Does Visual Speed of Processing Training Improve Health-Related Quality of Life in Assisted and Independent Living Communities?: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: Visual speed of processing training had clinically and statistically significant beneficial effects on health-related quality of life among 2,802 healthy community-dwelling adults aged 65-94 years at 2 and 5 years post-training in the Advanced Cognitive Training for Independent and Vital Elderly randomized controlled trial. We examined whether that effect would be found among older adults in assisted and independent living communities. RESEARCH DESIGN AND METHODS: We conducted a two-arm, parallel randomized controlled trial stratified by assisted versus independent settings in 31 senior living communities and enrolled 351 adults aged 55-102 years. The targeted intervention dose was 10 hr at baseline with 4-hr boosters at 5 and 11 months. The intervention group received computerized visual speed of processing training, while the attention control group solved computerized crossword puzzles. The health-related quality of life outcomes were the Short-Form 36-item Health Survey's mental and physical component T scores. Linear mixed-effect models were used. RESULTS: Visual speed of processing, assisted living, and their interaction had no clinically or statistically significant effects on the physical component T scores. However, visual speed of processing (p = .022), assisted living (p = .022), and their interaction (p = .007) had clinically and statistically significant effects on the mental component T scores. The estimated marginal means revealed a small effect-sized positive 2.2 point visual speed of processing training effect in the independent living communities, but a clinically important harmful -4.2 point visual speed of processing training effect in the assisted living communities. DISCUSSION AND IMPLICATIONS: Given the medium-sized harmful effect of visual speed of processing training among those in the assisted living communities, caution is advised when using these two visual speed of processing training modalities in assisted living communities until further research verifies or refutes our findings and the underlying etiological pathways.

Urokinase Plasminogen Activator Overexpression Reverses Established Lung Fibrosis.

INTRODUCTION: Impaired plasminogen activation (PA) is causally related to the development of lung fibrosis. Prior studies demonstrate that enhanced PA in the lung limits the severity of scarring following injury and in vitro studies indicate that PA promotes matrix degradation and fibroblast apoptosis. These findings led us to hypothesize that increased PA in an in vivo model would enhance the resolution of established lung fibrosis in conjunction with increased myofibroblast apoptosis. METHODS: Transgenic C57BL/6 mice with doxycycline inducible lung-specific urokinase plasminogen activator (uPA) expression or littermate controls were treated (day 0) with bleomycin or saline. Doxycycline was initiated on days 1, 9, 14, or 21. Lung fibrosis, stiffness, apoptosis, epithelial barrier integrity, and inflammation were assessed. RESULTS: Protection from fibrosis with uPA upregulation from day 1 through day 28 was associated with reduced parenchymal stiffness as determined by atomic force microscopy. Initiation of uPA expression beginning in the late inflammatory or the early fibrotic phase reduced stiffness and fibrosis at day 28. Induction of uPA activity in mice with established fibrosis decreased lung collagen and lung stiffness while increasing myofibroblast apoptosis. Upregulation of uPA did not alter lung inflammation but was associated with improved epithelial cell homeostasis. CONCLUSION: Restoring intrapulmonary PA activity diminishes lung fibrogenesis and enhances the resolution of established lung fibrosis. This PA-mediated resolution is associated with increased myofibroblast apoptosis and improved epithelial cell homeostasis. These studies support the potential capacity of the lung to resolve existing scar in murine models.

Speed of processing training and depression in assisted and independent living: A randomized controlled trial.

Late life depression is widely associated with lower quality of life and greater disability, making it an important target for prevention. Earlier randomized controlled trials [RCTs] demonstrated that speed of processing training [SOPT] led to reductions in depressive symptoms and clinical depression in community-dwelling adults. Our purpose was to evaluate depression outcomes related to SOPT among older adults who live in supported senior living settings. This two-arm, parallel RCT included 351 participants aged 55-102 years who resided in assisted and independent settings in 31 senior living communities. Participants were randomized within sites to computerized SOPT vs. computerized crossword puzzles with a targeted dose of 10 hours of playtime at baseline plus 4 hours of booster training at five and eleven months. Depression outcomes included the 9-item Patient Health Questionnaire [PHQ-9] scores, categorical levels, and dichotomous indicators. Random effects linear mixed effect models estimated SOPT effects in intention-to-treat complete case and multiple imputation analyses. Mean age of the sample was 81.0 years, 72.2% were women, and 41.0% resided in assisted living. At baseline 65.7% had no depression [PHQ-9 scores < 5] and 6.6% had clinically meaningful depression [PHQ-9 scores ≥ 10]. At 12 months we found significantly increased PHQ-9 scores [p = 0.006] and categorical levels [p = 0.003], and higher percentages of PHQ-2 scores > 3 [p = 0.016] and major depressive syndrome [p = 0.045] among the assisted living SOPT group. No significant change in depression was observed in the independent living SOPT or attention control groups. In summary, the SOPT known as Road Tour/Double Decision significantly increased, rather than decreased, the burden of depressive symptoms among participants residing in assisted living. Given these risks, this SOPT program should be avoided among older people in assisted living settings, and other SOPT interventions should be combined with systematic depression monitoring.

