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Objective: This meta-analysis with a systematic review was undertaken to assess the association between APOE allelic genotypes and the risk of Alzheimer's disease (AD) in the Italian population. Methods: The Web of Science, PubMed, and Scopus databases were searched until 15 November 2023. The odds ratio (OR) with a 95% confidence interval (CI) was calculated using fixed and random effect models, depending on the I2 statistic value. The systematic review and meta-analysis were conducted in agreement with the PRISMA guideline and registered with PROSPERO (CRD42023492580). Results: Our meta-analysis based on 15 studies revealed a higher risk of AD among Italian individuals carrying the APOE ε4 allele (OR = 3.60, 95% CI [2.90–4.47], p < 0.0001). The association of AD genotype APOE ε2ε4 (OR = 1.36, 95% CI [0.76–2.41], p = 0.29) was not statistically significant, while APOE ε3ε4 (OR = 3.43, 95% CI [2.95–3.99], p < 0.0001) has a high risk of AD development; the risk is more notably in the APOE ε4ε4 genotype (OR = 7.08, 95% CI [4.22–11.86], p < 0.0001). The APOE ε2 allele has a protective effect (APOE ε2 (OR = 0.47, 95% CI [0.29–0.74], p = 0.0013)), and similar results were achieved by APOE ε3 (OR  =  0.49, 95% CI [0.37–0.65], p < 0.0001). Subgroup analysis of three areas of Italy (southern, northern, and center) revealed that that APOE ε4 allele was a risk factor with a higher OR in northern Italy (OR 4.22; 95% CI [3.46–5.16], p < 0.0001) compared to southern and center Italy (OR 3.02; 95% CI [2.28–4.01], p < 0.0001 and OR 3.97; 95% CI [1.37–11.56], p < 0.0001, respectively). As well, APOE ε4ε4 genotype carriers had a significantly higher OR in northern Italy (OR 9.69; 95% CI [4.94–18.99], p < 0.0001) compared to in southern and center Italy (OR 4.38; 95% CI [1.54–12.47], p < 0.0001 and OR 3.59; 95% CI [0.87–14.86], p < 0.0001, respectively). Conclusions: This systematic review with a meta-analysis of the Italian population on APOE alleles, genotyping, and AD incidence, highlights that individuals harboring APOE ε4 have a higher risk of developing AD compared to those with other alleles. It also supports the protective effect of the APOE ε2 allele against the progress of AD. The qualitative analysis on the complex genetic interactions influencing Alzheimer risk emphasizes the need for further research on genetic and environmental factors for effective prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that the prevalence of all-variants Alzheimer's disease (AD) and frontotemporal dementia (FTD) both increase with age, even before the age of 65. However, it is not known whether their different clinical presentations all increase in prevalence with age in the same way. Methods: We studied the prevalence of the different clinical presentations of young-onset AD and FTD by 5-year age groups in a population-based study identifying all dementia patients with a diagnosis of AD and FTD and symptoms onset before age 65 in the Modena province, Italy. By using regression models of cumulative occurrences, we also estimated age-specific prevalence and compared the growth curves of the clinical presentations. Results: The prevalence of all-variants AD increased with age, from 18/1,000,000 in the 40–44 age group to 1411/1,000,000 in the 60–64 age group. The prevalence of all-variants FTD also increased with age, from 18/1,000,000 to 866/1,000,000. An estimation of age-specific prevalence functions of each clinical presentation showed that atypical non-amnestic AD and aphasic FTD grew the most in early ages, followed by the behavioural variant of FTD (bvFTD). Then, around the age of 60, amnestic AD took over and its age-specific prevalence continued to increase disproportionally compared to all the other clinical variants of AD and FTD, which, instead, started to decrease in prevalence. Conclusions: Amnestic AD is the clinical presentation that increases the most with advancing age, followed by bvFTD, suggesting that there is a differential vulnerability to the effect of ageing within the same neurodegenerative disease. [ABSTRACT FROM AUTHOR]

Background: Dementia is a progressive neurodegenerative condition, while metabolic syndrome (MetS) is characterized by a combination of metabolic abnormalities such as hypertension, high blood sugar, and obesity. There exists a connection and overlap between the two conditions in certain aspects, and both are influenced to varying degrees by the process of aging. This study presents an overview of the current research landscape regarding dementia and MetS through bibliometric analysis. Methods: A systematic search was conducted to retrieve relevant literature on dementia and MetS published between 1 January 2000, and 30 November 2023, from the Web of Science Core Collection database. Various bibliometric tools, including VOSviewer, CiteSpace, and the R software package “bibliometrix,” were utilized for analysis. Results: A total of 717 articles were identified, showing an upward trend in annual publications. Leading contributors included the United States, Italy, and China, with institutions such as the University of California System at the forefront. The Journal of Alzheimer’s Disease emerged as the top publisher, while research published in Neurology garnered significant citations. Noteworthy authors encompassed Panza, Francesco; Frisardi, Vincenza; and Feldman, Eva L, with Kristine Yaffe being the most cited author (280 citations). Recent studies have focused on themes like “gut microbiota,” “neuroinflammation,” “fatty acids,” and “microglia.” Conclusion: This bibliometric analysis summarizes the foundational knowledge structure in the realm of dementia and MetS from 2000 to 2023. By highlighting current research frontiers and trending topics, this analysis serves as a valuable reference for researchers in the field. [ABSTRACT FROM AUTHOR]

Background: The Rey's 15 words test is currently the most frequently used task in Italy to detect memory deficits in AD. The current standardised version is however quite outdated and lacks some cognitive indexes which may highlight problems in recall or encoding processes. The aim of the study was to update the normative data of the test and to consider some variables which were not accounted for in the original study, that is, recognition, learning rate and forgetfulness. We also adopted the process scores approach to ascertain the effects of serial position (primacy and recency). Methods: Three hundred ninety-six healthy participants were recruited. To detect any variables useful for intercepting the early stages of dementia, a group of 208 patients in the very early stage of AD was also recruited. Linear models were used to calculate the corrections scores for age, education, and gender, and ROCs were used to calculate cut-offs based on the maximum sum of sensitivity and specificity and the positive and negative predictive values. Results: All main indexes showed excellent Area Under the Curve (0.90–1), strong sensitivity and PPVs for distinguishing between the HCs and AD participants. However, the Intrusions index performed poorly in all parameters. Conclusion: The study provides updated, normative data which may be reliably used as a cognitive marker to detect early AD. The strength of the study is the large sample size and the number of indexes which make it possible to explore the utility of memory test process scores. [ABSTRACT FROM AUTHOR]

