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Background: Several chronic diseases accelerate cognitive decline; however, it is still unknown how different patterns of multimorbidity influence individuals' trajectories across the cognitive continuum., Objectives: We aimed to investigate the impact of multimorbidity and of specific multimorbidity patterns on the transitions across cognitive stages (normal cognition, cognitive impairment, no dementia [CIND], dementia) and death., Methods: We included 3122 dementia-free individuals from the Swedish National study on Aging and Care in Kungsholmen. Using fuzzy c-means cluster analysis, multimorbid participants were classified into mutually exclusive groups characterized by commonly coexisting chronic diseases. Participants were followed up to 18 years to detect incident CIND, dementia, or death. Transition hazard ratios (HRs), life expectancies, and time spent in different cognitive stages were estimated using multistate Markov models., Results: At baseline, five multimorbidity patterns were identified: neuropsychiatric, cardiovascular, sensory impairment/cancer, respiratory/metabolic/musculoskeletal, and unspecific. Compared to the unspecific pattern, the neuropsychiatric and sensory impairment/cancer ones showed reduced hazards of reverting from CIND to normal cognition (HR 0.53, 95% CI 0.33-0.85 and HR 0.60, 95% CI 0.39-0.91). Participants in the cardiovascular pattern exhibited an increased hazard of progression from CIND to dementia (HR 1.70, 95% CI 1.15-2.52) and for all transitions to death. Subjects with the neuropsychiatric and cardiovascular patterns showed reduced life expectancy at age 75, with an anticipation of CIND (up to 1.6 and 2.2 years, respectively) and dementia onset (up to 1.8 and 3.3 years, respectively)., Conclusions: Multimorbidity patterns differentially steer individual trajectories across the cognitive continuum of older adults and may be used as a risk stratification tool., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Objective: Dementia among migrants is an emerging phenomenon worldwide and the development of neuropsychological tests sensitive to cultural differences is increasingly regarded as a priority. The Clock Drawing Test (CDT) is one of the most used screening tools for the detection of cognitive decline. Nevertheless, there is still a debate about its adoption as a cross-cultural assessment., Methods: To identify cultural variables influencing performance at CDT, we performed a systematic review of literature on three databases of all studies considering the role of at least one of the following: (1) language; (2) education; (3) literacy; (4) acculturation; and (5) ethnicity., Results: We extrapolated 160 analyses from 105 studies. Overall, an influence of cultural determinants on performance at CDT was found in 127 analyses (79.4%). Regarding specific cultural factors, 22 analyses investigated the effect of ethnicity on CDT scores, reporting conflicting results. Only two scoring systems turned out to be sufficiently accurate in a multicultural population. Language influenced performance in only 1 out of 8 analyses. A higher level of education positively influenced test performance in 118 out of 154 analyses (76.6%), and a better quality of education in 1 analysis out of 2. A negative influence of illiteracy on CDT performance emerged in 9 out of 10 analyses. Acculturation affected performances at CDT in 1 out of 2 studies., Conclusions: Based on the present findings, caution is needed when using CDT in a multicultural context, even if it requires limited linguistic competence.

Background: A crucial step for planning effective public health policies for migrants with dementia is the collection of data on the local dimensions of the phenomenon and patients' characteristics., Objective: This study aimed to identify and characterize migrants with dementia in the Lazio region using health administrative databases., Methods: Residents with dementia aged 50 years or older, living in the Lazio region as of December 31, 2018, were identified using a validated algorithm based on hospital discharge(s), claims for antidementia drugs, and co-payment exemption for dementia. Migrants were defined as people born abroad and grouped in migrants from High Migratory Pressure Countries (HMPCs) and Highly Developed Countries (HDCs). Overall and age-specific prevalence rates were estimated in native- and foreign-born patients., Results: Dementia was ascertained in 38,460 residents. Among them, 37,280 (96.9%) were born in Italy, 337 (0.9%) were migrants from HDCs, and 843 (2.2%) from HMPCs. Dementia prevalence was higher among natives (1.15%, 95% CI 1.14-1.16) relative to migrants from HDCs (0.60%, 95% CI 0.54-0.67) and HMPCs (0.29%, 95% CI 0.27-0.31). The prevalence of comorbidities did not differ between groups. Migrants with dementia had a lower likelihood of receiving antidementia treatments compared with natives (51.6% in migrants from HDCs, 49.3% in migrants from HMPCs, and 53.5% among Italians)., Conclusion: Routinely collected data in healthcare administrative databases can support the identification of migrants with dementia. Migrants exhibited a lower age-standardized prevalence of registered dementia and lower access to dedicated treatments than Italians. These findings are suggestive of underdiagnosis and undertreatment of dementia in migrants.

