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 .

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.

Predicting Memory Score Using Paralinguistic Features.

An automated method of assessing short term memory can act as a dementia risk predictor, as poor short-term memory is strongly linked to early signs of dementia. While previous works show the feasibility of using speech to predict healthy and diagnosed dementia participants, there are still gaps in predicting 'dementia risk' and clear difficulties distinguishing early dementia with regular ageing. We extracted paralinguistic features from audio of individuals completing an over the phone episodic memory test, LOGOS. These paralinguistic features were used to discriminate between those with strong and poor short term memory performance. This work also explored various feature selection methods and tested this method across multiple datasets. Our best result was achieved using a Support Vector Machine (SVM) classifier, obtaining accuracy of 84% per audio recording.Clinical relevance- This work establishes the efficacy of using speech from older participants completing the LOGOS episodic memory test to estimate risk of dementia.

The effects of computerised cognitive training on post-CABG delirium and cognitive change: A prospective randomised controlled trial.

Background: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG). Improving cognition pre- and post-operatively using computerised cognitive training (CCT) may be an effective approach to improve cognitive outcomes in CABG patients. Objectives: Investigate the effect of remotely supervised CCT on cognitive outcomes, including delirium, in older adults undergoing CABG surgery. Methods: Thirty-six participants, were analysed in a single-blinded randomised controlled trial (CCT Intervention: n = 18, Control: n = 18). CCT was completed by the intervention group pre-operatively (every other day, 45-60-minute sessions until surgery) and post-operatively, beginning 1-month post-CABG (3 x 45-60-minute sessions/week for 12-weeks), while the control group maintained usual care plus weekly phone calls. Cognitive assessments were conducted pre- and post-operatively at multiple follow-ups (discharge, 4-months and 6-months). Post-operative delirium incidence was assessed daily until discharge. Cognitive change data were calculated at each follow-up for each cognitive test (Addenbrooke's Cognitive Examination III and CANTAB; z-scored). Results: Adherence to the CCT intervention (completion of three pre-operative or 66% of post-operative sessions) was achieved in 68% of pre-CABG and 59% of post-CABG participants. There were no statistically significant effects of CCT on any cognitive outcome, including delirium incidence. Conclusion: Adherence to the CCT program was comparatively higher than previous feasibility studies, possibly due to the level of supervision and support provided (blend of face-to-face and home-based training, with support phone calls). Implementing CCT interventions both pre- and post-operatively is feasible in those undergoing CABG. No statistically significant benefits from the CCT interventions were identified for delirium or cognitive function post-CABG, likely due to the sample size available (study recruitment greatly impacted by COVID-19). It also may be the case that multimodal intervention would be more effective.

Factors Associated with Participation in a Multidomain Web-Based Dementia Prevention Trial: Evidence from Maintain Your Brain (MYB).

BACKGROUND: The Maintain Your Brain (MYB) trial aims to prevent cognitive decline and dementia through multidomain, web-based risk-reduction. To facilitate translation, it is important to understand drivers of participation. OBJECTIVE: To describe characteristics associated with participation in MYB. METHODS: This was an observational ancillary study of MYB, a randomized controlled trial nested within the 45 and Up Study in New South Wales, Australia. We linked 45 and Up Study survey and MYB participation data. The study cohort comprised 45 and Up Study participants, aged 55-77 years at 1 January 2018, who were invited to participate in MYB. 45 and Up Study participant characteristics and subsequent MYB consent and participation were examined. RESULTS: Of 98,836 invited, 13,882 (14%) consented to participate and 6,190 participated (6%). Adjusting for age and sex, a wide range of factors were related to participation. Higher educational attainment had the strongest relationship with increased MYB participation (university versus school non-completion; AdjOR = 5.15; 95% CI:4.70-5.64) and lower self-rated quality of life with reduced participation (Poor versus Excellent: AdjOR = 0.19; 95% CI:0.11-0.32). A family history of Alzheimer's disease was related to increased participation but most other dementia risk factors such as diabetes, obesity, stroke, high blood pressure, and current smoking were associated with reduced participation. CONCLUSION: Higher socio-economic status, particularly educational attainment, is strongly associated with engagement in online dementia prevention research. Increasing population awareness of dementia risk factors, and better understanding the participation barriers in at-risk groups, is necessary to ensure online interventions are optimally designed to promote maximum participation.

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.

Reliability, Validity, and User-Experience of Remote Unsupervised Computerized Neuropsychological Assessments in Community-Living 55- to 75-Year-Olds.

