Publications by authors named "Matteo Cesari"

447 Publications

Supporting and Protecting People with Dementia in the COVID-19 Pandemic.

J Alzheimers Dis 2021 Jun 30. Epub 2021 Jun 30.

Department of Human Neuroscience, Sapienza University, Rome, Italy.

We aimed to explore the awareness and preparedness of dementia caregivers and people with mild cognitive deficits on how to prevent COVID-19 infection and cope with the indirect consequences of the pandemic. A total of 139 patient-caregiver dyads received a telephone survey and 109 completed the survey. The majority of respondents reported having a moderate-to-good knowledge of the typical manifestations of COVID-19. Conversely, only few of them were informed of the atypical presentations and on how to recognize emergency warning signs. Filling the knowledge gaps on COVID-19 in the most vulnerable people may represent a significant resource to tackle the pandemic.
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http://dx.doi.org/10.3233/JAD-210264DOI Listing
June 2021

Arousal Characteristics in Patients with Parkinson's Disease and Isolated Rapid Eye Movement Sleep Behavior Disorder.

Sleep 2021 Jul 2. Epub 2021 Jul 2.

Danish Center for Sleep Medicine, Department of Clinical Neurophysiology, Rigshospitalet, Denmark.

Study Objectives: Patients diagnosed with isolated rapid eye movement (REM) sleep behavior disorder (iRBD) and Parkinson's disease (PD) have altered sleep stability reflecting neurodegeneration in brainstem structures. We hypothesize that neurodegeneration alters the expression of cortical arousals in sleep.

Methods: We analyzed polysomnography data recorded from 88 healthy controls (HC), 22 iRBD patients, 82 de novo PD patients without RBD and 32 with RBD (PD+RBD). These patients were also investigated at a 2-year follow-up. Arousals were analyzed using a previously validated automatic system, which used a central EEG lead, electrooculography, and chin electromyography. Multiple linear regression models were fitted to compare group differences at baseline and change to follow-up for arousal index (ArI), shifts in electroencephalographic signals associated with arousals, and arousal chin muscle tone. The regression models were adjusted for known covariates affecting the nature of arousal.

Results: In comparison to HC, patients with iRBD and PD+RBD showed increased ArI during REM sleep and their arousals showed a significantly lower shift in α-band power at arousals and a higher muscle tone during arousals. In comparison to HC, the PD patients were characterized by a decreased ArI in NREM sleep at baseline. ArI during NREM sleep decreased further at the 2-year follow-up, although not significantly.

Conclusions: Patients with PD and iRBD present with abnormal arousal characteristics as scored by an automated method. These abnormalities are likely to be caused by neurodegeneration of the reticular activation system due to alpha-synuclein aggregation.
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http://dx.doi.org/10.1093/sleep/zsab167DOI Listing
July 2021

The Dilemma of Falls in Older Persons: Never Forget to Investigate the Syncope.

Medicina (Kaunas) 2021 Jun 15;57(6). Epub 2021 Jun 15.

IRCCS Istituti Clinici Scientifici Maugeri, 20138 Milan, Italy.

: Falls represent a major cause of morbidity, hospitalizations, and mortality in older persons. The identification of risk conditions for falling is crucial. This study investigated the presence of syncope as a possible cause of falls in older persons admitted to a Sub-Acute Care Unit (SACU) with a diagnosis of accidental fall after initial management in an emergency department and acute hospitalization. : A retrospective monocentric study of patients aged ≥65 years, consecutively admitted to a SACU with a diagnosis of fall-related trauma. All patients underwent a complete assessment of the index event and clinical status. Patients were categorized into three groups according to the identified cause of falls: (1) transient loss of consciousness (T-LOC), (2) unexplained fall (UF), and (3) definite accidental fall (AF). : A total of 100 patients were evaluated. T-LOC was present in 36 patients, UF in 37, and AF in 27. Of the 36 patients with T-LOC, a probable origin was identified in most cases ( = 33, 91%), 19 subjects (53%) had orthostatic hypotension, 9 (25%) a cardiac relevant disturbance, 2 (6%) a reproduced vaso-vagal syncope, 2 (6%) severe anemia, and 1 (3%) severe hypothyroidism. The T-LOC group was older and more clinically complex than the other groups. : In older patients who recently experienced a fall event, the prevalence of syncope is relevant. In frail and clinically complex patients with falls, the identification of the underlying cause is pivotal and can be achieved through prolonged monitoring and a comprehensive assessment of the person.
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http://dx.doi.org/10.3390/medicina57060623DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8232203PMC
June 2021

Distancing Measures in COVID-19 Pandemic: Loneliness, More than Physical Isolation, Affects Health Status and Psycho-Cognitive Wellbeing in Elderly Patients with Chronic Obstructive Pulmonary Disease.

COPD 2021 Jun 28:1-6. Epub 2021 Jun 28.

Geriatrics, Unit of Respiratory Pathophysiology, Campus Bio-Medico University and Teaching Hospital, Rome, Italy.

