A single post-exposure oxime RS194B treatment rapidly reactivates acetylcholinesterase and reverses acute symptoms in macaques exposed to diethylphosphorothioate parathion and chlorpyrifos insecticides.

Millions of individuals globally suffer from inadvertent, occupational or self-harm exposures from organophosphate (OP) insecticides, significantly impacting human health. Similar to nerve agents, insecticides are neurotoxins that target and inhibit acetylcholinesterase (AChE) in central and peripheral synapses in the cholinergic nervous system. Post-exposure therapeutic countermeasures generally include administration of atropine with an oxime to reactivate the OP-inhibited AChE. However, animal model studies and recent clinical trials using insecticide-poisoned individuals have shown minimal clinical benefits of the currently approved oximes and their efficacy as antidotes has been debated. Currently used oximes either reactivate poorly, do not readily cross the blood-brain barrier (BBB), or are rapidly cleared from the circulation and must be repeatedly administered. Zwitterionic oximes of unbranched and simplified structure, for example RS194B, have been developed that efficiently cross the BBB resulting in reactivation of OP-inhibited AChE and dramatic reversal of severe clinical symptoms in mice and macaques exposed to OP insecticides or nerve agents. Thus, a single IM injection of RS194B has been shown to rapidly restore blood AChE and butyrylcholinesterase (BChE) activity, reverse cholinergic symptoms, and prevent death in macaques following lethal inhaled sarin and paraoxon exposure. The present macaque studies extend these findings and assess the ability of post-exposure RS194B treatment to counteract oral poisoning by highly toxic diethylphosphorothioate insecticides such as parathion and chlorpyrifos. These OPs require conversion by P450 in the liver of the inactive thions to the active toxic oxon forms, and once again demonstrated RS194B efficacy to reactivate and alleviate clinical symptoms within 60 mins of a single IM administration. Furthermore, when delivered orally, the Tmax of RS194B at 1-2 h was in the same range as those administered IM but were maintained in the circulation for longer periods greatly facilitating the use of RS194B as a non-invasive treatment, especially in isolated rural settings.

Ambulatory Behavior Assessment Using Deep Learning.

This work leverages a custom implementation of a deep neural network-based object detection algorithm to detect people and a set of assistive devices relevant to clinical environments. The object detections form the basis for the quantification of different ambulatory activities and related behaviors. Using features extracted from detected people and objects as input to machine learning models, we quantify how a person ambulates and the mode of ambulation being used.Clinical relevance- This system provides the data required for clinicians and hospitalized patients to work together in the creation, monitoring, and adjustment of ambulatory goals.

Use of Real Time Clinical Video Telehealth to Home by primary care providers within the Veterans Health Administration during the first wave of the COVID-19 pandemic: variability across VA stations and with time.

Objective: Determine the extent to which use of Clinical Video Telehealth to Home (VT2H) for primary care licensed independent practitioner visits (PCLIPVs) varied over time and across the Veterans Health Administration (VA) during the first 18 months of the COVID pandemic, and if there was an association between VT2H usage and VA station characteristics. Materials and Methods: All outpatient encounters (n = 12 143 456) for Veterans (n = 4 373 638) that had VA PCLIPVs during the period of observation were categorized as conducted by VT2H, in-person, or telephone. The change over time in the percentage of total PCLIPVs conducted by VT2H was plotted and associations between VA station characteristics and VT2H usage were analyzed using simple statistics and negative binomial regression. Results: Between March 2020 and mid-August 2020, VT2H visits increased from <2% to 13% of all VA PCLIPVs. However, VT2H usage varied substantively by VA station and declined system-wide to <9% of PCLIPVs by July 2021. VA stations that serve a greater proportion of rural Veterans were found less likely to use VT2H. Discussion: The VA was successful in increasing the use of VT2H for PCLIPVs during the first phase of the COVID pandemic. However, VT2H usage varied by VA station and over time. Beyond rurality, it is unknown what station characteristics may be responsible for the variance in VT2H use. Conclusion: Future investigation is warranted to identify the unique practices employed by VA stations that were most successful in using VT2H for PCLIPVs and whether they can be effectively disseminated to other stations.

