The My Active and Healthy Aging (My-AHA) ICT platform to detect and prevent frailty in older adults: Randomized control trial design and protocol

[EN] Introduction Frailty increases the risk of poor health outcomes, disability, hospitalization, and death in older adults and affects 7%¿12% of the aging population. Secondary impacts of frailty on psychological health and socialization are significant negative contributors to poor outcomes for frail older adults. Method The My Active and Healthy Aging (My-AHA) consortium has developed an information and communications technology¿based platform to support active and healthy aging through early detection of prefrailty and provision of individually tailored interventions, targeting multidomain risks for frailty across physical activity, cognitive activity, diet and nutrition, sleep, and psychosocial activities. Six hundred adults aged 60 years and older will be recruited to participate in a multinational, multisite 18-month randomized controlled trial to test the efficacy of the My-AHA platform to detect prefrailty and the efficacy of individually tailored interventions to prevent development of clinical frailty in this cohort. A total of 10 centers from Italy, Germany, Austria, Spain, United Kingdom, Belgium, Sweden, Japan, South Korea, and Australia will participate in the randomized controlled trial. Results Pilot testing (Alpha Wave) of the My-AHA platform and all ancillary systems has been completed with a small group of older adults in Europe with the full randomized controlled trial scheduled to commence in 2018. Discussion The My-AHA study will expand the understanding of antecedent risk factors for clinical frailty so as to deliver targeted interventions to adults with prefrailty. Through the use of an information and communications technology platform that can connect with multiple devices within the older adult's own home, the My-AHA platform is designed to measure an individual's risk factors for frailty across multiple domains and then deliver personalized domain-specific interventions to the individual. The My-AHA platform is technology-agnostic, enabling the integration of new devices and sensor platforms as they emerge.This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 689582 and the Australian National Health and Medical Research Council (NHRMC) European Union grant scheme (1115818). M.J.S. reports personal fees from Eli Lilly (Australia) Pty Ltd and grants from Novotech Pty Ltd, outside the submitted work. All other authors report nothing to disclose.Summers, MJ.; Rainero, I.; Vercelli, AE.; Aumayr, GA.; De Rosario Martínez, H.; Mönter, M.; Kawashima, R. (2018). The My Active and Healthy Aging (My-AHA) ICT platform to detect and prevent frailty in older adults: Randomized control trial design and protocol. Alzheimer's and Dementia: Translational Research and Clinical Interventions. 4:252-262. https://doi.org/10.1016/j.trci.2018.06.004S2522624Blair, S. N. (1995). Changes in Physical Fitness and All-Cause Mortality. JAMA, 273(14), 1093. doi:10.1001/jama.1995.03520380029031Fried, L. P., Ferrucci, L., Darer, J., Williamson, J. D., & Anderson, G. (2004). Untangling the Concepts of Disability, Frailty, and Comorbidity: Implications for Improved Targeting and Care. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 59(3), M255-M263. doi:10.1093/gerona/59.3.m255Gillick, M. (2001). Guest Editorial: Pinning Down Frailty. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 56(3), M134-M135. doi:10.1093/gerona/56.3.m134Hamerman, D. (1999). Toward an Understanding of Frailty. Annals of Internal Medicine, 130(11), 945. doi:10.7326/0003-4819-130-11-199906010-00022Fried, L. P., Tangen, C. M., Walston, J., Newman, A. B., Hirsch, C., Gottdiener, J., … McBurnie, M. A. (2001). Frailty in Older Adults: Evidence for a Phenotype. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 56(3), M146-M157. doi:10.1093/gerona/56.3.m146Panza, F., Solfrizzi, V., Barulli, M. R., Santamato, A., Seripa, D., Pilotto, A., & Logroscino, G. (2015). Cognitive Frailty: A Systematic Review of Epidemiological and Neurobiological Evidence of an Age-Related Clinical Condition. Rejuvenation Research, 18(5), 389-412. doi:10.1089/rej.2014.1637Soong, J., Poots, A., Scott, S., Donald, K., Woodcock, T., Lovett, D., & Bell, D. (2015). Quantifying the prevalence of frailty in English hospitals. BMJ Open, 5(10), e008456. doi:10.1136/bmjopen-2015-008456Varadhan, R., Walston, J., Cappola, A. R., Carlson, M. C., Wand, G. S., & Fried, L. P. (2008). Higher Levels and Blunted Diurnal Variation of Cortisol in Frail Older Women. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 63(2), 190-195. doi:10.1093/gerona/63.2.190BROWN, I., RENWICK, R., & RAPHAEL, D. (1995). Frailty. International Journal of Rehabilitation Research, 18(2), 93-102. doi:10.1097/00004356-199506000-00001Buchner, D. M., & Wagner, E. H. (1992). Preventing Frail Health. Clinics in Geriatric Medicine, 8(1), 1-18. doi:10.1016/s0749-0690(18)30494-4Kojima, G., Iliffe, S., Jivraj, S., & Walters, K. (2016). Association between frailty and quality of life among community-dwelling older people: a systematic review and meta-analysis. Journal of Epidemiology and Community Health, 70(7), 716-721. doi:10.1136/jech-2015-206717Ory, M. G., Schechtman, K. B., Miller, J. P., Hadley, E. C., Fiatarone, M. A., … Province, M. A. (1993). Frailty and Injuries in Later Life: The FICSIT Trials. Journal of the American Geriatrics Society, 41(3), 283-296. doi:10.1111/j.1532-5415.1993.tb06707.xShamliyan, T., Talley, K. M. C., Ramakrishnan, R., & Kane, R. L. (2013). Association