Since the outbreak of the SARS-CoV-2 pandemic in 2020, many governments have been imposing confinement and physical distancing measures. No data exist on the effects of lockdowns on the health status of patients affected by chronic pathologies, specifically those with Chronic Obstructive Pulmonary Disease (COPD). Our study aims to establish variations across the psychological and cognitive profile of patients during the isolation period in Italy, in a cohort of patients affected by COPD, between February and May 2020. Forty patients with established COPD were comprehensively evaluated by geriatric multidimensional assessment before the spread of the epidemic in Italy, and submitted to a second evaluation during the subsequent lockdown. We assessed functional ability, basic and instrumental Activities of Daily Living (ADL and IADL), cognition and mood status. We compared the scores obtained at baseline against those obtained during the pandemic, and used mean differences for correlation with major clinical and functional indexes. The score differences from MMSE, ADL and IADL were statistically significant. Such differences were correlated to the presence of a caregiver and to the total number of family members living together. Remarkably, the loneliness dimension, more than the restrictions themselves, seemed to represent the major determinant of altered health status and depressed psycho-cognitive profile in our population. Also remarkably, we detected no correlation between the score variation and the respiratory function indexes of disease severity. The isolation measures adopted during the SARS-CoV-2 pandemic have triggered the classic clinical string associated to geriatric isolation, which leads to a deterioration of cognitive functions, independence and frailty levels in a population affected by a chronic degenerative disease, such as COPD. If considered from a multidimensional geriatric point of view, the individual benefit of isolation measures could be small or non-existent.
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http://dx.doi.org/10.1080/15412555.2021.1941834DOI Listing
June 2021

Last Year of Life, Frailty, and Out-of-Pocket Expenses in Older Adults: A Secondary Analysis of the Mexican Health and Aging Study.

J Appl Gerontol 2021 Jun 28:7334648211024790. Epub 2021 Jun 28.

Instituto Nacional de Geriatría, Ciudad de México, México.

Objective: To determine the association of frailty with out-of-pocket expenses (OOPEs) during the last year of life of Mexican older adults.

Methods: Cross-sectional secondary analysis of the Mexican Health and Aging Study (MHAS), a representative population-based cohort study. Health care expenses were estimated, and a probit model was used to estimate the probability that older adults had OOPE. A general linear model was applied to explain OOPE magnitudes.

Results: A total of 55.8% of individuals reported having OOPE with a mean of 3,261 USD. Average OOPE for hospitalization during the last year of life was 7,011.9 USD. Older adults taking their own medical decisions during the last year of life expended less than those who did not.

Conclusion: No affiliation to health services, frailty, and health decision-making by others increased the probability of OOPE. The magnitude is determined by age, hospitalization, medical visits, affiliation, frailty, and health decision-making by others.
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http://dx.doi.org/10.1177/07334648211024790DOI Listing
June 2021

Assessing Additional Characteristics of Muscle Function With Digital Handgrip Dynamometry and Accelerometry: Framework for a Novel Handgrip Strength Protocol.

J Am Med Dir Assoc 2021 Jun 21. Epub 2021 Jun 21.

Department of Health, Nutrition, and Exercise Sciences, North Dakota State University, Fargo, ND, USA.

Maximal handgrip strength (HGS) is a convenient and reliable, but incomplete, assessment of muscle function. Although low HGS is a powerful predictor of poor health, several limitations to maximal HGS exist. The predictive value of HGS is restricted because low HGS is associated with a wide range of unspecified health conditions, and other characteristics of muscle function aside from strength capacity are not evaluated. Current HGS protocol guidelines emphasize the ascertainment of maximal force, which is only a single muscle function characteristic. Muscle function is intrinsically multivariable, and assessing other attributes in addition to strength capacity will improve screenings for age-related disabilities and diseases. Digital handgrip dynamometers and accelerometers provide unique opportunities to examine several aspects of muscle function beyond strength capacity, while also maintaining procedural ease. Specifically, digital handgrip dynamometry and accelerometry can assess the rate of force development, submaximal force steadiness, fatigability, and task-specific tremoring. Moreover, HGS protocols can be easily refined to include an examination of strength asymmetry and bilateral strength. Therefore, evaluating muscle function with new HGS technologies and protocols may provide a more comprehensive assessment of muscle function beyond maximal strength, without sacrificing feasibility. This Special Article introduces a novel framework for assessing multiple attributes of muscle function with digital handgrip dynamometry, accelerometry, and refinements to current HGS protocols. Such framework may aid in the discovery of measures that better predict and explain age-related disability, biological aging, and the effects of comorbid diseases that are amenable to interventions. These additional HGS measures may also contribute to our understanding of concepts such as resilience. Using sophisticated HGS technologies that are currently available and modernizing protocols for developing a new muscle function assessment may help transform clinical practice by enhancing screenings that will better identify the onset and progression of the disabling process.
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http://dx.doi.org/10.1016/j.jamda.2021.05.033DOI Listing
June 2021

Frailty and Geriatric Medicine During the Pandemic.

Front Med (Lausanne) 2021 7;8:673814. Epub 2021 Jun 7.

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

The term in the era of coronavirus disease 2019 (COVID-19) has a manifold implication. The vast majority of the countries worldwide being hit by the pandemic have shown the frailty of their health and social care systems. Although the surprise factor could somehow justify the unpreparedness experienced during the first wave, the second wave still led to significant difficulties almost everywhere. Looking at Italy's situation, it is evident how the stress test applied by COVID-19 on the system has threatened its stability, getting it closer to collapsing many times. It is true that Italy, in particular the Northern regions, has been the epicenter of COVID-19 in Europe in a time when information about the severe acute respiratory syndrome coronavirus 2 was still lacking and confusing. Nevertheless, what happened has demonstrated significant issues in the structure, priorities, and organization of the system. It has exemplified the obsolete approach adopted in clinical practice, particularly when applied to frail older persons. The COVID-19 pandemic has made emerging the need for a substantial reshaping of our healthcare system. The hospital-centered model has dramatically failed. To adequately face the new challenges brought by the increasing complexity of our aging society, it is critical to move the barycenter of action toward the community/primary care, promoting the integration of services and centralization of clinical/administrative data. It is vital to train healthcare professionals in the identification and basic principles of geriatric conditions, clarifying the role that geriatricians play. In the present article, some cornerstone concepts of geriatric medicine (i.e., definition of geriatrics, multidisciplinarity, integrated care, and development of clinical databases for filling the evidence-based medicine gaps) are presented, explaining the challenges they have faced during the COVID-19 pandemic and possible solutions for implementing improvements in the future.
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http://dx.doi.org/10.3389/fmed.2021.673814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215135PMC
June 2021

Describing the relationship between atrial fibrillation and frailty: Clinical implications and open research questions.

