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Nowell J, Blunt E, Gupta D, et al., 2023, Antidiabetic agents as a novel treatment for Alzheimer's and Parkinson's disease., Ageing Res Rev, Vol: 89
Therapeutic strategies for neurodegenerative disorders have commonly targeted individual aspects of the disease pathogenesis to little success. Neurodegenerative diseases, including Alzheimer's disease (AD) and Parkinson's disease (PD), are characterized by several pathological features. In AD and PD, there is an abnormal accumulation of toxic proteins, increased inflammation, decreased synaptic function, neuronal loss, increased astrocyte activation, and perhaps a state of insulin resistance. Epidemiological evidence has revealed a link between AD/PD and type 2 diabetes mellitus, with these disorders sharing some pathological commonalities. Such a link has opened up a promising avenue for repurposing antidiabetic agents in the treatment of neurodegenerative disorders. A successful therapeutic strategy for AD/PD would likely require a single or several agents which target the separate pathological processes in the disease. Targeting cerebral insulin signalling produces numerous neuroprotective effects in preclinical AD/PD brain models. Clinical trials have shown the promise of approved diabetic compounds in improving motor symptoms of PD and preventing neurodegenerative decline, with numerous further phase II trials and phase III trials underway in AD and PD populations. Alongside insulin signalling, targeting incretin receptors in the brain represents one of the most promising strategies for repurposing currently available agents for the treatment of AD/PD. Most notably, glucagon-like-peptide-1 (GLP-1) receptor agonists have displayed impressive clinical potential in preclinical and early clinical studies. In AD the GLP-1 receptor agonist, liraglutide, has been demonstrated to improve cerebral glucose metabolism and functional connectivity in small-scale pilot trials. Whilst in PD, the GLP-1 receptor agonist exenatide is effective in restoring motor function and cognition. Targeting brain incretin receptors reduces inflammation, inhibits apoptosis, prevents toxic p
Altomare D, Barkhof F, Caprioglio C, et al., 2023, Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients: The AMYPAD-DPMS Randomized Clinical Trial., JAMA Neurol, Vol: 80, Pages: 548-557
IMPORTANCE: Amyloid positron emission tomography (PET) allows the direct assessment of amyloid deposition, one of the main hallmarks of Alzheimer disease. However, this technique is currently not widely reimbursed because of the lack of appropriately designed studies demonstrating its clinical effect. OBJECTIVE: To assess the clinical effect of amyloid PET in memory clinic patients. DESIGN, SETTING, AND PARTICIPANTS: The AMYPAD-DPMS is a prospective randomized clinical trial in 8 European memory clinics. Participants were allocated (using a minimization method) to 3 study groups based on the performance of amyloid PET: arm 1, early in the diagnostic workup (within 1 month); arm 2, late in the diagnostic workup (after a mean [SD] 8 [2] months); or arm 3, if and when the managing physician chose. Participants were patients with subjective cognitive decline plus (SCD+; SCD plus clinical features increasing the likelihood of preclinical Alzheimer disease), mild cognitive impairment (MCI), or dementia; they were assessed at baseline and after 3 months. Recruitment took place between April 16, 2018, and October 30, 2020. Data analysis was performed from July 2022 to January 2023. INTERVENTION: Amyloid PET. MAIN OUTCOME AND MEASURE: The main outcome was the difference between arm 1 and arm 2 in the proportion of participants receiving an etiological diagnosis with a very high confidence (ie, ≥90% on a 50%-100% visual numeric scale) after 3 months. RESULTS: A total of 844 participants were screened, and 840 were enrolled (291 in arm 1, 271 in arm 2, 278 in arm 3). Baseline and 3-month visit data were available for 272 participants in arm 1 and 260 in arm 2 (median [IQR] age: 71 [65-77] and 71 [65-77] years; 150/272 male [55%] and 135/260 male [52%]; 122/272 female [45%] and 125/260 female [48%]; median [IQR] education: 12 [10-15] and 13 [10-16] years, respectively). After 3 months, 109 of 272 participants (40%) in arm 1 had a diagnosis with very high confidence vs 30 of
