Citrus supplementation in subjective cognitive decline: results of a 36-week, randomized, placebo-controlled trial.

Background: Developing interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD.

Cognitive, psychological, and physiological effects of a web-based mindfulness intervention in older adults during the COVID-19 pandemic: an open study.

Background: The development of effective strategies to maintain good mental health of older adults is a public health priority. Mindfulness-based interventions have the potential to improve psychological well-being and cognitive functions of older adults, but little is known about the effect of such interventions when delivered through internet. During the COVID-19 pandemic we evaluated short- and long-term cognitive, psychological, and physiological effects of a mindfulness-based intervention (MBI) delivered via web-based videoconference in healthy older adults.

Augmented reality versus standard tests to assess cognition and function in early Alzheimer's disease.

Augmented reality (AR) apps, in which the virtual and real world are combined, can recreate instrumental activities of daily living (IADL) and are therefore promising to measure cognition needed for IADL in early Alzheimer's disease (AD) both in the clinic and in the home settings. The primary aim of this study was to distinguish and classify healthy controls (HC) from participants with AD pathology in an early AD stage using an AR app. The secondary aims were to test the association of the app with clinical cognitive and functional tests and investigate the feasibility of at-home testing using AR.

Correction: Ethical challenges of using remote monitoring technologies for clinical research: A case study of the role of local research ethics committees in the RADAR-AD study.

[This corrects the article DOI: 10.1371/journal.pone.

Ethical challenges of using remote monitoring technologies for clinical research: A case study of the role of local research ethics committees in the RADAR-AD study.

Introduction: Clinical research with remote monitoring technologies (RMTs) has multiple advantages over standard paper-pencil tests, but also raises several ethical concerns. While several studies have addressed the issue of governance of big data in clinical research from the legal or ethical perspectives, the viewpoint of local research ethics committee (REC) members is underrepresented in the current literature. The aim of this study is therefore to find which specific ethical challenges are raised by RECs in the context of a large European study on remote monitoring in all syndromic stages of Alzheimer's disease, and what gaps remain.

A low-dimensional cognitive-network space in Alzheimer's disease and frontotemporal dementia.

Background: Alzheimer's disease (AD) and frontotemporal dementia (FTD) show network dysfunctions linked with cognitive deficits. Within this framework, network abnormalities between AD and FTD show both convergent and divergent patterns. However, these functional patterns are far from being established and their relevance to cognitive processes remains to be elucidated.

Disclosure of Genetic Risk Factors for Alzheimer's Disease to Cognitively Healthy Individuals-From Current Practice towards a Personalised Medicine Scenario.

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 () is the first discovered genetic risk factor for AD.

Cognitive and biological effects of citrus phytochemicals in subjective cognitive decline: a 36-week, randomized, placebo-controlled trial.

Background: Auraptene (AUR) and naringenin (NAR) are citrus-derived phytochemicals that influence several biological mechanisms associated with cognitive decline, including neuronal damage, oxidative stress and inflammation. Clinical evidence of the efficacy of a nutraceutical with the potential to enhance cognitive function in cohorts at risk of cognitive decline would be of great value from a preventive perspective. The primary aim of this study is to determine the cognitive effects of a 36-week treatment with citrus peel extract standardized in levels of AUR and NAR in older adults experiencing subjective cognitive decline (SCD).

Psychological Impact of Predictive Genetic Testing for Inherited Alzheimer Disease and Frontotemporal Dementia: The IT-DIAfN Protocol.

Aim: Our aim was to evaluate the psychological impact of predictive genetic testing in individuals at-risk for inherited dementia who underwent a structured counseling and testing protocol.

Methods: Participants were healthy at-risk relatives from families with at least one affected patient, in whom a disease-associated genetic variant had been ascertained. A comprehensive psychological assessment (personality, anxiety and depression, quality of life, coping strategies, resilience and health-related beliefs) was administered at baseline, at 6 months and 12 months follow-up.

Brain network modulation in Alzheimer's and frontotemporal dementia with transcranial electrical stimulation.