Background: The identification and staging of Alzheimer's Disease (AD) represent a challenge, especially in the prodromal stage of Mild Cognitive Impairment (MCI), when cognitive changes can be subtle. Worldwide efforts were dedicated to select and harmonize available neuropsychological instruments. In Italy, the Italian Network of Neuroscience and Neuro-Rehabilitation has promoted the adaptation of the Uniform Data Set Neuropsychological Test Battery (I-UDSNB), collecting normative data from 433 healthy controls (HC). Here, we aimed to explore the ability of I-UDSNB to differentiate between a) MCI and HC, b) AD and HC, c) MCI and AD. Methods: One hundred thirty-seven patients (65 MCI, 72 AD) diagnosed after clinical-neuropsychological assessment, and 137 HC were included. We compared the I-UDSNB scores between a) MCI and HC, b) AD and HC, c) MCI and AD, with t-tests. To identify the test(s) most capable of differentiating between groups, significant scores were entered in binary logistic and in stepwise regressions, and then in Receiver Operating Characteristic curve analyses. Results: Two episodic memory tests (Craft Story and Five Words test) differentiated MCI from HC subjects; Five Words test, Semantic Fluency (vegetables), and TMT-part B differentiated AD from, respectively, HC and MCI. Conclusions: Our findings indicate that the I-UDSNB is a suitable tool for the harmonized and concise assessment of patients with cognitive decline, showing high sensitivity and specificity for the diagnosis of MCI and AD. [ABSTRACT FROM AUTHOR]

INTRODUCTION: The goal of the present work was to assess the incidence of dementia with onset before the age of 65 years (i.e., young‐onset dementia [YOD]) and define the frequencies of young‐onset Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD), and dementia with Lewy bodies (DLB) in the general population. METHODS: The study was conducted from January 1, 2019 to December 31, 2019 in Brescia province (population: 1,268,455). During the study period, all new YOD cases (incident YOD) were counted, and all patients' records reviewed. The incidence was standardized to the Italian general population in 2019. RESULTS: A total of 29 YOD patients were diagnosed. The age‐sex standardized incidence rate was 4.58 (95% confidence interval, 3.07–6.58) per 100,000 person‐years. No difference in incidence rate between YOD due to AD or FTLD (P = 0.83) and between sexes (P = 0.81) was observed. YOD incidence increased with age, reaching its peak after 60 years. DISCUSSION: Presenting neurodegenerative YOD phenotypes encompasses both AD and FTLD. Improved knowledge on YOD epidemiology is essential to adequately plan and organize health services. [ABSTRACT FROM AUTHOR]

Background: Engaging in physical activity could help improve the quality of life in patients with Alzheimer's disease. The objective of this study was to determine the association between the levels of physical activity and lifestyle, life expectancy, and quality of life in patients with Alzheimer's disease in Iran and Italy. Methods: A total of 165 participants from Iran and Italy were enrolled in this cross-sectional study. In Iran, 85 patients participated in the study. In Italy, we enrolled 80 patients at the Sapienza University teaching hospital, Policlinico Umberto 1 in Rome. The inclusion criteria in this study include patients over 60 years old, non-smokers, and non-users of antidepressants and hypnotics. Results: The results of Tukey's post hoc test of the study conducted in Iran showed that the lifestyle of patients with moderate (p = 0.001) and low (p = 0.009) physical activity levels was significantly better than inactive patients. Life expectancy in patients with moderate physical activity levels was significantly higher than inactive patients (p = 0.011). The quality of life was significantly better in patients with moderate (p = 0.001) and low (p = 0.002) physical activity levels than inactive patients. On the other hand, the findings of Tukey's post hoc test of the study in Italy showed that the quality of life in patients with low (p = 0.001) and moderate physical activity levels (p = 0.01) was significantly higher than inactive patients. Conclusions: A low to moderate level of physical activity could be associated with an improved lifestyle, life expectancy, and quality of life in patients with Alzheimer's disease compared to inactivity. [ABSTRACT FROM AUTHOR]

Dementia is on the rise in the world population and has been defined by the World Health Organization as a global public health priority. In Italy, according to demographic projections, in 2051 there will be 280 elderly people for every 100 young people, with an increase in all age-related chronic diseases, including dementia. Currently the total number of patients with dementia is estimated to be over 1 million (mainly with Alzheimer's disease (AD) and Parkinson's disease (PD)). In-depth studies of the etiology and physiology of dementia are complicated due to the complexity of these diseases and their long duration. In this work we present a dataset on mortality rates (in the form of Standardized Mortality Ratios, SMR) for AD e PD in Italy at provincial level over a period of 8 years (2012–2019). Access to long-term, spatially detailed and ready-to-use data could favor both health monitoring and the research of new treatments and new drugs as well as innovative methodologies for early diagnosis of dementia. [ABSTRACT FROM AUTHOR]

No disease-modifying therapies are currently available for Alzheimer's disease (AD) in Europe. Current evidence from clinical trials testing anti-beta amyloid (Aβ) monoclonal antibodies (mAbs) in patients with early AD, though, suggests a likely marketing authorization in the next years. Since the implementation of disease-modifying therapies for AD in the clinical practice will evidently require a huge change of dementia care in all countries, a group of prominent AD clinical experts in Italy met to discuss patients' selection and management strategies. The current diagnostic–therapeutic standard of care in Italy was taken as the starting point. The prescription of new therapies cannot ignore the definition of a biological diagnosis through the assessment of both amyloid- and tau-related biomarkers. The high risk/benefit ratio of anti-Aβ immunotherapies, moreover, needs a highly specialized diagnostic work-up and a thorough exclusion criteria assessment, which should be provided by a neurology specialist. The Expert Panel also suggests a reorganization of the Centers for dementia and cognitive decline in Italy into 3 levels of increasing complexity: community center, first- and second-level center. Tasks and requirements for each level were defined. Finally, specific characteristics of a center deputed to prescribe anti-Aβ mAbs were discussed. [ABSTRACT FROM AUTHOR]

Objective: Alzheimer's disease (AD) is a major disease that affects the elderly worldwide. Several studies have revealed that vitamins may influence the risk of developing AD. However, information in this field remains ambiguous. Therefore, this study aimed to examine the relationship between AD and vitamins, identify journal publications and collaborators, and analyze keywords and research trends using a bibliometric method. Methods: We systematically searched the Web of Science (WOS) Core Collection for papers published on AD and vitamins. Retrieved data regarding institutions, journals, countries, authors, journal distribution, keywords, and so on. SPSS 25 software was used for the statistical analysis, and CiteSpace V.6.1.R6 was used to visualize the information through collaborative networks. Results: A total of 2,838 publications were ultimately included in accordance with the specified inclusion criteria. The number of publications gradually increased from 1996 to 2023, with papers published in 87 countries/regions and 329 institutions. China (centrality: 0.02) and the University of Kentucky (centrality: 0.09) were the major research countries and institutions, respectively. NEUROLOGY was cited most frequently, reaching 1,573, and had the greatest impact. The cited keywords show that "Alzheimer's disease," "oxidative stress," "vitamin E," and "dementia" have been research hotspots in recent years. Beta-carotene emerged in 2023 and was identified as a developmental trend in this field. Conclusion: This is the first bibliometric analysis of vitamins associated with AD. We identified 2,838 articles in the field of vitamins and AD, analyzed the information of major countries/regions, institutions, and core journals in this field, and summarized the research hotspots and frontiers. These findings provide useful information for researchers to explore the role of vitamins in AD further. [ABSTRACT FROM AUTHOR]

