Publications by authors named "Marco Canevelli"

83 Publications

Identifying Frail Populations for Disease Risk Prediction and Intervention Planning in the Covid-19 Era: A Focus on Social Isolation and Vulnerability.

Front Psychiatry 2021 20;12:626682. Epub 2021 Aug 20.

Cognitive Computational Neuroscience Center, IRCCS Mondino Foundation, Pavia, Italy.

The early identification of fragile populations in the Covid-19 era would help governments to allocate resources and plan strategies to contain consequences of the pandemic. Beyond frailty, social vulnerability to environmental stressors, such as the social distancing enforced to reduce the SARS-CoV2 contagion, can modify long-term disease risk and induce health status changes in the general population. We assessed frailty and social vulnerability indices in 1,258 Italian residents during the first lockdown phase an on-line survey. We compared indices taking into account age categories and gender. While frailty showed a linear increase with age and was greater in females than in males, social vulnerability was higher in young adults and elders compared to middle aged and older adults, and in males than females. Both frailty and social vulnerability contributed in explaining the individual perception of the impact of Covid-19 emergency on health, which was further influenced by proactive attitudes/behaviors and social isolation. Social isolation and loneliness following the Covid-19 outbreak may exert dramatic psychosocial effects in the general population. The early detection of vulnerable categories, at risk to become ill and develop long-lasting health status changes, would help to prevent consequences on general well-being by allocating resources to targeted interventions managing psychosocial distress and increasing young adults and elderly resilience toward the post-Covid-19 crisis.
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http://dx.doi.org/10.3389/fpsyt.2021.626682DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417585PMC
August 2021

A National Survey of Centers for Cognitive Disorders and Dementias in Italy.

J Alzheimers Dis 2021 Aug 24. Epub 2021 Aug 24.

National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Rome, Italy.

Background: Italy has one of the oldest populations in the World and more than one million dementia cases can be estimated at the national level.

Objective: The objectives of this national survey include: 1) to report the administrative features and the professional competencies of Centers for Cognitive Disorders and Dementias (CCDDs); 2) to document possible discrepancies by geographic macro-area; and 3) to identify the features of CCDDs that are associated with a better quality in the provision of care.

Methods: A survey of Italian CCDDs was conducted between February 2014 and December 2015. A list of CCDDs was obtained through direct interactions with designed delegates from each Italian region. A questionnaire was defined on five sections concerning: 1) location of the CCDD; 2) access to the CCDD; 3) organization of the CCDD; 4) services and treatments provided; and 5) quantitative data on the activities of the CCDD.

Results: Overall, 577 out of the 597 eligible CCDDs returned the completed survey questionnaire (response rate: 96.6%): 260 (45.1%) from Northern Italy, 103 (17.8%) from Central Italy, and 214 (37.1%) from Southern-Islands Italy. More than a third of CCDDs were open only once or twice weekly. A median of 450 (IQR: 200-800) patients regularly attended these services. Most patients (70%) were affected by dementia or mild cognitive impairment (19%).

Conclusion: We have provided a snapshot of the organization and activities of CCDDs in Italy and documented existing inequalities in the provision of care.
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http://dx.doi.org/10.3233/JAD-210634DOI Listing
August 2021

"Real world" eligibility for aducanumab.

J Am Geriatr Soc 2021 Jul 31. Epub 2021 Jul 31.

Geriatric Unit, IRCCS Istituti Clinici Scientifici Maugeri, Milan, Italy.

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http://dx.doi.org/10.1111/jgs.17390DOI Listing
July 2021

Cortical complexity alterations in the medial temporal lobe are associated with Alzheimer's disease psychosis.

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2021 Jul 22:1-11. Epub 2021 Jul 22.

Department of Psychology, Sapienza University of Rome, Rome, Italy.

Psychosis is frequent in Alzheimer's disease (AD) and it is associated with a worse disease course. AD psychosis may represent a distinct AD phenotype, though its specific neurobiological underpinnings have yet to be identified. This study investigated neural underpinnings of AD psychosis using surface-based-morphometry.Data from 32 AD patients, 17 with psychosis (AD-P) and 15 without were analyzed. Average cortical complexity (fractal dimension, FD) was estimated for each theoretically motivated ROI and patient. First, we compared regional FD in AD-P and AD patients. Then we calculated the correlation coefficients between FD and the severity of misidentification and paranoid psychotic symptoms. AD-P showed decreased FD in ventral-visual-stream compared to AD, suggesting that perceptual processes might be pivotal in psychosis. A negative correlation was found between misidentification severity and FD in the entorhinal cortex suggesting that misidentification may be specifically associated with alterations in regions involved in high-level perceptual and contextualization processes.
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http://dx.doi.org/10.1080/13825585.2021.1958139DOI Listing
July 2021

[Aducanumab and Alzheimer's disease: a critical reflection.]

Recenti Prog Med 2021 Jul-Aug;112(7):495-498

Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, Istituto Superiore di Sanità, Roma - Dipartimento di Neuroscienze Umane, Sapienza Università di Roma.