The impact of solvents on the toxicity of the banned parathion insecticide.

The aerial crop dusting and spraying of fields with the phosphorothioate insecticide parathion in the late 1900s, significantly improved crop yields but resulted in high levels of occupational toxicity in handlers and agricultural workers, as well as cases of intentional self-harm poisoning, culminating in its banning in many western countries by early 2000s. However because of the low solubility and volatility of parathion, most available products were formulated using organic solvents e.g. xylene, to increase the efficacy of the aerosols and dusts. In the present study, the toxicity of parathion was assessed when formulated in an aqueous solvents (ethanol/PBS (1:9)), and delivered to macaques as an aerosol. Doses of 780 µg/kg and 1.56 mg/kg were delivered one day apart, using a modified nebulizer calculated to result in lung deposition of ∼480 µg/kg with a similar or larger amount being swallowed; these doses being similar to the estimated lethal oral dose 286ug/kg - 1.43 mg/kg of formulated parathion in humans. Surprisingly, this dose (a combined amount of ∼14 mg) caused only low AChE inhibition and moderate BChE inhibition with no clinical symptoms, indicating that the use of organic solvents may have previously played a critical role in the severity of parathion toxicity following inhalation exposure. In addition, unlike constitutively toxic OPs, which are highly toxic when inhaled, these results are consistent with the idea that phosphorothioate insecticides appear to be more intoxicating following oral than inhalation exposure. However, this still remains uncertain because the presence of organic solvents in the ingested parathion studies was not always known.

Rapid conversion of Tai Chi classes from face-to-face to virtual during the COVID-19 pandemic: A quality improvement project.

PURPOSE: The purpose of this quality improvement project was to examine the feasibility of rapidly converting a Tai Chi program for older Veterans from face-to-face to virtual classes. METHODS: Eighteen Veterans attending our face-to-face Tai Chi course were invited to transition to virtual classes. Feasibility was defined as the ability of program staff and participants to successfully connect and complete the initial and subsequent classes by VA Video Connect (VVC) with little to no technical difficulties, participant ability to participate in the course without safety concerns, and favorable feedback from participants and program staff. RESULTS: Nine of 18 Veterans agreed to transition to the virtual program and attended a median (interquartile range) of 11 (4-15) classes; they were younger (62.7 + 11.5 vs. 70.5 + 7.0 years, p < .05) and more likely to have the knowledge and equipment needed to participate (78% vs. 0%, p < .01) than nonparticipants. Tai Chi instructors and participating Veterans reported being able to connect to and complete the classes virtually with only minimal technical problems. No adverse events were reported. Feedback from the instructors and Veterans was positive and included comments on ease of use and enjoyability. CONCLUSION: Results suggest that virtual Tai Chi classes via VVC are feasible for some older Veterans.

Improved patient-specific hyperthermia planning based on parametrized electromagnetic and thermal models for the SIGMA-30 applicator.