BACKGROUND: Self-administered computerized neuropsychological assessments (CNAs) provide lower cost, more accessible alternatives to traditional in-person assessments but lack critical information on psychometrics and subjective experience of older adults in remote testing environments. OBJECTIVE: We used an online brief battery of computerized tasks selected from the Cogstate Brief Battery (CBB) and Cambridge Brain Sciences (CBS) to 1) determine test-retest reliability in an unsupervised setting; 2) examine convergent validity with a comprehensive 'gold standard' paper-and-pencil neuropsychological test battery administered in-person; and 3) explore user-experience of remote computerized testing and individual tests. METHODS: Fifty-two participants (mean age 65.8±5.7 years) completed CBB and CBS tests on their own computer, unsupervised from home, on three occasions, and visited a research center for an in-person paper-and-pencil assessment. They also completed a user-experience questionnaire. RESULTS: Test-retest reliabilities varied for individual measures (ICCs = 0.20 to 0.83). Global cognition composites showed excellent reliability (ICCs > 0.8 over 1-month follow-up). A strong relationship between a combination of CNA measures and paper-and-pencil battery was found (canonical correlation R = 0.87, p = 0.04). Most tests were rated as enjoyable with easy-to-understand instructions. Ratings of general experience with online testing were mostly favorable; few had difficulty concentrating (17%) or using the computer for tasks (10%), although over one-third experienced performance anxiety (38%). CONCLUSION: A combined brief online battery selected from two CNAs demonstrated robust psychometric standards for reliability (global composite), and convergent validity with a gold standard battery, and mostly good usability and acceptability in the remote testing environment.

Autologous skin-derived neural precursor cell therapy reverses canine Alzheimer dementia-like syndrome in a proof of concept veterinary trial.

BACKGROUND: Older companion dogs naturally develop a dementia-like syndrome with biological, clinical and therapeutic similarities to Alzheimer disease (AD). Given there has been no new safe, clinically effective and widely accessible treatment for AD for almost 20 years, an all-new cell therapeutic approach was trialled in canine veterinary patients, and further modelled in aged rats for more detailed neurobiological analysis. METHODS: A Phase 1/2A veterinary trial was conducted in N = 6 older companion dogs with definitive diagnosis of Canine Cognitive Dysfunction (CCD). Treatment comprised direct microinjection of 250,000 autologous skin-derived neuroprecursors (SKNs) into the bilateral hippocampus using MRI-guided stereotaxis. Safety was assessed clinically and efficacy using the validated Canine Cognitive Dysfunction Rating Scale (CCDR) at baseline and 3-month post treatment. Intention to treat analysis imputed a single patient that had a surgical adverse event requiring euthanasia. Three dog brains were donated following natural death and histology carried out to quantify Alzheimer pathology as well as immature neurons and synapses; these were compared to a brain bank (N = 12) of untreated aged dogs with and without CCD. Further, an age-related memory dysfunction rat model (N = 16) was used to more closely evaluate intrahippocampal engraftment of canine SKN cells, focusing on mnemonic and synaptic effects as well as donor cell survival, neurodifferentation and electrophysiologic circuit integration in a live hippocampal slice preparation. RESULTS: Four out-of-five dogs improved on the primary clinical CCDR endpoint, three fell below diagnostic threshold, and remarkably, two underwent full syndromal reversal lasting up to 2 years. At post mortem, synaptic density in the hippocampus specifically was nine standard deviations above non-treated dogs, and intensity of new neurons also several fold higher. There was no impact on AD pathology or long-term safety signals. Modelling in aged rats replicated the main canine trial findings: hippocampally-dependent place memory deficits were reversed and synaptic depletion rescued. In addition, this model confirmed donor cell survival and migration throughout the hippocampus, neuronal differentiation in situ, and physiologically-correct integration into pyramidal layer circuits. CONCLUSIONS: With further development, SKN cell therapy may have potential for treating carefully chosen AD patients based on neurosynaptic restoration in the hippocampus.

Advancing Australian public health initiatives targeting dementia risk reduction.

Public health initiatives aim to improve health outcomes for populations by preventing disease and ill-health consequences of environmental hazards and natural or human-made disasters. Whilst public health initiatives have been used successfully to modify behaviours for chronic diseases, many initiatives targeting reduced dementia risk in older adults suffer from conceptual and statistical flaws that greatly limit their usefulness. The limited success in modifying lifestyle dementia risk factors has led us to fall short in building a successful roadmap to dementia risk reduction. Here we argue for adopting a population-level, holistic approach to dementia risk reduction strategies across the lifespan. This approach is supplemented by 10 strategies that focus on improving social policies, harnessing existing policy, legislature and incentive schemes, and identifying feasible approaches to increase recreational and transport-related physical activity to creating best practice health care that supports healthy brain ageing for all.

Has the time come for regional periprosthetic joint infection centers in the United States? A first-year experience.

Several fields of orthopedics have concluded benefits from volume thresholds. We postulate that we could similarly optimize periprosthetic joint infection (PJI) treatment by creating a regional referral center, concentrating expertise and resources. Here, we review our reasoning and our first-year experience of a PJI referral center in the United States.

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.

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.

Harmonisation and Between-Country Differences of the Lifetime of Experiences Questionnaire in Older Adults.