of frailty with survival: A systematic literature review. Ageing Research Reviews, 12(2), 719-736. doi:10.1016/j.arr.2012.03.001Woodhouse, K. W., & O’Mahony, M. S. (1997). Frailty and ageing. Age and Ageing, 26(4), 245-246. doi:10.1093/ageing/26.4.245CAMPBELL, A. J., & BUCHNER, D. M. (1997). Unstable disability and the fluctuations of frailty. Age and Ageing, 26(4), 315-318. doi:10.1093/ageing/26.4.315Drey, M., Pfeifer, K., Sieber, C. C., & Bauer, J. M. (2011). The Fried Frailty Criteria as Inclusion Criteria for a Randomized Controlled Trial: Personal Experience and Literature Review. Gerontology, 57(1), 11-18. doi:10.1159/000313433Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., … Phelps, C. H. (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7(3), 270-279. doi:10.1016/j.jalz.2011.03.008Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999). Mild Cognitive Impairment. Archives of Neurology, 56(3), 303. doi:10.1001/archneur.56.3.303Winblad, B., Palmer, K., Kivipelto, M., Jelic, V., Fratiglioni, L., Wahlund, L.-O., … Petersen, R. C. (2004). Mild cognitive impairment - beyond controversies, towards a consensus: report of the International Working Group on Mild Cognitive Impairment. Journal of Internal Medicine, 256(3), 240-246. doi:10.1111/j.1365-2796.2004.01380.xDubois, B., Hampel, H., Feldman, H. H., Scheltens, P., Aisen, P., … Andrieu, S. (2016). Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria. Alzheimer’s & Dementia, 12(3), 292-323. doi:10.1016/j.jalz.2016.02.002Moher, D., Hopewell, S., Schulz, K. F., Montori, V., Gotzsche, P. C., Devereaux, P. J., … Altman, D. G. (2010). CONSORT 2010 Explanation and Elaboration: updated guidelines for reporting parallel group randomised trials. BMJ, 340(mar23 1), c869-c869. doi:10.1136/bmj.c869Gray, L. C., Bernabei, R., Berg, K., Finne-Soveri, H., Fries, B. E., Hirdes, J. P., … Ariño-Blasco, S. (2008). Standardizing Assessment of Elderly People in Acute Care: The interRAI Acute Care Instrument. Journal of the American Geriatrics Society, 56(3), 536-541. doi:10.1111/j.1532-5415.2007.01590.xRadloff, L. S. (1977). The CES-D Scale. Applied Psychological Measurement, 1(3), 385-401. doi:10.1177/014662167700100306Guralnik, J. M., Simonsick, E. M., Ferrucci, L., Glynn, R. J., Berkman, L. F., Blazer, D. G., … Wallace, R. B. (1994). A Short Physical Performance Battery Assessing Lower Extremity Function: Association With Self-Reported Disability and Prediction of Mortality and Nursing Home Admission. Journal of Gerontology, 49(2), M85-M94. doi:10.1093/geronj/49.2.m85Powell, L. E., & Myers, A. M. (1995). The Activities-specific Balance Confidence (ABC) Scale. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 50A(1), M28-M34. doi:10.1093/gerona/50a.1.m28Kendzierski, D., & DeCarlo, K. J. (1991). Physical Activity Enjoyment Scale: Two Validation Studies. Journal of Sport and Exercise Psychology, 13(1), 50-64. doi:10.1123/jsep.13.1.50Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). «Mini-mental state». Journal of Psychiatric Research, 12(3), 189-198. doi:10.1016/0022-3956(75)90026-6Brandt, J. (1991). The hopkins verbal learning test: Development of a new memory test with six equivalent forms. Clinical Neuropsychologist, 5(2), 125-142. doi:10.1080/13854049108403297Lubben, J. E. (1988). Assessing social networks among elderly populations. Family & Community Health, 11(3), 42-52. doi:10.1097/00003727-198811000-00008Russell, D., Peplau, L. A., & Cutrona, C. E. (1980). The revised UCLA Loneliness Scale: Concurrent and discriminant validity evidence. Journal of Personality and Social Psychology, 39(3), 472-480. doi:10.1037/0022-3514.39.3.472De Vries, O. J., Peeters, G. M. E. E., Lips, P., & Deeg, D. J. H. (2013). Does frailty predict increased risk of falls and fractures? A prospective population-based study. Osteoporosis International, 24(9), 2397-2403. doi:10.1007/s00198-013-2303-zTheou, O., Stathokostas, L., Roland, K. P., Jakobi, J. M., Patterson, C., Vandervoort, A. A., & Jones, G. R. (2011). The Effectiveness of Exercise Interventions for the Management of Frailty: A Systematic Review. Journal of Aging Research, 2011, 1-19. doi:10.4061/2011/569194Cadore, E. (2014). Strength and Endurance Training Prescription in Healthy and Frail Elderly. Aging and Disease, 5(3), 183. doi:10.14336/ad.2014.0500183Cadore, E. L., Rodríguez-Mañas, L., Sinclair, A., & Izquierdo, M. (2013). Effects of Different Exercise Interventions on Risk of Falls, Gait Ability, and Balance in Physically Frail Older Adults: A Systematic Review. Rejuvenation Research, 16(2), 105-114. doi:10.1089/rej.2012.1397Gardner, M. M. (2001). Practical implementation of an exercise-based falls prevention programme. Age and Ageing, 30(1), 77-83. doi:10.1093/ageing/30.1.77Eng, J. J. (2010). Fitness and Mobility Exercise Program for Stroke. Topics in Geriatric Rehabilitation, 26(4), 310-323. doi:10.1097/tgr.0b013e3181fee736Wadlinger, H. A., & Isaacowitz, D. M. (2008). Looking happy: The experimental manipulation of a positive visual attention bias. Emotion, 8(1), 121-126. doi:10.1037/1528-3542.8.1.121MacLeod, C. (2012). Cognitive bias modification procedures in the management of mental disorders. Current Opinion in Psychiatry, 25(2), 114-120. doi:10.1097/yco.0b013e32834fda4aMensink, R. P., & Katan, M. B. (1989). Effect of a Diet Enriched with Monounsaturated or Polyunsaturated Fatty Acids on Levels of Low-Density and High-Density Lipoprotein Cholesterol in Healthy Women and Men. New England Journal of Medicine, 321(7), 436-441. doi:10.1056/nejm19890817321070

