Do measures of physical capacity and walking self-efficacy relate to frailty in older adults with difficulty walking outdoors? A secondary data analysis.

PURPOSE: Measures of physical capacity and self-efficacy may help rehabilitation professionals better understand and detect frailty in older adults. We aimed to characterize frailty, walking self-efficacy, physical capacity, and their inter-relationships in older adults with difficulty walking outdoors. MATERIALS AND METHODS: A secondary analysis of baseline data from 187 older adults (age ≥ 65 years) with mobility limitations was performed. Frailty was evaluated using the cardiovascular health study frailty index. Physical capacity was measured using the 10-meter walk test (10mWT), 6-min walk test (6MWT), 30-second sit-to-stand test (30STST), mini balance evaluation systems test (mini-BESTest), and hand dynamometry. Self-efficacy was assessed using the ambulatory self-confidence questionnaire (ASCQ). We evaluated associations between scores on physical capacity and walking self-efficacy measures and frailty level using an ANOVA or the Kruskal Wallis H-test. RESULTS: The percentage of participants not frail, pre-frail, and frail was 33.7%, 57.2%, and 9.1%, respectively. Median score on the 10mWT-comfortable pace, 10mWT-fast pace, 6MWT, 30STST, mini-BESTest, grip strength, and ASCQ was 1.06 m/s, 1.42 m/s, 354.0 m, 9.0 repetitions, 22 points, 23.0 kg, and 8.1 points, respectively. Scores on physical capacity and walking self-efficacy measures were associated with frailty level (p < 0.01). CONCLUSIONS: Findings provide insight into the utility of rehabilitation measures to indicate frailty among older adults with mobility limitations.

The comparative effects of mGlu5 receptor positive allosteric modulators VU0409551 and VU0360172 on cognitive deficits and signalling in the sub-chronic PCP rat model for schizophrenia.

In schizophrenia, mGlu5 receptor hypofunction has been linked with neuropathology and cognitive deficits, making it an attractive therapeutic target. The cognitive impairment associated with schizophrenia remains an unmet clinical need, with existing antipsychotics primarily targeting positive symptoms, with weaker and more variable effects on cognitive deficits. Using the sub-chronic phencyclidine rat model, widely shown to mimic the cognitive impairment and neuropathology of schizophrenia, we have investigated two mGlu5 receptor positive allosteric modulators (PAMs), VU0409551 and VU0360172. We compared the efficacy of these compounds in restoring cognitive deficits and, since these two PAMs have reportedly distinct signalling mechanisms, changes in mGlu5 receptor signalling molecules AKT and MAPK in the PFC. Although not effective at 0.05 and 1 mg/kg, cognitive deficits were significantly alleviated by both PAMs at 10 and 20 mg/kg. The compounds appeared to have differential effects on the scPCP-induced increases in AKT and MAPK phosphorylation: VU0409551 induced a significant decrease in expression of p-AKT, whereas VU0360172 had this effect on p-MAPK levels. Thus, the beneficial effects of PAMs on scPCP-induced cognitive impairment are accompanied by at least partial reversal of scPCP-induced elevated levels of p-MAPK and p-AKT, whose dysfunction is strongly implicated in schizophrenia pathology. These promising data imply an important role for mGlu5 receptor signalling pathways in improving cognition in the scPCP model and provide support for mGlu5 receptor PAMs as a possible therapeutic intervention for schizophrenia.