the prevention of dementia and will increase our understanding of the benefits of a MedDiet in a Western country.

Polymicrobial Colonization of Prosthetic Joint Infections Treated With Open Wound Management.

BACKGROUND: Open wound management in prosthetic joint infection (PJI) patients has been used in problematic dehisced wounds hoping to stimulate granulation tissue and closure. However, infections that start as a monomicrobial PJI can become polymicrobial with resultant worse outcomes following open wound management. This study assessed the relationship between open wound management and the development of polymicrobial periprosthetic joint infections. METHODS: We reviewed patients referred with a synovial cutaneous fistula. Patients with an open wound measuring less than 2 cm and less than two weeks of open wound management were excluded. Variables included original organisms cultured, type and length of open wound management, and organisms cultured at the time of revision infection surgery. RESULTS: Of the 65 patients with a previous monomicrobial infection treated with open wound management, 22/65 (34%) progressed to a polymicrobial infection. Thirty (46%) wounds were packed open with gauze, 20 (31%) were managed with negative pressure wound therapy, and 15 (23%) had surface dressings only. Of the 22 patients who converted to a polymicrobial infection, only 10 (45%) were infection free at follow-up. In contrast, 30 of 43 patients (70%) whose infections remained monomicrobial were infection free at follow-up. CONCLUSION: Open wound management can lead to conversion from a monomicrobial to a polymicrobial PJI, a rate of 34% in this series. Open prosthetic wound management should be discontinued for a fear of converting a monomicrobial infection to a difficult to treat polymicrobial infection. Surgeons must be prudent in the use of open wound management. LEVEL OF EVIDENCE: Level IV, Retrospective Case Series.

High-Dose Antibiotic Cement Spacers Independently Increase the Risk of Acute Kidney Injury in Revision for Periprosthetic Joint Infection: A Prospective Randomized Controlled Clinical Trial.

BACKGROUND: Standard treatment for periprosthetic joint infection (PJI) involves 2-stage exchange with placement of an antibiotic-impregnated cement spacer (ACS). Conflicting evidence exists on the role of ACS in development of acute kidney injury (AKI) after first-stage surgery. In this randomized clinical trial, we aimed to compare the incidence of AKI between the first-stage of a planned 2-stage exchange vs 1-stage exchange. This study design isolates the effect of the ACS in otherwise identical treatment groups. METHODS: The primary outcome variable was AKI, defined as a creatinine ≥1.5 times baseline or an increase of ≥0.3 mg/dL. Risk factors for AKI were evaluated using bivariate statistical tests and multivariable logistic regression. RESULTS: Patients who underwent the first stage of a planned 2-stage exchange were significantly more likely to develop AKI compared with the 1-stage exchange group (15 [22.7%] vs 4 [6.6%], P = .011). On multivariable regression analysis, ACS placement (odds ratio 7.48, 95% confidence limit 1.77-31.56) and chronic kidney disease (odds ratio 3.84, 95% confidence limit 1.22-12.08) were independent risk factors for AKI. CONCLUSION: Our study provides evidence that high-dose antibiotic cement spacers for treatment of PJI are an independent risk factor for AKI. Therefore, efforts to minimize nephrotoxicity should be employed in revision for PJI when possible.

Whitepaper: Defining and investigating cognitive reserve, brain reserve, and brain maintenance.

Several concepts, which in the aggregate get might be used to account for "resilience" against age- and disease-related changes, have been the subject of much research. These include brain reserve, cognitive reserve, and brain maintenance. However, different investigators have use these terms in different ways, and there has never been an attempt to arrive at consensus on the definition of these concepts. Furthermore, there has been confusion regarding the measurement of these constructs and the appropriate ways to apply them to research. Therefore the reserve, resilience, and protective factors professional interest area, established under the auspices of the Alzheimer's Association, established a whitepaper workgroup to develop consensus definitions for cognitive reserve, brain reserve, and brain maintenance. The workgroup also evaluated measures that have been used to implement these concepts in research settings and developed guidelines for research that explores or utilizes these concepts. The workgroup hopes that this whitepaper will form a reference point for researchers in this area and facilitate research by supplying a common language.

