| 1. |
- Calderón-Larrañaga, Amaia, et al.
(author)
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Body mass trajectories and multimorbidity in old age : 12-year results from a population-based study
- 2021
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In: Clinical Nutrition. - : Elsevier BV. - 0261-5614 .- 1532-1983. ; 5, s. 52-53
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Journal article (peer-reviewed)abstract
- Background & aims: Body weight changes reflect and impact several health conditions in older age, but little is known about its relationship with multimorbidity. We aimed to study the association of long-terms trajectories of body mass index (BMI) with contemporaneous changes in multimorbidity −and multimorbidity type− development in a population-based cohort of older adults.Methods: Twelve-year BMI trajectories (2001–2013) were identified in subjects aged 60+ years from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) using growth mixture models (N = 2189). Information on 60 chronic diseases and multimorbidity was ascertained based on clinical examinations, lab tests, medications, and inpatient and outpatient medical records. Linear mixed models were used to study the association between BMI trajectories and the speed of chronic disease accumulation, in general and by groups of cardiovascular and neuropsychiatric diseases.Results: Eighty percent of the study population was included in what we defined a stable BMI trajectory, 18% in a slow-decline trajectory with an accelerated BMI decline from age 78 onwards, and 2% in a fast-decline trajectory that reached underweight values before age 85. A significantly higher yearly rate of chronic disease accumulation was observed in the fast-decline versus stable trajectory (β = 0.221, 95% CI 0.090–0.352) after adjusting the model for age cohort, sex, education and time to death. Subjects in the slow-decline trajectory showed a significantly higher yearly rate of cardiovascular disease accumulation (β = 0.016, 95% CI 0.000–0.031); those in the fast-decline trajectory showed a faster accumulation of both cardiovascular (β = 0.020, 95% CI -0.025, 0.064) and neuropsychiatric diseases (β = 0.102, 95% CI 0.064–0.139), even if the former association did not reach statistical significance.Conclusion: Our results provide further evidence of the importance of carefully monitoring older adults with sustained weight loss, which is an early indicator of accelerated health deterioration, reflected in our study by a faster accumulation of chronic −especially neuropsychiatric− diseases.
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| 2. |
- Clark, Christopher E., et al.
(author)
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Associations Between Systolic Interarm Differences in Blood Pressure and Cardiovascular Disease Outcomes and Mortality : Individual Participant Data Meta-Analysis, Development and Validation of a Prognostic Algorithm: The INTERPRESS-IPD Collaboration
- 2021
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In: Hypertension. - 1524-4563. ; 77:2, s. 650-661
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Journal article (peer-reviewed)abstract
- Systolic interarm differences in blood pressure have been associated with all-cause mortality and cardiovascular disease. We undertook individual participant data meta-analyses to (1) quantify independent associations of systolic interarm difference with mortality and cardiovascular events; (2) develop and validate prognostic models incorporating interarm difference, and (3) determine whether interarm difference remains associated with risk after adjustment for common cardiovascular risk scores. We searched for studies recording bilateral blood pressure and outcomes, established agreements with collaborating authors, and created a single international dataset: the Inter-arm Blood Pressure Difference - Individual Participant Data (INTERPRESS-IPD) Collaboration. Data were merged from 24 studies (53 827 participants). Systolic interarm difference was associated with all-cause and cardiovascular mortality: continuous hazard ratios 1.05 (95% CI, 1.02-1.08) and 1.06 (95% CI, 1.02-1.11), respectively, per 5 mm Hg systolic interarm difference. Hazard ratios for all-cause mortality increased with interarm difference magnitude from a ≥5 mm Hg threshold (hazard ratio, 1.07 [95% CI, 1.01-1.14]). Systolic interarm differences per 5 mm Hg were associated with cardiovascular events in people without preexisting disease, after adjustment for Atherosclerotic Cardiovascular Disease (hazard ratio, 1.04 [95% CI, 1.00-1.08]), Framingham (hazard ratio, 1.04 [95% CI, 1.01-1.08]), or QRISK cardiovascular disease risk algorithm version 2 (QRISK2) (hazard ratio, 1.12 [95% CI, 1.06-1.18]) cardiovascular risk scores. Our findings confirm that systolic interarm difference is associated with increased all-cause mortality, cardiovascular mortality, and cardiovascular events. Blood pressure should be measured in both arms during cardiovascular assessment. A systolic interarm difference of 10 mm Hg is proposed as the upper limit of normal. Registration: URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42015031227.