Efferocytosis of apoptotic alveolar epithelial cells is sufficient to initiate lung fibrosis.

Type II alveolar epithelial cell (AEC) apoptosis is a prominent feature of fibrotic lung diseases and animal models of pulmonary fibrosis. While there is growing recognition of the importance of AEC injury and apoptosis as a causal factor in fibrosis, the underlying mechanisms that link these processes remain unknown. We have previously shown that targeting the type II alveolar epithelium for injury by repetitively administering diphtheria toxin to transgenic mice expressing the diphtheria toxin receptor off of the surfactant protein C promoter (SPC-DTR) develop lung fibrosis, confirming that AEC injury is sufficient to cause fibrosis. In the present study, we find that SPC-DTR mice develop increased activation of caspase 3/7 after initiation of diphtheria toxin treatment consistent with apoptosis within AECs. We also find evidence of efferocytosis, the uptake of apoptotic cells, by alveolar macrophages in this model. To determine the importance of efferocytosis in lung fibrosis, we treated cultured alveolar macrophages with apoptotic type II AECs and found that the uptake induced pro-fibrotic gene expression. We also found that the repetitive intrapulmonary administration of apoptotic type II AEC or MLE-12 cells induces lung fibrosis. Finally, mice lacking a key efferocytosis receptor, CD36, developed attenuated fibrosis in response to apoptotic MLE-12 cells. Collectively, these studies support a novel mechanism linking AEC apoptosis with macrophage pro-fibrotic activation via efferocytosis and reveal previously unrecognized therapeutic targets.

Speed-of-Processing Training in Assisted and Independent Living: A Randomized Controlled Trial.

OBJECTIVES: To examine speed-of-processing training (SOPT) in older adults in senior living communities, especially those in assisted living. DESIGN: Two-arm, parallel, randomized controlled trial. SETTING: Assisted and independent residence settings in 31 senior living communities. PARTICIPANTS: Individuals aged 55 to 102 (mean 81.0, 73.8% female, 76.4% living alone, 47.0% residing in assisted living; N=351). INTERVENTION: The intervention was 10 hours of computerized SOPT at baseline with 4-hour boosters at 5 and 11 months; the attention control was 10 hours of solving computerized crossword puzzles at baseline with 4-hour boosters at 5 and 11 months. MEASURES: Outcomes were useful field of view (UFOV) scores and improvements of 0.5 standard deviations (SDs) or more (> 158.4 ms). Data collection occurred at baseline, after training, and 6 and 12 months. Random-effects linear mixed-effect models were used to estimate SOPT effects in intention-to-treat complete-case and multiple imputation analyses. RESULTS: We found statistically significantly small standardized effect sizes (Cohen's ds 0.25-0.40) for SOPT, reflecting processing speed improvements on UFOV scores (of 39-63 ms) and greater percentages (9.8 to 14.9 percentage point advantages) for achieving more than 0.5 SD improvements (> 158.4 ms) over the 3 time periods. CONCLUSION: These findings support public health messaging about the potential benefits of SOPT for older adults in senior living communities and support the feasibility and acceptability of SOPT in assisted and independent living for older adults.

Computerized Cognitive Training to Improve Mood in Senior Living Settings: Design of a Randomized Controlled Trial.

PURPOSE: This two-arm, randomized controlled trial was designed to evaluate a computerized cognitive speed of processing (SOP) training known as Road Tour in the generally older group of adults residing in assisted living (AL) and related senior housing. Study aims focused on depression-related outcomes that were observed in earlier SOP studies using Road Tour with younger, home-dwelling seniors. Study design and baseline outcomes are discussed. PARTICIPANTS AND METHODS: A community-based design engaged AL and related senior living settings as partners in research. Selected staff served as on-site research assistants who were trained to recruit, consent, and train a target of 300 participants from AL and independent living (IL) programs to use the intervention and attention-control computerized training. Ten hours of initial computerized training was followed by two booster sessions at 5 and 11 months. Outcome measures included Useful Field of View (UFOV), 9-item Patient Health Questionnaire (PHQ-9), 12-item Centers for Epidemiological Studies Depression scale (CESD-12), 7-item Generalized Anxiety Disorders GAD-7), Brief Pain Inventory (BPI) and SF-36 Health Survey. Assessments occurred before randomization (pre-training), post-training, 26 and 52 weeks. RESULTS: A total of 351 participants were randomized to the intervention (n=173) and attention-control (n=178) groups. There were no significant differences between groups in demographic characteristics with the exception of education and reported osteoporosis. There were no significant differences in study outcomes between groups at baseline. Participants in AL had significantly lower SOP and self-rated health, and significantly higher depression, anxiety and pain when compared to those in IL programs on the same campus. CONCLUSIONS: Compared to earlier SOP training studies using Road Tour, this sample of senior living participants were older, reported more health conditions and poorer overall health, had lower UFOV scores and greater depressive symptoms at baseline. Moreover, participants in AL had greater health challenges than those in IL.