Introduction: Acetylcholinesterase inhibitors (AChEIs) and memantine are currently the only anti-dementia drugs (ADDs) approved for treating Alzheimer's disease (AD) in Italy. This nationwide study aims to characterize dementia drug utilization in a population > 65 years, during 2018–2020. Methods: Different administrative healthcare databases were queried to collect both aggregate and individual data. Results: ADD consumption remained stable throughout the study period (~ 9 DDD/1000 inhabitants per day). AChEI consumption was over 5 DDD/1000 inhabitants per day. Memantine consumption was nearly 4 DDD/1000 inhabitants per day, representing 40% of ADD consumption. The prevalence of use of memantine represented nearly half of ADD consumption, substantially unchanged over the 3 years. Comparing the AD prevalence with the prevalence of ADDs use, the gap becomes wider as age increases. In 2019, the proportion of private purchases of ADDs was 38%, mostly represented by donepezil and rivastigmine. In 2020, memantine was the only ADD with an increase in consumption (Δ% 19–20, 1.3%). Discussion: To our knowledge, this study represents the first attempt to investigate the ADD prescription pattern in Italy with a Public Health approach. In 2019, the proportion of ADD private purchases point out several issues concerning the reimbursability of ADDs. From a regulatory perspective, ADDs can be reimbursed by the National Health System only to patients diagnosed with AD; therefore, the off-label use of ADDs in patients with mild cognitive impairment may partially explain this phenomenon. The study extends knowledge on the use of ADDs, providing comparisons with studies from other countries that investigate the prescription pattern of ADDs. [ABSTRACT FROM AUTHOR]

Providing evidence on donepezil and memantine administration as extemporaneous combination (DM-EXT) to treat Alzheimer Disease (AD) in Italy, and describing demographic and clinical features of AD patients prescribed DM-EXT. Retrospective observational study using IQVIA Italian LifeLink Treatment Dynamics (LRx) and Longitudinal Patient Database (LPD). Prevalent users of DM-EXT were identified on the databases (cohorts DMpLRx and DMpLPD) including patients with donepezil and memantine overlapping prescriptions during the selection period (DMpLRx: "July 2018–June 2021"; DMpLPD: "July 2012–June 2021"). Demographic and clinical profiles of patients were provided. Starting from cohort DMpLPD, new users of DM-EXT were selected to calculate treatment adherence. Three additional cohorts of prevalent users of DM-EXT were identified on IQVIA LRx over subsequent 12-month periods, from July 2018 to June 2021, to get national-level yearly estimates accounting for database representativeness. Cohorts DMpLRx and DMpLPD included 9862 and 708 patients, respectively. For both cohorts, two-third of patients were female, and more than half were aged 80+. Concomitant conditions and co-treatments prevalence was very high; most frequent comorbidities included psychiatric and cardiovascular diseases. An intermediate-to-high adherence was observed in 57% of DM-EXT new users. National-level yearly estimates showed an increasing trend (+4%) in DM-EXT prescription, which led to estimate about 10,000 patients being treated during the period "July 2020–June 2021". Prescription of DM-EXT is a common practice in Italy. Because the administration of fixed-dose (FDCs) instead of extemporaneous combinations improves treatment adherence, the introduction of an FDC containing donepezil and memantine might enhance AD patients' management and reduce caregiver burden. [ABSTRACT FROM AUTHOR]

Introduction: Growth Differentiation Factor 15 (GDF15) is a mitochondrial-stress-responsive molecule whose expression strongly increases with aging and age-related diseases. However, its role in neurodegenerative diseases, including Alzheimer's disease (AD), is still debated. Methods: We have characterized the expression of GDF15 in brain samples from AD patients and non-demented subjects (controls) of different ages. Results: Although no difference in CSF levels of GDF15 was found between AD patients and controls, GDF15 was expressed in different brain areas and seems to be predominantly localized in neurons. The ratio between its mature and precursor form was higher in the frontal cortex of AD patients compared to age-matched controls (p<0.05). Moreover, this ratio was even higher for centenarians (p<0.01), indicating that aging also affects GDF15 expression and maturation. A lower expression of OXPHOS complexes I, III, and V in AD patients compared to controls was also noticed, and a positive correlation between GDF15 and IL-6 mRNA levels was observed. Finally, when GDF15 was silenced in vitro in dermal fibroblasts, a decrease in OXPHOS complexes transcript levels and an increase in IL-6 levels were observed. Discussion: Although GDF15 seems not to be a reliable CSF marker for AD, it is highly expressed in aging and AD brains, likely as a part of stress response aimed at counteracting mitochondrial dysfunction and neuroinflammation. [ABSTRACT FROM AUTHOR]

Recent extensive evidence suggests that ambient fine particulate matter (PM2.5, with an aerodynamic diameter ≤2.5 μm) may be neurotoxic to the brain and cause central nervous system damage, contributing to neurodevelopmental disorders, such as autism spectrum disorders, neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, and mental disorders, such as schizophrenia, depression, and bipolar disorder. PM2.5 can enter the brain via various pathways, including the blood–brain barrier, olfactory system, and gut-brain axis, leading to adverse effects on the CNS. Studies in humans and animals have revealed that PM2.5-mediated mechanisms, including neuroinflammation, oxidative stress, systemic inflammation, and gut flora dysbiosis, play a crucial role in CNS damage. Additionally, PM2.5 exposure can induce epigenetic alterations, such as hypomethylation of DNA, which may contribute to the pathogenesis of some CNS damage. Through literature analysis, we suggest that promising therapeutic targets for alleviating PM2.5-induced neurological damage include inhibiting microglia overactivation, regulating gut microbiota with antibiotics, and targeting signaling pathways, such as PKA/CREB/BDNF and WNT/β-catenin. Additionally, several studies have observed an association between PM2.5 exposure and epigenetic changes in neuropsychiatric disorders. This review summarizes and discusses the association between PM2.5 exposure and CNS damage, including the possible mechanisms by which PM2.5 causes neurotoxicity. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a genetically complex disorder. In addition to the relatively small number of pathogenic variants causing autosomal dominant AD, many others have been associated with the much more common sporadic form. The E4 allele of the Apolipoprotein E (APOE) is the first discovered genetic risk factor for AD. In addition, more than 70 genetic risk loci contributing to AD have been identified. Current guidelines do not recommend AD susceptibility genetic testing in cognitively healthy adults because the implications for clinical care are limited. However, secondary prevention clinical trials of disease-modifying therapies enrol individuals based on genetic criteria, and participants are often informed of APOE testing results. Moreover, the availability of direct-to-consumer genetic testing allows individuals to learn their own AD genetic risk profile without medical supervision. A number of research protocols for AD susceptibility genetic testing have been proposed. In Italy, disclosure processes and protocols beyond those developed for inherited dementia have not been established yet. We reviewed the literature on the current practice and clinical issues related to disclosing AD genetic risk to cognitively healthy individuals and provide suggestions that may help to develop specific guidelines at the national level. [ABSTRACT FROM AUTHOR]

