NZB/NZW mice were treated with various immunosuppressive drugs used in human SLE. Cyclophosphamide (5 mg/kg 6 days out of 7), alone or with prednisolone, was better than azathioprine, prednisolone, or azathioprineplus-prednisolone, in prolonging survival and/or reducing proteinuria, Coomb's antibodies, antinuclear antibodies, and glomerular deposits of y-globulin. Intermittent bolus therapy with cyclophosphamide (50 mg/kg/lO days) was as effective as daily therapy. However, 61 % of the mice receiving any cyclophosphamide regimen developed malignant tumors compared to none in the other groups. immune complex glomerulonephritis and numerous circulating autoantibodies, many of which are directed against nuclear constituents. Their illness resembles systemic lupus erythematosus (SLE) in man. Therefore, they provide a useful model for studies of therapeutic agents used in SLE.Numerous reports demonstrate the efficacy of various immunosuppressive agents in New Zealand mice. These include single-drug therapy with corticosteroids ( 1 3 , azathioprine (2-4), and cyclophosphamide (2,5-9), as well as studies of various combinations of these drugs (3,lO). In this investigation, we have compared the effects and toxicities of a) single-drug, high-dose, long-term therapy with azathioprine, prednisolone, and cyclophosphamide, b) double-drug therapy with azathioprine-plus-prednisolone and cyclophosphamide-plus-prednisolone, and c) intermittent and daily cyclophosphamide therapy. Cyclophosphamide proved to be the best agent for suppressing the immune disorder, whether used on a daily basis, intermittently, or in combination with corticosteroid. Unfortunately all cyclophosphamide regimens, in contrast to the other therapies, were associated with a high incidence of malignancy. MATERIALS AND METHODSAnimals. NZB/NZW F, hybrids were bred from NZB/B, and NZW stock colonies maintained a t Washington University. Each therapeutic group contained 20 mice, approximately half of which were female a n d half male.
Background: Mild cognitive impairment (MCI) is a critical pre-dementia target for preventive interventions. There are few brief screening tools based on self-reported personal lifestyle and health-related information for predicting MCI that have been validated for their generalizability and utility in primary care and community settings. Objective: To develop and validate a MCI risk prediction index, and evaluate its field application in a pilot community intervention trial project. Design: Two independent population-based cohorts in the Singapore Longitudinal Ageing Study (SLAS). We used SLAS1 as a development cohort to construct the risk assessment instrument, and SLA2 as a validation cohort to verify its generalizability. Setting: community-based screening and lifestyle intervention Participants: (1) SLAS1 cognitively normal (CN) aged ≥55 years with average 3 years (N=1601); (2) SLAS2 cohort (N=3051) with average 4 years of follow up. (3) 437 participants in a pilot community intervention project. Measurements: The risk index indicators included age, female sex, years of schooling, hearing loss, depression, life satisfaction, number of cardio-metabolic risk factors (wide waist circumference, pre-diabetes or diabetes, hypertension, dyslipidemia). Weighted summed scores predicted probabilities of MCI or dementia. A self-administered questionnaire field version of the risk index was deployed in the pilot community project and evaluated using pre-intervention baseline cognitive function of participants. Results: Risk scores were associated with increasing probabilities of progression to MCI-or-dementia in the development cohort (AUC=0.73) and with increased prevalence and incidence of MCI-or-dementia in the validation cohort (AUC=0.74). The field questionnaire risk index identified high risk individuals with strong correlation with RBANS cognitive scores in the community program (p<0.001). Conclusions: The SLAS risk index is accurate and replicable in predicting MCI, and is applicable in community interventions for dementia prevention.
