Exploring mechanisms of improvement in the Active Brains intervention for older adults with chronic pain and early cognitive decline.

OBJECTIVES: We iteratively developed, optimized, and established the feasibility of a virtual, group-based, mind-body activity program (Active Brains, AB), supported by Fitbit for older adults with chronic pain (CP) and early cognitive decline (ECD). Guided by the principles of the NIH stage model we 1) explore signals of improvement in AB outcomes and hypothesized mechanisms of action and 2) explore relationships between changes in outcomes with changes in mechanisms. METHODS: Participants were N = 15 older adults (age ≥ 60) with CP-ECD from two NIH stage 1 pilot studies of AB. We conducted paired t-tests to explore pre-post improvements, and correlations to investigate associations between changes in outcomes and mechanisms. RESULTS: We observed small to large improvements across co-primary and secondary outcomes (d = 0.24-1.09). We observed small to medium improvements in 4 out of 5 hypothesized mechanisms (d = 0.23-0.47). Overall, improvements in outcomes had moderate to large associations with improvements in hypothesized mechanisms. CONCLUSION: AB was associated with improvements across several co-primary and secondary outcomes, and hypothesized mechanisms. Pain-specific coping and general coping skills are promising treatment targets to address the CP-ECD comorbidity among older adults.

Validation of a rapid remote digital test for impaired cognition using clinical dementia rating and mini-mental state examination: An observational research study.

Background: The Clinical Dementia Rating (CDR) and Mini-Mental State Examination (MMSE) are useful screening tools for mild cognitive impairment (MCI). However, these tests require qualified in-person supervision and the CDR can take up to 60 min to complete. We developed a digital cognitive screening test (M-CogScore) that can be completed remotely in under 5 min without supervision. We set out to validate M-CogScore in head-to-head comparisons with CDR and MMSE. Methods: To ascertain the validity of the M-CogScore, we enrolled participants as healthy controls or impaired cognition, matched for age, sex, and education. Participants completed the 30-item paper MMSE Second Edition Standard Version (MMSE-2), paper CDR, and smartphone-based M-CogScore. The digital M-CogScore test is based on time-normalised scores from smartphone-adapted Stroop (M-Stroop), digit-symbols (M-Symbols), and delayed recall tests (M-Memory). We used Spearman's correlation coefficient to determine the convergent validity between M-CogScore and the 30-item MMSE-2, and non-parametric tests to determine its discriminative validity with a CDR label of normal (CDR 0) or impaired cognition (CDR 0.5 or 1). M-CogScore was further compared to MMSE-2 using area under the receiver operating characteristic curves (AUC) with corresponding optimal cut-offs. Results: 72 participants completed all three tests. The M-CogScore correlated with both MMSE-2 (rho = 0.54, p < 0.0001) and impaired cognition on CDR (Mann Whitney U = 187, p < 0.001). M-CogScore achieved an AUC of 0.85 (95% bootstrapped CI [0.80, 0.91]), when differentiating between normal and impaired cognition, compared to an AUC of 0.78 [0.72, 0.84] for MMSE-2 (p = 0.21). Conclusion: Digital screening tests such as M-CogScore are desirable to aid in rapid and remote clinical cognitive evaluations. M-CogScore was significantly correlated with established cognitive tests, including CDR and MMSE-2. M-CogScore can be taken remotely without supervision, is automatically scored, has less of a ceiling effect than the MMSE-2, and takes significantly less time to complete.

Markers of early changes in cognition across cohorts of adults with Down syndrome at risk of Alzheimer's disease.

INTRODUCTION: Down syndrome (DS), a genetic variant of early onset Alzheimer's disease (AD), lacks a suitable outcome measure for prevention trials targeting pre-dementia stages. METHODS: We used cognitive test data collected in several longitudinal aging studies internationally from 312 participants with DS without dementia to identify composites that were sensitive to change over time. We then conducted additional analyses to provide support for the utility of the composites. The composites were presented to an expert panel to determine the most optimal cognitive battery based on predetermined criteria. RESULTS: There were common cognitive domains across site composites, which were sensitive to early decline. The final composite consisted of memory, language/executive functioning, selective attention, orientation, and praxis tests. DISCUSSION: We have identified a composite that is sensitive to early decline and thus may have utility as an outcome measure in trials to prevent or delay symptoms of AD in DS.

Topographical disorientation after ischemic mini infarct in the dorsal hippocampus: whispers in silence.

Silent focal ischemic mini infarcts in the brain are thought to cause no clinically overt symptoms. Some populations of hippocampal cells are particularly sensitive to ischemic events, however, rendering hippocampal functions especially vulnerable to ischemia-induced deficits. The present study investigated whether an otherwise silent ischemic mini infarct in the hippocampus (HPC) can produce impairments in spatial performance in rats. Spatial performance was assessed in the ziggurat task (ZT) using a 10-trial spatial learning protocol for 4 days prior to undergoing hippocampal ischemic lesion or sham surgery. Hippocampal silent ischemia was induced by infusion of endothelin-1 (ET-1), a potent vasoconstrictor, into either the dorsal or the ventral hippocampus (dHPC and vHPC). When tested postoperatively in the ZT using a standard testing protocol for 8 days, rats with hippocampal lesions exhibited no spatial deficit. Although spatial learning and memory in the ZT were not affected by the ET-1-induced silent ischemia, rats with dHPC stroke showed more returns when navigating the ZT as opposed to the vHPC rats. Comparison of region-specific HPC lesions in the present study indicated that dorsal hippocampal function is critically required for topographic orientation in a complex environment. Topographic disorientation as reflected by enhanced return behaviors may represent one of the earliest predictors of cognitive decline after silent ischemic insult that may be potentially traced with sensitive clinical examination in humans.