OBJECTIVE: To create an improved planning method for pediatric regional hyperthermia (RHT) using the SIGMA-30 applicator (SIGMA-30). MATERIALS AND METHODS: An electromagnetic model of SIGMA-30 was generated for use with the finite-difference time-domain (FDTD) method. Applying special MATLAB-based algorithms, voxel models of a pediatric patient with pelvic rhabdomyosarcoma were created from Computed-Tomography (CT) contours for use with the FDTD method and the finite-difference (FD) method capable of using either temperature-independent or temperature-dependent perfusion models for solving the Bioheat Transfer Equation (BHTE). Patient models were parametrized regarding, first, the positioning in the applicator, second, the absorbed power range and, third, different perfusion models, resulting in the so-called Parametrized Treatment Models (PTMs). A novel dedicated optimization procedure was developed based on quantitative comparison of numerical calculations against temperature and power measurements from two RHT therapies. RESULTS: Using measured data, a realistic absorbed power range in the patient model was estimated. Within this range, several FDTD and BHTE runs were performed and, applying the aforementioned optimization scheme, the best PTMs and perfusion models were identified for each therapy via a retrospective comparison with measurements in 14 temperature sensor positions: 5 in the tumor, 8 in rectum and one in bladder. CONCLUSION: A novel dedicated optimization procedure for identification of suitable patient-specific electromagnetic and thermal models, which can be used for improved patient planning, was developed and evaluated by comparison with treatment-derived measurements using SIGMA-30. The optimization procedure can be extended to other hyperthermia applicators and to other patient types, including adults.

An outpatient Tai Chi program: Effects on veterans' functional outcomes.

PURPOSE: To evaluate the effectiveness of an evidence-based 12-week Tai Chi course designed to improve balance and physical function in a population of older veterans. METHODS: Community dwelling veterans of all ages with gait and balance problems were invited to participate in the Tai Chi program. Participants completed the Berg Balance Scale (BBS), the Timed Up and Go (TUG) test, and the Falls Efficacy Scale-International (FES-I) at baseline and again at the end of the program. Descriptive statistics were used to summarize study participants' characteristics. The change from baseline to the end of the 12-week program was calculated for each of the three primary outcome variables (BBS, TUG, FES-I). RESULTS: Twenty-two veterans, aged 58 years and above, with perceived gait and/or balance issues were enrolled in the program with completion by 11 veterans. Veterans who completed their final assessments showed the BBS, improved significantly (p = 0.004) from baseline to the 12-week assessment. The TUG scores improved by a median of 1.3 s (p = 0.022). There was not a significant change in the FES-I. CONCLUSIONS: Preliminary findings provide evidence of the effectiveness of a 12-week Tai Chi program to improve functional outcomes for older veterans with mild to moderate gait and balance problems.

An Interdisciplinary Approach to Educating Medical Students About Dementia Assessment and Treatment Planning.

BACKGROUND: Many general practitioners consider dementia care beyond their clinical domain and feel that dementia assessment and treatment should be addressed by specialists, such as geriatricians, geriatric psychiatrists, or neurologists. An urgent need exists to educate all medical trainees in dementia care, regardless of their specialization interests. OBSERVATIONS: We developed a multicomponent, experiential, brief curriculum using team-based learning to expose senior medical students who rotated through the US Department of Veterans Affairs Memory Disorders Clinic at the Central Arkansas Veterans Healthcare System in Little Rock to an interdisciplinary assessment of dementia. The curriculum included didactics, clinical experience, and team-based learning. In pre- and postevaluation, students rated their perception of the role of interdisciplinary team members in assessing and managing dementia, their personal abilities to assess cognition, behavioral problems, caregiver burden, and their perception of the impact of behavioral problems on dementia care. CONCLUSIONS: Dementia knowledge gaps were prevalent in this cohort of senior medical students. Providing interdisciplinary geriatric educational experience improved students perception of their ability to assess for dementia and their recognition of the roles of interdisciplinary team members. Plans are in place to continue and expand the program to other complex geriatric syndromes.

Subject Identification Using a Depth Camera for Patient Ambulation Monitoring.

Our work identifies subjects based on their height and the distance between their joints. Using a depth sensing camera, we obtained the position of a person's joints in 3D space relative to each other. The distances between adjacent joints and height of a subject's head are used to create a vector of eight features for an individual to use for identification. Using modified KNN, full and partial feature sets were used to identify subjects. Additionally, our classifier can be utilized to assess ambulation (such as walking's velocity and distance) of subject, when identified.

Selective serotonin reuptake inhibitors-associated apathy syndrome: A cross sectional study.