Cardiac lymphatics in health and disease

The lymphatic vasculature, which accompanies the blood vasculature in most organs, is indispensable in the maintenance of tissue fluid homeostasis, immune cell trafficking, and nutritional lipid uptake and transport, as well as in reverse cholesterol transport. In this Review, we discuss the physiological role of the lymphatic system in the heart in the maintenance of cardiac health and describe alterations in lymphatic structure and function that occur in cardiovascular pathology, including atherosclerosis and myocardial infarction. We also briefly discuss the role that immune cells might have in the regulation of lymphatic growth (lymphangiogenesis) and function. Finally, we provide examples of how the cardiac lymphatics can be targeted therapeutically to restore lymphatic drainage in the heart to limit myocardial oedema and chronic inflammation.Peer reviewe

Alterations of aorta intima and media transcriptome in swine fed high-fat diet over 1-year follow-up period and of the switch to normal diet

Background and aim: We previously showed that 12-month high-fat diet (HFD) in pigs led to fattening and increased artery intima-media-thickness, which were partly reversed after 3-month return to control diet (CD). The aim of this study was to decipher underlying mechanism of action by using transcriptomic analyses of intima and media of aorta.Methods and results: Thirty-two pigs were divided into three groups: CD for 12 months; HFD for 12 months; switch diet group (regression diet; RD): HFD for 9 months followed by CD for 3 months. After 12 months, RNA was isolated from aorta intima and media for nutrigenomic analyses. HFD significantly affected gene expression in intima, while RD gene expression profile was distinct from the CD group. This suggests that switch to CD is not sufficient to correct gene expression alterations induced by HFD but counteracted expression of a group of genes. HFD also affected gene expression in media and as for intima, the expression profile of media of pigs on RD differed from that of these on CD.Conclusions: This study revealed nutrigenomic modifications induced by long-term HFD consumption on arterial intima and media. The return to CD was not sufficient to counteract the genomic effect of HFD