Although young-onset dementia (YOD) affects the whole family system, this population is still under-represented in literature, and no progress in care provision has been made. Hence, additional evidence is necessary to understand how family and social relationships are affected by YOD and care challenges, as to provide recommendations for clinical practice and service improvement from a family perspective. Family carers were recruited via one memory clinic and the local Alzheimer's Associations in Italy. Semi-structured interviews explored their experiences with YOD, the impact of the condition on their lives, family and social relationships, and the support and care they received. Transcripts were coded by three researchers and analysed using inductive thematic analysis. Thirty-eight interviews were conducted with 26 spouses and 12 adult children. Three themes emerged: 1) Problems around diagnosis, 2) Lack of post-diagnostic support, and 3) Living with YOD as a family. Overall, problems occurred across the dementia pathway. Without appropriate support, it was difficult for families to adjust to living with YOD and to the associated changes in family roles and relationships. Since optimal care depends on good family relationships, better support for families in the adaptation to condition would likely benefit patient care while ensuring social inclusion and health equity for vulnerable groups. [ABSTRACT FROM AUTHOR]

Early-onset Alzheimer's disease (EOAD) is the most common form of earlyonset dementia. Although three major genes have been identified as causative, the genetic contribution to the disease remains unsolved in many patients. Recent studies have identified pathogenic variants in genes representing a risk factor for developing Alzheimer's disease (AD) and in causative genes for other degenerative dementias as responsible for EOAD. To study them further, we investigated a panel of candidate genes in 102 Italian EOAD patients, 45.10% of whom had a positive family history and 21.74% with a strong family history of dementia. We found that 10.78% of patients carried pathogenic or likely pathogenic variants, including a novel variant, in PSEN1, PSEN2, or APP, and 7.84% showed homozygosity for the +4 APOE allele. Additionally, 7.84% of patients had a moderate risk allele in PSEN1, PSEN2, or TREM2 genes. Besides, we observed that 12.75% of our patients carried only a variant in genes associated with other neurodegenerative diseases. The combination of these variants contributes to explain 46% of cases with a definite familiarity and 32% of sporadic forms. Our results confirm the importance of extensive genetic screening in EOAD for clinical purposes, to select patients for future treatments and to contribute to the definition of overlapping pathogenic mechanisms between AD and other forms of dementia. [ABSTRACT FROM AUTHOR]

Although originally multi-ethnic in its structure, nowadays the Calabria region of southern Italy represents an area with low genetic heterogeneity and a high level of consanguinity that allows rare mutations to be maintained due to the founder effect. A complex research methodology—ranging from clinical activity to the genealogical reconstruction of families/populations across the centuries, the creation of databases, and molecular/genetic research—was modelled on the characteristics of the Calabrian population for more than three decades. This methodology allowed the identification of several novel genetic mutations or variants associated with neurodegenerative diseases. In addition, a higher prevalence of several hereditary neurodegenerative diseases has been reported in this population, such as Alzheimer's disease, frontotemporal dementia, Parkinson's disease, Niemann–Pick type C disease, spinocerebellar ataxia, Creutzfeldt–Jakob disease, and Gerstmann–Straussler–Scheinker disease. Here, we summarize and discuss the results of research data supporting the view that Calabria could be considered as a genetic isolate and could represent a model, a sort of outdoor laboratory—similar to very few places in the world—useful for the advancement of knowledge on neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Background: Neuropsychological testing plays a cardinal role in the diagnosis and monitoring of Alzheimer's disease. A major concern is represented by the heterogeneity of the neuropsychological batteries currently adopted in memory clinics and healthcare centers. The current study aimed to solve this issue. Methods: Following the initiative of the University of Washington's National Alzheimer's Coordinating Center (NACC), we presented the Italian adaptation of the Neuropsychological Test Battery of the Uniform Data Set (I-UDSNB). We collected data from 433 healthy Italian individuals and employed regression models to evaluate the impact of demographic variables on the performance, deriving the reference norms. Results: Higher education and lower age were associated with a better performance in the majority of tests, while sex affected only fluency tests and Digit Span Forward. Conclusions: The I-UDSNB offers a valuable and harmonized tool for neuropsychological testing in Italy, to be used in clinical and research settings. [ABSTRACT FROM AUTHOR]

Objective: This study characterizes glucose metabolism and tau protein deposition distribution in patients with Alzheimer's disease (AD) and to evaluate the relationships between neuropsychological performance and tau protein deposition or glucose metabolism using 18F-FDG and 18F-AV1451 positron emission tomography/computed tomography (PET/CT). Methods: Sixty-four patients with β-amyloid-positive (Aβ+) AD and twenty-five healthy participants were enrolled in this study. All participants underwent 18F-FDG and 18F-AV1451 PET/CT. Clinical data and neuropsychological scores were collected. Patients with AD were divided into mild, moderate, and severe groups according to mini-mental state examination (MMSE) scores. The standardized uptake value ratios (SUVRs) for both FDG and AV1451 PET images were calculated using the cerebellar vermis as reference. The SUVRs of the whole cerebral cortex and each brain region were calculated. The volume of interest (VOI) was obtained using automated anatomical atlas (AAL) and Brodmann regions. Student's t -test was used to perform intergroup comparisons of SUVR. The partial correlation coefficient between SUVR and neuropsychological scores was computed in an inter-subject manner using age and education as covariates. Results: The mild subgroup showed a reduction in glucose metabolism and aggregation of tau protein in the temporoparietal cortex. With a decline in neuropsychiatric performance, the SUVR on FDG PET decreased and SUVR on tau PET increased gradually. The areas of glucose metabolism reduction and tau protein deposition appeared first in the parietal cortex, followed by the temporal and frontal cortex, successively. Both FDG and tau SUVRs significantly correlated with MMSE, Montreal cognitive assessment (MOCA), auditory verbal learning test (AVLT), Boston naming test (BNT), clock drawing task (CDT), and verbal fluency test (VFT) (p < 0.05). The SUVR on FDG PET significantly correlated with activities of daily living (ADL) and the Hamilton depression scale (HAMD). There was no significant correlation between the tau SUVRs and ADL or HAMD. Conclusion: The extension of tau protein deposition was similar but not exactly consistent with the area of glucose metabolism reduction. Both tau and FDG SUVRs correlated with cognitive function in domain-specific patterns, and the results of FDG PET more closely correlated with neuropsychological function than tau PET results did. [ABSTRACT FROM AUTHOR]

Multitarget anti-Alzheimer agents are the focus of very intensive research. Through a comprehensive bibliometric analysis of the publications in the period 1990–2020, we have identified trends and potential gaps that might guide future directions. We found that: (i) the number of publications boomed by 2011 and continued ascending in 2020; (ii) the linked-pharmacophore strategy was preferred over design approaches based on fusing or merging pharmacophores or privileged structures; (iii) a significant number of in vivo studies, mainly using the scopolamine-induced amnesia mouse model, have been performed, especially since 2017; (iv) China, Italy and Spain are the countries with the largest total number of publications on this topic, whereas Portugal, Spain and Italy are the countries in whose scientific communities this topic has generated greatest interest; (v) acetylcholinesterase, β-amyloid aggregation, oxidative stress, butyrylcholinesterase, and biometal chelation and the binary combinations thereof have been the most commonly pursued, while combinations based on other key targets, such as tau aggregation, glycogen synthase kinase-3β, NMDA receptors, and more than 70 other targets have been only marginally considered. These results might allow us to spot new design opportunities based on innovative target combinations to expand and diversify the repertoire of multitarget drug candidates and increase the likelihood of finding effective therapies for this devastating disease. [ABSTRACT FROM AUTHOR]