On June 7, 2021, the US Food and Drug Administration (FDA) approved aducanumab, a monoclonal amyloid targeting β-amyloid, for the treatment for Alzheimer's disease (AD). This decision was achieved through the Accelerated Approval Pathway and was essentially motivated by the evidence that aducanumab reduces brain amyloid plaques. This news is causing a heated debate in the scientific community. On the one hand, aducanumab is the first drug to be approved for the treatment of the disease since 2003 and is the first drug to act on the alleged pathophysiological mechanisms of AD. At the same time, the evidence of clinical benefit coming from two phase 3 clinical trials is contradictory and still inconclusive. The aim of the present editorial is to provide some points to consider that can help understand the peculiarities and implications of this approval and feed the scientific debate underway.
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http://dx.doi.org/10.1701/3638.36183DOI Listing
July 2021

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

J Alzheimers Dis 2021 ;83(1):43-49

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
September 2021

Anticancer drugs repurposed for Alzheimer's disease: a systematic review.

Alzheimers Res Ther 2021 05 5;13(1):96. Epub 2021 May 5.

National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Via Giano della Bella 34, 00162, Rome, Italy.

Background: The relationship between cancer and dementia is triggering growing research interest. Several preclinical studies have provided the biological rationale for the repurposing of specific anticancer agents in Alzheimer's disease (AD), and a growing number of research protocols are testing their efficacy and safety/tolerability in patients with AD.

Methods: The aim of the present systematic review was to provide an overview on the repurposing of approved anticancer drugs in clinical trials for AD by considering both ongoing and completed research protocols in all phases. In parallel, a systematic literature review was conducted on PubMed, ISI Web, and the Cochrane Library to identify published clinical studies on repurposed anticancer agents in AD.

Results: Based on a structured search on the ClinicalTrials.gov and the EudraCT databases, we identified 13 clinical trials testing 11 different approved anticancer agents (five tyrosine kinase inhibitors, two retinoid X receptor agonists, two immunomodulatory agents, one histone deacetylase inhibitor, and one monoclonal antibody) in the AD continuum. The systematic literature search led to the identification of five published studies (one phase I, three phase II, and one phase IIb/III) reporting the effects of antitumoral treatments in patients with mild cognitive impairment or AD dementia. The clinical findings and the methodological characteristics of these studies are described and discussed.

Conclusion: Anticancer agents are triggering growing interest in the context of repurposed therapies in AD. Several clinical trials are underway, and data are expected to be available in the near future. To date, data emerging from published clinical studies are controversial. The promising results emerging from preclinical studies and identified research protocols should be confirmed and extended by larger, adequately designed, and high-quality clinical trials.
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http://dx.doi.org/10.1186/s13195-021-00831-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101105PMC
May 2021

Decreasing trend in the incidence and prevalence of dementia: a systematic review.

Minerva Med 2021 Aug 21;112(4):430-440. Epub 2021 Apr 21.

National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Rome, Italy -

Introduction: The progressive ageing of the population is one of the main socio-demographic phenomena, taking place at a global level. Several recent population-based studies conducted worldwide suggest that the age-specific risk of dementia may be changing in some countries and areas.

Evidence Acquisition: This systematic review was performed using the methodology proposed by the Cochrane handbook for systematic reviews and reported following the PRISMA statement. A structured bibliographic search was performed on the databases PubMed, ISI Web of Science and the Cochrane Database of Systematic Reviews. All included studies were qualitatively assessed using the Methodological Evaluation of Observational REsearch (MORE).

Evidence Synthesis: The bibliographic search yielded 2394 records. Three more articles were retrieved from other sources. A total of ten studies were included, five reported data on a possible reduction in the prevalence of dementia, and five reported data on a possible reduction in its incidence.

Conclusions: The present systematic review focused on the recent observations of a possible decrease in the frequency of dementia and cognitive impairment in some Western countries (USA, UK, Sweden, the Netherlands, France, Iceland) between 1977 and 2014. The included studies have a high heterogeneity in terms of the clinical criteria used to diagnose dementia, and of the criteria used to define the clinical condition preceding dementia, such as isolated cognitive impairment. Moreover, the methodological quality with which they were conducted was also heterogeneous, with scores ranging from 1 to 7 using the MORE tool.
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http://dx.doi.org/10.23736/S0026-4806.21.07454-1DOI Listing
August 2021

Operationalization of a frailty index in patients with multiple sclerosis: A cross-sectional investigation.

Mult Scler 2021 Feb 10:1352458520987541. Epub 2021 Feb 10.

Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy/IRCCS Neuromed, Pozzilli, Italy.

Background: Frailty is an age-related status of increased vulnerability to stressors caused by the accumulation of multiple health deficits. This construct may allow to capture the clinical complexity of patients with multiple sclerosis (MS).

Objective: To investigate the relationship between frailty and the clinical manifestations of MS.

Methods: Patients with MS were consecutively enrolled at five tertiary dedicated services. Disability and fatigue were assessed. The phenotypes of MS were also identified. Frailty was measured using a frailty index (FI), computed by cumulatively considering 42 age-related multidimensional health deficits.