Can Computerized Cognitive Training Improve Cognition in Patients With Heart Failure?: A Review.

BACKGROUND: Cognitive impairment is highly prevalent in patients with heart failure (HF), negatively impacting self-care and consequently increasing mortality. Although computerized cognitive training (CCT) has been found to be efficacious in improving cognition in older adults, little is known about the efficacy of CCT in patients with HF. PURPOSE: This brief systematic review examined the feasibility and efficacy of CCT on cognitive functioning in patients with HF. METHODS: PubMed, Embase, and PsychINFO electronic databases were searched to identify randomized controlled trials (RCTs) of CCT in patients with HF published from January 1, 2000, to December 31, 2017. A narrative synthesis of intervention effectiveness on individual cognitive domains and functional outcomes was provided. Risk of bias of the studies was also rated. RESULTS: The search yielded 4 RCTs describing 3 cognitive training interventions (n = 138). Preliminary evidence indicated that CCT may enhance the processing speed and working memory of patients with HF. Intervention effects also seemed to confer transferrable benefits to functional outcomes of daily living. The outcomes of the assembled studies were assessed using the Grades of Recommendation, Assessment, Development and Evaluation system, and the quality of the evidence was found to be of moderate to low quality. CONCLUSION: Computerized cognitive trainings show promise in enhancing the cognition of patients with HF. The stability of the current findings would need to be tested in RCTs with larger sample sizes to validate the use of CCTs in targeting cognitive impairment and self-care abilities for patients with HF.

Reliability and validity of a Mediterranean diet and culinary index (MediCul) tool in an older population with mild cognitive impairment.

Dementia is a leading cause of morbidity and mortality without pharmacologic prevention or cure. Mounting evidence suggests that adherence to a Mediterranean dietary pattern may slow cognitive decline, and is important to characterise in at-risk cohorts. Thus, we determined the reliability and validity of the Mediterranean Diet and Culinary Index (MediCul), a new tool, among community-dwelling individuals with mild cognitive impairment (MCI). A total of sixty-eight participants (66 % female) aged 75·9 (sd 6·6) years, from the Study of Mental and Resistance Training study MCI cohort, completed the fifty-item MediCul at two time points, followed by a 3-d food record (FR). MediCul test-retest reliability was assessed using intra-class correlation coefficients (ICC), Bland-Altman plots and κ agreement within seventeen dietary element categories. Validity was assessed against the FR using the Bland-Altman method and nutrient trends across MediCul score tertiles. The mean MediCul score was 54·6/100·0, with few participants reaching thresholds for key Mediterranean foods. MediCul had very good test-retest reliability (ICC=0·93, 95 % CI 0·884, 0·954, P<0·0001) with fair-to-almost-perfect agreement for classifying elements within the same category. Validity was moderate with no systematic bias between methods of measurement, according to the regression coefficient (y=-2·30+0·17x) (95 % CI -0·027, 0·358; P=0·091). MediCul over-estimated the mean FR score by 6 %, with limits of agreement being under- and over-estimated by 11 and 23 %, respectively. Nutrient trends were significantly associated with increased MediCul scoring, consistent with a Mediterranean pattern. MediCul provides reliable and moderately valid information about Mediterranean diet adherence among older individuals with MCI, with potential application in future studies assessing relationships between diet and cognitive function.

Posterior compensatory network in cognitively intact elders with hippocampal atrophy.

Functional compensation in late life is poorly understood but may be vital to understanding long-term cognitive trajectories. To study this we first established an empirically derived threshold to distinguish hippocampal atrophy in those with Mild Cognitive Impairment (MCI n = 34) from those with proficient cognition (PRO n = 22), using data from a population-based cohort. Next, to identify compensatory networks we compared cortical activity patterns during a graded spatial working memory (SWM) task in only cognitively proficient individuals, either with (PROATR ) or without hippocampal atrophy (PRONIL ). Multivariate Partial Least Squares analyses revealed that these groups engaged spatially distinct SWM-related networks. In those with hippocampal atrophy and under conditions of basic-SWM demand, expression of a posterior compensatory network (PCN) comprised calcarine and posterior parietal cortex strongly correlated with superior SWM performance (r = -0.96). In these individuals, basic level SWM response times were faster and no less accurate than in those with no hippocampal atrophy. Cognitively proficient older individuals with hippocampal atrophy may, therefore, uniquely engage posterior brain areas when performing simple spatial working memory tasks.

Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers.

BACKGROUND: New effective interventions to attenuate age-related cognitive decline are a global priority. Computerized cognitive training (CCT) is believed to be safe and can be inexpensive, but neither its efficacy in enhancing cognitive performance in healthy older adults nor the impact of design factors on such efficacy has been systematically analyzed. Our aim therefore was to quantitatively assess whether CCT programs can enhance cognition in healthy older adults, discriminate responsive from nonresponsive cognitive domains, and identify the most salient design factors. METHODS AND FINDINGS: We systematically searched Medline, Embase, and PsycINFO for relevant studies from the databases' inception to 9 July 2014. Eligible studies were randomized controlled trials investigating the effects of ≥ 4 h of CCT on performance in neuropsychological tests in older adults without dementia or other cognitive impairment. Fifty-two studies encompassing 4,885 participants were eligible. Intervention designs varied considerably, but after removal of one outlier, heterogeneity across studies was small (I(2) = 29.92%). There was no systematic evidence of publication bias. The overall effect size (Hedges' g, random effects model) for CCT versus control was small and statistically significant, g = 0.22 (95% CI 0.15 to 0.29). Small to moderate effect sizes were found for nonverbal memory, g = 0.24 (95% CI 0.09 to 0.38); verbal memory, g = 0.08 (95% CI 0.01 to 0.15); working memory (WM), g = 0.22 (95% CI 0.09 to 0.35); processing speed, g = 0.31 (95% CI 0.11 to 0.50); and visuospatial skills, g = 0.30 (95% CI 0.07 to 0.54). No significant effects were found for executive functions and attention. Moderator analyses revealed that home-based administration was ineffective compared to group-based training, and that more than three training sessions per week was ineffective versus three or fewer. There was no evidence for the effectiveness of WM training, and only weak evidence for sessions less than 30 min. These results are limited to healthy older adults, and do not address the durability of training effects. CONCLUSIONS: CCT is modestly effective at improving cognitive performance in healthy older adults, but efficacy varies across cognitive domains and is largely determined by design choices. Unsupervised at-home training and training more than three times per week are specifically ineffective. Further research is required to enhance efficacy of the intervention. Please see later in the article for the Editors' Summary.

BDNF and COMT polymorphisms have a limited association with episodic memory performance or engagement in complex cognitive activity in healthy older adults.

Cognitive decline is a major factor in lowering the quality of life in older populations, and contributes substantially to social, economic, and health costs. As humans age, cognitive function decreases differentially, and individual differences in cognitive ageing are likely attributed to a range of causes, including environmental and genetic influences. The current study included 360 participants (240 females and 120 males) aged between 50 and 79years from the Tasmanian Healthy Brain Project. The brain-derived neurotrophic factor (BDNF) Val66Met and Catechol-O-Methyltransferase (COMT) Val158Met polymorphisms were examined for their association with visual and auditory episodic memory performance. The polymorphisms were also investigated for their association with reported life-long engagement in complex cognitive activity using a retrospective questionnaire. Relative to the demographic variables, the gene variations were found to have no association with episodic memory performance, with the exception of the COMT polymorphism on a single measure of auditory memory (RAVLT). Several other studies also demonstrated that these polymorphisms have no, small, or inconsistent effects on memory function. The BDNF Val66Met and COMT Val158Met polymorphisms were also found to be of little significance to active engagement in complex cognitive activity throughout most of the lifespan. An association was detected between BDNF Val66Met and engagement in cognitive activity in early life (p=.04, d=.23), however this did not reach significance when adjusted for multiple comparisons. The biological mechanisms that underlie engagement in cognitive activity are elusive, thus the potential relationship between BDNF Val66Met genotype and early life cognitive engagement warrants further investigation.

Cognitive and social lifestyle: links with neuropathology and cognition in late life.