Transcriptomic Alterations of the Aortic Intima and Media in Long-term High-fat Diet Fed Pigs and Its Reversal

Topical Area: Nutrient-Gene InteractionsObjectives : We have previously shown that 12 months (mo.) high-fat diet (HFD) in pigs led to pathophysiological alterations, incl. fattening and increased femoral artery intima-media-thickness, which were partly reversed after 3 mo. return to control diet (Zabek et al., PLoS One 2017). The aim of this study was to decipher underlying mechanism of action of these dietary interventions on the arteries by nutrigenomics analyses of intima and media of aorta.Methods : 32 female pigs were divided into 3 groups: Control diet (CD) for 12 mo.; HFD for 12 mo.; 3) Reversal diet group (RD): HFD for 9 mo. followed by CD for 3 mo. After 12 mo. animals were killed and abdominal aorta collected. RNA was isolated from aorta intima and media for whole genome microarray analyses followed by bioinformatics analyses.Results :HFD compared to CD group significantly affected gene expression profile in intima with genes belonging to the chemotaxis, inflammation or endothelial permeability. RD induced gene expression profile was distinct from the CD group. This suggests that 3 mo. of reversal to CD is not sufficient to correct gene expression changes induced by HFD. Comparison of RD profile with that of HFD group revealed a group of genes with opposite expression, e.g. genes regulating inflammation, toll-like cell signaling pathway or cytoskeleton organization involved in the regulation of cell permeability. This suggests that return to the RD only partly restored gene expression alterations due to the HFD. Significant changes in expression of genes in media following HFD were also observed, such as genes involved in cytoskeleton organization and migration MAPK signaling. As for intima, the expression profile of media of pigs on RD was different on that of these on CD diet. Compared to HFD, a group of genes involved in PI3K or MAPK pathways presented opposite expression suggesting that RD can partly correct the changes in genomic effect induced by HFD.Conclusions : This study revealed genomic modifications induced by long-term HFD consumption on arterial intima and media. The return to normal diet for 3 mo. was not sufficient to counteract the genomic effect of long-term HFD consumption.Funding Sources : WROVASC Integrated Cardiovascular Centre, co-financed by the European Regional Development Fund

Effect of High-Fat Diet and its Reversal on the Thoracic Duct Lymph Composition in Pigs

National audienceHigh-fat, carbohydrate and low fiber diet is linked to increased CV risk as demonstrated in both experimental animals and epidemiological studies. Reversal to the healthy diet is known to decrease CV risk. Lymph transports both lipids absorbed in intestine and cholesterol from tissues (reverse cholesterol transport). Lipid composition of both post-nodal and pre-nodal lymph is affected by several pathophysiological conditions. Thus, the aim of the presents study was to evaluate how long-term changes in dietary fat intake in pigs alter the lymph lipid and lipoproteins. MATERIALS AND METHODS: Thirty-two female pigs were divided into three experimental groups: Group 1 - control: regular diet (RD - low fat – 3%) for 12 months; Group 2 – increased fat diet ad libitum (HFD) for 12 months (first 6 months moderate-fat (7.5%) diet and following 6 months high-fat diet (16% fat); Group 3: Reversal diet (HRD): HFD for 9 months followed by RD for 3 months. Pigs were examined every 3 months for: body weight, blood pressure, lipidemia, arterial stiffness and elasticity, intima-media complex (IMC) measured by ultrasound. After 12 months on the respective diets, all animals were killed after 24 hours fasting and thoracic duct lymph was collected. Samples from eight animals from each group were used for lymph lipid and lipoprotein distribution analysis by density gradient ultracentrifugation. RESULTS: Lipid lymph analysis revealed higher total cholesterol concentration in HFD fed animals than in these on the control diet. Lymph lipoprotein distribution showed that HFD caused an increase in chylomicron and HDL cholesterol levels, but did not affected VLDL and LDL cholesterol. The return from the HFD to the RD partly restored lymph cholesterol levels to values found in the control (RD) group. In conclusion, our findings support that the level of dietary fat affects lymphatic reverse cholesterol transport