Selective serotonin reuptake inhibitors (SSRIs), commonly used to treat depression, are associated with loss of motivation, anergy, and lack of curiosity often referred collectively as apathy. However, this association has not been systematically assessed using a specific rating scale for measuring apathy syndrome. Our objective was to study the association between SSRI use and apathy syndrome.We conducted a retrospective chart review of 125 patients enrolled in an outpatient psychiatry clinic. The prevalence of apathy syndrome and its clinical significance (based on standardized assessment) were compared between patients treated and not treated with SSRIs. Apathy was assessed using the Apathy Evaluation Scale-clinician version with a score ranging 18-72 with higher score for worse apathy. A score of greater than 30 is considered clinically significant apathy.Among 119 patients, the mean apathy scores were significantly higher in those treated with SSRIs compared to those not treated with SSRIs (42.5 ±â€Š9.2 vs 31.3 ±â€Š6, P < .0001). The SSRI group also had a significantly higher percentage of patients with clinically significant apathy (92% vs 61%, P < .0001). Use of all SSRIs was associated with the presence of apathy. Apathy was seen in all mental health diagnostic categories with highest Apathy evaluation scale-clinician version scores in those with dementia.SSRI use may be associated with higher rates of apathy syndrome. Clinicians should specifically inquire about iatrogenic apathy syndrome when evaluating patients on an SSRI if there is suspicion of loss of motivation. Limitations of this study included retrospective nature of this study, and that majority of the sample was males. Prospective studies are needed to elucidate information regarding the prevalence, etiology, and treatment response for SSRI-associated apathy syndrome.

Novel Toxicology Program to Support the Development of Inhaled VentaProst.

Currently, off-label continuous administration of inhaled epoprostenol is used to manage hemodynamics during mitral valve surgery. A toxicology program was developed to support the use of inhaled epoprostenol during mechanical ventilation as well as pre- and postsurgery via nasal prongs. To support use in patients using nasal prongs, a Good Laboratory Practice (GLP), 14-day rat, nose-only inhalation study was performed. No adverse findings were observed at ∼50× the dose rate received by patient during off-label use. To simulate up to 48 hours continuous aerosol exposure during mechanical ventilation, a GLP toxicology study was performed using anesthetized, intubated, mechanically ventilated dogs. Dogs inhaled epoprostenol at approximately 6× and 13× the dose rate reported in off-label human studies. This novel animal model required establishment of a dog intensive care unit providing sedation, multisystem support, partial parenteral nutrition, and management of the intubated mechanically ventilated dogs for the 48-hour duration of study. Aerosol was generated by a vibrating mesh nebulizer with novel methods required to determine dose and particle size in-vitro. Continuous pH 10.5 epoprostenol was anticipated to be associated with lung injury; however, no adverse findings were observed. As no toxicity at pH 10.5 was observed with a formulation that required refrigeration, a room temperature stable formulation at pH 12 was evaluated in the same ventilated dog model. Again, there were no adverse findings. In conclusion, current toxicology findings support the evaluation of inhaled epoprostenol at pH 12 in surgical patients with pulmonary hypertension for up to 48 hours continuous exposure.

Critical care resource use, cost, and mortality associated with firearm-related injuries in US children's hospitals.

