Assessing the impact of physical exercise on cognitive function in older medical patients during acute hospitalization: secondary analysis of a randomized trial

Background: Acute illness requiring hospitalization frequently is a sentinel event leading to long-term disability in older people. Prolonged bed rest increases the risk of developing cognitive impairment and dementia in acutely hospitalized older adults. Exercise protocols applied during acute hospitalization can prevent functional decline in older patients, but exercise benefits on specific cognitive domains have not been previously investigated. We aimed to assess the effects of a multicomponent exercise intervention for cognitive function in older adults during acute hospitalization. Methods and findings: We performed a secondary analysis of a single-blind randomized clinical trial (RCT) conducted from February 1, 2015, to August 30, 2017 in an Acute Care of the Elderly (ACE) unit in a tertiary public hospital in Navarre (Spain). 370 hospitalized patients (aged ≥75 years) were randomly allocated to an exercise intervention (n = 185) or a control (n = 185) group (usual care). The intervention consisted of a multicomponent exercise training program performed during 5–7 consecutive days (2 sessions/day). The usual care group received habitual hospital care, which included physical rehabilitation when needed. The main outcomes were change in executive function from baseline to discharge, assessed with the dual-task (i.e., verbal and arithmetic) Gait Velocity Test (GVT) and the Trail Making Test Part A (TMT-A). Changes in the Mini Mental State Examination (MMSE) test and verbal fluency ability were also measured after the intervention period. The physical exercise program provided significant benefits over usual care. At discharge, the exercise group showed a mean increase of 0.1 m/s (95% confidence interval [CI], 0.07, 0.13; p < 0.001) in the verbal GVT and 0.1 m/s (95% CI, 0.08, 0.13; p < 0.001) in the arithmetic GVT over usual care group. There was an apparent improvement in the intervention group also in the TMT-A score (−31.1 seconds; 95% CI, −49.5, −12.7 versus −3.13 seconds; 95% CI, −16.3, 10.2 in the control group; p < 0.001) and the MMSE score (2.10 points; 95% CI, 1.75, 2.46 versus 0.27 points; 95% CI, −0.08, 0.63; p < 0.001). Significant benefits were also observed in the exercise group for the verbal fluency test (mean 2.16 words; 95% CI, 1.56, 2.74; p < 0.001) over the usual care group. The main limitations of the study were patients’ difficulty in completing all the tasks at both hospital admission and discharge (e.g., 25% of older patients were unable to complete the arithmetic GVT, and 47% could not complete the TMT-A), and only old patients with relatively good functional capacity at preadmission (i.e., Barthel Index score ≥60 points) were included in the study. Conclusions: An individualized, multicomponent exercise training program may be an effective therapy for improving cognitive function (i.e., executive function and verbal fluency domains) in very old patients during acute hospitalization. These findings support the need for a shift from the traditional (bedrest-based) hospitalization to one that recognizes the important role of maintaining functional capacity and cognitive function in older adults, key components of intrinsic capacity.This study was funded by a Gobierno de Navarra project Resolución grant 2186/2014 and acknowledged with the 'Beca Ortiz de Landazuri' as the best research clinical project in 2014, as well as by a research grant PI17/01814 of the Ministerio de Economía, Industria y Competitividad (ISCIII, FEDER)

Lipidomic signatures from physically frail and robust older adults at hospital admission

