Incidence of young‐onset dementia in Italy: The Brescia register study

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

Classification and Quantification of Physical Therapy Interventions across Multiple Neurological Disorders: An Italian Multicenter Network

Despite their relevance in neurorehabilitation, physical therapy (PT) goals and interventions are poorly described, compromising a proper understanding of PT effectiveness in everyday clinical practice. Thus, this paper aims to describe the prevalence of PT goals and interventions in people with neurological disorders, along with the participants' clinical features, setting characteristics of the clinical units involved, and PT impact on outcome measures. A multicenter longitudinal observational study involving hospitals and rehabilitation centers across Italy has been conducted. We recruited people with stroke (n = 119), multiple sclerosis (n = 48), and Parkinson's disease (n = 35) who underwent the PT sessions foreseen by the National Healthcare System. Clinical outcomes were administered before and after the intervention, and for each participant the physical therapists completed a semi-structured interview to report the goals and interventions of the PT sessions. Results showed that the most relevant PT goals were related to the ICF activities with "walking" showing the highest prevalence. The most used interventions aimed at improving walking performance, followed by those aimed at improving organ/body system functioning, while interventions targeting the cognitive-affective and educational aspects have been poorly considered. Considering PT effectiveness, 83 participants experienced a clinically significant improvement in the outcome measures assessing gait and balance functions

Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly

The pathway leading from amyloid-β deposition to cognitive impairment is believed to be a cornerstone of the pathogenesis of Alzheimer's disease (AD). However, what drives amyloid buildup in sporadic nongenetic cases of AD is still unknown. AD brains feature an inflammatory reaction around amyloid plaques, and a specific subset of the gut microbiota (GMB) may promote brain inflammation. We investigated the possible role of the GMB in AD pathogenesis by studying the association of brain amyloidosis with (1) GMB taxa with pro- and anti-inflammatory activity; and (2) peripheral inflammation in cognitively impaired patients. We measured the stool abundance of selected bacterial GMB taxa (Escherichia/Shigella, Pseudomonas aeruginosa, Eubacterium rectale, Eubacterium hallii, Faecalibacterium prausnitzii, and Bacteroides fragilis) and the blood expression levels of cytokines (pro-inflammatory cytokines: CXCL2, CXCL10, interleukin [IL]-1β, IL-6, IL-18, IL-8, inflammasome complex (NLRP3), tumor necrosis factor-alpha [TNF-α]; anti-inflammatory cytokines: IL-4, IL-10, IL-13) in cognitively impaired patients with (n = 40, Amy+) and with no brain amyloidosis (n = 33, Amy-) and also in a group of controls (n = 10, no brain amyloidosis and no cognitive impairment). Amy+ patients showed higher levels of pro-inflammatory cytokines (IL-6, CXCL2, NLRP3, and IL-1β) compared with both controls and with Amy- patients. A reduction of the anti-inflammatory cytokine IL-10 was observed in Amy+ versus Amy-. Amy+ showed lower abundance of E. rectale and higher abundance of Escherichia/Shigella compared with both healthy controls (fold change, FC = -9.6, p < 0.001 and FC = +12.8, p < 0.001, respectively) and to Amy- (FC = -7.7, p < 0.001 and FC = +7.4, p = 0.003). A positive correlation was observed between pro-inflammatory cytokines IL-1β, NLRP3, and CXCL2 with abundance of the inflammatory bacteria taxon Escherichia/Shigella (rho = 0.60, p < 0.001; rho = 0.57, p < 0.001; and rho = 0.30, p = 0.007, respectively) and a negative correlation with the anti-inflammatory E. rectale (rho = -0.48, p < 0.001; rho = -0.25, p = 0.024; rho = -0.49, p < 0.001). Our data indicate that an increase in the abundance of a pro-inflammatory GMB taxon, Escherichia/Shigella, and a reduction in the abundance of an anti-inflammatory taxon, E. rectale, are possibly associated with a peripheral inflammatory state in patients with cognitive impairment and brain amyloidosis. A possible causal relation between GMB-related inflammation and amyloidosis deserves further investigation

Clinical presentation and outcomes of SARS-CoV-2 related encephalitis: the ENCOVID multicentre study

