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Background: Controversies exist around the external validity of clinical trials on disease-modifying treatments for Alzheimer's disease (AD). Detailed information on the clinical characteristics of research participants is lacking, hampering the understanding of their representativeness., Objective: This study aimed to systematically review the baseline comorbidities and health status of patients with AD enrolled in clinical trials., Methods: A systematic review of scientific and gray literature was conducted. Randomized controlled trials, enrolling participants in the AD continuum, and testing amyloid- and tau-targeting monoclonal antibodies were selected. Data on the type of study and intervention and the baseline clinical characteristics of participants were extracted. The proportion of studies reporting information on comorbidities, integrative measures of health (e.g., number of chronic diseases and multimorbidity, frailty, and gait speed), and non-neurological concomitant therapies of participants was calculated., Results: Thirty-six articles, referring to 41 studies (21,952 participants) were included. None of the retained trials provided information on the comorbidities or other integrative measures reflecting the baseline health status of participants. Only three studies reported data on non-neurological concomitant therapies. Five documents providing relevant information were identified through gray literature searches covering the websites of regulatory agencies and pharmaceutical manufacturers., Conclusions: The health characteristics of patients with AD included in randomized controlled trials are poorly reported. Therefore, the external validity of the study findings cannot be fully appreciated., Competing Interests: Declaration of conflicting interestsMarco Toccaceli Blasi is an Editorial Board Member of this journal but was not involved in the peer-review process of this article nor had access to any information regarding its peer-review.

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.

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: Monoclonal antibodies (mAbs) are currently among the most investigated targets for potential disease-modifying therapies in Alzheimer's disease (AD)., Objective: Our objectives were to identify all registered trials investigating mAbs in MCI due to AD or AD at any stage, retrieve available published and unpublished data from all registered trials, and analyze data on safety and efficacy outcomes., Methods: A systematic search of all registered trials on ClinicalTrials.gov and EUCT was performed. Available results were searched on both platforms and on PubMed, ISI Web of Knowledge, and The Cochrane Library., Results: Overall, 101 studies were identified on 27 mAbs. Results were available for 50 trials investigating 12 mAbs. For 18 trials, data were available from both published and unpublished sources, for 21 trials only from published sources, and for 11 trials only from unpublished sources. Meta-analyses of amyloid-related imaging abnormalities (ARIA) events showed overall risk ratios of 10.65 for ARIA-E and of 1.75 for ARIA-H. The meta-analysis of PET-SUVR showed an overall significant effect of mAbs in reducing amyloid (SMD -0.88), but when considering clinical efficacy, data on CDR-SB showed that treated patients had a statistically significant but clinically non-relevant lower worsening (MD -0.15)., Conclusion: Our results suggest that the risk-benefit profile of mAbs remains unclear. Research should focus on clarifying the effect of amyloid on cognitive decline, providing data on treatment response rate, and accounting for minimal clinically important difference. Research on mAbs should also investigate the possible long-term impact of ARIA events, including potential factors predicting their onset.

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: 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.

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).

Several studies have established the sortilin-related receptor gene (SORL1) as a susceptibility locus for Alzheimer's disease (AD). Single nucleotide polymorphisms of SORL1 reported in literature as being associated with AD were investigated in an Italian case-control data set, and their role as a risk factor of conversion to AD was studied in an independent sample of subjects diagnosed with mild cognitive impairment (MCI) at baseline. rs641120, rs2070045, and rs1010159 were genotyped in 734 subjects diagnosed with AD (n = 338) and MCI (n = 181) and in healthy controls (n = 215). Our results confirmed the association between rs641120 and AD (p = 0.01). In the MCI cohort, rs1010159 was associated with conversion to AD (HR = 1.56, p = 0.002). Taken together, these findings confirm that SORL1 is associated with AD and might be a potential tool for identifying MCI subjects at high risk of conversion to AD.