Identifying serum biomarkers that can predict physical frailty in older adults would have tremendous clinical value for primary care, as this condition is inherently related to poor quality of life and premature mortality. We compared the serum lipid profile of physically frail and robust older adults to identify specific lipid biomarkers that could be used to assess physical frailty in older patients at hospital admission. Forty-three older adults (58.1% male), mean (range) age 86.4 (78–100 years) years, were classified as physically frail (n = 18) or robust (n = 25) based on scores from the Short Physical Performance Battery (≤ 6 points). Non-targeted metabolomic study by ultra-high performance liquid chromatography coupled to mass spectrometry (UHPLC-MS) analysis with later bioinformatics data analysis. Once the significantly different metabolites were identified, the KEGG database was used on them to establish which were the metabolic pathways mainly involved. Area under receiver-operating curve (AUROC) analysis was used to test the discriminatory ability of lipid biomarkers for frailty based on the Short Physical Performance Battery. We identified a panel of five metabolites including ceramides Cer (40:2), Cer (d18:1/20:0), Cer (d18:1/23:0), cholesterol, and hosphatidylcholine (PC) (14:0/20:4) that were significantly increased in physically frail older adults compared with robust older adults at hospital admission. The most interesting in the physically frail metabolome study found with the KEGG database were the metabolic pathways, vitamin digestion and absorption, AGE-RAGE signaling pathway in diabetic complications, and insulin resistance. In addition, Cer (40:2) (AUROC 0.747), Cer (d18:1/23:0) (AUROC 0.720), and cholesterol (AUROC 0.784) were identified as higher values of physically frail at hospital admission. The non-targeted metabolomic study can open a wide view of the physically frail features changes at the plasma level, which would be linked to the physical frailty phenotype at hospital admission. Also, we propose that metabolome analysis will have a suitable niche in personalized medicine for physically frail older adults.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This study was funded by a Gobierno de Navarra project Resolución grant 2186/2014 and acknowledged with the 'Beca Ortiz de Landázuri' as the best research clinical project in 2014, as well as by a research grant PI17/01814 of the Ministerio de Economía, Industria y Competitividad (ISCIII, FEDER). A.G.-H. is a Miguel Servet Fellow (Instituto de Salud Carlos III – CP18/0150). N.M.-V. received funding from 'la Caixa' Foundation (ID 100010434), under agreement LCF/PR/PR15/51100006. R.R.-V. is funded in part by a Postdoctoral Fellowship Resolution ID 420/2019 of the Universidad Pública de Navarra

Specific multimorbidity patterns modify the impact of an exercise intervention in older hospitalized adults

Background: Different multimorbidity patterns present with different prognoses, but it is unknown to what extent they may influence the effectiveness of an individualized multicomponent exercise program offered to hospitalized older adults. Methods: This study is a secondary analysis of a randomized controlled trial conducted in the Department of Geriatric Medicine of a tertiary hospital. In addition to the standard care, an exercise-training multicomponent program was delivered to the intervention group during the acute hospitalization period. Multimorbidity patterns were determined through fuzzy c-means cluster analysis, over 38 chronic diseases. Functional, cognitive and affective outcomes were considered. Results: Three hundred and six patients were included in the analyses (154 control; 152 intervention), with a mean age of 87.2 years, and 58.5% being female. Four patterns of multimorbidity were identified: heart valves and prostate diseases (26.8%); metabolic diseases and colitis (20.6%); psychiatric, cardiovascular and autoimmune diseases (16%); and an unspecific pattern (36.6%). The Short Physical Performance Battery (SPPB) test improved across all patterns, but the intervention was most effective for patients in the metabolic/colitis pattern (2.48-point difference between intervention/control groups, 95% CI 1.60-3.35). Regarding the Barthel Index and the Mini Mental State Examination (MMSE), the differences were significant for all multimorbidity patterns, except for the psychiatric/cardio/autoimmune pattern. Differences concerning quality of life were especially high for the psychiatric/cardio/autoimmune pattern (16.9-point difference between intervention/control groups, 95% CI 4.04, 29.7). Conclusions: Patients in all the analyzed multimorbidity patterns improved with this tailored program, but the improvement was highest for those in the metabolic pattern. Understanding how different chronic disease combinations are associated with specific functional and cognitive responses to a multicomponent exercise intervention may allow further tailoring such interventions to older patients’ clinical profile.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article. This work was supported by the Gobierno de Navarra project grant 2186/2014 and acknowledged with the “Beca Ortiz de Landázuri” as the best research clinical project in 2014, as well as by a research grant PI17/01814 of the Ministerio de Economía, Industria y Competitividad (ISCIII, FEDER). Additional contributions: NM-V received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/PR15/51100006