The default mode (DMN) and the salience (SN) networks show functional hypo-connectivity in Alzheimer's disease (AD) and the behavioral variant of frontotemporal dementia (bvFTD), respectively, along with patterns of hyper-connectivity. We tested the clinical and neurobiological effects of noninvasive stimulation over these networks in 45 patients (AD and bvFTD) who received either anodal (target network: DMN in AD, SN in bvFTD) or cathodal stimulation (target network: SN in AD, DMN in bvFTD). We evaluated changes in clinical, cognitive, functional and structural connectivity, and perfusion measures.

Norms for Automatic Estimation of Hippocampal Atrophy and a Step Forward for Applicability to the Italian Population.

Introduction: Hippocampal volume is one of the main biomarkers of Alzheimer's Dementia (AD). Over the years, advanced tools that performed automatic segmentation of Magnetic Resonance Imaging (MRI) T13D scans have been developed, such as FreeSurfer (FS) and ACM-Adaboost (AA). Hippocampal volume is considered abnormal when it is below the 5th percentile of the normative population.

Genetic counselling and testing for inherited dementia: single-centre evaluation of the consensus Italian DIAfN protocol.

Background: A consensus protocol for genetic counselling and testing of familial dementia, the Italian Dominantly Inherited Alzheimer's and Frontotemporal Network (IT-DIAfN) protocol, has been developed in Italy by a network of expert dementia centres. The aim of this study is to evaluate feasibility and acceptability of the genetic counselling and testing process, as undertaken according to the IT-DIAfN protocol in one of the IT-DIAfN dementia research centres.

Methods: The protocol was tested by a multidisciplinary team at the IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy, on affected individuals with suspected inherited forms of Alzheimer's disease (AD) or frontotemporal dementia (FTD), and to healthy at-risk relatives.

Medical Informatics Platform (MIP): A Pilot Study Across Clinical Italian Cohorts.

With the shift of research focus to personalized medicine in Alzheimer's Dementia (AD), there is an urgent need for tools that are capable of quantifying a patient's risk using diagnostic biomarkers. The Medical Informatics Platform (MIP) is a distributed e-infrastructure federating large amounts of data coupled with machine-learning (ML) algorithms and statistical models to define the biological signature of the disease. The present study assessed (i) the accuracy of two ML algorithms, i.

CSF cutoffs for MCI due to AD depend on APOEε4 carrier status.

Amyloid and tau pathological accumulation should be considered for Alzheimer's disease (AD) definition and before subjects' enrollment in disease-modifying trials. Although age, APOEε4, and sex influence cerebrospinal fluid (CSF) biomarker levels, none of these variables are considered by current normality/abnormality cutoffs. Using baseline CSF data from 2 independent cohorts (PharmaCOG/European Alzheimer's Disease Neuroimaging Initiative and Alzheimer's Disease Neuroimaging Initiative), we investigated the effect of age, APOEε4 status, and sex on CSF Aβ42/P-tau distribution and cutoff extraction by applying mixture models with covariates.

miR-146a Plasma Levels Are Not Altered in Alzheimer's Disease but Correlate With Age and Illness Severity.

miR-146a is a microRNA (miRNA) involved in neuroinflammation and aging; alterations in its expression were described in Alzheimer's disease (AD). However, most of the studies conducted so far on this miRNA included a limited number of participants and produced contradictory results. We compared miR-146a levels in plasma from 33 AD patients vs.

Age at onset reveals different functional connectivity abnormalities in prodromal Alzheimer's disease.

Age at symptom onset (AAO) underlies different Alzheimer's disease (AD) clinical variants: late-onset AD (LOAD) is characterized by memory deficits, while early-onset AD (EOAD) presents predominantly with non-memory symptoms. The involvement of different neural networks may explain these distinct clinical phenotypes. In this study, we tested the hypothesis of an early and selective involvement of neural networks based on AAO in AD.

Randomized controlled trial on the efficacy of a multilevel non-pharmacologic intervention in older adults with subjective memory decline: design and baseline findings of the E.Mu.N.I. study.

Background: Alzheimer's Disease (AD) is a multifactorial disorder driven by genetic and modifiable lifestyle risk factors. Lifestyle primary prevention initiatives may reduce the prevalence and incidence of dementia in older adults.

Objectives: The E.

Biomarker-based prognosis for people with mild cognitive impairment (ABIDE): a modelling study.