The CD33 gene encodes for a member of the sialic-acid-binding immunoglobulin-type lectin (Siglec) family, and is one of the top-ranked Alzheimer's disease (AD) risk genes identified by genome-wide association studies (GWAS). Many CD33 polymorphisms are associated with an increased risk of AD, but the function and potential mechanism of many CD33 single-nucleotide polymorphisms (SNPs) in promoting AD have yet to be elucidated. We recently identified the CD33 SNP rs2455069-A>G (R69G) in a familial form of dementia. Here, we demonstrate an association between the G allele of the rs2455069 gene variant and the presence of AD in a cohort of 195 patients from southern Italy. We carried out in silico analysis of the 3D structures of CD33 carrying the identified SNP to provide insights into its functional effect. Structural models of the CD33 variant carrying the R69G amino acid change were compared to the CD33 wild type, and used for the docking analysis using sialic acid as the ligand. Our analysis demonstrated that the CD33-R69G variant may bind sialic acid at additional binding sites compared to the wild type, thus potentially increasing its affinity/specificity for this molecule. Our results led to a new hypothesis of rs2455069-A>G SNP as a risk factor for AD, suggesting that a long-term cumulative effect of the CD33-R69G variant results from the binding of sialic acid, acting as an enhancer of the CD33 inhibitory effects on amyloid plaque degradation. [ABSTRACT FROM AUTHOR]

Background: Early in-vivo diagnosis of Alzheimer's disease (AD) is crucial for accurate management of patients, in particular, to select subjects with mild cognitive impairment (MCI) that may evolve into AD, and to define other types of MCI non-AD patients. The application of artificial intelligence to functional brain [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography(CT) aiming to increase diagnostic accuracy in the diagnosis of AD is still undetermined. In this field, we propose a radiomics analysis on advanced imaging segmentation method Statistical Parametric Mapping (SPM)-based completed with a Machine-Learning (ML) application to predict the diagnosis of AD, also by comparing the results with following Amyloid-PET and final clinical diagnosis. Methods: From July 2016 to September 2017, 43 patients underwent PET/CT scans with FDG and Florbetaben brain PET/CT and at least 24 months of clinical/instrumental follow-up. Patients were retrospectively evaluated by a multidisciplinary team (MDT = Neurologist, Psychologist, Radiologist, Nuclear Medicine Physician, Laboratory Clinic) at the G. Giglio Institute in Cefalù, Italy. Starting from the cerebral segmentations applied by SPM on the main cortical macro-areas of each patient, Pyradiomics was used for the feature extraction process; subsequently, an innovative descriptive-inferential mixed sequential approach and a machine learning algorithm (i.e., discriminant analysis) were used to obtain the best diagnostic performance in prediction of amyloid deposition and the final diagnosis of AD. Results: A total of 11 radiomics features significantly predictive of cortical beta-amyloid deposition (n = 6) and AD (n = 5) were found. Among them, two higher-order features (original_glcm_Idmn and original_glcm_Id), extracted from the limbic enthorinal cortical area (ROI-1) in the FDG-PET/CT images, predicted the positivity of Amyloid-PET/CT scans with maximum values of sensitivity (SS), specificity (SP), precision (PR) and accuracy (AC) of 84.92%, 75.13%, 73.75%, and 79.56%, respectively. Conversely, for the prediction of the clinical-instrumental final diagnosis of AD, the best performance was obtained by two higher-order features (original_glcm_MCC and original_glcm_Maximum Probability) extracted from ROI-2 (frontal cortex) with a SS, SP, PR and AC of 75.16%, 80.50%, 77.68%, and 78.05%, respectively, and by one higher-order feature (original_glcm_Idmn) extracted from ROI-3 (medial Temporal cortex; SS = 80.88%, SP = 76.85%, PR = 75.63%, AC = 78.76%. Conclusions: The results obtained in this preliminary study support advanced segmentation of cortical areas typically involved in early AD on FDG PET/CT brain images, and radiomics analysis for the identification of specific high-order features to predict Amyloid deposition and final diagnosis of AD. [ABSTRACT FROM AUTHOR]

Vascular alterations often overlap with neurodegeneration, resulting in mixed forms of dementia (MD) that are hard to differentiate from Alzheimer's Disease (AD). The 26 bp intergenic polymorphism of VAMP2 , a key component of SNARE complex, as well as its mRNA and protein levels are associated with neurological diseases. We evaluated ApoE4 and VAMP2 26 bp Ins/Del genotype distribution in 177 AD, 132 MD, 115 Mild Cognitive Impairment (MCI) and 250 individuals without cognitive decline (CT), as well as VAMP2 gene expression in a subset of 73 AD, 122 MD, 103 MCI and 140 CT. Forty-two MCI evolved to AD (22 MCI-AD) or MD (20 MCI-MD) over time. VAMP2 mRNA was higher in MD compared to AD (p = 0.0013) and CT (p = 0.0017), and in MCI-MD compared to MCI-AD (p < 0.001) after correcting for age, gender, MMSE and ApoE4 +/− covariates (p c = 0.004). A higher VAMP2 expression was observed in subjects carrying the minor allele Del compared to those carrying the Ins/Ins genotype (p = 0.012). Finally, Del/Del genotype was more frequently carried by MD/MCI-MD compared to CT (p c = 0.036). These results suggest that VAMP2 mRNA expression can discriminate mixed form of dementia from AD, possibly being a biomarker of AD evolution in MCI patients. [ABSTRACT FROM AUTHOR]

Caregivers of patients with early-onset Alzheimer's disease (EOAD) experience higher level of burden, stress, and depression, due to premature role changes and social isolation. Moreover, the SARS-CoV-2 pandemic compelled restrictions regarding social interactions and mobility in Italy from March 2020, prompting telemedicine approaches for supporting patients and their families confined at home. We reported our experience regarding the effects of psychological phone-intervention (phone-I) on EOAD caregivers during pandemic. Twenty caregivers of EOAD patients were randomly assigned to treatment (TG) or control (CG) group. TG weekly underwent a phone-I for one month. All participants were assessed for caregiver burden and needs, anxiety and depression levels, and subjective impact of traumatic events at baseline (T0), at the fifth week (T1) and after 6 months (T2) from phone-I. We observed higher vulnerability to post-traumatic stress in TG compared to CG in all timepoints (p ≤ 0.05). Decreased stress effects and caregiver burden were revealed in TG at T1 compared to T0 (p ≤ 0.05), although showing an increase of these measures at T2 in the treated caregivers. Our findings suggest that although TG showed a peculiar vulnerability to post-traumatic stress, they showed increased wellbeing immediately after phone-I. However, this benefit disappeared six months later, along with the second infection wave, probably due to "exhaustion stage" achievement in "General Adaptation Syndrome". This trend may suggest a beneficial but not solving role of a prompt phone-I on burden of caregivers of EOAD patients during the SARS-CoV-2 emergency. [ABSTRACT FROM AUTHOR]