Results: Overall, 745 MS patients (mean age = 48.2 years, standard deviation = 11.7 years; women 68%) were considered. The median FI value was 0.12 (interquartile range = 0.05-0.19) and the 99th percentile was 0.40. FI scores were associated with MS disease duration, disability, fatigue, as well as with the number of previous disease-modifying treatments and current symptomatic therapies. A logistic regression analysis model showed that FI score was independently associated with the secondary progressive phenotype.

Conclusion: Frailty is significantly associated with major characteristics of MS. The findings of the present cross-sectional investigation should be explored in future longitudinal studies.
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http://dx.doi.org/10.1177/1352458520987541DOI Listing
February 2021

The Italian national survey on Coronavirus disease 2019 epidemic spread in nursing homes.

Int J Geriatr Psychiatry 2021 06 2;36(6):873-882. Epub 2021 Jan 2.

National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Rome, Italy.

Introduction: Residents in facilities such as nursing homes (NHs) are particularly vulnerable to Coronavirus disease 2019 (COVID-19). A national survey was carried out to collect information on the spreading and impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in nursing homes, and on how suspected and/or confirmed cases were managed. We carried out a survey between 25 March 2020 and 5 May 2020.

Materials And Methods: All Italian nursing homes either public or providing services both privately and within the NHS were included in the study. An on-line questionnaire was sent to 3292 nursing homes across all Italian regions. Nursing homes were also contacted by telephone to provide assistance in completing the questionnaire.

Results: A total of 1356 nursing homes voluntarily participated to the survey, hosting a total of 100,806 residents. Overall, 9154 residents died due to any cause from February 1 to the time when the questionnaire was completed (from March 25 to May 5). Of these, 7.4% had COVID-19 and 33.8% had flu-like symptoms, corresponding to a cumulative incidence of 0.7 and 3.1, respectively. Lack of personnel, difficulty in transferring patients to hospital or other facility, isolating residents with COVID-19, number of beds and geographical area were the main factor positively associated to the presence of COVID-19 in nursing homes.

Discussion: This survey showed the dissemination and impact of SARS-CoV-2 infection in Italian nursing homes and on how older and potentially chronically ill people residing in these long-term care facilities were managed.
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http://dx.doi.org/10.1002/gps.5487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247061PMC
June 2021

Taking care of minor migrants' health: the professionals' perception and training needs.

Ann Ist Super Sanita 2020 Oct-Dec;56(4):470-477

Centro Nazionale per la Prevenzione delle Malattie e la Promozione della Salute, Istituto Superiore di Sanità, Rome, Italy.

Introduction: In Italy, minor migrants represent 21.8% of the non-EU citizens. The care of minor migrants might be challenging as this population is characterized by higher vulnerability and special needs. The study aim was to describe the perceptions on the provision of care, the bio-psycho-social needs of migrant children and the professional training needs.

Methods: The study is qualitative descriptive. In May 2019 three focus group, involving health and social professionals, cultural mediators and NGOs operators, were organized.

Results: The study explored different areas of the provision of care to minor migrants including bio-psycho-social needs, care provision, barriers to care and professionals' training needs.

Discussion And Conclusions: The provision of care should consider the specific migration journey and narrative. In some cases healthcare is fragmented, generating obstacles to access especially in minors with lower levels of health literacy. Training plays a key role in the development of cultural competence.
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http://dx.doi.org/10.4415/ANN_20_04_09DOI Listing
December 2020

Prevalence and clinical correlates of dementia among COVID-19-related deaths in Italy.

Alzheimers Dement (Amst) 2020 14;12(1):e12114. Epub 2020 Nov 14.

Department of Cardiovascular, Endocrine-metabolic Diseases and Aging Istituto Superiore di Sanità Rome Italy.

Introduction: We aimed at exploring the proportion of patients dying with COVID-19 and concomitant dementia in Italy, as well as their clinical characteristics and trajectories of care.

Methods: The proportion of COVID-19-related deaths occurring in people with dementia and the clinical characteristics of deceased individuals according to their dementia status were explored by considering the medical charts of a representative sample of patients deceased in Italian hospitals (n = 2621).

Results: A total of 415 individuals with dementia were identified in the study population, accounting for 15.8% of overall COVID-19-related deaths. Patients with dementia less frequently presented with cough, had lower chance of receiving supportive therapies and intensive care approaches, and showed a faster clinical worsening as compared with individuals with intact cognition.

Discussion: Dementia confers a relevant risk of adverse outcomes in case of SARS-CoV-2 infection and influences the clinical presentation, course and management of affected individuals.
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http://dx.doi.org/10.1002/dad2.12114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666428PMC
November 2020

Biomarkers and phenotypic expression in Alzheimer's disease: exploring the contribution of frailty in the Alzheimer's Disease Neuroimaging Initiative.

Geroscience 2021 04 19;43(2):1039-1051. Epub 2020 Nov 19.