BACKGROUND/PURPOSE: To assess trends and resource use attributable to firearm-related injuries in US pediatric intensive care units (PICUs). METHODS: Retrospective data from Pediatric Health Information Systems (PHIS) database from 2004 to 2017. RESULTS: Of 5,984,938 admissions to 28 children's hospitals, 3707 were for firearm injuries. A total of 1088 of 3707 hospitalizations (29.9%) required PICU admission. Median PICU length of stay was 2 days (IQR, 1-6 days), and the median cost for PICU patients was $37,569.31 (IQR, $19,243.83-$77,856.32). Use of mechanical ventilation (674/1088 admissions [61.9%]), surgical procedures (744/1088 admissions [68.3%]), blood transfusions (429/1088 admissions [39.9%]), and intracranial pressure monitoring devices (30/1088 admissions [2.8%]) increased in PICU patients. Computed tomography showed an overall increase (197/287 [68.6%] to 138/177 [78%], P = .037) from 2004 to 2007 to 2016-2017. Mortality among PICU patients (140/1058 [13.23%]) attributable to firearm-related injuries increased insignificantly (34/285 (11.93%] to 25/172 [14.53%], P = .746). CONCLUSIONS: Using PHIS data, we found a significant increase in median cost per hospitalization and an increase in critical care resource use, including the frequency of invasive mechanical ventilatory assistance, neuromonitoring, operations performed, and transfusion of blood products. Further research is needed to continue to characterize the burden of pediatric critical firearm injury. TYPE OF STUDY: Retrospective cohort study. LEVEL OF EVIDENCE: Level III.

Increasing the availability of Tai Chi to veterans through a training of trainers course.

PURPOSE: The purpose of this nurse-led project was to increase the number of interprofessional Tai Chi instructors for veterans through a 5-week (32 hours) training of trainers (ToT) course led by a Tai Chi master trainer. METHODS: This project was designed to evaluate the effectiveness of using the ToT model to increase the availability of Tai Chi to veterans. To understand how well the ToT course met learners' needs, a two-phase course evaluation was conducted. RESULTS: Fifteen interprofessional employees enrolled in and completed the course. Most learners were white (67%) females (67%) with a median age of 50 years. All agreed that the training provided the skills, materials, and confidence to lead Tai Chi classes. Most (93%) indicated experiencing positive health benefits from the training and none experienced any negative effects. The 3-month follow-up evaluation indicated that 10 (67%) were teaching veterans in individual or group classes with two others assisting. Twelve instructors taught more than 150 veterans. CONCLUSIONS: Overall, learners evaluated this ToT course positively and indicated their needs were met and felt prepared to teach Tai Chi despite being inexperienced. The course was a success with 80% of new instructors teaching or coteaching Tai Chi to veterans.

Aerosolized recombinant human butyrylcholinesterase delivered by a nebulizer provides long term protection against inhaled paraoxon in macaques.

The recent intentional use of nerve agents and pesticides in Europe and Afghanistan highlights the need for an effective countermeasure against organophosphates (OP) toxins. The most developed pretreatment candidate to date is plasma (native) human butyrylcholinesterase (HuBChE), which is limited in availability and because of its 1:1 stoichiometry with OPs, a large dose will present challenges when delivered parenterally both in terms of pharmacokinetics and manageability in the field. A tetrameric recombinant (r) form of human BChE produced in CHO-K1 cells with similar structure, in vivo stability and antidotal efficacy as the native form, has been developed to deliver rHuBChE as an aerosol (aer) to form a pulmonary bioshield capable of neutralizing inhaled OPs in situ and prevent AChE inhibition in the blood and in the brain; the latter associated with the symptoms of OP toxicity. Previous proof-of-concept macaque studies demonstrated that delivery of 9 mg/kg using a microsprayer inserted down the trachea, resulted in protection against an inhaled dose of 15ug/kg of aer-paraoxon (aer-Px) given 72 h later. In the present studies, pulmonary delivery of rHuBChE in macaques was achieved using Aerogen vibrating mesh nebulizers, similar to that used for human self-administration. The promising findings indicate that despite the poor lung deposition observed in macaques using nebulizers (13-20%), protective levels of RBC-AChE were still present in the blood even when exposure aer-Px (55 µg/kg) was delayed for five days. This long term retention of 5 mg/kg rHuBChE deposited in the lung bodes well for the use of an aer-rHuBChE pretreatment in humans where a user-friendly customized nebulizer with increased lung deposition up to 50% will provide even longer protection at a lower dose.

Tutorial for using SliceOmatic to calculate thigh area and composition from computed tomography images from older adults.