Background. The objective of this study was to evaluate the reliability and validity of the lifestyle (Miller-Smith) and life expectancy (Schneider) questionnaires in the Italian setting in order to make this instrument available for the determination of lifestyle and hope level in the different domains of everyday life. Method. Before testing their psychometric properties, the original versions of the two questionnaires, lifestyle (Miller-Smith) and life expectancy (Schneider), were translated into the Italian language. We tested the instrument's psychometric properties on a sample of 18 patients over 60 years old with Alzheimer's disease in the Sapienza University of Rome teaching hospital, policlinico Umberto 1. Internal consistency was considered to assess the reliability of the results across items within the adopted scale by using Cronbach's α coefficient. Using Kolmogorov-Smirnov's test, the normality distribution was evaluated to guarantee the applicability of a parametric or non-parametric test. The software used to analyze data was SPSS version 26 for Windows. Results. According to the outcome of our statistical analysis, the lifestyle scale showed high overall internal consistency, and the Cronbach's α coefficient for the total 20-item scale was 0.80 in the Italian population. On the other hand, using the 12-item questionnaire about life expectancy resulted in a high overall internal consistency of 0.93, according to the Cronbach's alpha test. Conclusions. The outcome of our study shows that the Italian versions of the lifestyle (Miller-Smith) and life expectancy (Schneider) questionnaires demonstrated good psychometric properties and good characteristics of factorial validity for future epidemiological studies aimed at evaluating lifestyle and lifestyle expectancy in the Italian population and can as well be used in clinical practice and research. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by cortical dementia and irreversibly progressive developments leading to a vegetative state and, finally, to death. Although many aspects of its etiology, diagnosis and treatment still remain obscure and the current approach to the disease mostly suffers from limited and low-efficiency therapeutic means, nevertheless, recent interventions have aimed at improving patients' quality of life through nonpharmacological approaches, including animal-assisted therapy (AAT), arousing growing interest. In order to assess the physiological and neuropsychological effects of AAT on AD, 24 residents of a rest house in northern Italy were enrolled. The intervention consisted of one 45-minute AAT session per week over ten weeks. Twelve residents (six AD and six non-AD) received AAT and twelve (six AD and six non-AD) were controls. In order to evaluate the physiological and clinical effect of AAT on AD residents, three cardiac parameters, including the systolic and diastolic blood pressure and heart rate, were measured. Moreover, the neurocognitive and depressive states were assessed by the Mini Mental State Examination and the Geriatric Depression Scale, respectively. Analyses were performed by a four-way ANOVA model (including two ways for repeated measures) considering each main effect and interaction possible in the design. Our findings, despite the small sample size, suggest that AAT has a positive significant effect on physiological parameters and neurocognitive impairment, while no effect was observed on the depression level. [ABSTRACT FROM AUTHOR]

Background: Behavioral and psychological symptoms of dementia (BPSD) have a large impact on the quality of life of patients with Alzheimer's disease (AD). Few studies have compared BPSD between early-onset (EOAD) and late-onset (LOAD) patients, finding conflicting results.Objective: The aims of this study were to: 1) characterize the presence, overall prevalence, and time of occurrence of BPSD in EOAD versus LOAD; 2) estimate the prevalence over time and severity of each BPSD in EOAD versus LOAD in three stages: pre-T0 (before the onset of the disease), T0 (from onset to 5 years), and T1 (from 5 years onwards); 3) track the manifestation of BPSD sub-syndromes (i.e., hyperactivity, psychosis, affective, and apathy) in EOAD versus LOAD at T0 and T1.Methods: The sample includes 1,538 LOAD and 387 EOAD diagnosed from 1996 to 2018. Comprehensive assessment batteries, including the Neuropsychiatric Inventory (NPI), were administered at the first medical assessment and at different follow-up period.Results: The overall prevalence for the most of BPSD was significantly higher in EOAD compared to LOAD whereas most BPSD appeared significantly later in EOAD patients. Between the two groups, from pre-T0 to T1 we recorded a different pattern of BPSD prevalence over time as well as for BPSD sub-syndromes at T0 and T1. Results on severity of BPSD did not show significant differences.Conclusion: EOAD and LOAD represent two different forms of a single entity not only from a neuropathological, cognitive, and functional level but also from a psychiatric point of view. [ABSTRACT FROM AUTHOR]

Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD) are the two major neurodegenerative diseases with distinct clinical and neuropathological profiles. The aim of this report is to conduct a population-based investigation in well-characterized APP , PSEN1 , PSEN2 , MAPT , GRN , and C9orf72 mutation carriers/pedigrees from the north, the center, and the south of Italy. We retrospectively analyzed the data of 467 Italian individuals. We identified 21 different GRN mutations, 20 PSEN1 , 11 MAPT , 9 PSEN2 , and 4 APP . Moreover, we observed geographical variability in mutation frequencies by looking at each cohort of participants, and we observed a significant difference in age at onset among the genetic groups. Our study provides evidence that age at onset is influenced by the genetic group. Further work in identifying both genetic and environmental factors that modify the phenotypes in all groups is needed. Our study reveals Italian regional differences among the most relevant AD/FTD causative genes and emphasizes how the collaborative studies in rare diseases can provide new insights to expand knowledge on genetic/epigenetic modulators of age at onset.

The aim of this pilot, feasibility study was to assess health improvements in 16 institutionalized older people with Alzheimer's disease, after the Biodanza intervention, a nonpharmacological dance movement-based treatment. Biodanza significantly decreased agitated and neuropsychiatric behaviors. Effectiveness studies will be performed in order to assess the implication of such interventions. [ABSTRACT FROM AUTHOR]

See related editorial by Lundebjerg et al. [ABSTRACT FROM AUTHOR]