Edison P, 2023, Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, & Neuroimaging Advancing the Field of Neurology., Brain Connect, Vol: 13, Pages: 175-177
Crook H, Ramirez A, Hosseini A, et al., 2023, European Working Group on SARS-CoV-2: Current Understanding, Unknowns, and Recommendations on the Neurological Complications of COVID-19., Brain Connect, Vol: 13, Pages: 178-210
Background: The emergence of COVID-19 was rapidly followed by infection and the deaths of millions of people across the globe. With much of the research and scientific advancement rightly focused on reducing the burden of severe and critical acute COVID-19 infection, the long-term effects endured by those who survived the acute infection has been previously overlooked. Now, an appreciation for the post-COVID-19 condition, including its neurological manifestations, is growing, although there remain many unknowns regarding the etiology and risk factors of the condition, as well as how to effectively diagnose and treat it. Methods: Here, drawing upon the experiences and expertise of the clinicians and academics of the European working group on COVID-19, we have reviewed the current literature to provide a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Results: In this review, we provide a summary of the neurological symptoms associated with the post-COVID-19 condition, before discussing the possible mechanisms which may underly and manifest these symptoms. Following this, we explore the risk factors for developing neurological symptoms as a result of COVID-19 and the post-COVID-19 condition, as well as how COVID-19 infection may itself be a risk factor for the development of neurological disease in the future. Lastly, we evaluate how the post-COVID condition could be accurately diagnosed and effectively treated, including examples of the current guidelines, clinical outcomes, and tools that have been developed to aid in this process, as well as addressing the protection provided by COVID-19 vaccines against the post-COVID-19 condition. Conclusions: Overall, this review provides a comprehensive overview of the neurological sequalae of the post-COVID-19 condition. Impact statement With our understanding of the neurological complications of the post-COVID-19 condition currently lacking sufficient depth, this review aimed at highlightin
Edison P, 2023, Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, & Neuroimaging Advancing the Field of Neurology, BRAIN CONNECTIVITY, Vol: 13, Pages: 117-119, ISSN: 2158-0014
Fleming B, Edison P, Kenny L, 2023, Cognitive impairment after cancer treatment: mechanisms, clinical characterization, and management., BMJ, Vol: 380
Cognitive impairment is a debilitating side effect experienced by patients with cancer treated with systemically administered anticancer therapies. With around 19.3 million new cases of cancer worldwide in 2020 and the five year survival rate growing from 50% in 1970 to 67% in 2013, an urgent need exists to understand enduring side effects with severe implications for quality of life. Whereas cognitive impairment associated with chemotherapy is recognized in patients with breast cancer, researchers have started to identify cognitive impairment associated with other treatments such as immune, endocrine, and targeted therapies only recently. The underlying mechanisms are diverse and therapy specific, so further evaluation is needed to develop effective therapeutic interventions. Drug and non-drug management strategies are emerging that target mechanistic pathways or the cognitive deficits themselves, but they need to be rigorously evaluated. Clinically, consistent use of objective diagnostic tools is necessary for accurate diagnosis and clinical characterization of cognitive impairment in patients treated with anticancer therapies. This should be supplemented with clinical guidelines that could be implemented in daily practice. This review summarizes the recent advances in the mechanisms, clinical characterization, and novel management strategies of cognitive impairment associated with treatment of non-central nervous system cancers.