OBJECTIVE: Area of muscle, fat, and bone is often measured in thigh CT scans when tissue composition is a key outcome. SliceOmatic software is commonly referenced for such analysis but published methods may be insufficient for new users. Thus, a quick start guide to calculating thigh composition using SliceOmatic has been developed. METHODS: CT images of the thigh were collected from older (69 ± 4 yrs, N = 24) adults before and after 12-weeks of resistance training. SliceOmatic was used to segment images into seven density regions encompassing fat, muscle, and bone from -190 to +2000 Hounsfield Units [HU]. The relative contributions to thigh area and the effects of tissue density overlap for skin and marrow with muscle and fat were determined. RESULTS: The largest contributors to the thigh were normal fat (-190 to -30 HU, 29.1 ± 7.4%) and muscle (35 to 100 HU, 48.9 ± 8.2%) while the smallest were high density (101 to 150 HU, 0.79 ± 0.50%) and very high density muscle (151 to 200 HU, 0.07 ± 0.02%). Training significantly (P<0.05) increased area for muscle in the very low (-29 to -1 HU, 5.5 ± 7.9%), low (0 to 34 HU, 9.6 ± 16.8%), normal (35 to 100 HU, 4.2 ± 7.9%), and high (100 to 150 HU, 70.9 ± 80.6%) density ranges for muscle. Normal fat, very high density muscle and bone did not change (P>0.05). Contributions to area were altered by ~1% or less and the results of training were not affected by accounting for skin and marrow. CONCLUSIONS: When using SliceOmatic to calculate thigh composition, accounting for skin and marrow may not be necessary. We recommend defining muscle as -29 to +200 HU but that smaller ranges (e.g. low density muscle, 0 to 34 HU) can easily be examined for relationships with the health condition and intervention of interest. TRIAL REGISTRATION: Clinicaltrials.gov NCT02261961.

Repetitive transcranial magnetic stimulation for apathy in mild cognitive impairment: A double-blind, randomized, sham-controlled, cross-over pilot study.

Apathy is a common and disabling behavioral concomitant of many neurodegenerative conditions. The presence of apathy with Mild Cognitive Impairment (MCI) is linked with heightened rates of conversion to Alzheimer's disease. Improving apathy may slow the neurodegenerative process. The objective was to establish the efficacy of repetitive transcranial magnetic stimulation (rTMS) in improving apathy in older adults with MCI. An 8-week, double-blind, randomized, sham-controlled cross-over study was conducted in nine subjects (66 ± 9 years) with apathy and MCI. Subjects were randomized to rTMS or sham treatment (5 days/week) for 2 weeks following which they underwent a 4-week treatment-free period. Subjects then crossed-over to receive the other treatment for 2 weeks. The primary (apathy (AES-C)) and secondary (cognition (3MS & MMSE), executive function (TMT-A & TMT-B), and clinical global impression (CGI)) outcomes were assessed at baseline, 2, 6, and 8 weeks. After adjusting for baseline, there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment at 2 weeks. There was significantly greater improvement in 3MS, MMSE, TMT-A, and CGI-I with rTMS compared to the sham treatment. This study establishes that rTMS is efficacious in improving apathy in subjects with MCI.

Methylphenidate for Apathy in Community-Dwelling Older Veterans With Mild Alzheimer's Disease: A Double-Blind, Randomized, Placebo-Controlled Trial.