Background: The term sundowning is used to describe the emergence or worsening of neuropsychiatric symptoms in late afternoon or early evening in people with dementia., Objective: Our aim was to evaluate sundowning's prevalence and clinical manifestations among patients attending a tertiary memory clinic and to investigate its clinical and neuropsychological correlates., Methods: Patients with dementia attending our memory clinic were enrolled in the study. Sundowning was identified through a specifically designed questionnaire. Sociodemographic and clinical features of sundowners and non-sundowners were compared, and a logistic regression was performed to identify the variables associated with the phenomenon. A subgroup of patients underwent a complete neuropsychological assessment., Results: Among 184 recruited patients, 39 (21.2%) exhibited sundowning, mostly expressed as agitation (56.4%), irritability (53.8%), and anxiety (46.2%). Sundowners were significantly older, had a later dementia onset, exhibited more severe cognitive and functional impairment, more frequent nocturnal awakenings, and hearing loss relative to non-sundowners. They were also more likely to use anticholinergic medications and antipsychotics, and less likely to use memantine. In a multi-adjusted model, the factors significantly associated with sundowning were the Clinical Dementia Rating score (OR 3.88; 95% CI 1.39-10.90) and the use of memantine (OR 0.20; 95% CI 0.05-0.74). Participants with and without sundowning obtained similar results in single domain neuropsychological tests., Conclusion: Sundowning is commonly experienced by patients with dementia and appears as a multiply determined condition. Its presence should always be evaluated in clinical practice and a multidimensional approach should be adopted to identify its predictors.

The Italian Fund for Alzheimer's and other dementias was approved and signed in December 2021. The Fund is financed with 15 million euros in three years. The main goal is to provide new strategies in the field of dementia with a Public Health perspective. The Fund includes eight main activities that will be monitored and supervised by the Italian National Institute of Health: 1) development of a guideline for the assessment, management and support for people with dementia and their families/carers; 2) updating of the Dementia National Plan (DNP); 3) implementation of the documents of the DNP; 4) conducting surveys dedicated to the Italian Dementia Services; 5) promotion of dementia prevention strategies; 6) training strategies for healthcare professionals, families and caregivers; 7) creation of a National Electronic Record for Dementia; 8) evaluation and monitoring of activities promoted by Regions and Autonomous Provinces in the field of dementia, together with the dementia National Permanent Table. These activities are outlined in detail in the present paper.