Background: Biomarker-based risk predictions of dementia in people with mild cognitive impairment are highly relevant for care planning and to select patients for treatment when disease-modifying drugs become available. We aimed to establish robust prediction models of disease progression in people at risk of dementia.

Methods: In this modelling study, we included people with mild cognitive impairment (MCI) from single-centre and multicentre cohorts in Europe and North America: the European Medical Information Framework for Alzheimer's Disease (EMIF-AD; n=883), Alzheimer's Disease Neuroimaging Initiative (ADNI; n=829), Amsterdam Dementia Cohort (ADC; n=666), and the Swedish BioFINDER study (n=233).

Prognostic value of Alzheimer's biomarkers in mild cognitive impairment: the effect of age at onset.

Objective: The aim of this study is to assess the impact of age at onset on the prognostic value of Alzheimer's biomarkers in a large sample of patients with mild cognitive impairment (MCI).

Methods: We measured Aβ42, t-tau, hippocampal volume on magnetic resonance imaging (MRI) and cortical metabolism on fluorodeoxyglucose-positron emission tomography (FDG-PET) in 188 MCI patients followed for at least 1 year. We categorised patients into earlier and later onset (EO/LO).

Biomarker Matrix to Track Short Term Disease Progression in Amnestic Mild Cognitive Impairment Patients with Prodromal Alzheimer's Disease.

Background: Assessment of human brain atrophy in temporal regions using magnetic resonance imaging (MRI), resting state functional MRI connectivity in the left parietal cortex, and limbic electroencephalographic (rsEEG) rhythms as well as plasma amyloid peptide 42 (Aβ42) has shown that each is a promising biomarker of disease progression in amnestic mild cognitive impairment (aMCI) patients with prodromal Alzheimer's disease (AD). However, the value of their combined use is unknown.

Objective: To evaluate the association with cognitive decline and the effect on sample size calculation when using a biomarker composite matrix in prodromal AD clinical trials.

Head-to-Head Comparison among Semi-Quantification Tools of Brain FDG-PET to Aid the Diagnosis of Prodromal Alzheimer's Disease.

Background: Several automatic tools have been implemented for semi-quantitative assessment of brain [18]F-FDG-PET.

Objective: We aimed to head-to-head compare the diagnostic performance among three statistical parametric mapping (SPM)-based approaches, another voxel-based tool (i.e.

Two-Year Longitudinal Monitoring of Amnestic Mild Cognitive Impairment Patients with Prodromal Alzheimer's Disease Using Topographical Biomarkers Derived from Functional Magnetic Resonance Imaging and Electroencephalographic Activity.

Auditory "oddball" event-related potentials (aoERPs), resting state functional magnetic resonance imaging (rsfMRI) connectivity, and electroencephalographic (rsEEG) rhythms were tested as longitudinal functional biomarkers of prodromal Alzheimer's disease (AD). Data were collected at baseline and four follow-ups at 6, 12, 18, and 24 months in amnesic mild cognitive impairment (aMCI) patients classified in two groups: "positive" (i.e.

Plasma Aβ42 as a Biomarker of Prodromal Alzheimer's Disease Progression in Patients with Amnestic Mild Cognitive Impairment: Evidence from the PharmaCog/E-ADNI Study.

It is an open issue whether blood biomarkers serve to diagnose Alzheimer's disease (AD) or monitor its progression over time from prodromal stages. Here, we addressed this question starting from data of the European FP7 IMI-PharmaCog/E-ADNI longitudinal study in amnesic mild cognitive impairment (aMCI) patients including biological, clinical, neuropsychological (e.g.

Predicting and Tracking Short Term Disease Progression in Amnestic Mild Cognitive Impairment Patients with Prodromal Alzheimer's Disease: Structural Brain Biomarkers.

Background: Early Alzheimer's disease (AD) detection using cerebrospinal fluid (CSF) biomarkers has been recommended as enrichment strategy for trials involving mild cognitive impairment (MCI) patients.

Objective: To model a prodromal AD trial for identifying MRI structural biomarkers to improve subject selection and to be used as surrogate outcomes of disease progression.

Methods: APOE ɛ4 specific CSF Aβ42/P-tau cut-offs were used to identify MCI with prodromal AD (Aβ42/P-tau positive) in the WP5-PharmaCog (E-ADNI) cohort.