Background Cognitive training can improve cognition in healthy older adults. Objective The objectives are to evaluate the implementation of community-based computerized cognitive training (CCT) and its effectiveness on cognition, gait, and balance in healthy older adults. Methods A single-blind randomized controlled trial with baseline and follow-up assessments was conducted at two community centers in Singapore. Healthy community-dwelling adults aged 55 years and older participated in a 10-week CCT program with 2-hour instructor-led group classes twice a week. Participants used a mobile app to play games targeting attention, memory, decision making, visuospatial abilities, and cognitive flexibility. Implementation was assessed at the participant, provider, and community level (eg, reach, implementation, and facilitators and barriers). Effectiveness measures were the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Color Trails Test 2 (CTT-2), Berg Balance Scale, and GAITRite walkway measures (single and dual task gait speed, dual task cost, and single and dual task gait variability index [GVI]). Results A total of 94 healthy community-dwelling adults participated in the CCT program (mean age 68.8 [SD 6.3] years). Implementation measures revealed high reach (125/155, 80.6%) and moderate adherence but poor penetration of sedentary older adults (43/125, 34.4%). The effectiveness data were based on intention-to-treat (ITT) and per-protocol (PP) analysis. In the ITT analysis, single task GVI increased ( b =2.32, P =.02, 95% CI [0.30 to 4.35]) and RBANS list recognition subtest deteriorated ( b =–0.57, P =.01, 95% CI [–1.00 to –0.14]) in both groups. In the PP analysis, time taken to complete CTT-2 ( b =–13.5, P =.01, 95% CI [–23.95 to –3.14]; Cohen d effect size = 0.285) was faster in the intervention group. Single task gait speed was not statistically significantly maintained in the intervention group ( b =5.38, P =.06, 95% CI [–0.30 to 11.36]) and declined in the control group (Cohen d effect size = 0.414). PP analyses also showed interaction terms for RBANS list recall subtest ( b =–0.36, P =.08, 95% CI [–0.75 to 0.04]) and visuospatial domain ( b =0.46, P =.08, 95% CI [–0.05 to 0.96]) that were not statistically significant. Conclusions CCT can be implemented in community settings to improve attention and executive function among healthy older adults. Findings help to identify suitable healthy aging programs that can be implemented on a larger scale within communities. T...
BACKGROUND Cognitive training can improve cognition in healthy older adults OBJECTIVE The objectives are to evaluate the implementation of a community-based computerized cognitive training (CCT) and its effectiveness on cognition, gait, and balance in healthy older adults. METHODS A single-blind randomized controlled trial with baseline and follow-up assessments was conducted in two community centers (CCs) in Singapore. A total of 94 healthy community-dwelling adults aged 55 and above participated in a ten-week CCT program with two-hour instructor-led group classes conducted twice a week. Participants used a mobile application to play games targeting attention, memory, decision making, visuospatial abilities, and cognitive flexibility. Implementation was assessed at the participant-, provider-, and community-level (e.g., reach, implementation, and facilitators & barriers). Effectiveness measures were the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), Color Trails Test Part 2 (CTT2), Berg Balance Scale, and GAITRite® walkway measures (single & dual task gait speed, dual task cost, and single & dual task gait variability index (GVI)). RESULTS The data was based on Intention-to-treat (ITT) and Per-protocol (PP) analysis. In the ITT group, single task GVI increased (b = 2.32, P = .02, 95% CI [0.30, 4.35]) and RBANS List Recognition subtest deteriorated (b = -0.57, P = .01, 95% CI [-1.00, -0.14]) in both groups. In the PP group, time taken to complete CCT2 (b = -13.5, P = .01, 95% CI [-23.95, -3.14]) was faster in the intervention group. Single task gait speed was also marginally significantly maintained in the intervention group (b = 5.38, P = .063, 95% CI [-0.30, 11.36]) but declined in the control group. For RBANS subtests, Picture Naming (b = 0.43, P = .04, 95% CI [0.01, 0.85]) improved significantly in both groups while List Recognition subtests (b = -0.54, P = .02, 95% CI [-1.00, -0.08]) performance deteriorated. CONCLUSIONS CCT can be successfully implemented in community settings to improve attention, executive function, and visuospatial abilities while maintaining gait speed amongst healthy older adults. Findings help to identify suitable healthy ageing programs that can be implemented on a larger scale within communities. CLINICALTRIAL ClinicalTrials.gov Identifier NCT04439591
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