Background: More than 500,000 dementia cases can be estimated among migrants living in Europe. There is the need to collect "real world" data on the preparedness of healthcare services to support the inclusion of migrants in the public health response to dementia. The present study aimed (i) to estimate the number of migrants referred to Italian memory clinics (Centers for Cognitive Disorders and Dementia [CCDDs]) and (ii) to identify possible barriers and resources for the provision of diversity-sensitive care., Methods: A survey of all Italian CCDDs was conducted between December 2020 and April 2021. An online questionnaire was developed to obtain information on the number of migrants referred to Italian CCDDs in 2019, the challenges encountered in the diagnostic approach, and possible facilitators in the provision of care., Results: Overall, 343 of the 570 contacted CCDDs completed the survey questionnaire (response rate: 60.2%). Nearly 4527 migrants were referred to these services in 2019. Migrants accounted for a median 1.1% (IQR: 0.9%-2.8%) of overall CCDD referrals. More than one-third of respondents reported that the number of migrants referred to their facilities had increased in the last 5 years. The overall quality of the migrants' cognitive assessment was deemed to be very poor or insufficient in most cases. A minority of CCDDs had translated information material on dementia and reported the possibility to contact cultural mediators and interpreters., Conclusions: A relevant number of migrants are being referred to Italian CCDDs that are still not adequately prepared to deliver diversity-sensitive care and support., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: The occurrence of dementia among individuals with a migration background and composing ethnic minorities is being recognized as a global public health issue., Aims: In the present study, we sought to explore if and how this phenomenon is mentioned and addressed by the existing National Dementia Plans (NDPs)., Methods: The 32 NDPs listed on the Alzheimer's Disease International (ADI)'s website were considered for the present analysis. First, the plans mentioning the issue of dementia among migrants and/or ethnic minorities were identified. Subsequently, the sections addressing this topic and the pertaining proposed actions were analyzed and their contents were unbundled in descriptive categories., Results: Overall, nine NDPs (28.1% of the total), namely those promulgated by Australia, Austria, England, Israel, Norway, Switzerland, Taiwan, United States, and Wales, mentioned the issue of dementia among migrants and/or ethnic minorities and only eight proposed targeted actions to tackle this issue. With few exceptions, the proposed strategies were only marginally dashed within NDPs and crucial information on their objectives, timeline, conduction, and monitoring was missing., Discussion and Conclusions: To our knowledge, this is the first attempt to describe and discuss how the issue of dementia among migrants and ethnic minority groups is addressed within NDPs. The issue of dementia in migrants and ethnic minorities is assuming a growing relevance under a of global health perspective. The timely identification and implementation of dedicated policies at the national and international level are fundamental to limit its future clinical and socioeconomic burden., (© 2019. Springer Nature Switzerland AG.)

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.

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.

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

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.

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)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: The phenomenon of dementia occurring in migrants and minority groups constitutes an emerging issue for Western countries. Nevertheless, it has been poorly explored from the perspective of "real-world" clinical services. We aimed to quantify the number of migrants from LMIC attending an Italian university memory clinic and to document its modifications over time., Methods: All the subjects undergoing a first neurological and cognitive assessment between 2001 and 2017 were considered for the present analyses., Results: The proportion of subjects from LMIC performing a first cognitive evaluation was found to remain substantially stable between 2001 and 2017. No statistically significant difference was found between "HIC" and "LMIC" individuals with regard to sociodemographic and clinical characteristics., Conclusion: These findings seem to indicate that cognitive disorders in LMIC migrants still constitute a marginal public health issues for Italian dementia services. Nevertheless, the identification of eventual sociocultural and healthcare barriers may help to understand the real magnitude and relevance of this phenomenon.

Introduction: The phenomenon of dementia among immigrants and ethnic minorities represents an emerging challenge for Western countries. The aim of the present study was to estimate the number of dementia cases among immigrant subjects residing in Italy and in each Italian region to provide pivotal information on the magnitude of such public health issue., Method: The number of immigrant individuals, aged 65 years or older, living in Italy and in the 20 Italian regions was derived by the 2017 data of the National Institute for Statistics. The dementia prevalence rates were taken from the European data provided by the Neurologic Diseases in the Elderly Research Group. The estimated dementia cases were calculated by multiplying the number of immigrants with the age- and sex-specific prevalence rates., Results:  Overall, 186,373 older immigrant subjects lived in Italy in January 2017. Nearly 7700 dementia cases were estimated in this population (5022 among women, 2725 among men). When considering each specific Italian region, the number of estimated cases ranged from 19 (Basilicata) to 1500 (Lombardia) with a marked inter-regional variability., Discussion: Our findings indicate that the occurrence of dementia among immigrants and ethnic minorities constitutes a novel but already relevant issue for our healthcare systems. A non-negligible number of immigrant individuals is probably already seeking or might seek help for cognitive disturbances, thus potentially referring to general practitioners and/or to the Italian dementia services. The forecasted increasing magnitude of this phenomenon reinforces the need for tailored and locally oriented initiatives and policies.