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| 3. |
- Cruz-Jentoft, Alfonso J., et al.
(author)
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Using the Multidimensional Prognostic Index (MPI) to improve cost-effectiveness of interventions in multimorbid frail older persons : results and final recommendations from the MPI_AGE European Project
- 2020
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In: Aging Clinical and Experimental Research. - : Springer Science and Business Media LLC. - 1594-0667 .- 1720-8319. ; 32:5, s. 861-868
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Journal article (peer-reviewed)abstract
- MPI_AGE is a European Union co-funded research project aimed to use the Multidimensional Prognostic Index (MPI), a validated Comprehensive Geriatric Assessment (CGA)-based prognostic tool, to develop predictive rules that guide clinical and management decisions in older people in different European countries. A series of international studies performed in different settings have shown that the MPI is useful to predict mortality and risk of hospitalization in community-dwelling older subjects at population level. Furthermore, studies performed in older people who underwent a CGA before admission to a nursing home or receiving homecare services showed that the MPI successfully identified groups of persons who could benefit, in terms of reduced mortality, of specific therapies such as statins in diabetes mellitus and coronary artery disease, anticoagulants in atrial fibrillation and antidementia drugs in cognitive decline. A prospective trial carried out in nine hospitals in Europe and Australia demonstrated that the MPI was able to predict not only in-hospital and long-term mortality, but also institutionalization, re-hospitalization and receiving homecare services during the one-year follow-up after hospital discharge. The project also explored the association between MPI and mortality in hospitalized older patients in need of complex procedures such as transcatheter aortic valve implantation or enteral tube feeding. Evidence from these studies has prompted the MPI_AGE Investigators to formulate recommendations for healthcare providers, policy makers and the general population which may help to improve the cost-effectiveness of appropriate health care interventions for older patients.
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| 4. |
- Dewan, Ramita, et al.
(author)
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Pathogenic Huntingtin Repeat Expansions in Patients with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis.
- 2021
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In: Neuron. - : Elsevier BV. - 1097-4199 .- 0896-6273. ; 109:3
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Journal article (peer-reviewed)abstract
- We examined the role of repeat expansions in the pathogenesis of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) by analyzing whole-genome sequence data from 2,442 FTD/ALS patients, 2,599 Lewy body dementia (LBD) patients, and 3,158 neurologically healthy subjects. Pathogenic expansions (range, 40-64 CAG repeats) in the huntingtin (HTT) gene were found in three (0.12%) patients diagnosed with pure FTD/ALS syndromes but were not present in the LBD or healthy cohorts. We replicated our findings in an independent collection of 3,674 FTD/ALS patients. Postmortem evaluations of two patients revealed the classical TDP-43 pathology of FTD/ALS, as well as huntingtin-positive, ubiquitin-positive aggregates in the frontal cortex. The neostriatal atrophy that pathologically defines Huntington's disease was absent in both cases. Our findings reveal an etiological relationship between HTT repeat expansions and FTD/ALS syndromes and indicate that genetic screening of FTD/ALS patients for HTT repeat expansions should be considered.
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| 5. |
- Hoogendijk, Emiel O., et al.