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

The present study aimed at investigating if the main biomarkers of Alzheimer's disease (AD) neuropathology and their association with cognitive disturbances and dementia are modified by the individual's frailty status. We performed a cross-sectional analysis of data from participants with normal cognition, mild cognitive impairment (MCI), and AD dementia enrolled in the Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) study. Frailty was operationalized by computing a 40-item Frailty Index (FI). The following AD biomarkers were considered and analyzed according to the participants' frailty status: CSF Aβ, P-tau, and T-tau; MRI-based hippocampus volume; cortical glucose metabolism at the FDG PET imaging; amyloid deposition at the F-AV-45 PET imaging. Logistic regression models, adjusted for age, sex, and education, were performed to explore the association of biomarkers with cognitive status at different FI levels. Subjects with higher FI scores had lower CSF levels of Aβ, hippocampus volumes at the MRI, and glucose metabolism at the FDG PET imaging, and a higher amyloid deposition at the F-AV-45 PET. No significant differences were observed among the two frailty groups concerning ApoE genotype, CSF T-tau, and P-tau. Increasing frailty levels were associated with a weakened relationship between dementia and F-AV-45 uptake and hippocampus volume and with a stronger relationship of dementia with FDG PET. Frailty contributes to the discrepancies between AD pathology and clinical manifestations and influences the association of AD pathological modifications with cognitive changes. AD and dementia should increasingly be conceived as "complex diseases of aging," determined by multiple, simultaneous, and interacting pathophysiological processes.
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http://dx.doi.org/10.1007/s11357-020-00293-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8110661PMC
April 2021

Adverse Events in Italian Nursing Homes During the COVID-19 Epidemic: A National Survey.

Front Psychiatry 2020 30;11:578465. Epub 2020 Sep 30.

National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, Rome, Italy.

Older people living in nursing homes (NHs) are particularly vulnerable in the ongoing COVID-19 pandemic, due to the high prevalence of chronic diseases and disabilities (e.g., dementia). The phenomenon of adverse events (AEs), intended as any harm or injury resulting from medical care or to the failure to provide care, has not yet been investigated in NHs during the pandemic. We performed a national survey on 3,292 NHs, either public or providing services both privately and within the national health system, out of the 3,417 NHs covering the whole Italian territory. An online questionnaire was addressed to the directors of each facility between March 24 and April 27, 2020. The list of NHs was provided by the Dementia Observatory, an online map of Italian services for people with dementia, which was one of the objectives of the implementation of the Italian National Dementia Plan. About 26% of residents in the Italian NHs for older people listed within the Dementia Observatory site had dementia. The objective of our study was to report the frequency of AEs that occurred during the months when SARS-CoV-2 spreading rate was at its highest in the Italian NHs and to identify which conditions and attributes were most associated with the occurrence of AEs by means of multivariate regression logistic analysis. Data are referred to 1,356 NHs that participated in the survey. The overall response rate was 41.2% over a time-period of six weeks (from March 24 to May 5). About one third of the facilities (444 out of 1,334) (33.3%) reported at least 1 adverse event, with a total of 2,000 events. Among the included NHs, having a bed capacity higher than the median of 60 beds (OR=1.57, CI95% 1.17-2.09; p=0.002), an observed increased in the use of psychiatric drugs (OR=1.80, CI95% 1.05-3.07; p=0.032), adopting physical restraint measures (OR=1.97, CI95% 1.47-2.64; p<0.001), residents hospitalized due to flu-like symptoms (OR =1.73, CI95% 1.28-2.32; p<0.001), and being located in specific geographic areas (OR=3.59, CI95% 1.81-7.08; OR = 2.90, CI95% 1.45-5.81 and OR = 4.02, CI05% 2.01-8.04 for, respectively, North-West, North-East and Centre vs South, p<0.001) were all factors positively associated to the occurrence of adverse events in the facility. Future recommendations for the management and care of residents in NHs during the COVID-19 pandemic should include specific statements for the most vulnerable populations, such as people with dementia.
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http://dx.doi.org/10.3389/fpsyt.2020.578465DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561357PMC
September 2020

The Pipeline of Therapeutics Testing During the Emergency Phase of the COVID-19 Outbreak.

Front Med (Lausanne) 2020 24;7:552991. Epub 2020 Sep 24.

Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.

The coronavirus disease 19 (COVID-19) pandemic poses a serious threat to the sustainability of healthcare systems and is currently having a significant effect on living conditions worldwide. No therapeutic agent has yet proven to be effective for the treatment of COVID-19. The management of this disease currently relies on supportive care and the off-label and compassionate use of antivirals and immunomodulators. Nevertheless, there has been a great worldwide effort to progress research and test the efficacy and safety/tolerability profiles of numerous candidate agents that may positively affect the various clinical syndromes associated with COVID-19. In parallel, vaccination and chemoprophylaxis strategies are being investigated. This article provides a summary of interventional studies targeting COVID-19 during the emergency phase of the outbreak to broadly inform clinicians and researchers on what happened and what they can expect in upcoming months. The clinicaltrials.gov database and the European Union (EU) Clinical Trials Register were investigated on March 31, 2020, to identify all ongoing phase 1-4 research protocols testing pharmacological interventions targeting SARS-CoV-2 infection and/or clinical syndromes associated with COVID-19. Overall, six phase 1, four phase 1-2, 14 phase 2, ten phase 2-3, 19 phase 3, and nine phase 4 studies were identified, and the features of these studies are described in the present review. We also provide an updated overview of the change overtime in the pipeline following this emergency phase and based on the current epidemiology of the COVID-19 pandemic.
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http://dx.doi.org/10.3389/fmed.2020.552991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542224PMC
September 2020

Sex differences in clinical phenotype and transitions of care among individuals dying of COVID-19 in Italy.