Exp Gerontol 2021 Sep 18;152:111455. Epub 2021 Jun 18.

Geriatric Unit, IRCCS Istituti Clinici Scientifici Maugeri, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Italy.

In the recent years a lot of attention has been gathered by the issue of frailty outside the boundaries of the geriatric medicine, for example in the field of cardiovascular medicine. Atrial fibrillation (AF) is known as a very common cardiological condition, often burdened by high level of clinical complexity. Aim of this narrative review is to examine the most relevant evidence about the relationship between frailty and AF, focusing also on its impact on clinical management and natural history of patients with this condition. Data reported underline how a relevant relationship exists between these two conditions, even though the burden of frailty among AF cohorts is still unclear. Frailty seems to affect the clinical management, even though no definitive data are yet available. Lastly, frailty significantly increases the risk of all-cause mortality but it's still unclear the impact on thromboembolic and bleeding events. Despite several data are already available, more research is still needed to fully elucidate the relationship between these two clinical entities.
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http://dx.doi.org/10.1016/j.exger.2021.111455DOI Listing
September 2021

Intrinsic Capacity Assessment by a Mobile Geriatric Team During the Covid-19 Pandemic.

Front Med (Lausanne) 2021 25;8:664681. Epub 2021 May 25.

Hôpital Erasme, Service de Gériatrie, Université Libre de Bruxelles, Bruxelles, Belgium.

In the autumn of 2020, the second wave of the COVID-19 pandemic hit Europe. In this context, because of the insufficient number of beds in geriatric COVID units, non-geriatric wards were confronted with a significant number of admissions of geriatric patients. In this perspective article, we describe the role of a mobile geriatric team in the framework of the COVID-19 pandemic and specifically how it assisted other specialists in the management of hospitalized geriatric patients by implementing a new approach: the systematic assessment and optimization of Intrinsic Capacity functions. For each patient, assessed by this consultative team, an individualized care plan, including an anticipated end-of-life decision-making process, was established. Intensity of care was most often not stated by considering chronological age but rather the comorbidity burden, the frailty status, and the patient's wishes. Further studies are needed to determine if this mobile geriatric team approach was beneficial in terms of mortality, length of stay, or functional, psychological, and cognitive outcomes in COVID-19 geriatric patients.
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http://dx.doi.org/10.3389/fmed.2021.664681DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186549PMC
May 2021

No association between frailty index and epigenetic clocks in Italian semi-supercentenarians.

Mech Ageing Dev 2021 Jul 4;197:111514. Epub 2021 Jun 4.

Geriatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

Centenarians experience successful ageing, although they still present high heterogeneity in their health status. The frailty index is a biomarker of biological age, able to capture such heterogeneity, even at extreme old age. At the same time, other biomarkers (e.g., epigenetic clocks) may be informative the biological age of the individual and potentially describe the ageing status in centenarians. In this article, we explore the relationship between epigenetic clocks and frailty index in a cohort of Italian centenarians. No association was reported, suggesting that these two approaches may describe different aspects of the same ageing process.
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http://dx.doi.org/10.1016/j.mad.2021.111514DOI Listing
July 2021

Sarcopenia and Menopause: The Role of Estradiol.

Front Endocrinol (Lausanne) 2021 19;12:682012. Epub 2021 May 19.

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

During aging and menopausal transition in women, a progressive muscle degeneration ( decrease in quality and muscle function) occurs. This muscle dysfunction, caused by decreased proliferation of muscle satellite cells, increased levels of inflammatory markers, and altered levels of sex hormones, exposes women to a raised incidence of sarcopenia. In this regard, hormonal balance and, in particular, estradiol, seems to be essential in skeletal muscle function. The role of the estradiol on satellite cells and the release of inflammatory cytokines in menopausal women are reviewed. In particular, estradiol has a beneficial effect on the skeletal muscle by stimulating satellite cell proliferation. Skeletal muscle can respond to estrogenic hormonal control due to the presence of specific receptors for estradiol at the level of muscle fibers. Additionally, estradiol can limit inflammatory stress damage on skeletal muscle. In this review, we primarily focused on the role of estradiol in sarcopenia and on the possibility of using Estradiol Replacement Therapy, which combined with nutritional and physical activity programs, can counteract this condition representing a valid tool to treat sarcopenia in women.
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http://dx.doi.org/10.3389/fendo.2021.682012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170301PMC
May 2021

Neuroimaging correlates of persistent fatigue in older adults: A secondary analysis from the Multidomain Alzheimer Preventive Trial (MAPT) trial.

Aging Ment Health 2021 Jun 4:1-7. Epub 2021 Jun 4.

Gerontopole of Toulouse, Toulouse University Hospital (CHU Toulouse), Toulouse, France.

Objectives: Fatigue has been suggested as a marker of biological aging. It seems plausible that this symptom might be associated with changes in brain health. The objective of this study was to examine the associations between persistent fatigue and neuroimaging correlates in a non-disease-specific population of community-dwelling older adults.

