Purpose
We aim to report the quality of accuracy studies investigating the utility of
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Ffluorodeoxyglucose (FDG)-PET in supporting the diagnosis of prodromal Alzheimer’s Disease (AD), ...frontotemporal lobar degeneration (FTLD) and prodromal dementia with Lewy bodies (DLB) in mild cognitive impairment (MCI) subjects, and the corresponding recommendations made by a panel of experts.
Methods
Seven panellist, four from the European Association of Nuclear Medicine, and three from the European Academy of Neurology, produced recommendations taking into consideration the incremental value of FDG-PET, as added on clinical-neuropsychological examination, to ascertain the aetiology of MCI (AD, FTLD or DLB). A literature search using harmonized population, intervention, comparison, and outcome (PICO) strings was performed, and an evidence assessment consistent with the European Federation of Neurological Societies guidance was provided. The consensual recommendation was achieved based on Delphi rounds.
Results
Fifty-four papers reported the comparison of interest. The selected papers allowed the identification of FDG patterns that characterized MCI due to AD, FTLD and DLB. While clinical outcome studies supporting the diagnosis of MCI due to AD showed varying accuracies (ranging from 58 to 100%) and varying areas under the receiver-operator characteristic curves (0.66 to 0.97), no respective data were identified for MCI due to FTLD or for MCI due to DLB. However, the high negative predictive value of FDG-PET and the existence of different disease-specific patterns of hypometabolism support the consensus recommendations for the clinical use of this imaging technique in MCI subjects.
Conclusions
FDG-PET has clinical utility on a fair level of evidence in detecting MCI due to AD. Although promising also in detecting MCI due to FTLD and MCI due to DLB, more research is needed to ultimately judge the clinical utility of FDG-PET in these entities.
Purpose
A joint effort of the European Association of Nuclear Medicine (EANM) and the European Academy of Neurology (EAN) aims at clinical guidance for the use of FDG-PET in neurodegenerative ...diseases. This paper addresses the diagnostic utility of FDG-PET over clinical/neuropsychological assessment in the differentiation of the three forms of primary progressive aphasia (PPA).
Methods
Seven panelists were appointed by the EANM and EAN and a literature search was performed by using harmonized PICO (Population, Intervention, Comparison, Outcome) question keywords. The studies were screened for eligibility, and data extracted to assess their methodological quality. Critical outcomes were accuracy indices in differentiating different PPA clinical forms. Subsequently Delphi rounds were held with the extracted data and quality assessment to reach a consensus based on both literature and expert opinion.
Results
Critical outcomes for this PICO were available in four of the examined papers. The level of formal evidence supporting clinical utility of FDG-PET in differentiating among PPA variants was considered as poor. However, the consensual recommendation was defined on Delphi round I, with six out of seven panelists supporting clinical use.
Conclusions
Quantitative evidence demonstrating utility or lack thereof is still missing. Panelists decided consistently to provide interim support for clinical use based on the fact that a typical atrophy or metabolic pattern is needed for PPA according to the diagnostic criteria, and the synaptic failure detected by FDG-PET is an earlier phenomenon than atrophy. Also, a normal FDG-PET points to a non-neurodegenerative cause.
Abstract Background Artificial intelligence (AI) has become a pivotal tool in advancing contemporary personalised medicine, with the goal of tailoring treatments to individual patient conditions. ...This has heightened the demand for access to diverse data from clinical practice and daily life for research, posing challenges due to the sensitive nature of medical information, including genetics and health conditions. Regulations like the Health Insurance Portability and Accountability Act (HIPAA) in the U.S. and the General Data Protection Regulation (GDPR) in Europe aim to strike a balance between data security, privacy, and the imperative for access. Results We present the Gemelli Generator - Real World Data (GEN-RWD) Sandbox, a modular multi-agent platform designed for distributed analytics in healthcare. Its primary objective is to empower external researchers to leverage hospital data while upholding privacy and ownership, obviating the need for direct data sharing. Docker compatibility adds an extra layer of flexibility, and scalability is assured through modular design, facilitating combinations of Proxy and Processor modules with various graphical interfaces. Security and reliability are reinforced through components like Identity and Access Management (IAM) agent, and a Blockchain-based notarisation module. Certification processes verify the identities of information senders and receivers. Conclusions The GEN-RWD Sandbox architecture achieves a good level of usability while ensuring a blend of flexibility, scalability, and security. Featuring a user-friendly graphical interface catering to diverse technical expertise, its external accessibility enables personnel outside the hospital to use the platform. Overall, the GEN-RWD Sandbox emerges as a comprehensive solution for healthcare distributed analytics, maintaining a delicate equilibrium between accessibility, scalability, and security.