(author)
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Gait speed as predictor of transition into cognitive impairment: Findings from three longitudinal studies on aging
- 2020
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In: Experimental Gerontology. - : Elsevier BV. - 0531-5565 .- 1873-6815. ; 129
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Journal article (peer-reviewed)abstract
- © 2019 The Authors Objectives: Very few studies looking at slow gait speed as early marker of cognitive decline investigated the competing risk of death. The current study examines associations between slow gait speed and transitions between cognitive states and death in later life. Methods: We performed a coordinated analysis of three longitudinal studies with 9 to 25 years of follow-up. Data were used from older adults participating in H70 (Sweden; n = 441; aged ≥70 years), InCHIANTI (Italy; n = 955; aged ≥65 years), and LASA (the Netherlands; n = 2824; aged ≥55 years). Cognitive states were distinguished using the Mini-Mental State Examination. Slow gait speed was defined as the lowest sex-specific quintile at baseline. Multistate models were performed, adjusted for age, sex and education. Results: Most effect estimates pointed in the same direction, with slow gait speed predicting forward transitions. In two cohort studies, slow gait speed predicted transitioning from mild to severe cognitive impairment (InCHIANTI: HR = 2.08, 95%CI = 1.40–3.07; LASA: HR = 1.33, 95%CI = 1.01–1.75) and transitioning from a cognitively healthy state to death (H70: HR = 3.30, 95%CI = 1.74–6.28; LASA: HR = 1.70, 95%CI = 1.30–2.21). Conclusions: Screening for slow gait speed may be useful for identifying older adults at risk of adverse outcomes such as cognitive decline and death. However, once in the stage of more advanced cognitive impairment, slow gait speed does not seem to predict transitioning to death anymore.
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| 6. |
- Lagou, Vasiliki, et al.
(author)
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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
- 2021
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In: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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| 7. |
- Marengoni, Alessandra, et al.
(author)
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Beyond Chronological Age : Frailty and Multimorbidity Predict In-Hospital Mortality in Patients With Coronavirus Disease 2019
- 2021
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In: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press (OUP). - 1079-5006 .- 1758-535X. ; 76:3, s. e38-e45
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Journal article (peer-reviewed)abstract
- Background: We evaluated whether frailty and multimorbidity predict in-hospital mortality in patients with COVID-19 beyond chronological age.Method: A total of 165 patients admitted from March 8th to April 17th, 2020, with COVID-19 in an acute geriatric ward in Italy were included. Predisease frailty was assessed with the Clinical Frailty Scale (CFS). Multimorbidity was defined as the co-occurrence of >= 2 diseases in the same patient. The hazard ratio (HR) of in-hospital mortality as a function of CFS score and number of chronic diseases in the whole population and in those aged 70+ years were calculated.Results: Among the 165 patients, 112 were discharged, 11 were transferred to intensive care units, and 42 died. Patients who died were older (81.0 vs 65.2 years, p < .001), more frequently multimorbid (97.6 vs 52.8%; p < .001), and more likely frail (37.5 vs 4.1%; p < .001). Less than 2.0% of patients without multimorbidity and frailty, 28% of those with multimorbidity only, and 75% of those with both multimorbidity and frailty died. Each unitary increment in the CFS was associated with a higher risk of in-hospital death in the whole sample (HR = 1.3; 95% CI = 1.05-1.62) and in patients aged 70+ years (HR = 1.29; 95% CI = 1.04-1.62), whereas the number of chronic diseases was not significantly associated with higher risk of death. The CFS addition to age and sex increased mortality prediction by 9.4% in those aged 70+ years.Conclusions: Frailty identifies patients with COVID-19 at risk of in-hospital death independently of age. Multimorbidity contributes to prognosis because of the very low probability of death in its absence.
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| 8. |
- Tian, Qu, et al.