BACKGROUND: Several preclinical and clinical investigations have argued for nervous system involvement in SARS-CoV-2 infection. Some sparse case reports have described various forms of encephalitis in COVID-19 disease, but very few data have focused on clinical presentations, clinical course, response to treatment and outcomes.METHODS: The ENCOVID multicentre study included patients with encephalitis with full infectious screening, CSF, EEG, MRI data and confirmed SARS-CoV-2 infection recruited from 13 centres in northern Italy. Clinical presentation and laboratory markers, severity of COVID-19 disease, response to treatment and outcomes were recorded.RESULTS: twenty-five cases of encephalitis positive for SARS-CoV-2 infection were included. CSF showed hyperproteinorrachia and/or pleocytosis in 68% of cases whereas SARS-CoV-2 RNA by RT-PCR resulted negative. Based on MRI, cases were classified as ADEM (n=3), limbic encephalitis (LE, n=2), encephalitis with normal imaging (n=13) and encephalitis with MRI alterations (n=7). ADEM and LE cases showed a delayed onset compared to the other encephalitis (p=0.001) and were associated with previous more severe COVID-19 respiratory involvement. Patients with MRI alterations exhibited worse response to treatment and final outcomes compared to other encephalitis.CONCLUSIONS: SARS-CoV-2 infection is associated with a wide spectrum of encephalitis characterized by different clinical presentation, response to treatment and outcomes

The instruments used by the Italian centres for cognitive disorders and dementia to diagnose mild cognitive impairment (MCI)

Aims: The purpose of this study was to examine the tools used in Italy to diagnose mild cognitive impairment (MCI). Methods: In collaboration with the Luigi Amaducci Research Consortium, the Italian Network of Alzheimer Evaluation Units prepared a questionnaire to describe how MCI is diagnosed in the Italian Centres for cognitive disorders and dementia (CCDD). Results: Most of the ninety-two CCDDs participating in the survey were located in hospitals (54.7%); large percentages were coordinated by neurologists (50.8%) and geriatricians (44.6%). Almost all (98.5%) used the Mini Mental State Examination to diagnose MCI; the Clock Drawing Test was also frequently used (83.9%). Other neuropsychological, imaging and biomarker tests were utilized less frequently and a wide diversity in the instruments used was noted. Conclusions: According to the results, diagnoses of MCI are based on a multitude of instruments, with major differences in the clinical assessment of geriatricians and neurologists. Standardized testing protocols, validated instruments and cut-off points need to be identified and adopted by the CCDDs for assessing MCI

Assessment of the incremental diagnostic value of florbetapir F 18 imaging in patients with cognitive impairment: The incremental diagnostic value of amyloid PET with [ 18 F]-florbetapir (INDIA-FBP) study

Importance Cerebral amyloidosis is a key abnormality in Alzheimer disease (AD) and can be detected in vivo with positron emission tomography (PET) ligands. Although amyloid PET has clearly demonstrated analytical validity, its clinical utility is debated. Objective To evaluate the incremental diagnostic value of amyloid PET with florbetapir F 18 in addition to the routine clinical diagnostic assessment of patients evaluated for cognitive impairment. Design, Setting, and Participants The Incremental Diagnostic Value of Amyloid PET With [18F]-Florbetapir (INDIA-FBP) Study is a multicenter study involving 18 AD evaluation units from eastern Lombardy, Northern Italy, 228 consecutive adults with cognitive impairment were evaluated for AD and other causes of cognitive decline, with a prescan diagnostic confidence of AD between 15% and 85%. Participants underwent routine clinical and instrumental diagnostic assessment. A prescan diagnosis was made, diagnostic confidence was estimated, and drug treatment was provided. At the time of this workup, an amyloid PET/computed tomographic scan was performed, and the result was communicated to physicians after workup completion. Physicians were asked to review the diagnosis, diagnostic confidence, and treatment after the scan. The study was conducted from August 5, 2013, to December 31, 2014. Main Outcomes and Measures Primary outcomes were prescan to postscan changes of diagnosis, diagnostic confidence, and treatment. Results Of the 228 participants, 107 (46%) were male; mean (SD) age was 70.5 (7) years. Diagnostic change occurred in 46 patients (79%) having both a previous diagnosis of AD and an amyloid-negative scan (P\u2009<\u2009.001) and in 16 (53%) of those with non-AD diagnoses and an amyloid-positive scan (P\u2009<\u2009.001). Diagnostic confidence in AD diagnosis increased by 15.2% in amyloid-positive (P\u2009<\u2009.001; effect size Cohen d\u2009=\u20091.04) and decreased by 29.9% in amyloid-negative (P\u2009<\u2009.001; d\u2009=\u2009 121.19) scans. Acetylcholinesterase inhibitors and memantine hydrochloride were introduced in 61 (65.6%) patients with positive scan results who had not previously received those drugs, and the use of the drugs was discontinued in 6 (33.3%) patients with negative scan results who were receiving those drugs (P\u2009<\u2009.001). Conclusions and Relevance Amyloid PET in addition to routine assessment in patients with cognitive impairment has a significant effect on diagnosis, diagnostic confidence, and drug treatment. The effect on health outcomes, such as morbidity and mortality, remains to be assessed