This longitudinal study explores whether the working situation (no change in working hours despite care, reduction of working hours due to care or not working) moderates mental and physical health of informal caregivers of older people with Alzheimer's disease (AD) in Italy. Data from a sample of 146 caregivers of older people with moderate AD involved in the UP-TECH trial across three waves were analysed. Multivariate analyses were used to study the association between independent variables (caregivers' work situation) and dependent variables (caregivers' psycho-physical health). In a second model, elements relating to the caregiver, the cared-for individual and the caregiving situation were added as controls. Being forced to reduce working hours due to care tasks or not being employed independently from care was negatively associated with informal caregiver's physical health, compared with working carers not experiencing reduction of working hours. In the extended model, this result was confirmed. In comparison with working carers not forced to reduce working hours, non-working carers experienced higher levels of caregiver burden and depression, however these results were not confirmed in the adjusted model. Other factors also emerged as important including weekly hours of care, the cared-for older individual's ADL/IADL scores and informal support network. Given the positive effect of labour force participation on health of informal caregivers of older people with AD, policy makers should promote their employment avoiding their forced reduction of working hours, while also putting measures in place to decrease the intensity of informal care provision. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is one of the most disabling conditions worldwide and the disease burden increases with the aging global population. There are only a few prospective studies using real-world data to support effective healthcare resource utilization (HCRU) in AD.Objective: To confirm the association between HCRU and AD severity in a real-world population, including patients with all cognitive impairment (CI) severities.Methods: Data were drawn from a multi-national, cross-sectional survey of physicians and their consulted patients with all stages (very mild, mild, moderate, and severe) of CI including AD conducted in France, Germany, Italy, Spain, UK, US, and Canada. Elements of HCRU including medical consultations, professional caregiver hours, hospitalization, and institutionalization were compared between CI severity subgroups, and by country and region.Results: 6,143 CI patients were included with very mild (n = 659), mild (n = 2,473), moderate (n = 2,603), and severe (n = 408) dementia. HCRU increased with increasing CI severity (p < 0.001) for the majority of elements measured. Further analyses of overall and regional populations also confirmed significant increases in most HCRU elements with increasing disease severity. The general trend toward increased HCRU with increased CI severity was also seen in individual countries. Individual country data appeared to indicate that earlier intervention decreased hospitalizations and full-time institutionalization at the later (more severe) disease stages.Conclusion: Our findings confirmed that HCRU increases with increasing CI severity. Effective intervention in early disease could therefore reduce or delay incurring greater HCRU costs associated with more severe disease. Further studies are needed to confirm this hypothesis. [ABSTRACT FROM AUTHOR]

Background: Despite the crucial role played by general practitioners in the identification and care of people with cognitive impairment, few data are available on how they may improve the early recognition of patients with Alzheimer dementia (AD), especially those with long (i.e., 10 years and longer) medical history. Aims: To investigate the occurrence and the predictors of AD during a 10-year or longer period prior AD diagnosis in primary care patients aged 60 years or older. Materials and Methods: A cohort study with a nested case-control analysis has been conducted. Data were extracted from the Italian Health Search Database (HSD), an Italian database with primary care data. AD cases have been defined in accordance with the International Classification of Diseases, ninth edition (ICD-9-CM) codes and coupled with the use of anti-dementia drugs. Prevalence and incidence rates of AD have been calculated. To test the association between candidate predictors, being identified in a minimum period of 10 years, and incident cases of AD, we used a multivariate conditional logistic regression model. Results: As recorded in the primary care database, AD prevalence among patients aged 60 years or older was 0.8% during 2016, reaching 2.4% among nonagenarians. Overall, 1,889 incident cases of AD have been identified, with an incidence rate as high as 0.09% person-year. Compared with 18,890 matched controls, history of hallucinations, agitation, anxiety, aberrant motor behavior, and memory deficits were positively associated with higher odds of AD (p < 0.001 for all) diagnosis. A previous diagnosis of depression and diabetes and the use of low-dose aspirin and non-steroidal anti-inflammatory drugs were associated with higher odds of AD (p < 0.05 for all). Conclusion: Our findings show that, in accordance with primary care records, 1% of patients aged 60 years and older have a diagnosis of AD, with an incident AD diagnosis of 0.1% per year. AD is often under-reported in primary care settings; yet, several predictors identified in this study may support general practitioners to early identify patients at risk of AD. [ABSTRACT FROM AUTHOR]

Objective: The aims of the present study were: (a) to obtain new normative data of the Italian version of the Mini-Mental Examination State (MMSE) (Measso et al. in Dev Neuropsychol 9:77–85, 1993) by administering the tool to a sample of normal Italian individuals more representative of the current Italian population; (b) to compare the sensitivity of this tool in detecting patients suffering from Alzheimer's disease (AD according to NIA-AA), as compared to the those reported in previous normative Italian studies. Methods: MMSE was administered to 314 normal subjects recruited among individuals (and/or their relatives) attending the Offices of General Practitioners (GP) or Memory Clinics in Campania (Italy) by convenience sampling. A group of 47 patients with AD were included into the study. The effect of demographic variables on the raw MMSE scores of normal subjects was checked by multiple linear regression assuming MMSE scores as dependent variable and age, gender and education as the independent one(s). Therefore, a simultaneous regression model was constructed to correct the raw scores according the sensitive variables. Correction grid and equivalent scores were devised to classify subject's performance. Results: The mean raw MMSE score was 27.78 (SD = 1.80) (range 22–30/30). There was no significant difference between scores achieved by men or women (p = 0.688). Multiple linear regression analysis showed a significant effect of age and years of school attendance on the MMSE raw score, whereas gender did not show any significant effect. The cutoff score, distinguishing between pathological and normal performances, was fixed at the fifth centile corresponding to 24.9/30, higher than the current score of 23.8/30. The new cutoff value was able to identify 44/47 patients with AD, in contrast to 38/47 subjects detected by currently used norms. Conclusions: (1) A more updated and representative population sample; (2) a new cutoff threshold able to distinguish between normal and pathological performances; (3) a correction grid that reduces the risk of false-positive and false-negative values due to the influence of the main demographic factors; (4) greater sensitivity, compared to previous Italian normative studies in identifying people with dementia. [ABSTRACT FROM AUTHOR]

Background: The association between the extremely low-frequency magnetic field generated by overhead power lines and neurodegenerative disease is still a matter of debate.Methods: A population-based case-control study was carried out on the residents in the Milan metropolitan area between 2011 and 2016 to evaluate the possible association between exposure to extremely low-frequency magnetic fields generated by high-voltage overhead power lines and Alzheimer's dementia and Parkinson's disease. A statistical analysis was performed on cases and controls matched by sex, year of birth and municipality of residence (with a case to controls ratio of 1 : 4) using conditional logistic regression models adjusted for socio-economic deprivation and distance from the major road network as potential confounders.Results: Odds ratios for residents <50 m from the source of exposure compared with residents at ≥600 m turned out to be 1.11 (95% confidence interval: 0.95-1.30) for Alzheimer's dementia and 1.09 (95% confidence interval: 0.92-1.30) for Parkinson's disease.Conclusions: The finding of a weak association between exposure to the extremely low-frequency magnetic field and neurodegenerative diseases suggests the continuation of research on this topic. Moreover, the low consistency between the results of the already existing studies emphasises the importance of increasingly refined study designs. [ABSTRACT FROM AUTHOR]

APOE is a well-studied gene with multiple effects on aging and longevity. The gene has three alleles: e2, e3, and e4, whose frequencies vary by ethnicity. While the e2 is associated with healthy cognitive aging, the e4 allele is associated with Alzheimer's disease and early mortality and therefore its prevalence among people with extreme longevity (EL) is low. Using the PopCluster algorithm, we identified several ethnically different clusters in which the effect of the e2 and e4 alleles on EL changed substantially. For example, PopCluster discovered a large group of 1,309 subjects enriched of Southern Italian genetic ancestry with weaker protective effect of e2 (odds ratio [OR] = 1.27, p = .14) and weaker damaging effect of e4 (OR = 0.82, p = .31) on the phenotype of EL compared to other European ethnicities. Further analysis of this cluster suggests that the odds for EL in carriers of the e4 allele with Southern Italian genetic ancestry differ depending on whether they live in the United States (OR = 0.29, p = .009) or Italy (OR = 1.21, p = .38). PopCluster also found clusters enriched of subjects with Danish ancestry with varying effect of e2 on EL. The country of residence (Denmark or United States) appears to change the odds for EL in the e2 carriers. [ABSTRACT FROM AUTHOR]