Effects of cognitive speed of processing training on a composite neuropsychological outcome: results at one-year from the IHAMS randomized controlled trial.

BACKGROUND: Age-related cognitive decline is common and well-documented. Cognitive speed of processing training (SOPT) has been shown to improve trained abilities (Useful Field of View; UFOV), but transfer to individual non-trained cognitive outcomes or neuropsychological composites is sparse. We examine the effects of SOPT on a composite of six equally weighted tests--UFOV, Trail-making A and B, Symbol Digit Modality, Controlled Oral Word Association, Stroop Color and Word, and Digit Vigilance. METHODS: 681 patients were randomized separately within two age-bands (50-64, ≥ 65) to three SOPT groups (10 initial hours on-site, 10 initial hours on-site plus 4 hours of boosters, or 10 initial hours at-home) or an attention-control group (10 initial hours on-site of crossword puzzles). At one-year, 587 patients (86.2%) had complete data. A repeated measures linear mixed model was used. RESULTS: Factor analysis revealed a simple unidimensional structure with Cronbach's α of 0.82. The time effect was statistically significant (p < 0.001; ηp2 = 0.246), but the time by treatment group (p = 0.331), time by age-band (p = 0.463), and time by treatment group by age-band (p = 0.564) effects were not. CONCLUSION: Compared to the attention-control group who played a computerized crossword puzzle game, assignment to 10-14 hours of SOPT did not significantly improve a composite measure of cognitive abilities.

The effect of cognitive speed of processing training on the development of additional IADL difficulties and the reduction of depressive symptoms: results from the IHAMS randomized controlled trial.

OBJECTIVE: We evaluated the effects of cognitive speed of processing training (SOPT) on the development of additional Instrumental Activities of Daily Living (IADL) difficulties and the reduction of depressive symptoms in the Iowa Healthy and Active Minds Study (IHAMS). METHOD: Six hundred eighty-one patients were randomized to 4 groups: 10 hr of on-site SOPT, 10 hr of on-site SOPT plus 4 hr of boosters, 10 hr of at-home SOPT, or 10 hr of on-site attention-control (crossword puzzles). Developing additional difficulties with IADLs and reductions in depressive symptoms 1 year later were evaluated using multiple logistic regression. RESULTS: The on-site SOPT with boosters group had reduced odds of developing additional difficulties with IADLs (adjusted odds ratio [AOR] = 0.45, p = .044) compared with attention-controls. The on-site SOPT with boosters group also had increased odds of reduced depressive symptom levels (AOR = 2.93, p = .003) compared with attention-controls. DISCUSSION: These findings provide evidence that SOPT transfers beyond the cognitive skills trained to meaningful downstream improvements in the lives of middle-aged and older adults.

A randomized controlled trial of cognitive training using a visual speed of processing intervention in middle aged and older adults.

BACKGROUND: Age-related cognitive decline is common and may lead to substantial difficulties and disabilities in everyday life. We hypothesized that 10 hours of visual speed of processing training would prevent age-related declines and potentially improve cognitive processing speed. METHODS: Within two age bands (50-64 and ≥ 65) 681 patients were randomized to (a) three computerized visual speed of processing training arms (10 hours on-site, 14 hours on-site, or 10 hours at-home) or (b) an on-site attention control group using computerized crossword puzzles for 10 hours. The primary outcome was the Useful Field of View (UFOV) test, and the secondary outcomes were the Trail Making (Trails) A and B Tests, Symbol Digit Modalities Test (SDMT), Stroop Color and Word Tests, Controlled Oral Word Association Test (COWAT), and the Digit Vigilance Test (DVT), which were assessed at baseline and at one year. 620 participants (91%) completed the study and were included in the analyses. Linear mixed models were used with Blom rank transformations within age bands. RESULTS: All intervention groups had (p<0.05) small to medium standardized effect size improvements on UFOV (Cohen's d = -0.322 to -0.579, depending on intervention arm), Trails A (d = -0.204 to -0.265), Trails B (d = -0.225 to -0.320), SDMT (d = 0.263 to 0.351), and Stroop Word (d = 0.240 to 0.271). Converted to years of protection against age-related cognitive declines, these effects reflect 3.0 to 4.1 years on UFOV, 2.2 to 3.5 years on Trails A, 1.5 to 2.0 years on Trails B, 5.4 to 6.6 years on SDMT, and 2.3 to 2.7 years on Stroop Word. CONCLUSION: Visual speed of processing training delivered on-site or at-home to middle-aged or older adults using standard home computers resulted in stabilization or improvement in several cognitive function tests. Widespread implementation of this intervention is feasible. TRIAL REGISTRATION: ClinicalTrials.gov NCT-01165463.