Background: Dementia, including Alzheimer's disease (AD), is one of the most burdensome medical conditions. Usually, the reviews that aim at calculating the prevalence of dementia include estimates from studies without assessing their methodological quality. Alzheimer's Disease International (ADI) proposed a score to assess the methodological quality of population-based studies aimed at estimating the prevalence of dementia. During the last three years, the European Commission has funded three projects (Eurodem, EuroCoDe, and ALCOVE) in order to estimate the prevalence of dementia in Europe., Objective: The aim of this study was to perform a systematic review and meta-analysis of data on the prevalence of dementia in Europe derived from studies that included only subjects with a diagnosis of dementia according to the DSM IV criteria, and that had a high quality score according to ADI criteria., Methods: We considered the studies selected by the two projects EuroCoDe (1993-2007) and Alcove (2008-2011), and we performed a new bibliographic search. For the systematic review, we only selected the subset of articles that included subjects with a diagnosis of dementia according to the DSM IV criteria. The studies were qualitatively assessed using the ADI tool., Results: The meta-analysis considered 9 studies that were carried out in Europe between 1993 and 2018 including a total of 18,263 participants, of which 2,137 were diagnosed with dementia. The prevalence rate standardized for age and sex resulted 7.1%., Discussion: This is the first systematic review on the prevalence of dementia in Europe considering only high-quality studies adopting the same diagnostic criteria (i.e., DSM IV).

Mild cognitive impairment (MCI) is a nosological entity proposed by Petersen in 1999 with the objective of identifying an early stage of dementia. The new diagnostic criteria for dementia, both those promoted by the International Working Group (IWG) and those defined by the National Institute of Aging (NIA), subsequently introduced a new model that starts with a preclinical phase, then proceeds with a prodromal phase, and ends with a phase of dementia. The condition known as subjective cognitive disorder (SCD) is included between the preclinic and the prodromal phases. Most clinicians improperly consider MCI and SCD as diseases, and not as risk factors for dementia. This ambiguous scenario requires the application of a public-health standard. A diagnosis of either SCD or MCI comes with several uncertainties, raising issues pertaining to both the research setting and clinical practice. A large proportion of subjects with either SCD or MCI will never progress to dementia, and part of them may even revert to a normal cognitive profile. Thus, communicating of these diagnoses to a subject has ethical implications that cannot be underestimated. The frequency of these diagnoses in general population is starting to show the characteristics of both the phenomena of over-diagnosis, and consequently over-treatment. Moreover, the new criteria require the use of biomarkers, that are not yet validated for the use in clinical practice. No population studies are currently available performed based on the new diagnostic criteria for dementia. This means that future estimates will probably be more than twice the current ones, and will include also subjects that will not progress to dementia. This undefined framework, thus, urges the implementation of public-health programs aimed at both the primary and secondary prevention of dementias. Moreover, clinical trials on drugs in MCI currently use endpoints based on non-validated biomarkers, thus raising the issue of the external validity. A public guideline would thus be crucial to support clinicians in identifying all the possible causes that can determine a cognitive decline people that are mainly elder, with multiple comorbidities, and taking multiple medications. Moreover, the widespread use of neuro-psychological assessment tools in current clinical practice requires an accurate validation of these instruments.

Objective: Inappropriate sexual behaviors (ISBs) represent challenging and stressful manifestations of dementia and are highly burdening for patients, families, and healthcare providers. Nevertheless, ISBs have so far attracted limited clinical and scientific interest compared with other neuropsychiatric symptoms occurring in dementing illnesses. The authors aimed to systematically investigate the prevalence and characteristics of ISBs in a population of patients with dementia attending a memory clinic., Methods: In this cross-sectional study, individuals with dementia attending our memory clinic were consecutively enrolled between January 2015 and February 2016. Participating subjects underwent a detailed medical history collection and a comprehensive cognitive, functional, and neuropsychiatric assessment. The presence of ISBs (in the previous 30 days) was investigated by the adoption of an ad hoc questionnaire, administered to informants. A logistic regression model was carried out to identify sociodemographic and clinical variables associated with ISBs., Results: In the 195 patients (48.7% women) with dementia recruited for the study, ISBs were detected in 35 patients (17.9% of the total sample). The logistic regression model showed that male sex (OR: 5.14; 95% CI: 1.44-18.41) and anxiety (OR: 4.92; 95% CI: 1.44-16.84) were statistically significantly associated with the presence of ISBs., Conclusion: ISBs represent common manifestations of dementing illnesses. Given the significant burden of ISBs on patients and families and the impact on care management, their occurrence should always be investigated in the clinical care of individuals with dementia. For this purpose, specific screening/assessment tools should be properly designed and validated., (Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.)