Methods: We performed a cross-sectional analysis using data from The Multidomain Alzheimer Preventive Trial (MAPT). We included 458 subjects. Persistent fatigue was defined as meeting exhaustion criterion of Fried frailty phenotype in two consecutive clinical visits six months apart between study baseline and one year. Brain imaging correlates, assessed by magnetic resonance imaging (MRI), were the outcomes. The associations between persistent fatigue and brain correlates were explored using mixed model linear regressions with random effect at the center level.

Results: The mean age of the participants was 74.8 ± 4 years old, and 63% of the subjects were women. Forty-seven participants (10%) exhibited a persistent fatigue profile. People with persistent fatigue were older compared to subjects without persistent fatigue (76.2 years ± 4.3 vs.74.7 ± 3.9  = 0.009). Persistent fatigue was associated with higher white matter hyperintensity volume in the fully adjusted analysis. We did not find any cross-sectional association between persistent fatigue and sub-cortical volumes and global and regional cortical thickness.

Conclusion: Persistent fatigue was cross-sectionnally associated with higher white matter hyperintensity volume in older adults. Further longitudinal studies, using an assessment tool specifically designed and validated for measuring fatigue, are needed to confirm our findings.
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http://dx.doi.org/10.1080/13607863.2021.1932737DOI Listing
June 2021

Joint Effort towards Preventing Nutritional Deficiencies at the Extremes of Life during COVID-19.

Nutrients 2021 May 12;13(5). Epub 2021 May 12.

Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.

The COVID-19 (Coronavirus disease 2019) pandemic is posing a threat to communities and healthcare systems worldwide. Malnutrition, in all its forms, may negatively impact the susceptibility and severity of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) infection in both children and older adults. Both undernutrition and obesity have been evoked as conditions associated with a higher susceptibility to the infection and poor prognosis. In turn, the COVID-19 infection may worsen the nutritional status through highly catabolic conditions, exposing individuals to the risk of malnutrition, muscle wasting, and nutritional deficiencies. Accordingly, the relationship between malnutrition and COVID-19 is likely to be bidirectional. Furthermore, the modification of nutritional behaviors and physical activity, required to limit the spread of the virus, are posing a challenge to health at both the extremes of life. Thus far, even the most advanced healthcare systems have failed to address the alarming consequences of malnutrition posed by this pandemic. If not properly addressed, we may run the risk that new and old generations will experience the consequences of COVID-19 related malnutrition.
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http://dx.doi.org/10.3390/nu13051616DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150599PMC
May 2021

Association between frailty index, lung function, and major clinical determinants in chronic obstructive pulmonary disease.

Aging Clin Exp Res 2021 Aug 19;33(8):2165-2173. Epub 2021 May 19.

Geriatric Unit, Maugeri Clinical Research Institutes IRCCS, Milan, Italy.

Background: Airflow limitation alone is unable to capture the complexity of chronic obstructive pulmonary disease (COPD), better explained by comprehensive disease-specific indexes. Frailty is a clinical condition characterized by high vulnerability to internal and external stressors and represents a strong predictor of adverse outcomes.

Aims: Primary objective was to test the association between indexes of lung function and COPD severity with frailty index (FI), and secondary to evaluate the association between FI and comorbidities, cognitive and physical function, BODE index, and mortality.

Methods: 150 stable COPD outpatients were enrolled and followed up to 4 years. At baseline, participants performed a geriatric multidimensional assessment, pulmonary function tests, arterial blood gas analysis, 6-min walking test, and bioimpedance analysis. BODE and FI were calculated. Spearman's ρ was used to assess correlations. Mortality was assessed using Kaplan-Meier curves.

Results: Participants were followed up for a median of 39 months. Mean age was 73 years and median frailty index 0.15 (IQR 0.11-0.19). FI was higher in frequent exacerbators (≥ 2/year) (mean 0.18 vs 0.15, p 0.01) and dyspnoeic patients (mMRC ≥ 2) (mean 0.21 vs 0.14, p < 0.01) and correlated with lung volumes, expiratory flows, and pressure of arterial oxygen. FI was positively correlated with the number of comorbidities, depressive symptoms, cognitive decline, and BODE index. Mortality was higher in patients with BODE higher than 3 (HR 3.6, 95% CI 1.2-10.9), and not associated with FI.

Discussion: FI positively correlates with all clinical drivers orienting the choice of treatment in COPD.

Conclusions: FI associates with lung function and COPD severity, but does not associate with mortality.
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http://dx.doi.org/10.1007/s40520-021-01878-zDOI Listing
August 2021

Molecular imaging in MSK radiology: Where are we going?

Eur J Radiol 2021 Jul 28;140:109737. Epub 2021 Apr 28.

Department of Radiology, Ospedale Evangelico Internazionale, Corso Solferino, 1a, 16122, Genoa, Italy. Electronic address:

Musculoskeletal (MSK) pathologies are one of the leading causes of disability worldwide. However, treatment options and understanding of pathogenetic processes are still partially unclear, mainly due to a limited ability in early disease detection and response to therapy assessment. In this scenario, thanks to a strong technological advancement, structural imaging is currently established as the gold-standard of diagnosis in many MSK disorders but each single diagnostic modality (plain films, high-resolution ultrasound, computed tomography and magnetic resonance) still suffer by a low specificity regarding the characterization of inflammatory processes, the quantification of inflammatory activity levels, and the degree of response to therapy. To overcome these limitations, molecular imaging techniques may play a promising role. Starting from the strengths and weaknesses of structural anatomical imaging, the present narrative review aims to highlight the promising role of molecular imaging in the assessment of non-neoplastic MSK diseases with a special focus on its role to monitor treatment response.
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http://dx.doi.org/10.1016/j.ejrad.2021.109737DOI Listing
July 2021

Determinants of cardiac structure in frail and sarcopenic elderly adults.