Biol Sex Differ 2020 10 16;11(1):57. Epub 2020 Oct 16.

Department of Cardiovascular, Endocrine-metabolic Diseases and Aging, Istituto Superiore di Sanità, Via Giano della Bella, 34, 00161, Rome, Italy.

Background: Among the unknowns posed by the coronavirus disease 2019 (COVID-19) outbreak, the role of biological sex to explain disease susceptibility and progression is still a matter of debate, with limited sex-disaggregated data available.

Methods: A retrospective analysis was performed to assess if sex differences exist in the clinical manifestations and transitions of care among hospitalized individuals dying with laboratory-confirmed SARS-CoV-2 infection in Italy (February 27-June 11, 2020). Clinical characteristics and the times from symptoms' onset to admission, nasopharyngeal swab, and death were compared between sexes. Adjusted multivariate analysis was performed to identify the clinical features associated with male sex.

Results: Of the 32,938 COVID-19-related deaths that occurred in Italy, 3517 hospitalized and deceased individuals with COVID-19 (mean 78 ± 12 years, 33% women) were analyzed. At admission, men had a higher prevalence of ischemic heart disease (adj-OR = 1.76, 95% CI 1.39-2.23), chronic obstructive pulmonary disease (adj-OR = 1.7, 95% CI 1.29-2.27), and chronic kidney disease (adj-OR = 1.48, 95% CI 1.13-1.96), while women were older and more likely to have dementia (adj-OR = 0.73, 95% CI 0.55-0.95) and autoimmune diseases (adj-OR = 0.40, 95% CI 0.25-0.63), yet both sexes had a high level of multimorbidity. The times from symptoms' onset to admission and nasopharyngeal swab were slightly longer in men despite a typical acute respiratory illness with more frequent fever at the onset. Men received more often experimental therapy (adj-OR = 2.89, 95% CI 1.45-5.74) and experienced more likely acute kidney injury (adj-OR = 1.47, 95% CI 1.13-1.90).

Conclusions: Men and women dying with COVID-19 had different clinical manifestations and transitions of care. Identifying sex-specific features in individuals with COVID-19 and fatal outcome might inform preventive strategies.
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http://dx.doi.org/10.1186/s13293-020-00334-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7562690PMC
October 2020

COVID-19 mortality among migrants living in Italy.

Ann Ist Super Sanita 2020 Jul-Sep;56(3):373-377

Dipartimento Malattie Cardiovascolari, Endocrino-Metaboliche e Invecchiamento, Istituto Superiore di Sanità, Rome, Italy.

We aimed to compare COVID-19-specific and all-cause mortality rates among natives and migrants in Italy and to investigate the clinical characteristics of individuals dying with COVID-19 by native/migrant status. The mortality rates and detailed clinical characteristics of natives and migrants dying with COVID-19 were explored by considering the medical charts of a representative sample of patients deceased in Italian hospitals (n = 2,687) between February 21st and April 29th, 2020. The migrant or native status was assigned based on the individual's country of birth. The expected all-cause mortality among natives and migrants living in Italy was derived by the last available (2018) dataset provided by the Italian National Institute of Statistics. Overall, 68 individuals with a migration background were identified. The proportions of natives and migrants among the COVID-19-related deaths (97.5% and 2.5%, respectively) were similar to the relative all-cause mortality rates estimated in Italy in 2018 (97.4% and 2.6%, respectively). The clinical phenotype of migrants dying with COVID-19 was similar to that of natives except for the younger age at death. International migrants living in Italy do not have a mortality advantage for COVID-19 and are exposed to the risk of poor outcomes as their native counterparts.
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http://dx.doi.org/10.4415/ANN_20_03_16DOI Listing
October 2020

Migration and dementia in Europe: towards a culturally competent approach and provision of care. Editorial.

Ann Ist Super Sanita 2020 Jul-Sep;56(3):260-262

Centro Nazionale per la Prevenzione delle Malattie e la Promozione della Salute, Istituto Superiore di Sanità, Rome, Italy.

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http://dx.doi.org/10.4415/ANN_20_03_02DOI Listing
August 2021

Use of Biomarkers in Ongoing Research Protocols on Alzheimer's Disease.

J Pers Med 2020 Jul 24;10(3). Epub 2020 Jul 24.

National Center for Disease Prevention and Health Promotion, Italian National Institute of Health, 00161 Rome, Italy.