In recent years, the possibility of favorably influencing the cognitive trajectory through promotion of lifestyle modifications has been increasingly investigated. In particular, the relationship between nutritional habits and cognitive health has attracted special attention. The present review is designed to retrieve and discuss recent evidence (published over the last 3 years) coming from randomized controlled trials (RCTs) investigating the efficacy of nutritional interventions aimed at improving cognitive functioning and/or preventing cognitive decline in non-demented older individuals. A systematic review of literature was conducted, leading to the identification of 11 studies of interest. Overall, most of the nutritional interventions tested by the selected RCTs were found to produce statistically significant cognitive benefits (defined as improved neuropsychological test scores). Nevertheless, the clinical meaningfulness of such findings was not adequately discussed and appears controversial. In parallel, only 2 studies investigated between-group differences concerning incident dementia and mild cognitive impairment cases, reporting conflicting results. Results of the present review suggest that several dietary patterns and nutritional components may constitute promising strategies in postponing, slowing, and preventing cognitive decline. However, supporting evidence is overall weak and further studies are needed.

The Italian Dementia National Plan was formulated in October 2014 by the Italian Ministry of Health in close cooperation with the regions, the National Institute of Health and the three major national associations of patients and carers. The main purpose of this strategy was to provide directive indications for promoting and improving interventions in the dementia field, not limiting to specialist and therapeutic actions, but particularly focusing on the support of patients and families throughout the pathways of care. Four main objectives are indicated: 1) promote health- and social-care interventions and policies; 2) create/strengthen the integrated network of services for dementia based on an integrated approach; 3) implement strategies for promoting appropriateness and quality of care; and 4) improve the quality of life of persons with dementia and their families by supporting empowerment and stigma reduction. These objectives and the pertaining actions are described in the present paper.

Subjective cognitive complaints (SCCs) are being increasingly recognized as a preclinical phase of dementia. Thus, SCCs may represent a "promising" stage for planning and implementing preventive interventions aimed at reducing the incidence of cognitive disorders. The aim of the present study is to present and discuss the available evidence coming from clinical trials adopting cognitive interventions in individuals with SCCs. A systematic review of literature was conducted to evaluate the available trials testing nonpharmacological cognitive interventions for the prevention of dementia in subjects with SCCs. Six studies were included in the present study. Overall, most interventions showed to objectively improve cognitive performance in subjects with SCCs. A relevant heterogeneity was found concerning their characteristics and feasibility. Conversely, there is a current lack of evidence in the literature about the efficacy of nonpharmacological cognitive interventions for preventing dementia or cognitive impairment.

INTRODUCTION: We explored the variations of blood biomarkers of Alzheimer's disease (AD) by chronic diseases and systemic inflammation. METHODS: We explored the association of AD blood biomarkers with chronic diseases and systemic inflammation (interleukin‐6 [IL‐6]), in 2366 dementia‐free participants of the Swedish National Study on Aging and Care‐in Kungsholmen, using quantile regression models. RESULTS: A greater number of co‐occurring chronic diseases was associated with higher concentrations of phosphorylated‐tau 181 (p‐tau181), total‐tau (t‐tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) (p < 0.01). Anemia, kidney, cerebrovascular, and heart diseases were associated with variations in the levels of AD blood biomarkers. Participants in the highest (vs. lowest) interleukin‐6 (IL‐6) tertile had higher NfL concentration. Systemic inflammation amplified the associations between several chronic diseases and p‐tau181, t‐tau, NfL, and GFAP. DISCUSSION: In the community, the concentration of AD blood biomarkers varies in relation to medical conditions and systemic inflammation. Recognizing these influences is crucial for the accurate interpretation and clinical implementation of blood biomarkers. Highlights: Participants with a complex clinical profile (i.e., multiple co‐occurring diseases or specific disease combinations) display elevated levels of AD blood‐biomarkers.Anemia, heart, cerebrovascular, and kidney diseases are associated with variations is the levels of AD blood biomarkers in cognitively intact older adults.Systemic inflammation amplifies the association between several chronic diseases and AD blood biomarkers. [ABSTRACT FROM AUTHOR]