Exp Gerontol 2021 07 14;150:111351. Epub 2021 Apr 14.

Department of Medicine and Surgery, University Medical School of Parma, Parma, Italy; University-Hospital of Parma, Parma, Italy; Geriatric Clinic Unit, University-Hospital of Parma, Parma, Italy.

Background: Cardiac structure and function change with age. The higher prevalence of left ventricular hypertrophy (LVH) with concentric remodeling is indicative of a typical geometric pattern of aging associated with a higher cardiovascular (CV) risk and diseases. The recent associations found between low left ventricular and skeletal mass in older patients with frailty and sarcopenia have raised great interest in investigating cardiac characteristics and determinants of left ventricular mass (LVM) in this population.

Design: Cross-sectional study.

Methods: We evaluated 100 sarcopenic and physically frail outpatients, 33 men (M), 67 women (F), aged ≥70 years (mean age 79 ± 5) and enrolled in the Parma site of European multicenter SPRINTT population.

Results: All male and female participants showed LVH, assessed as indexed LVM to body surface area (LVM/BSA) (M = 128 ± 39 g/m; F = 104 ± 26 g/m), and were more prone to have concentric geometry, as demonstrated by relative wall thickness value (0.41 in both sexes). After backward regression analysis, including covariates such as age, sex, office or ABPM systolic blood pressure (SBP), heart rate, BSA, use of β blockers, ACE-inhibitors, angiotensin receptor blockers, calcium channel blockers, diuretics, physical activity, hemoglobin level, and Mini Mental State examination - the most powerful determinants of LVM were clinical SBP (β = 1.51 ± 0.31, p = 0.0005), BSA (β = 165.9 ± 41.4, p = 0.0001), while less powerful determinants were 24 h, daily and nightly SBP (p = 0.02, p = 0.002, p = 0.004 respectively).

Conclusions: Older sarcopenic and physically frail patients showed LVH with a tendency towards concentric geometry. The main determinant of LVM was SBP, highlighting the key role that hemodynamic condition plays in determining LVH in this population.
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http://dx.doi.org/10.1016/j.exger.2021.111351DOI Listing
July 2021

Flexor digitorum superficialis muscular activity is more reliable than mentalis muscular activity for rapid eye movement sleep without atonia quantification.

Sleep 2021 Apr 12. Epub 2021 Apr 12.

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.

Study Objectives: To evaluate interrater reliability for artefact correction in the context of semi-automated quantification of rapid eye movement (REM) sleep without atonia (RWA) in the mentalis and flexor digitorum superficialis (FDS) muscles.

Methods: We included video-polysomnographies of 14 subjects with apnea-hypopnea-index in REM sleep (AHIREM)<15/h and 11 subjects with AHIREM≥15/h. Eight subjects had isolated REM sleep behavior disorder. A validated algorithm (www.osg.be) automatically scored phasic and "any" EMG activity in the mentalis muscle, and phasic EMG activity in the FDS muscles. Four independent expert scorers performed artefact correction according to the SINBAR (Sleep Innsbruck Barcelona) recommendations. Interrater reliability for artefact correction was computed with B-statistics. The variability across scorers of four RWA indices (phasic mentalis, "any" mentalis, phasic FDS and SINBAR - i.e. "any" mentalis and/or phasic FDS - EMG activity indices) was computed. With Friedman tests we compared B-statistics obtained for mentalis and FDS muscles, and the variability of the RWA indices. Influence of AHIREM and RBD diagnosis on the RWA indices variability was evaluated with linear regressions.

Results: Interrater reliability for artefact correction was higher in the FDS than in the mentalis muscle (p<0.001). Phasic FDS activity was minimally affected by artefacts. Accordingly, the phasic FDS EMG activity index had the lowest variability across scorers (p<0.001). Variability across scorers of the RWA indices including the mentalis muscle increased with AHIREM and was independent from RBD diagnosis.

Conclusions: Due to the consistently found low number of artefacts, phasic FDS activity is a reliable measure of RWA.
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http://dx.doi.org/10.1093/sleep/zsab094DOI Listing
April 2021

Hypothetical COVID-19 protection mechanism: hints from centenarians.

Immun Ageing 2021 Mar 30;18(1):15. Epub 2021 Mar 30.

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

The risk of serious complications and the fatality rate due to COVID-19 pandemic have proven particularly higher in older persons, putting a further strain in healthcare system as we dramatically observed.COVID-19 is not exclusively gerophile (géro "old" and philia "love") as young people can be infected, even if older people experience more severe symptoms and mortality due to their greater frailty. Indeed, frailty could complicate the course of COVID-19, much more than the number of years lived. As demonstration, there are centenarians showing remarkable capacity to recover after coronavirus infection.We hypothesize that centenarian's portfolio could help in identifying protective biological mechanisms underlying the coronavirus infection.The human leukocyte antigen (HLA) is one of the major genetic regions associated with human longevity, due to its central role in the development of adaptive immune response and modulation of the individual's response to life threatening diseases. The HLA locus seems to be crucial in influencing susceptibility and severity of COVID-19.In this hypothesis, we assume that the biological process in which HLA are involved may explain some aspects of coronavirus infection in centenarians, although we cannot rule out other biological mechanisms that these extraordinary persons are able to adopt to cope with the infection.
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http://dx.doi.org/10.1186/s12979-021-00226-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008020PMC
March 2021

Malnutrition and physical performance in nursing home residents: results from the INCUR study.

Aging Clin Exp Res 2021 Aug 26;33(8):2299-2303. Epub 2021 Mar 26.

Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.