Edison P, 2023, Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, & Neuroimaging Advancing the Field of Neurology, BRAIN CONNECTIVITY, Vol: 13, Pages: 61-63, ISSN: 2158-0014
Edison P, 2023, Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, & Neuroimaging Advancing the Field of Neurology, BRAIN CONNECTIVITY, Vol: 13, Pages: 1-3, ISSN: 2158-0014
Caprioglio C, Ribaldi F, Visser LNC, et al., 2023, Analysis of Psychological Symptoms Following Disclosure of Amyloid-Positron Emission Tomography Imaging Results to Adults With Subjective Cognitive Decline., JAMA Netw Open, Vol: 6
IMPORTANCE: Individuals who are amyloid-positive with subjective cognitive decline and clinical features increasing the likelihood of preclinical Alzheimer disease (SCD+) are at higher risk of developing dementia. Some individuals with SCD+ undergo amyloid-positron emission tomography (PET) as part of research studies and frequently wish to know their amyloid status; however, the disclosure of a positive amyloid-PET result might have psychological risks. OBJECTIVE: To assess the psychological outcomes of the amyloid-PET result disclosure in individuals with SCD+ and explore which variables are associated with a safer disclosure in individuals who are amyloid positive. DESIGN, SETTING, AND PARTICIPANTS: This prospective, multicenter study was conducted as part of The Amyloid Imaging to Prevent Alzheimer Disease Diagnostic and Patient Management Study (AMYPAD-DPMS) (recruitment period: from April 2018 to October 2020). The setting was 5 European memory clinics, and participants included patients with SCD+ who underwent amyloid-PET. Statistical analysis was performed from July to October 2022. EXPOSURES: Disclosure of amyloid-PET result. MAIN OUTCOMES AND MEASURES: Psychological outcomes were defined as (1) disclosure related distress, assessed using the Impact of Event Scale-Revised (IES-R; scores of at least 33 indicate probable presence of posttraumatic stress disorder [PTSD]); and (2) anxiety and depression, assessed using the Hospital Anxiety and Depression scale (HADS; scores of at least 15 indicate probable presence of severe mood disorder symptoms). RESULTS: After disclosure, 27 patients with amyloid-positive SCD+ (median [IQR] age, 70 [66-74] years; gender: 14 men [52%]; median [IQR] education: 15 [13 to 17] years, median [IQR] Mini-Mental State Examination [MMSE] score, 29 [28 to 30]) had higher median (IQR) IES-R total score (10 [2 to 14] vs 0 [0 to 2]; P < .001), IES-R avoidance (0.00 [0.00 to 0.69] vs 0.00 [0.00 to 0.00]; P <&thi
Leng F, Hinz R, Gentleman S, et al., 2022, Neuroinflammation is independently associated with brain network dysfunction in Alzheimer's disease, MOLECULAR PSYCHIATRY, ISSN: 1359-4184
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Edison P, 2022, Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, & Neuroimaging Advancing the Field of Neurology, BRAIN CONNECTIVITY, Vol: 12, Pages: 847-849, ISSN: 2158-0014
Nowell J, Blunt E, Edison P, 2022, Incretin and insulin signaling as novel therapeutic targets for Alzheimer's and Parkinson's disease, MOLECULAR PSYCHIATRY, ISSN: 1359-4184
Edison P, 2022, Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, and Neuroimaging Advancing the Field of Neurology, BRAIN CONNECTIVITY, Vol: 12, Pages: 683-685, ISSN: 2158-0014
Pasqualetti G, Thayanandan T, Edison P, 2022, Influence of genetic and cardiometabolic risk factors in Alzheimer?s disease, AGEING RESEARCH REVIEWS, Vol: 81, ISSN: 1568-1637
Edison P, 2022, Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, and Neuroimaging Advancing the Field of Neurology, BRAIN CONNECTIVITY, Vol: 12, Pages: 599-601, ISSN: 2158-0014
Mohamed MA, Zeng Z, Gennaro M, et al., 2022, Astrogliosis in aging and Parkinson’s disease dementia: a new clinical study with 11C-BU99008 PET, Brain Communications, Vol: 4, ISSN: 2632-1297
The role of astrogliosis in the pathology of brain aging and neurodegenerative diseases has recently drawn great attention. Imidazoline-2 binding sites (I2BS) represent a possible target to map the distribution of reactive astrocytes. In this study, we use 11C-BU99008, an I2BS-specific PET radioligand, to image reactive astrocytes in vivo in healthy controls (HCs) andpatients with established Parkinson’s disease dementia (PDD).Eighteen HCs (age: 45−78 years) and six patients with PDD (age: 64−77 years) had one 11C-BU99008 PET-CT scan with arterial input function. All subjects underwent one 3T MRI brain scan to facilitate the analysis of the PET-CT data and to capture individual cerebral atrophy. Regional 11C-BU99008 volumes of distribution (VT) were calculated for each subject by two-tissue compartmental modelling.Positive correlations between 11C-BU99008 VT values and age were found for all tested regions across the brain within HCs (p<0.05); furthermore, multiple regression indicated that aging affects 11C-BU99008 VT values in a region-specific manner. Independent samples t-test indicated that there was no significant group difference in 11C-BU99008 VT values betweenPDD (n=6; mean age = 71.97±4.66 years) and older HCs (n=9; mean age = 71.90±5.51 years).Our dataset shows that astrogliosis is common with aging in a region-specific manner. However, in this set-up, 11C-BU99008 PET cannot differentiate patients with PDD from healthy controls of similar age.