Background and purpose: The aim was to determine whether frailty is associated with the relationship between neuropsychological markers and global cognition in older adults. Methods: Cross‐sectional analyzes were conducted of baseline data from three large cohort studies: National Alzheimer's Coordinating Center (NACC), Rush Memory and Aging Project (MAP) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Studies recruited North American participants along the spectrum of cognitive functioning (44% no cognitive impairment at baseline). A frailty index was computed in each dataset. Frailty indices, neuropsychological tests (including measures of processing speed, episodic, semantic and working memory) and Mini‐Mental State Examination (MMSE) scores were the variables of interest, with age, sex, education and apolipoprotein E ε4 evaluated as confounders. Results: Across all studies, 23,819 participants aged 55–104 (57% female) were included in analyzes. Frailty index scores were significantly and inversely associated with MMSE scores and significantly moderated relationships between neuropsychological test scores and MMSE scores. In participants with higher frailty index scores, lower neuropsychological test scores were more strongly associated with lower MMSE scores (standardized interaction coefficients ranged from −0.19 to −1.17 in NACC, −0.03 to −2.27 in MAP and −0.04 to −0.38 in ADNI, depending on the neuropsychological test). These associations were consistent across the different databases and were mostly independent of the composition of frailty indices (i.e., after excluding possible symptoms of dementia). Conclusions: Amongst older Americans, frailty is associated with the cognitive expression of neuropsychological deficits. Implementation of frailty assessment in routine neurological and neuropsychological practice should be considered to optimize care outcomes for older adults. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Behavioral and psychological symptoms of dementia (BPSD) have a high prevalence, and their presence is associated with a severe impact in terms of social costs. However, dedicated clinical tools or biomarkers to detect these symptoms are lacking. Thus, BPSD management in clinical settings is challenging. The aim of this study was to investigate the perception and the treatment strategies for BPSD in Italian centers working in the dementia field. Methods: A multicenter, national survey was developed by BPSD Study Group of the Italian Neurological Society for Dementia (SINDEM). The survey consisted of a semi-structured questionnaire that was e-mailed to SINDEM members, dementia centers part of the national network of memory clinics (Centers for Cognitive Deterioration and Dementia [CDCD]), and clinicians working in dementia care settings. The questions were focused on (1) perceived global frequency and relevance of BPSD; (2) tools used to assess BPSD; (3) pharmacological treatment for psychosis, apathy, agitation, aggression, depression, anxiety, sleep, and nutrition disturbances; (4) non-pharmacological treatments; (5) drugs side effects. Results: One-hundred and thirty-six clinicians participated in this study. Seventy-nine participants worked in a CDCD and 57 in other settings. The perceived frequency of BPSD was 74%. BPSD are detected by means of a clinical assessment for 96.3% or a caregiver interview for 97%. For psychosis treatment the first choice was atypical antipsychotics (83.3%), followed by typical antipsychotic (8.9%) and antidepressants (4.8%). For agitation, atypical antipsychotics were the first-choice treatment in 64% of cases and antidepressants in 16.1%. For aggression, the most used drugs were atypical antipsychotics (82.9%). For anxiety, 55.2% use antidepressants, 17.9% use atypical antipsychotics, and 16.9% use benzodiazepines. Interestingly, most of the centers apply non-pharmacological treatments for BPSD. Some differences emerged comparing the responses from CDCD and other care settings. Conclusion: The survey results revealed many differences in BPSD perception, treatment options, and observed side effect according to the clinical setting. This variability can be explained by the absence of clear guidelines, by differences in patients' characteristics, and by clinical practice based on subjective experience. These results suggest that producing guidelines for the pharmacological treatment of BPSD is a major need. [ABSTRACT FROM AUTHOR]