The present study aimed to describe and discuss the state of the art of biomarker use in ongoing Alzheimer's disease (AD) research. A review of 222 ongoing phase 1, 2, 3, and 4 protocols registered in the clinicaltrials.gov database was performed. All the trials (i) enrolling subjects with clinical disturbances and/or preclinical diagnoses falling within the AD continuum; and (ii) testing the efficacy and/or safety/tolerability of a therapeutic intervention, were analyzed. The use of biomarkers of amyloid deposition, tau pathology, and neurodegeneration among the eligibility criteria and/or study outcomes was assessed. Overall, 58.2% of ongoing interventional studies on AD adopt candidate biomarkers. They are mostly adopted by studies at the preliminary stages of the drug development process to explore the safety profile of novel therapies, and to provide evidence of target engagement and disease-modifying properties. The biologically supported selection of participants is mostly based on biomarkers of amyloid deposition, whereas the use of biomarkers as study outcomes mostly relies on markers of neurodegeneration. Biomarkers play an important role in the design and conduction of research protocols targeting AD. Nevertheless, their clinical validity, utility, and cost-effectiveness in the "real world" remain to be clarified.
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http://dx.doi.org/10.3390/jpm10030068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7564515PMC
July 2020

The continuum between neurodegeneration, brain plasticity, and movement: a critical appraisal.

Rev Neurosci 2020 10;31(7):723-742

Department of Neurology, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, 260 Stetson Street, Cincinnati, 45219, OH, USA.

While the "physiological" aging process is associated with declines in motor and cognitive features, these changes do not significantly impair functions and activities of daily living. Differently, motor and cognitive impairment constitute the most common phenotypic expressions of neurodegeneration. Both manifestations frequently coexist in the same disease, thus making difficult to detect "pure" motor or cognitive conditions. Movement disorders are often characterized by cognitive disturbances, and neurodegenerative dementias often exhibit the occurrence of movement disorders. Such a phenotypic overlap suggests approaching these conditions by highlighting the commonalities of entities traditionally considered distinct. In the present review, we critically reappraised the common clinical and pathophysiological aspects of neurodegeneration in both animal models and patients, looking at motricity as a trait d'union over the spectrum of neurodegeneration and focusing on synaptopathy and oscillopathy as the common pathogenic background. Finally, we discussed the possible role of movement as neuroprotective intervention in neurodegenerative conditions, regardless of the etiology. The identification of commonalities is critical to drive future research and develop novel possible disease-modifying interventions.
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http://dx.doi.org/10.1515/revneuro-2020-0011DOI Listing
October 2020

Providing Simultaneous COVID-19-sensitive and Dementia-Sensitive Care as We Transition from Crisis Care to Ongoing Care.

J Am Med Dir Assoc 2020 07 21;21(7):968-969. Epub 2020 May 21.

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

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http://dx.doi.org/10.1016/j.jamda.2020.05.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241363PMC
July 2020

Clinical Characteristics of Hospitalized Individuals Dying With COVID-19 by Age Group in Italy.

J Gerontol A Biol Sci Med Sci 2020 09;75(9):1796-1800

Department of Cardiovascular, Endocrine-metabolic Diseases and Aging, Istituto Superiore di Sanità, Rome, Italy.

Background: Aim of the present study is to describe characteristics of COVID-19-related deaths and to compare the clinical phenotype and course of COVID-19-related deaths occurring in adults (<65 years) and older adults (≥65 years).

Method: Medical charts of 3,032 patients dying with COVID-19 in Italy (368 aged < 65 years and 2,664 aged ≥65 years) were revised to extract information on demographics, preexisting comorbidities, and in-hospital complications leading to death.

Results: Older adults (≥65 years) presented with a higher number of comorbidities compared to those aged <65 years (3.3 ± 1.9 vs 2.5 ± 1.8, p < .001). Prevalence of ischemic heart disease, atrial fibrillation, heart failure, stroke, hypertension, dementia, COPD, and chronic renal failure was higher in older patients (≥65 years), while obesity, chronic liver disease, and HIV infection were more common in younger adults (<65 years); 10.9% of younger patients (<65 years) had no comorbidities, compared to 3.2% of older patients (≥65 years). The younger adults had a higher rate of non-respiratory complications than older patients, including acute renal failure (30.0% vs 20.6%), acute cardiac injury (13.5% vs 10.3%), and superinfections (30.9% vs 9.8%).

Conclusions: Individuals dying with COVID-19 present with high levels of comorbidities, irrespective of age group, but a small proportion of deaths occur in healthy adults with no preexisting conditions. Non-respiratory complications are common, suggesting that the treatment of respiratory conditions needs to be combined with strategies to prevent and mitigate the effects of non-respiratory complications.
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http://dx.doi.org/10.1093/gerona/glaa146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7314182PMC
September 2020

Frailty Index as a clinical measure of biological age in psychiatry.

J Affect Disord 2020 05 6;268:183-187. Epub 2020 Mar 6.

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

Background: Serious mental illnesses may be characterized by accelerated biological aging, and over the last years the research on the topic has been stimulated by studies exploring the molecular underpinnings of senescence.

Methods: In the present manuscript we propose that measuring frailty, a general product of organismal ageing, through the "Frailty Index" (FI), a recently-emerged macroscopic indicator of functional status and biological age, adds an important marker to the measurements currently implemented in the study of accelerated biological age in psychiatric illnesses.