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. Twenty memory clinic patients with prodromal AD (i.e., mild cognitive impairment with an AD-like cerebrospinal fluid profile) and 30 healthy controls underwent a cognitive evaluation and a resting state functional MRI exam. Independent component analysis was performed to assess functional connectivity (FC) in the following networks: default mode, frontoparietal, limbic, visual, and sensorimotor. Patients were stratified into late-onset (pLOAD) and early-onset (pEOAD) prodromal AD according to the AAO and controls were stratified into younger and older groups accordingly. Decreased FC within the default mode and the limbic networks was observed in pLOAD, while pEOAD showed lower FC in the frontoparietal and visual networks. The sensorimotor network did not show differences between groups. A significant association was found between memory and limbic network FC in pLOAD, and between executive functions and frontoparietal network FC in pEOAD, although the latter association did not survive multiple comparison correction. Our findings indicate that aberrant connectivity in memory networks is associated with pLOAD, while networks underlying executive and visuo-spatial functions are affected in pEOAD. These findings are in line with the hypothesis that the pathophysiological mechanisms underlying EOAD and LOAD are distinct.
Since the late ninety, research on Alzheimer’s disease has been focused on the search of drugs able to modify the disease course. Patients and caregivers waiting for news on this topic, received ...enthusiastically the advice of the approval of Aducanumab—anti-amyloid β monoclonal antibody—by the FDA, and that of its rejection by the EMA with even greater disappointment. To estimate the number of patients that we would be able to treat–hypothesizing a possible future approval by EMA- in the memory clinic of the IRCCS S. Giovanni di Dio FBF of Brescia, we analyzed 1561 patients undergone a first geriatric visit in January 1st to December 31st 2019. Applying the EMERGE and ENGAGE studies criteria, only 15 of them (1%) could be eligible for Aducanumab. The communication of scientific news should be transparent, more balanced and less sensationalistic, to avoid the rise of false hopes and consequent disillusionment.
Purpose
There are no comprehensive guidelines for the use of FDG PET in the following three clinical scenarios: (1) diagnostic work-up of patients with idiopathic Parkinson’s disease (PD) at risk of ...future cognitive decline, (2) discriminating idiopathic PD from progressive supranuclear palsy, and (3) identifying the underlying neuropathology in corticobasal syndrome.
Methods
We therefore performed three literature searches and evaluated the selected studies for quality of design, risk of bias, inconsistency, imprecision, indirectness and effect size. Critical outcomes were the sensitivity, specificity, accuracy, positive/negative predictive value, area under the receiving operating characteristic curve, and positive/negative likelihood ratio of FDG PET in detecting the target condition. Using the Delphi method, a panel of seven experts voted for or against the use of FDG PET based on published evidence and expert opinion.
Results
Of 91 studies selected from the three literature searches, only four included an adequate quantitative assessment of the performance of FDG PET. The majority of studies lacked robust methodology due to lack of critical outcomes, inadequate gold standard and no head-to-head comparison with an appropriate reference standard. The panel recommended the use of FDG PET for all three clinical scenarios based on nonquantitative evidence of clinical utility.
Conclusion
Despite widespread use of FDG PET in clinical practice and extensive research, there is still very limited good quality evidence for the use of FDG PET. However, in the opinion of the majority of the panellists, FDG PET is a clinically useful imaging biomarker for idiopathic PD and atypical parkinsonism associated with dementia.
Background
Most people with dementia are cared for by family members. The workload associated with caregiving tasks is often associated with physical, mental, and social impairment. In line with the ...WHO’s Global Action Plan on Dementia 2017‐2025 (WHO, 2017), calling for the provision of affordable and accessible interventions for dementia caregivers, we tested an eHealth intervention to improve self‐efficacy and mental health in dementia caregivers.
Method
8‐week eHealth psycho‐educational intervention aiming at increasing the knowledge of neurocognitive disorders, their at‐home management, and the presence of national and local support services. The intervention was conducted by an experienced psychotherapist assisted by a professional expert (e.g., geriatrician, educator, social worker, lawyer and advocacy patient organisations), according to the topic of each meeting. A pre‐post study design was used and validated psychosocial self‐report questionnaires were administered before and after the intervention (e.g., State‐Trait Anxiety Inventory ‐STAI‐Y1‐2, Zarit Burden Interview ‐ZBI, Beck Depression Inventory‐II BDI‐II, Revised Scale of Caregiving Self‐Efficacy ‐RSCSE). Pre‐post differences were tested with paired t‐test, correlations between scales with Pearson correlation coefficient
Result
41 caregivers (mean age: 57; range 31‐82; female: 78%; children: 61%) completed the study. The intervention had high participation (88% attended at least seven meetings). Following the intervention, the self‐efficacy regarding the ability to respond to the patient’s disruptive behaviours effectively improved (RSCSE‐RDB subscale: t(40) = ‐2.817, p = 0.007), anxiety and burden levels decreased (STAI‐Y1: t(40) = 3.170, p = 0.003; STAI‐Y2: t(40) = 2.327, p = 0.025; ZBI: t(40) = 2.290, p = 0.027), while depression scores did not change significantly (BDI‐II: t(40) = 1.164, p = 0.251). Correlation analysis showed that the change of STAI‐Y1 was positively associated with the change of STAY‐Y2 (r = 0.440, p = 0.004), and the increase of RSCE‐RDB subscale was positively associated with the improvement of caregiver burden (r = 0.430, p = 0.005).