We investigated the association between the risk of malnutrition, assessed through the Mini Nutritional Assessment-Short Form (MNA-SF), and physical performance, measured with the Short Physical Performance Battery (SPPB), in nursing home residents. Moreover, we evaluated which MNA-SF items were most related to the SPPB and the association of the MNA-SF with each SPPB subtest. A total of 499 older people enrolled in the Incidence of pNeumonia and related ConseqUences in nursing home Residents cohort study were examined. Higher scores of MNA-SF were associated with better physical performance (in particular with gait speed). Food intake deficiency, mobility impairment, and recent psychological stress or acute disease were the items of the MNA-SF most associated with the SPPB. In nursing home residents, the MNA-SF and three of its sub-items were significantly correlated with physical performance, independently of potential confounders. In particular, the association was evident for the gait speed subtask of the SPPB.
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http://dx.doi.org/10.1007/s40520-021-01798-yDOI Listing
August 2021

The sTREM2 Concentrations in the Blood: A Marker of Neurodegeneration?

Front Mol Biosci 2020 9;7:627931. Epub 2021 Mar 9.

Geriatric Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Microglia performs a variety of functions during brain development designed to maintain brain homeostasis. Triggering receptor expressed on myeloid cells 2 (TREM2) is expressed in microglial cells modulating phagocytosis, cytokine production, cell proliferation, and cell survival. Interestingly, the levels of soluble TREM2 (the secreted ectodomain of TREM2, sTREM2) were higher in cerebrospinal fluid (CSF) from Alzheimer's disease (AD) patients than subjects without cognitive decline. It is noteworthy that, while CSF sTREM2 levels have been extensively studied, few studies have investigated sTREM2 in blood producing conflicting results. We aimed to investigate the levels of sTREM2 in CSF and blood from a cohort of well-characterized AD comparing the results to those obtained in patients suffering from idiopathic normal pressure hydrocephalus (iNPH), a potentially reversible cognitive impairment. Our findings underlined a significantly lower plasma sTREM2 concentration in AD patients compared to iNPH subjects [39.1 ng/mL (standard deviation (SD), 15.0) and 47.2 ng/mL (SD, 19.5), respectively; = 0.01], whereas no difference was revealed between the two groups in the CSF sTREM2 levels. The adjusted regression analyses evidenced in AD patients an association between plasma and CSF sTREM2 levels [ = 0.411; 95% confidence interval (CI), 0.137-0.685, = 0.004], as well as β-amyloid concentrations ( = 0.035; 95% CI, 0.007-0.063, = 0.01) and an association between CSF sTREM2 and phospho-Tau concentrations ( = 0.248; 95% CI, 0.053-0.443; = 0.01). No significant relation was found in iNPH patients. In conclusion, these differences in sTREM2 profiles between AD and iNPH reinforce the notion that this receptor has a role in neurodegeneration.
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http://dx.doi.org/10.3389/fmolb.2020.627931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985346PMC
March 2021

Nutrition and Muscle Health.

Nutrients 2021 Feb 28;13(3). Epub 2021 Feb 28.

Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy.

The increase in human life expectancy at birth and the rapid aging of the population represent major social phenomena of this time.[...].
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http://dx.doi.org/10.3390/nu13030797DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997193PMC
February 2021

Retraction of: Identification of biological markers for better characterization of older subjects with physical frailty and sarcopenia.

Transl Neurosci 2020 11;11(1):334. Epub 2020 Sep 11.

Gérontopôle, Centre Hospitalier Universitaire de Toulouse, Toulouse, France.

[This retracts the article DOI: 10.1515/tnsci-2015-0009.].
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http://dx.doi.org/10.1515/tnsci-2020-0142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724002PMC
September 2020

Effects of pre-dialysis resistance training on sarcopenia, inflammatory profile, and anemia biomarkers in older community-dwelling patients with chronic kidney disease: a randomized controlled trial.

Int Urol Nephrol 2021 Feb 20. Epub 2021 Feb 20.

Programa de Pós-Graduação em Educação Física, Universidade Católica de Brasília, Brasília, DF, Brazil.

Background: Sarcopenia and chronic kidney disease (CKD) have been associated with negative outcomes in older people, including inflammatory profile and anemia biomarkers.

Aims: To investigate the effects of pre-dialysis resistance training (RT) on sarcopenia, inflammatory profile, and anemia biomarkers in older patients with CKD.

Methods: A total of 107 patients with CKD (65.4 ± 3.7 years) were randomly allocated into four groups: sarcopenic RT (n = 37), non-sarcopenic RT (n = 20), sarcopenic control (n = 28), and non-sarcopenic control (n = 22). DXA and handgrip strength were used to classify sarcopenia according to EWGSOP-2. Treatment groups underwent a 24-week intervention with RT before each dialysis session, three times per week. Blood sample analysis for ferritin, hepcidin, iron availability, and inflammatory profile (TNFα, IL-6, and IL-10) was conducted. All-cause mortality was recorded over 5 years.

Results: Sarcopenic RT group increased iron availability after the intervention, while their counterparts decreased. Ferritin and hepcidin significantly decreased in sarcopenic RT group. RT elicited a reduction in both TNFα and IL-6, while increasing IL-10 in both intervention groups. The rate of sarcopenic subjects substantially decreased after the intervention period (from 37 to 17 in the RT group; p = 0.01). The proportion of deaths was higher (P = 0.033) for sarcopenic subjects (Controls 35.7% vs RT 29.7%) when compared to non-sarcopenic subjects (Controls 18% vs RT 10%). The proportion of deaths decreased according to the randomization group (X2 = 8.704; P < 0.1).