Interim analyses from a randomised controlled trial to improve visual processing speed in older adults: the Iowa Healthy and Active Minds Study.

Objectives The Iowa Healthy and Active Minds Study is a four-arm randomised controlled trial of a visual processing speed training programme (Road Tour). This article presents the preplanned interim results immediately after training (6-8 weeks post-randomisation) for the primary outcome. Design Within two age strata (50-64 vs ≥65), 681 men and women attending general internal and family medicine clinics were randomised to four training groups: (1) supervised, on-site standard (10 h) dose of Road Tour training; (2) supervised, on-site standard dose of Road Tour training with 4 h of subsequent booster training scheduled to occur at 11 months post-randomisation (ie, no booster training had occurred at the time of this interim analysis); (3) supervised, on-site standard dose of attention control (crossword puzzles) training and (4) self-administered, at-home standard dose of Road Tour training. The primary outcome was the Useful Field of View (UFOV) test. Three intent-to-treat interim analyses were conducted, including (1) multiple linear regression models of composite UFOV scores using Blom rank transformations, (2) general linear mixed effects models and (3) multiple logistic regression models among the 620 participants (91%) with complete data. Results In the linear regression analyses of both age strata, random assignment to any Road Tour training group versus the attention control group was significant (p<0.001), with an effect size of -0.558 (adjusted for the Blom rank transformed UFOV score at randomisation). Similar results were obtained for each Road Tour group and within each age stratum and from the general linear and logistic regression models. Conclusions Assignment to a standard dose of Road Tour training yielded medium-sized post-training improvements in visual processing speed. Road Tour was equally effective whether administered under laboratory supervision or self-administered in the patient's home and for participants in both age strata (50-64 vs ≥65). Clinical trial registration number NCT01165463.

Protocol for a randomised controlled trial to improve cognitive functioning in older adults: the Iowa Healthy and Active Minds Study.

OBJECTIVES: Gradual age-related cognitive deteriorations are common and are hypothesised to be partially attributable to declines in information-processing speed. The Iowa Healthy and Active Minds Study will evaluate the efficacy and effectiveness of a computerised visual processing speed training programme (Road Tour, Posit Science Corporation, San Francisco, California). METHODS AND ANALYSIS: Using a 3:3:4:4 ratio within two age strata (50-64 vs ≥ 65 years old), 681 men and women attending family care clinics were randomised to four treatment groups: 10 h of on-site Road Tour training, 10 h of on-site Road Tour training with 4 h of booster training at 11 months postrandomisation, 10 h of on-site attention control using computerised crossword puzzles (Boatload of Crosswords, Boatload Puzzles, LLC, Yorktown Heights, New York) and 10 h of at-home Road Tour training using the participant's personal computer. The primary outcome, visual processing speed, was assessed at randomisation and post-training (6-8 weeks postrandomisation), and is being reassessed at 1-year postrandomisation using the Useful Field of View test. Five secondary outcomes (Symbol Digit Modalities Test, Trail Making Tests A and B, Controlled Oral Word Association Test, Digit Vigilance Test, and the Stroop Colour and Word Test) were assessed at randomisation and will be reassessed at 1-year postrandomisation. Seven hypotheses will be tested using intent-to-treat analyses involving multiple linear, logistic, Poisson and negative binomial regression. ETHICS AND DISSEMINATION: Ethics approval was provided by the University of Iowa Institutional Review Board (IRB-03 protocol 200908789). All participants completed signed informed consent prior to enrollment. Road Tour is commercially available from Posit Science Corporation, which provided it to Iowa Healthy and Active Minds Study at no cost. All participants will receive a free copy of Road Tour for unlimited perpetual use at study completion. Clinical Trial Registration Number NCT01165463.