Conclusion
Our study showed that the eHealth intervention improved the caregiver’s ability to deal effectively with the disruptive behaviours of patients, and this change was associated with a reduction of caregiver burden. The results and participation rates support the implementation of online psycho‐educational interventions to meet the need for knowledge of disease management and avoid detrimental effects on caregivers’ health.
Background
Most people with dementia are cared for by family members. The workload associated with caregiving tasks is often associated with physical, mental, and social impairment. In line with the ...WHO’s Global Action Plan on Dementia 2017‐2025 (WHO, 2017), calling for the provision of affordable and accessible interventions for dementia caregivers, we tested an eHealth intervention to improve self‐efficacy and mental health in dementia caregivers.
Method
8‐week eHealth psycho‐educational intervention aiming at increasing the knowledge of neurocognitive disorders, their at‐home management, and the presence of national and local support services. The intervention was conducted by an experienced psychotherapist assisted by a professional expert (e.g., geriatrician, educator, social worker, lawyer and advocacy patient organisations), according to the topic of each meeting. A pre‐post study design was used and validated psychosocial self‐report questionnaires were administered before and after the intervention (e.g., State‐Trait Anxiety Inventory ‐STAI‐Y1‐2, Zarit Burden Interview ‐ZBI, Beck Depression Inventory‐II BDI‐II, Revised Scale of Caregiving Self‐Efficacy ‐RSCSE). Pre‐post differences were tested with paired t‐test, correlations between scales with Pearson correlation coefficient
Result
41 caregivers (mean age: 57; range 31‐82; female: 78%; children: 61%) completed the study. The intervention had high participation (88% attended at least seven meetings). Following the intervention, the self‐efficacy regarding the ability to respond to the patient’s disruptive behaviours effectively improved (RSCSE‐RDB subscale: t(40) = ‐2.817, p = 0.007), anxiety and burden levels decreased (STAI‐Y1: t(40) = 3.170, p = 0.003; STAI‐Y2: t(40) = 2.327, p = 0.025; ZBI: t(40) = 2.290, p = 0.027), while depression scores did not change significantly (BDI‐II: t(40) = 1.164, p = 0.251). Correlation analysis showed that the change of STAI‐Y1 was positively associated with the change of STAY‐Y2 (r = 0.440, p = 0.004), and the increase of RSCE‐RDB subscale was positively associated with the improvement of caregiver burden (r = 0.430, p = 0.005).
Conclusion
Our study showed that the eHealth intervention improved the caregiver’s ability to deal effectively with the disruptive behaviours of patients, and this change was associated with a reduction of caregiver burden. The results and participation rates support the implementation of online psycho‐educational interventions to meet the need for knowledge of disease management and avoid detrimental effects on caregivers’ health.
Aim
To assess the clinical utility of FDG-PET as a diagnostic aid for differentiating Alzheimer’s disease (AD; both typical and atypical forms), dementia with Lewy bodies (DLB), frontotemporal lobar ...degeneration (FTLD), vascular dementia (VaD) and non-degenerative pseudodementia.
Methods
A comprehensive literature search was conducted using the PICO model to extract evidence from relevant studies. An expert panel then voted on six different diagnostic scenarios using the Delphi method.
Results
The level of empirical study evidence for the use of FDG-PET was considered good for the discrimination of DLB and AD; fair for discriminating FTLD from AD; poor for atypical AD; and lacking for discriminating DLB from FTLD, AD from VaD, and for pseudodementia. Delphi voting led to consensus in all scenarios within two iterations. Panellists supported the use of FDG-PET for all PICOs—including those where study evidence was poor or lacking—based on its negative predictive value and on the assistance it provides when typical patterns of hypometabolism for a given diagnosis are observed.
Conclusion
Although there is an overall lack of evidence on which to base strong recommendations, it was generally concluded that FDG-PET has a diagnostic role in all scenarios. Prospective studies targeting diagnostically uncertain patients for assessing the added value of FDG-PET would be highly desirable.
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