Conclusions: The 24-week RT intervention elicited a better sarcopenia status, better inflammatory profile, and improved anemia biomarkers. Sarcopenia was associated with higher mortality rate in older patients with CKD.
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http://dx.doi.org/10.1007/s11255-021-02799-6DOI Listing
February 2021

A robust machine learning framework to identify signatures for frailty: a nested case-control study in four aging European cohorts.

Geroscience 2021 06 18;43(3):1317-1329. Epub 2021 Feb 18.

German Institute for Human Nutrition, Potsdam, Germany.

Phenotype-specific omic expression patterns in people with frailty could provide invaluable insight into the underlying multi-systemic pathological processes and targets for intervention. Classical approaches to frailty have not considered the potential for different frailty phenotypes. We characterized associations between frailty (with/without disability) and sets of omic factors (genomic, proteomic, and metabolomic) plus markers measured in routine geriatric care. This study was a prevalent case control using stored biospecimens (urine, whole blood, cells, plasma, and serum) from 1522 individuals (identified as robust (R), pre-frail (P), or frail (F)] from the Toledo Study of Healthy Aging (R=178/P=184/F=109), 3 City Bordeaux (111/269/100), Aging Multidisciplinary Investigation (157/79/54) and InCHIANTI (106/98/77) cohorts. The analysis included over 35,000 omic and routine laboratory variables from robust and frail or pre-frail (with/without disability) individuals using a machine learning framework. We identified three protective biomarkers, vitamin D3 (OR: 0.81 [95% CI: 0.68-0.98]), lutein zeaxanthin (OR: 0.82 [95% CI: 0.70-0.97]), and miRNA125b-5p (OR: 0.73, [95% CI: 0.56-0.97]) and one risk biomarker, cardiac troponin T (OR: 1.25 [95% CI: 1.23-1.27]). Excluding individuals with a disability, one protective biomarker was identified, miR125b-5p (OR: 0.85, [95% CI: 0.81-0.88]). Three risks of frailty biomarkers were detected: pro-BNP (OR: 1.47 [95% CI: 1.27-1.7]), cardiac troponin T (OR: 1.29 [95% CI: 1.21-1.38]), and sRAGE (OR: 1.26 [95% CI: 1.01-1.57]). Three key frailty biomarkers demonstrated a statistical association with frailty (oxidative stress, vitamin D, and cardiovascular system) with relationship patterns differing depending on the presence or absence of a disability.
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http://dx.doi.org/10.1007/s11357-021-00334-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190217PMC
June 2021

Interrater sleep stage scoring reliability between manual scoring from two European sleep centers and automatic scoring performed by the artificial intelligence-based Stanford-STAGES algorithm.

J Clin Sleep Med 2021 06;17(6):1237-1247

Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.

Study Objectives: The objective of this study was to evaluate interrater reliability between manual sleep stage scoring performed in 2 European sleep centers and automatic sleep stage scoring performed by the previously validated artificial intelligence-based Stanford-STAGES algorithm.

Methods: Full night polysomnographies of 1,066 participants were included. Sleep stages were manually scored in Berlin and Innsbruck sleep centers and automatically scored with the Stanford-STAGES algorithm. For each participant, we compared (1) Innsbruck to Berlin scorings (INN vs BER); (2) Innsbruck to automatic scorings (INN vs AUTO); (3) Berlin to automatic scorings (BER vs AUTO); (4) epochs where scorers from Innsbruck and Berlin had consensus to automatic scoring (CONS vs AUTO); and (5) both Innsbruck and Berlin manual scorings (MAN) to the automatic ones (MAN vs AUTO). Interrater reliability was evaluated with several measures, including overall and sleep stage-specific Cohen's κ.

Results: Overall agreement across participants was substantial for INN vs BER (κ = 0.66 ± 0.13), INN vs AUTO (κ = 0.68 ± 0.14), CONS vs AUTO (κ = 0.73 ± 0.14), and MAN vs AUTO (κ = 0.61 ± 0.14), and moderate for BER vs AUTO (κ = 0.55 ± 0.15). Human scorers had the highest disagreement for N1 sleep (κ = 0.40 ± 0.16 for INN vs BER). Automatic scoring had lowest agreement with manual scorings for N1 and N3 sleep (κ = 0.25 ± 0.14 and κ = 0.42 ± 0.32 for MAN vs AUTO).

Conclusions: Interrater reliability for sleep stage scoring between human scorers was in line with previous findings, and the algorithm achieved an overall substantial agreement with manual scoring. In this cohort, the Stanford-STAGES algorithm showed similar performances to the ones achieved in the original study, suggesting that it is generalizable to new cohorts. Before its integration in clinical practice, future independent studies should further evaluate it in other cohorts.
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http://dx.doi.org/10.5664/jcsm.9174DOI Listing
June 2021

Video-polysomnographic findings after acute COVID-19: REM sleep without atonia as sign of CNS pathology?

Sleep Med 2021 04 2;80:92-95. Epub 2021 Feb 2.

Medical University Innsbruck, Department of Neurology, Innsbruck, Austria. Electronic address:

Objective: Sleep complaints are frequent after acute COVID-19. Aim of this study was to videopolysomnographically evaluate sleep and sleep disorders after SARS-Cov2 infection.

Methods: Patients with suspected sleep disorders after acute COVID-19 underwent video-polysomnography (v-PSG) at the Sleep Disorders Clinic, Department of Neurology, Medical University Innsbruck. V-PSG was conducted 4.2 (SD = 1.3) months after diagnosis of SARS-CoV-2 infection.