Many studies report an association of cognitive and social experiential factors and related traits with dementia risk. Further, many clinical-pathologic studies find a poor correspondence between levels of neuropathology and the presence of dementia and level of cognitive impairment. The poor correspondence suggests that other factors contribute to the maintenance or loss of cognitive function, with factors associated with the maintenance of function referred to as neural or cognitive reserve. This has led investigators to examine the associations of cognitive and social experiential factors with neuropathology as a first step in disentangling the complex associations between these experiential risk factors, neuropathology, and cognitive impairment. Despite the consistent associations of a range of cognitive and social lifestyle factors with cognitive decline and dementia risk, the extant clinical-pathologic data find only a single factor from one cohort, linguistic ability, related to AD pathology. Other factors, including education, harm avoidance, and emotional neglect, are associated with cerebrovascular disease. Overall, the associations are weak. Some factors, such as education, social networks, and purpose in life, modify the relation of neuropathology to cognition. Finally, some factors such as cognitive activity appear to bypass known pathologies altogether suggesting a more direct association with biologic indices that promote person-specific differences in reserve and resilience. Future work will first need to replicate findings across more studies to ensure the veracity of the existing data. Second, effort is needed to identify the molecular substrates of neural reserve as potential mediators of the association of lifestyle factors with cognition.

Gender differences in factors associated with delirium severity in older adults with dementia.

The purpose of this descriptive correlational study was to explore potential gender differences in the relationship of dementia severity, age, APOE status, cognitive reserve and co-morbidity (two potentially modifiable factors), to delirium severity in older adults. Baseline data from an ongoing clinical trial and a Poisson regression procedure were used in the analyses. Participants were 148 elderly individuals with dementia and delirium admitted to post-acute care. In women, delirium severity was related to dementia severity (p=0.002) and co-morbidity moderated that effect (p=0.03). In men, education was marginally associated with delirium severity (p=0.06). Implications for research are discussed.

Critical periods for cognitive reserve building activities for late life global cognition and cognitive decline: the Sydney memory and aging cohort study.

Cognitive, social, and physical activities, collectively linked to cognitive reserve, are associated with better late-life cognitive outcomes. To better understand the building of cognitive reserve, we investigated which of these activities, during which stages of life, had the strongest associations with late-life cognitive performance. From the Sydney Memory and Aging Study, 546 older Australians, who were community-dwelling and without a dementia diagnosis at recruitment (Mage 80.13 years, 52.2% female), were asked about their engagement in social, physical, and cognitive activities throughout young adulthood (YA), midlife (ML), and late-life (LL). Comprehensive neuropsychological testing administered biennially over 6 years measured baseline global cognition and cognitive decline. In our study, YA, but not ML nor LL, cognitive activity was significantly associated with late-life global cognition (ß = 0.315, p < .001). A follow-up analysis pointed to the formal education component of the YA cognitive activity measure, rather than YA cognitive leisure activities, as a significant predictor of better late-life global cognition (ß = 0.146, p = .003). YA social activity and LL cognitive activity were significantly associated with less cognitive decline (ß = 0.023, p < .001, and ß = 0.016, p = .022, respectively). Physical activity was not found to be associated with global cognition or cognitive decline. Overall, YA cognitive activity was associated with better late-life cognition, and YA social and LL cognitive activities were associated with less cognitive decline. Formal education emerges as the key contributor in the association between YA cognitive activity and late-life global cognition.

Exergame and cognitive training for preventing falls in community-dwelling older people: a randomized controlled trial.