(author)
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Association of Dual Decline in Memory and Gait Speed With Risk for Dementia Among Adults Older Than 60 Years A Multicohort Individual-Level Meta-analysis
- 2020
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In: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:2
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Journal article (peer-reviewed)abstract
- Question Is a decline in both memory and gait speed with aging associated with a higher risk of dementia than no decline or a decline in memory or gait only in older adults? Findings In this meta-analysis of 6 studies including 8699 participants from the United States and Europe, a decline in both memory and gait was associated with 6.28 times higher risk of developing dementia than no decline. Meaning Older adults without dementia with parallel declines in memory and gait are associated with high risk of developing dementia and may be a group to target for prevention. This meta-analysis assesses whether parallel declines in memory and gait speed among older adults, compared with those who experience no decline or decline in either memory or gait speed only, are associated with risk of developing dementia. Importance Dual decline in both memory and gait speed may characterize a group of older individuals at high risk for future dementia. Objective To assess the risk of dementia in older persons who experience parallel declines in memory and gait speed compared with those who experience no decline or decline in either memory or gait speed only. Design, Setting, and Participants A multicohort meta-analysis was performed of 6 prospective cohort studies conducted between 1997 and 2018 in the United States and Europe. Participants were 60 years or older, had an initial gait speed of more than 0.6 m/s (ie, free of overt dismobility), with repeated measures of memory and gait speed before dementia diagnosis during a mean follow-up of 6.6 to 14.5 years. Within each study, participants were divided into 4 groups: memory decline only, gait speed decline only, dual decline, or no decline (hereafter referred to as usual agers). Gait decline was defined as a loss of 0.05 m/s or more per year; memory decline was defined as being in the cohort-specific lowest tertile of annualized change. Main Outcomes and Measures Risk of incident dementia according to group membership was examined by Cox proportional hazards regression with usual agers as the reference, adjusted for baseline age, sex, race/ethnicity, educational level, study site, and baseline gait speed and memory. Results Across the 6 studies of 8699 participants, mean age ranged between 70 and 74 years and mean gait speed ranged between 1.05 and 1.26 m/s. Incident dementia ranged from 5 to 21 per 1000 person-years. Compared with usual agers, participants with only memory decline had 2.2 to 4.6 times higher risk for developing dementia (pooled hazard ratio, 3.45 [95% CI, 2.45-4.86]). Those with only gait decline had 2.1 to 3.6 times higher risk (pooled hazard ratio, 2.24 [95% CI, 1.62-3.09]). Those with dual decline had 5.2 to 11.7 times the risk (pooled hazard ratio, 6.28 [95% CI, 4.56-8.64]). Conclusions and Relevance In this study, dual decline of memory and gait speed was associated with increased risk of developing dementia among older individuals, which might be a potentially valuable group for preventive or therapeutic interventions. Why dual decline is associated with an elevated risk of dementia and whether these individuals progress to dementia through specific mechanisms should be investigated by future studies.
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| 9. |
- Vetrano, Davide L., et al.
(author)
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Fostering healthy aging : The interdependency of infections, immunity and frailty
- 2021
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In: Ageing Research Reviews. - : Elsevier BV. - 1568-1637 .- 1872-9649. ; 69
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Research review (peer-reviewed)abstract
- Untangling the interdependency of infections, immunity and frailty may help to clarify their roles in the maintenance of health in aging individuals, and the recent COVID-19 pandemic has further highlighted such priority. In this scoping review we aimed to systematically collect the evidence on 1) the impact of common infections such as influenza, pneumonia and varicella zoster on frailty development, and 2) the role played by frailty in the response to immunization of older adults. Findings are discussed under a unifying framework to identify knowledge gaps and outline their clinical and public health implications to foster a healthier aging. Twenty-nine studies (113,863 participants) selected to answer the first question provided a moderately strong evidence of an association between infections and physical as well as cognitive decline – two essential dimensions of frailty. Thirteen studies (34,520 participants) investigating the second aim, showed that frailty was associated with an impaired immune response in older ages, likely due to immunosenescence. However, the paucity of studies, the absence of tools to predict vaccine efficacy, and the lack of studies investigating the efficacy of newer vaccines in presence of frailty, strongly limit the formulation of more personalized immunization strategies for older adults. The current evidence suggests that infections and frailty repeatedly cross each other pathophysiological paths and accelerate the aging process in a vicious circle. Such evidence opens to several considerations. First, the prevention of both conditions pass through a life course approach, which includes several individual and societal aspects. Second, the maintenance of a well-functioning immune system may be accomplished by preventing frailty, and vice versa. Third, increasing the adherence to immunization may delay the onset of frailty and maintain the immune system homeostasis, beyond preventing infections.
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