Results: The FI quantifies functional negative health attributes and measures their cumulative effect, thus providing a useful estimate of the individual's biological age and risk profile. Recent studies in older adults have observed significant associations between FI and molecular measures of aging.

Limitations: High FI values can be driven by causes different from aging per se, so FI may be a sensitive but not specific measure of biological aging.

Conclusions: FI, which is extensively used in geriatrics and gerontology but it has rarely been used in relation to mental health, may be of relevance in the evaluation of age-related phenomena associated with psychiatric diseases.
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http://dx.doi.org/10.1016/j.jad.2020.03.015DOI Listing
May 2020

Dementia among migrants and ethnic minorities in Italy: rationale and study protocol of the ImmiDem project.

BMJ Open 2020 01 7;10(1):e032765. Epub 2020 Jan 7.

National Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, Italy.

Introduction: Due to the ongoing demographic and epidemiological transitions, estimating the phenomenon of dementia in migrants and minority groups, exploring its characteristics and challenges and implementing dedicated healthcare policies, constitute emerging and urgent matters for Western countries. In the present paper we describe the rationale and design of the 'Dementia in immigrants and ethnic minorities living in Italy: clinical-epidemiological aspects and public health perspectives" (ImmiDem) project.

Methods And Analysis: Three main aims will be pursued by the ImmiDem project. First, a survey of all Italian dementia services will be conducted with dedicated questionnaires in order to estimate and describe the proportion and characteristics of migrants seeking help for cognitive disturbances. The different clinical approaches for diagnosing dementia and the challenges encountered in the assessment of cognitive functioning and in the provision of care in these groups of individuals will also be investigated. Second, record linkage procedures of data routinely collected in regional Health Information Systems will be conducted in order to identify and monitor migrant individuals with dementia living in the Lazio region. Third, tailored national and local care-coordination pathways and/or good practices dedicated to migrants affected by dementia and cognitive disorders will be identified and promoted.

Ethics And Dissemination: The study protocol was approved by the Ethics Committee of the Italian National Institute of Health (protocol 10749; 5 April 2018). The project was launched in November 2018 and will end in November 2021. The findings of the project will be disseminated through scientific peer-reviewed journals as well as to the public via the Dementia Observatory website (https://demenze.iss.it).
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http://dx.doi.org/10.1136/bmjopen-2019-032765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6955488PMC
January 2020

Mild Cognitive Impairment in the Migrant Population Living in Europe: An Epidemiological Estimation of the Phenomenon.

J Alzheimers Dis 2020 ;73(2):715-721

National Center for Disease Prevention and Health Promotion, National Institute of Health, Rome, Italy.

Background: The construct of mild cognitive impairment (MCI) is triggering growing clinical and research interest. The detection of MCI may be affected by diverse ethno-cultural determinants possibly influencing the personal and social perception of the individual cognitive functioning as well as the reliability of objective cognitive assessment. These challenges may acquire special relevance in subjects with a migration background and composing ethnic minority groups.

Objective: The present study is aimed at providing an estimate of the number of MCI cases occurring in the migrant population living in the extended European Union (EU) in 2018.

Methods: The number of MCI cases in older migrants living in Europe and in each of the 32 considered countries was estimated by multiplying the number of migrants, provided by Eurostat, with the age-specific prevalence rates, derived by the harmonized data produced by the COSMIC collaboration and based on different operational definitions of MCI.

Results: Nearly 686,000 cases of MCI were estimated in the extended EU by applying age-specific prevalence rates based on the International Working Group criteria. Higher figures were obtained when the Clinical Dementia Rating- and the Mini Mental State Examination-based criteria were applied. The proportion of MCI cases in migrant subjects ranged from 1.1% (Romania) to 54.1% (Liechtenstein) (median: 8.4%; IQR: 4.7%-14.2%).

Conclusions: MCI represents and will increasingly constitute a relevant issue in the migrant population living in Europe. The present data reinforce the need of developing approaches and models of care that may be diversity-sensitive and inclusive for a culturally variegated population.
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http://dx.doi.org/10.3233/JAD-191012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7029332PMC
November 2020

Integrated care pathways on dementia in Italy: a survey testing the compliance with a national guidance.

Neurol Sci 2020 Apr 13;41(4):917-924. Epub 2019 Dec 13.

National Center for Disease Prevention and Health Promotion, National Institute of Health, Via Giano della Bella no. 34, 00162, Rome, Italy.