OBJECTIVE: Apathy is a common behavioral problem in Alzheimer's disease. Apathy has profound consequences, such as functional impairment, higher service utilization, higher caregiver burden, and increased mortality. The authors' objective was to study the effects of methylphenidate on apathy in Alzheimer's disease. METHOD: A 12-week, prospective, double-blind, randomized, placebo-controlled trial (methylphenidate versus placebo) was conducted in community-dwelling veterans (N=60) with mild Alzheimer's disease. The primary outcome for apathy (Apathy Evaluation Scale-Clinician) and secondary outcomes for cognition (Mini-Mental State Examination, Modified Mini-Mental State Examination), functional status (activities of daily living, instrumental activities of daily living), improvement and severity (Clinical Global Impressions Scale [CGI]), caregiver burden (Zarit Burden Scale), and depression (Cornell Scale for Depression in Dementia) were measured at baseline and at 4, 8, and 12 weeks. RESULTS: Participants were all men (77 years old, SD=8). After adjusting for baseline, the methylphenidate group had significantly greater improvement in apathy than the placebo group at 4 weeks, 8 weeks, and 12 weeks. At 12 weeks, there was also greater improvement in cognition, functional status, caregiver burden, CGI scores, and depression in the methylphenidate group compared with the placebo group. CONCLUSIONS: Methylphenidate improved apathy in a group of community-dwelling veterans with mild Alzheimer's disease. Methylphenidate also improved cognition, functional status, caregiver burden, CGI scores, and depression.

Repeated dose inhalation developmental toxicity study in rats exposed to cellulose insulation with boric acid additive.

Cellulose insulation (CI), a common building material, is a mixture of cellulose fibers and borates. Borates are approximately 20% of the product weight and act as a flame retardant. Given possible exposure to workers and consumers, an inhalation toxicity study was conducted following Organization for Economic Co-operation and Development (OECD) 414 for Prenatal Development Toxicity to evaluate if CI is a developmental toxicant. Pregnant female rats were exposed by nose-only inhalation to CI aerosols containing 20% boric acid for six h/day, from gestational day (GD) 6-19, and fetuses were evaluated for developmental parameters. Respirable CI was produced by grinding to produce respirable particles (MMAD 2.7-2.9 µm, geometric standard deviations (GSD) 1.9-2.6), which were then aerosolized. Target air concentrations were 15, 90, and 270 mg CI/m3. Controls were exposed to air only. Slight body weight reductions (average decrease <7% vs. control) were observed in male and female GD 20 fetuses in the mid and high dose groups. No embryo/fetal developmental toxicity or alterations in any other measured variable were reported at any dose. The no observed adverse effect level (NOAEL) for developmental outcomes was 270 mg/m3.

Home-Based Exercise Program Improves Balance and Fear of Falling in Community-Dwelling Older Adults with Mild Alzheimer's Disease: A Pilot Study.

BACKGROUND/OBJECTIVE: Balance problems are common in older adults with Alzheimer's disease (AD). The objective was to study the effects of a Wii-Fit interactive video-game-led physical exercise program to a walking program on measures of balance in older adults with mild AD. METHODS: A prospective randomized controlled parallel-group trial (Wii-Fit versus walking) was conducted in thirty community-dwelling older adults (73±6.2 years) with mild AD. Home-based exercises were performed under caregiver supervision for 8 weeks. Primary (Berg Balance Scale, BBS) and secondary outcomes (fear of falls and quality of life) were measured at baseline, 8 weeks (end of intervention), and 16 weeks (8-weeks post-intervention). RESULTS: At 8 weeks, there was a significantly greater improvement (average inter-group difference [95% CI]) in the Wii-Fit group compared to the walking group in BBS (4.8 [3.3-6.2], p < 0.001), after adjusting for baseline. This improvement was sustained at 16 weeks (3.5 [2.0-5.0], p < 0.001). Analyses of the secondary outcome measures indicated that there was a significantly greater improvement in the Wii-Fit group compared to walking group in Activity-specific Balance Confidence scale (6.5 [3.6-9.4], p < 0.001) and Falls Efficacy Scale (-4.8 [-7.6 to -2.0], p = 0.002) at 8 weeks. However, this effect was not sustained at 16 weeks. Quality of life improved in both groups at 8 weeks; however, there were no inter-group differences (p = 0.445). CONCLUSION: Home-based, caregiver-supervised Wii-Fit exercises improve balance and may reduce fear of falling in community-dwelling older adults with mild AD.