Results: Eleven patients [nine men, age 52.5 (SD = 11.7) years; BMI 29 (SD = 5.2) kg/m] were included. At 60 days follow-up after diagnosis, persisting breathing complaints were present in 7/11 (64%) patients. After v-PSG four patients (36%) were diagnosed with obstructive sleep apnea (OSA). Respiratory frequency during sleep was normal and no tachypnea, thoracoabdominal asynchrony, or periodic deep sighing were detected. Four patients (36%) showed REM sleep without atonia (RWA), and two additional patients showed an RWA index within the highest range of normality.

Conclusion: We report videopolysomnographic findings in a series of eleven patients after acute COVID-19. A major finding of this study was the presence of isolated RWA, a recognized prodromal stage of RBD, in more than one third of the patients. Future videopolysomnographic investigations including quantification of RWA in patients after COVID-19 will give more insights into a possible acute or post-infectious CNS pathology related to the SARS-CoV-2 infection.
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http://dx.doi.org/10.1016/j.sleep.2021.01.051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985859PMC
April 2021

Evidence-based recommendations for resistance and power training to prevent frailty in community-dwellers.

Aging Clin Exp Res 2021 Aug 15;33(8):2069-2086. Epub 2021 Feb 15.

Università Cattolica del Sacro Cuore, 00168, Rome, Italy.

Frailty is a reversible state of reduced resilience to stressful events resulting from a multisystem impairment of the human body. As frailty progresses, people become more vulnerable to numerous adverse events, including falls and fractures, cognitive decline, disability, hospitalization, nursing home placement, and death. As such, substantial health care costs are associated with frailty. These features have led to the recognition of frailty as a public health problem. The identification of strategies for the management of frailty has, therefore, become a topic of extensive instigation. In this context, resistance (RT) and power training (PT) have received considerable attention, and experts in the field have recently suggested that both training modalities may improve frailty-related parameters. However, most studies have only included robust people and investigated frailty as a secondary outcome, so that current literature only allows RT and PT preventive programs against frailty to be designed. Here, we provide evidence-based critical recommendations for the prescription of RT and PT programs against incident frailty in community-dwellers.
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http://dx.doi.org/10.1007/s40520-021-01802-5DOI Listing
August 2021

Association between the uremic toxins indoxyl-sulfate and p-cresyl-sulfate with sarcopenia and malnutrition in elderly patients with advanced chronic kidney disease.

Exp Gerontol 2021 05 30;147:111266. Epub 2021 Jan 30.

Unit of Nephrology, Dialysis and Kidney Transplantation, Fondazione IRCCS Ca'Granda Ospedale Maggiore Policlinico di Milano, Milan, Italy. Electronic address:

Background: in patients with chronic kidney disease (CKD) indoxyl sulfate (IS) and p-cresyl sulfate (PCs) may induce sarcopenia either directly or via systemic inflammation. We evaluated whether IS and PCs were associated with: sarcopenia, systemic inflammation and nutritional status.

Methods: we examined cross sectionally 93 patients with advanced CKD. Sarcopenia was identified according to EWGSOP2 definition. Malnutrition was assessed by Malnutrition Inflammation Score (MIS) and Protein Energy Wasting syndrome (PEW). Inflammatory status was assessed by dosing: CRP, IL6, TNFα, MCP1, IL10, IL17, IL12p70.

Results: we did not find any association of sarcopenia with IS and PCs. IS was associated with LogTNFα and LogMCP-1 in the overall cohort (r = 0.30, p = 0.0043; r = 0.22 p = 0.047) and in not sarcopenic patients (r = 0.32, p = 0.0077; r = 0.25, p = 0.041). PCs was associated with LogIL10 and LogIL12p70 in sarcopenic patients (r = 0.58, p = 0.0042; r = 0.52, p = 0.013). IS was higher in patients without PEW (p = 0.029), while PCs was higher in patients with PEW (p = 0.0040). IS and PCs were not different in patients with normal or increased MIS.

Conclusions: IS and PCs were not associated with sarcopenia, although they were both associated with some inflammatory pathways. Notably, we found a positive association of PCs with PEW syndrome.
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http://dx.doi.org/10.1016/j.exger.2021.111266DOI Listing
May 2021

Diogenes syndrome in dementia: a case report.

BJPsych Open 2021 Feb 2;7(2):e43. Epub 2021 Feb 2.

Neurodegenerative Diseases Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.

Background: Diogenes syndrome is a neurobehavioural syndrome characterised by domestic squalor, hoarding and lack of insight. It is an uncommon but high-mortality condition, often associated with dementia.

Aims: To describe the clinical features and treatment of Diogenes syndrome secondary to behavioural variant frontotemporal dementia (bvFTD).

Method: We describe a case of bvFTD in a 77-year-old man presenting with Diogenes syndrome.

Results: The patient's medical and psychiatric histories were unremarkable, but in recent years he had begun packing his flat with 'art pieces'. Mental state examination revealed confabulation and more structured delusions. Neuropsychological evaluation outlined an impairment in selective attention and letter verbal fluency, but no semantic impairment, in the context of an overall preserved mental functioning. Brain magnetic resonance imaging and positron emission tomography (PET) with fluorodeoxyglucose showed mild bilateral temporo-insular atrophy and hypometabolism in the left-superior temporal gyrus respectively. An amyloid PET scan and genetic analysis covering the dementia spectrum were normal. A diagnosis of bvFTD was made.

Conclusions: The clinical framing of behavioural symptoms of dementia such as hoarding poses a diagnostic challenge. This case illustrates the importance of a deeper understanding of Diogenes syndrome, leading to timelier diagnosis and effective therapeutic strategies.
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http://dx.doi.org/10.1192/bjo.2020.171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8058863PMC
February 2021