Background: Most COVID-19-related deaths have occurred in older persons with comorbidities. Specific patterns of comorbidities related to COVID-19 deaths have not been investigated. Methods: A random sample of 6085 individuals in Italy who died in-hospital with confirmed COVID-19 between February and December 2020 were included. Observed to expected (O/E) ratios of disease pairs were computed and logistic regression models were used to determine the association between disease pairs with O/E values ≥ 1.5. Results: Six pairs of diseases exhibited O/E values ≥ 1.5 and statistically significant higher odds of co-occurrence in the crude and adjusted analyses: (1) ischemic heart disease and atrial fibrillation, (2) atrial fibrillation and heart failure, (3) atrial fibrillation and stroke, (4) heart failure and COPD, (5) stroke and dementia, and (6) type 2 diabetes and obesity. Conclusion: In those deceased in-hospital due to COVID-19 in Italy, disease combinations defined by multiple cardio-respiratory, metabolic, and neuropsychiatric diseases occur more frequently than expected. This finding indicates a need to investigate the possible role of these clinical profiles in the chain of events that lead to death in individuals who have contracted SARS-CoV-2. [ABSTRACT FROM AUTHOR]

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 Aβ1-42, 181P-tau, and T-tau; MRI-based hippocampus volume; cortical glucose metabolism at the FDG PET imaging; amyloid deposition at the 18F-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 Aβ1-42, hippocampus volumes at the MRI, and glucose metabolism at the FDG PET imaging, and a higher amyloid deposition at the 18F-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 18F-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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

• Race is an important health determinant. • Race is insufficiently considered in research protocols targeting AD. • Race may influence the efficacy and safety profiles of anti-dementia medications. • Blacks and Hispanics are underrepresented in clinical trials on AD. • The collecting and reporting of data on race should be improved. Race is an important health determinant and should adequately be considered in research and drug development protocols targeting Alzheimer's disease (AD). A systematic review of available randomized controlled trials (RCTs) on the currently marketed treatments for AD was conducted with the aim of 1) documenting the reporting of race, and 2) exploring the impact of race on the efficacy and safety/tolerability of the considered medications. Overall, 59.2% of the 49 retained RCTs reported information concerning the race of participants. Only a striking minority of enrolled patients was constituted of blacks and Hispanics. None on the retained studies reported results on the efficacy and safety/tolerability of the tested treatment separately for racial groups nor performed sensitivity analyses accounting for the race of participants. Race has insufficiently been reported in previous interventional studies on AD. Its potential association with the effectiveness and safety/tolerability of the tested medications has completely been neglected. [ABSTRACT FROM AUTHOR]

Objectives The issue of subjects with mild cognitive impairment (MCI) reverting to normal cognition (NC) has to date been taken in limited consideration, and no conclusive data are available on the rate of reversion. We aimed at systematically reviewing available longitudinal studies on MCI and meta-analyzing data with the purpose of estimating the proportion of subjects reverting to NC. Design We performed a systematic bibliographic search on PubMed, the Cochrane Library, and the ISI Web of Science databases. We included in the review all longitudinal studies on MCI published from 1999 up to November 2015. Only studies with a longitudinal design, a follow-up ≥2 years, enrolling subjects with MCI, and reporting the number or the percentage of subjects reverting to NC were included. Data extraction was performed independently by 2 authors. The methodological quality of studies was also assessed by 2 independent authors using the QUIPS tool. Results Twenty-five studies were included. The quality of evidence was found to be moderate. We observed an overall 18% (95% CI 14–22) reversion rate from MCI to NC. Results from the metaregression showed a significant association between effect size and study setting. In particular, estimates significantly varied according to study setting, with an 8% (95% CI 4–11) reversion rate in clinical-based studies and a 25% (95% CI 19–30) rate in population-based studies. The frequency of reversion from MCI to NC further increased to 26% when considering only studies of better quality. Only a few studies were designed to specifically investigate the reversion from MCI to NC, thus relevant information on this topic was frequently missing. Conclusion Our data confirm that reversion to normality is a common outcome in subjects with MCI, thus leading to recommend a more balanced view when approaching the construct of MCI both in a clinical and in a research setting. [ABSTRACT FROM AUTHOR]