Background: The Lifetime of Experiences Questionnaire (LEQ) assesses complex mental activity across the life-course and has been associated with brain and cognitive health. The different education systems and occupation classifications across countries represent a challenge for international comparisons. The objectives of this study were four-fold: to adapt and harmonise the LEQ across four European countries, assess its validity across countries, explore its association with brain and cognition and begin to investigate between-country differences in life-course mental activities. Method: The LEQ was administered to 359 cognitively unimpaired older adults (mean age and education: 71.2, 13.2 years) from IMAP and EU-funded Medit-Ageing projects. Education systems, classification of occupations and scoring guidelines were adapted to allow comparisons between France, Germany, Spain and United Kingdom. We assessed the LEQ's (i) concurrent validity with a similar instrument (cognitive activities questionnaire - CAQ) and its structural validity by testing the factors' structure across countries, (ii) we investigated its association with cognition and neuroimaging, and (iii) compared its scores between countries. Results: The LEQ showed moderate to strong positive associations with the CAQ and revealed a stable multidimensional structure across countries that was similar to the original LEQ. The LEQ was positively associated with global cognition. Between-country differences were observed in leisure activities across the life-course. Conclusions: The LEQ is a promising tool for assessing the multidimensional construct of cognitive reserve and can be used to measure socio-behavioural determinants of cognitive reserve in older adults across countries. Longitudinal studies are warranted to test further its clinical utility.

Distribution of tau hyperphosphorylation in canine dementia resembles early Alzheimer's disease and other tauopathies.

Some aged community dogs acquire a degenerative syndrome termed Canine Cognitive Dysfunction (CCD) that resembles human dementia because of Alzheimer's Disease (AD), with comparable cognitive and behavioral deficits. Dogs also have similar neuroanatomy, share our domestic environment and develop amyloid-ß plaques, making them likely a valuable ecological model of AD. However, prior investigations have demonstrated a lack of neurofibrillary tau pathology in aged dogs, an important hallmark of AD, though elevated phosphorylated tau (p-tau) at the Serine 396 (S396) epitope has been reported in CCD. Here using enhanced immunohistochemical methods, we investigated p-tau in six CCD brains and six controls using the AT8 antibody (later stage neurofibrillary pathology), and an antibody against S396 p-tau (earlier stage tau dysfunction). For the first time, we systematically assessed the Papez circuit and regions associated with Braak staging and found that all CCD dogs displayed elevated S396 p-tau labeling throughout the circuit. The limbic thalamus was particularly implicated, with a similar labeling pattern to that reported for AD neurofibrillary pathology, especially the anterior nuclei, while the hippocampus exhibited dysfunction confined to synaptic layers and efferent pathways. The cingulate and temporal lobes displayed significantly greater tauopathy than the frontal and occipital cortices, also reflective of early Braak staging patterns in AD. Immunofluorescence confirmed that S396 was accumulating within neuronal axons, somata and oligodendrocytes. We also observed AT8 labeling in one CCD brain, near the transentorhinal cortex in layer II neurons, one of the first regions to be affected in AD. Together, these data demonstrate a concordance in regional distribution of tauopathy between CCD and AD, most evident in the limbic thalamus, an important step in further validating CCD as a translational model for human AD and understanding early AD pathogenic mechanisms.

Theoretical frameworks and approaches used within the Reserve, Resilience and Protective Factors professional interest area of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment.

INTRODUCTION: Reserve, resilience, maintenance, and related concepts are intensely debated in aging and Alzheimer's disease research. METHODS: Through a short survey, we gathered information about theoretical concepts and methodologies used among research groups of the Reserve, Resilience, and Protective Factors Professional Interest Area of the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment. RESULTS: Overall 53 research groups responded. Reserve and resilience were the most frequently used conceptual frameworks. Education, occupation, leisure, and social activities were frequently used as measures, as were longitudinal designs. Neuropsychological assessments were almost universal, and usage of imaging biomarkers was frequent. In observational-epidemiological study designs, resilience and reserve together (vs reserve alone) were commonly used as theoretical frameworks. DISCUSSION: We provide a first description of concepts and methodologies used among reserve and resilience researchers. This will inform initiatives aiming to reach consensus on terminology and applications to establish common definitions.

Subject Independent Dementia Risk Prediction Models Using Paralinguistic and Memory Test Features with Feature Warping.

Clinical and biological changes during the prodromal stages of dementia are both complicated and expensive. A biomarker for cognitive reserve exposure would be highly useful as a dementia risk predictor, but has eluded researchers. Speech, which exhibits disfluencies due to dementia, is a good candidate as it is easy to collect and non-invasive. However, previous studies have only looked at the impact of dementia on speech after diagnosis. Here we extend our previous work that showed paralinguistic features extracted from audio recordings of older participants completing the LOGOS episodic memory test can be used to discriminate between high vs low cognitive reserve, hence low vs high risk of dementia. Specifically, we use the clinically validated Lifetime of Experiences Questionnaire (LEQ) to refine our ground truth estimate of cognitive reserve instead of an abridged version. Also, we improve the generalizability of our system by using feature warping to normalize across speakers. Our k-nearest neighbours (KNN) based classifier achieved an accuracy of 84% when trained with paralinguistic features alone and 91% with paralinguistic and episodic memory features.Clinical Relevance- This establishes efficacy of using speech from older participants completing the LOGOS episodic memory test to estimate risk of dementia.