Exergame training, in which video games are used to promote exercise, can be tailored to address cognitive and physical risk factors for falls and is a promising method for fall prevention in older people. Here, we performed a randomized clinical trial using the smart±step gaming system to examine the effectiveness of two home-based computer game interventions, seated cognitive training and step exergame training, for fall prevention in community-dwelling older people, as compared with a minimal-intervention control group. Participants aged 65 years or older (n = 769, 71% female) living independently in the community were randomized to one of three arms: (1) cognitive training using a computerized touchpad while seated, (2) exergame step training on a computerized mat or (3) control (provided with an education booklet on healthy ageing and fall prevention). The rate of falls reported monthly over 12 months-the primary outcome of the trial-was significantly reduced in the exergame training group compared with the control group (incidence rate ratio = 0.74, 95% confidence interval = 0.56-0.98), but was not statistically different between the cognitive training and control groups (incidence rate ratio = 0.86, 95% confidence interval = 0.65-1.12). No beneficial effects of the interventions were found for secondary outcomes of physical and cognitive function, and no serious intervention-related adverse events were reported. The results of this trial support the use of exergame step training for preventing falls in community-dwelling older people. As this intervention can be conducted at home and requires only minimal equipment, it has the potential for scalability as a public health intervention to address the increasing problem of falls and fall-related injuries. Australian and New Zealand Clinical Trial Registry identifier: ACTRN12616001325493 .

The effect of exercise training on cognitive function in older adults with mild cognitive impairment: a meta-analysis of randomized controlled trials.

OBJECTIVES: Investigations of exercise and cognition have primarily focused on healthy or demented older adults, and results have been equivocal in individuals with mild cognitive impairment (MCI). Our aim was to evaluate efficacy of exercise on cognition in older adults with MCI. DESIGN: We conducted a meta-analysis of random controlled trials (RCTs) of exercise effects on cognitive outcomes in adults with MCI. Searches were conducted in Medline, EMBASE, CINAHL, PEDro, SPORTSDICUS, PsychInfo, and PubMed. PARTICIPANTS: Adults aged over 65 years with MCI or Mini-Mental State Exam mean score 24-28 inclusive. MEASUREMENTS: Study quality was assessed using the PEDro scale; data on participant and intervention characteristics and outcomes were extracted, followed by meta-analysis. RESULTS: Fourteen RCTs (1,695 participants; age 65-95 years) met inclusion criteria. Quality was modest and under-powering for small effects prevalent. Overall, 42% of effect sizes (ESs) were potentially clinically relevant (ES >0.20) with only 8% of cognitive outcomes statistically significant. Meta-analysis revealed negligible but significant effects of exercise on verbal fluency (ES: 0.17 [0.04, 0.30]). No significant benefit was found for additional executive measures, memory, or information processing. Overall results were inconsistent with benefits varying across exercise types and cognitive domains. CONCLUSIONS: There is very limited evidence that exercise improves cognitive function in individuals with MCI, although published research is of moderate quality and inconclusive due to low statistical power. Questions remain regarding the magnitude, generalization, persistence, and mechanisms of benefits. Large-scale, high-quality RCTs are required to determine if exercise improves cognition or reduces dementia incidence in those with MCI.

The Tasmanian Healthy Brain Project (THBP): a prospective longitudinal examination of the effect of university-level education in older adults in preventing age-related cognitive decline and reducing the risk of dementia.

BACKGROUND: Differences in the level of cognitive compromise between individuals following brain injury are thought to arise from underlying differences in cognitive reserve. The level of cognitive reserve attained by an individual is influenced by both genetic and life experience factors such as educational attainment and occupational history. The Tasmanian Healthy Brain Project (THBP) is a world-first prospective study examining the capacity of university-level education to enhance cognitive reserve in older adults and subsequently reduce age-related cognitive decline and risk for neurodegenerative disease. METHODS: Up to 1,000 adults aged 50-79 years at the time of entry into the study will be recruited to participate in the THBP. All participants will be healthy and free of significant medical, psychological, or psychiatric illness. Of the participant sample, 90% will undertake a minimum of 12 months part-time university-level study as an intervention. The remaining 10% will act as a control reference group. Participants will complete an annual comprehensive assessment of neuropsychological function, medical health, socialization, and personal well-being. Premorbid estimates of past cognitive, education, occupational, and physical function will be used to account for the mediating influence of prior life experience on outcomes. Potential contributing genetic factors will also be explored. RESULTS: Participant results will be assessed annually. Participants displaying evidence of dementia on the comprehensive neuropsychological assessment will be referred to an independent psycho-geriatrician for screening and diagnosis. CONCLUSIONS: The THBP commenced in 2011 and is expected to run for 10-20 years duration. To date, a total of 383 participants have been recruited into the THBP.