Objectives To determine whether the Frailty Index ( FI) was associated with short-term cognitive decline (according to changes in Mini Mental State Examination ( MMSE) and Alzheimer's Disease Assessment Scale-Cognitive subscale ( ADAS-Cog) scores at 1-year follow-up) in individuals with Alzheimer's disease ( AD). Design Prospective cohort study. Setting Impact of Cholinergic Treatment USe study. Participants Individuals with mild-to-moderate AD (N = 973). Measurements Severity of dementia was assessed using the Clinical Dementia Rating ( CDR). FI was calculated as the ratio of actual to potential deficits (deficits present divided by 30). Linear regression analyses were performed and stratified according to severity of dementia. Results A 1-unit (0.033 points) increase in FI corresponded to significant and clinically relevant cognitive decline, after adjustments for age, sex, and years of education (0.63-4.63 points on the MMSE, P = .01; 2.87-11.1 points on the ADAS-Cog, P = .001) after 1 year of follow-up. Differences in changes in MMSE and ADAS-Cog scores between nonfrail and frail individuals were 0.67 and 1.6 points, respectively. Although statistically significant, the clinical relevance of this finding remains to be further investigated. Conclusion The FI may be a promising instrument for the assessment of the vulnerability of individuals with AD. Its implementation in clinical practice may support clinical decisions by identifying individuals at high risk of negative outcomes, specifically, short-term cognitive decline. [ABSTRACT FROM AUTHOR]

Behavioral and psychological symptoms of dementia (BPSD) represent common manifestations among patients affected by Alzheimer's disease (AD). Some reports have recently classified BPSD into specific clusters/subsyndromes exploring the internal structure of the Neuropsychiatric Inventory (NPI). We evaluated whether specific behavioral subsyndromes are associated with worsening cognitive function. Mild to moderate AD patients were recruited from the cohort of the Impact of Cholinergic Treatment USe (ICTUS) study. Neuropsychiatric symptoms were classified in three subsyndromes, identified at baseline, grouping different combinations of NPI items: (1) 'psychotic' ('delusions' and/or 'hallucinations'); (2) 'affective' ('agitation' and/or 'depression' and/or 'anxiety' and/or 'irritability'); and (3) 'behavioral' ('euphoria' and/or 'apathy' and/or 'disinhibition' and/or 'aberrant motor behavior'). Mixed model analyses were performed to measure six-monthly changes in the ADAS-Cog score over a follow-up of 2 years, according to these subsyndromes. All analyses were stratified according to AD severity as defined by the Clinical Dementia Rating (CDR). A total of 1,375 AD subjects were recruited. No NPI cluster was found to significantly ( p < 0.05) affect the rate of cognitive decline across the 3 CDR classes. Our results suggest that the cognitive course of AD is not substantially influenced by the presence of specific neuropsychiatric phenotypes. Further studies are needed to extend the present findings and identify possible biological and clinical bases for behavioral subsyndromes. [ABSTRACT FROM AUTHOR]

The concept of “mild behavioral impairment” (MBI) has been recently introduced and tentatively operationalized. The rationale supporting the need of such novel construct is that neuropsychiatric symptoms (NPS), even when they do not configure major psychiatric disorders, may still constitute early manifestations of neurodegenerative diseases, potentially anticipating the onset of dementia. The conception of MBI as a potential pre-dementia phenotype is surely of interest because posing special attention to neuropsychiatric symptoms and their negative implications. Nevertheless, several issues should be carefully considered in the definition of MBI and are discussed in the present Commentary. [ABSTRACT FROM AUTHOR]