Dementias are chronic, degenerative neurological disorders with a complex management that require the cooperation of different healthcare professionals. The Italian Ministry of Health produced the document "Guidance on Integrated Care pathway for People with Dementia" (GICPD) with the specific objective of providing a standardized framework for the definition, development, and implementation of integrated care pathways (ICP) dedicated to people with dementia. We searched all available Italian territorial ICPs. Two raters assessed the retrieved ICPs with a 2-point scale on a 43-item checklist based on the GICPD. Only 5 out of 21 regions and 5 out of 101 local health authorities had an ICP, with most ICPs having a moderate compliance to the GICPD, in particular for the items referring to the development and implementation of the care pathways. A low to moderate inter-rater agreement was observed, mainly due to a lack of standardized models to describe ICPs for dementias. Results suggest that policy- and decision-makers should pay more attention to the GICPD when producing ICPs. The direct communication with clinicians, and the implementation of more precise and appropriate clinical outcomes, could increase the involvement of clinicians, whose participation is crucial to guarantee that ICPs meet needs of patients and their carers.
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http://dx.doi.org/10.1007/s10072-019-04184-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160089PMC
April 2020

A Frailty Index based on clinical data to quantify mortality risk in dogs.

Sci Rep 2019 11 14;9(1):16749. Epub 2019 Nov 14.

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

Frailty is defined as a decline in an organism's physiological reserves resulting in increased vulnerability to stressors. In humans, a single continuous variable, the so-called Frailty Index (FI), can be obtained by multidimensionally assessing the biological complexity of an ageing organism. Here, we evaluate this variability in dogs and compare it to the data available for humans. In dogs, there was a moderate correlation between age and the FI, and the distribution of the FI increased with age. Deficit accumulation was strongly related to mortality. The effect of age, when combined with the FI, was negligible. No sex-related differences were evident. The FI could be considered in epidemiological studies and/or experimental trials to account for the potential confounding effects of the health status of individual dogs. The age-related deficit accumulation reported in dogs is similar to that demonstrated in humans. Therefore, dogs might represent an excellent model for human aging studies.
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http://dx.doi.org/10.1038/s41598-019-52585-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6856105PMC
November 2019

Methodological Issues in the Clinical Validation of Biomarkers for Alzheimer's Disease: The Paradigmatic Example of CSF.

Front Aging Neurosci 2019 17;11:282. Epub 2019 Oct 17.

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

The use of biomarkers is profoundly transforming medical research and practice. Their adoption has triggered major advancements in the field of Alzheimer's disease (AD) over the past years. For instance, the analysis of the cerebrospinal fluid (CSF) and neuroimaging changes indicative of neuronal loss and amyloid deposition has led to the understanding that AD is characterized by a long preclinical phase. It is also supporting the transition towards a biology-grounded framework and definition of the disease. Nevertheless, though sufficient evidence exists about the (i.e., accuracy, reliability, and reproducibility) of the candidate AD biomarkers, their (i.e., how well the test measures the clinical features, and the disease or treatment outcomes) and (i.e., if and how the test improves the patient's outcomes, confirms/changes the diagnosis, identifies at-risk individuals, influences therapeutic choices) have not been fully proven. In the present review, some of the methodological issues and challenges that should be addressed in order to better appreciate the potential benefits and limitations of AD biomarkers are discussed. The ultimate goal is to stimulate a constructive discussion aimed at filling the existing gaps and more precisely defining the directions of future research. Specifically, four main aspects of the clinical validation process are addressed and applied to the most relevant CSF biomarkers: (1) the definition of reference values; (2) the identification of reference standards for the disease of interest (i.e., AD); (3) the inclusion within the diagnostic process; and (4) the statistical process supporting the whole framework.
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http://dx.doi.org/10.3389/fnagi.2019.00282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6812267PMC
October 2019

A systematic review on the epidemiology of normal pressure hydrocephalus.

Acta Neurol Scand 2020 Feb 21;141(2):101-114. Epub 2019 Nov 21.

National Centre for Disease Prevention and Health Promotion, National Institute of Health, Rome, Italy.

Background: The aim of this systematic review is to gather all available studies reporting prevalence and incidence rates of iNPH and to assess their methodological quality and consistency.

Methods: All available studies published up to June 2019 were retrieved searching the databases PubMed, ISI Web of Science, and the Cochrane Database of Systematic Reviews. All included studies were qualitatively assessed by two independent reviewers using the MORE Checklist for Observational Studies of Incidence and Prevalence.

Key Results: Bibliographic searches and other sources yielded 659 records. A total of 28 studies were selected and applied the predefined inclusion and exclusion criteria. Fourteen studies were further excluded, and 14 studies (10 on prevalence and 6 on incidence) were included in the qualitative analysis. Results from the prevalence studies reported crude overall rates ranging from 10/100 000 to 22/100 000 for probable iNPH and 29/100 000 for possible iNPH, and age-specific rates ranging from 3.3/100 000 in people aged 50-59 to 5.9% in people aged ≥ 80 years. Results from incidence studies reported overall crude rates ranging from 1.8/100 000 to 7.3/100 000 per year, and age-specific rates ranging from 0.07/100 000/year in people aged < 60 years to 1.2/1000/year in people aged ≥ 70 years.

Conclusions & Inferences: The high methodological and clinical heterogeneity of included studies does not allow drawing adequate conclusions on the epidemiology of iNPH. Further, high-quality, population-based studies should be carried out to allow for a better understanding of the epidemiology of this condition. Moreover, the implementation in current clinical practice of guidelines on the diagnosis and management of iNPH should also be endorsed.
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http://dx.doi.org/10.1111/ane.13182DOI Listing
February 2020
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