Background: The wait for the upcoming disease-modifying therapies (DMT) for Alzheimer's disease in Europe is raising questions about the preparedness of national healthcare systems to conduct accurate diagnoses and effective prescriptions. In this article, we focus on the current situation in Italy., Objective: The primary goal is to propose a profile of the Italian Centers for Cognitive Disorders and Dementias (CCDDs) that could be taken into consideration by regional and autonomous provincial authorities when deciding on the prescribing centers for DMT., Methods: Based on responses to a national survey on CCDDs in Italy, we identified the CCDDs that meet the requirements for effective prescription: 1) Multidisciplinary team; 2) Minimum Core Test for the neuropsychological assessment; 3) PET, CSF, and Brain MRI assessments. Univariate and multivariate comparisons were conducted between CCDDs that met the criteria and the others., Results: Only 10.4% of CCDDs met the requirements for effective DMT prescription, mainly located in Northern Italy. They are also characterized by longer opening hours, a higher number of professionals, a university location, and a higher frequency of conducting genetic tests, and could potentially result in prescribing centers., Conclusions: The findings suggest that the Italian national healthcare system may benefit from further enhancements to facilitate the effective prescription of DMTs. This could involve initiatives to reduce fragmentation, ensure adequate resources and equipment, and secure sufficient funding to support this aspect of healthcare delivery.

Background: Il Paese Ritrovato is an Italian nursing home founded in 2018, it is based on the Alzheimer village model and admits people with mild-to-moderate dementia., Objective: Describe the impact of the SARS-CoV-2 pandemic on people living at Il Paese Ritrovato through a Comprehensive Geriatric Assessment (CGA) regularly administered prior to and during the pandemic., Methods: We explored the effects of a person-centered approach. We assessed 64 subjects (enrolled and followed between June 2018 and December 2020), who underwent at least 18 months of observation prior to the pandemic. Each subject was evaluated using a CGA on admission time (T0) and at defined time-points: T6, T12, T18. One last CGA evaluation was performed during the SARS-CoV-2 pandemic (TCovid-19). Temporal trends during T0-T18, and differences between T18 and TCovid-19 were calculated., Results: The mean age was 82 years with a prevalence for females (77.0%) and Alzheimer's disease diagnosis (60%). Psychiatric and behavioral disorders were the most common conditions (80%). We utilized a nonpharmacological approach aimed at promoting the residents' overall wellbeing and observed satisfactory performance during the first 18 months. In comparison with the pre-pandemic period, TCovid-19 enlightened +11.7% use of antidepressants and a decline of Mini-Mental State Examination mean values (not statistically significant), while engagement in activities dropped., Conclusions: The pandemic may have disrupted the existing model of care, but at the same time, it confirmed that the Il Paese Ritrovato approach, which encompasses symptoms improvement and multicomponent support, is in fact beneficial.

Alzheimer's disease is the most common age-related neurodegenerative disorder and its burden on patients, families, and society grows significantly with lifespan. Early modifications of risk-enhancing lifestyles and treatment initiation expand personal autonomy and reduce management costs. Many clinical trials with potentially disease-modifying drugs are devoted to mild cognitive impairment (MCI) prodromal-to-Alzheimer's disease. The identification of biomarkers for early diagnosis may thus be crucial for early intervention and identification of high-risk subjects, the most appropriate target of new drugs as soon as they will be discovered. INTERCEPTOR is a strategic project by the Italian Ministry of Health and the Italian Medicines Agency (AIFA), aiming to validate the best combination (highly accurate, non-invasive, available on the whole national territory and financially sustainable) of biomarkers and organizational model for early diagnosis. 500 MCI subjects will be enrolled at baseline and followed-up for 3 years for at least 400 of them in order to define a "hub & spoke" nationwide model with recruiting (spokes) centers for MCI identification and expert (hubs) centers for risk diagnosis. [ABSTRACT FROM AUTHOR]

Cognitive Function Instrument (CFI) is a questionnaire aimed at detecting very early changes in cognitive and functional abilities and useful for monitoring cognitive decline in individuals without clinical impairment. The Italian version has been recently validated. The aim of the present study was to investigate the utility of the Italian version of CFI in tracking early cognitive changes in a cohort of healthy elderly subjects. A consecutive series of 257 cognitively healthy and functionally independent subjects, recruited either among relatives of patients attending our Memory Clinic or as volunteers after advertisement, underwent a baseline neuropsychological assessment. Of them, 157 subjects performed a 1-year follow-up assessment. All subjects completed the CFI, a short questionnaire composed of 14 items administered to both the subject and the referent (study-partner). Cognitive performance was assessed by Mini-Mental State Examination (MMSE) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). At 1-year follow-up, Cronbach's α was 0.79 (95% CI, 0.74-0.84) in self-report and 0.83 (95% CI, 0.79-0.87) for partner-report. CFI self-report correlated with MMSE (rS = - 0.22, p = 0.006) and RBANS (rS = - 0.23, p = 0.004). CFI partner-report showed negative correlation with MMSE (rS = - 0.17, p = 0.037) and RBANS (rS = - 0.20, p = 0.014). CFI 1-year follow-up score correlated with baseline both in self-report (rS = 0.56, p < 0.001) and partner-report (rS = 0.66, p < 0.001). Baseline CFI partner-report (p = 0.014) and CFI self+partner report (p = 0.023) were associated with RBANS total score less than 85 at 1-year follow-up, while only a trend was found considering baseline CFI self-report. Our results support the suitability of the Italian version of CFI for tracking cognitive changes along aging. [ABSTRACT FROM AUTHOR]

Introduction: Frailty is a critical intermediate status of the aging process including physical, cognitive, and psychosocial phenotypes. We operationalized a biopsychosocial frailty construct, estimating its association with mild cognitive impairment (MCI) and its subtypes., Methods: In 1980, older individuals from the population-based Italian PRoject on the Epidemiology of Alzheimer's disease (IPREA), we investigated cross-sectional associations among biopsychosocial frailty, MCI, and its subtypes., Results: Participants with biopsychosocial frailty showed an increased odds ratio (OR) of MCI [OR: 4.36; 95% confidence interval (CI): 2.60-7.29; Fisher's exact p < 0.01], particularly for nonamnestic MCI single domain (naMCI-SD, OR:3.28; 95% CI: 1.35-7.97; Fisher's exact p = 0.02) and for nonamnestic MCI multiple domain (naMCI-MD, OR:6.92; 95% CI: 3.37-14.21; Fisher's exact p < 0.01). No statistically significant associations between amnestic MCI single or multiple domain and biopsychosocial frailty were observed., Discussion: In a large, older Italian cohort, a biopsychosocial frailty phenotype was associated with MCI, in particular, could be associated with some of its subtypes, that is, naMCI-SD, and naMCI-MD., (© 2023 the Alzheimer's Association.)