Edison P, 2022, Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, and Neuroimaging, BRAIN CONNECTIVITY, Vol: 12, Pages: 498-501, ISSN: 2158-0014
Edison P, 2022, Call for Papers: Brain Connectivity: A Journal of Clinical Neurology, Neuroscience, & Neuroimaging., Brain Connect, Vol: 12
Loreto F, Fitzgerald A, Golemme M, et al., 2022, Prevalence of depressive symptoms in a memory clinic cohort: a retrospective study, Journal of Alzheimer's Disease, Vol: 88, ISSN: 1387-2877
Background Depression has been suggested to be a cause of reversible cognitive impairment but also a risk factor for neurodegenerative disease. Studies suggest that depression prevalence may be high in early onset dementia, particularly Alzheimer’s disease, but this has not been systematically assessed in a biomarker-validated clinical dementia cohort to date. Objective To examine the prevalence, features and association with amyloid pathology of lifetime depressive symptoms in a memory clinic cohort meeting appropriate use criteria for amyloid PET imaging.Methods We included 300 patients from a single-centre memory clinic cohort that received diagnostic biomarker evaluation with amyloid PET imaging according to appropriate use criteria. History of lifetime depressive symptoms was retrospectively assessed through structured review of clinical correspondence. Results One-hundred-and-forty-two (47%) patients had a history of significant depressive symptoms (‘D+’). Of these, 89% had ongoing symptoms and 60% were on antidepressants at the time of presentation to our Clinic. Depressive symptoms were equally highly prevalent in the amyloid-positive and the heterogeneous group of amyloid-negative patients.Conclusions Approximately half of patients who meet appropriate use criteria for amyloid PET had a history of depressive symptoms. We suggest that depression is an important feature of both neurodegenerative and non-neurodegenerative cognitive impairment and may contribute to the diagnostic uncertainty behind referral to amyloid PET.
Edison P, 2022, Brain Connectivity???????: A Journal of Clinical Neurology and Neuroscience, BRAIN CONNECTIVITY, Vol: 12, Pages: 299-301, ISSN: 2158-0014
Young M, Crook H, Scott J, et al., 2022, Covid-19: virology, variants, and vaccines, BMJ Medicine, Vol: 1, ISSN: 2754-0413
As of 25 January 2022, over 349 million individuals have received a confirmed diagnosis of covid-19, with over 5.59 million confirmed deaths associated with the SARS-CoV-2 virus. The covid-19 pandemic has prompted an extensive global effort to study the molecular evolution of the virus and develop vaccines to prevent its spread. Although rigorous determination of SARS-CoV-2 infectivity remains elusive, owing to the continuous evolution of the virus, steps have been made to understand its genome, structure, and emerging genetic mutations. The SARS-CoV-2 genome is composed of several open reading frames and structural proteins, including the spike protein, which is essential for entry into host cells. As of 25 January 2022, the World Health Organization has reported five variants of concern, two variants of interest, and three variants under monitoring. Additional sublineages have since been identified, and are being monitored. The mutations harboured in these variants confer an increased transmissibility, severity of disease, and escape from neutralising antibodies compared with the primary strain. The current vaccine strategy, including booster doses, provides protection from severe disease. As of 24 January 2022, 33 vaccines have been approved for use in 197 countries. In this review, we discuss the genetics, structure, and transmission methods of SARS-CoV-2 and its variants, highlighting how mutations provide enhanced abilities to spread and inflict disease. This review also outlines the vaccines currently in use around the world, providing evidence for every vaccine's immunogenicity and effectiveness.
Edison P, 2022, Brain Connectivity: A Clinical Neurology and Neuroscience Journal, BRAIN CONNECTIVITY, Vol: 12, Pages: 207-209, ISSN: 2158-0014
Edison P, 2022, Brain Connectivity: A Journal of Clinical Neurology and Neuroscience, BRAIN CONNECTIVITY, Vol: 12, Pages: 109-111, ISSN: 2158-0014
Livingston NR, Calsolaro V, Hinz R, et al., 2022, Relationship between astrocyte reactivity, using novel C-11-BU99008 PET, and glucose metabolism, grey matter volume and amyloid load in cognitively impaired individuals, MOLECULAR PSYCHIATRY, Vol: 27, Pages: 2019-2029, ISSN: 1359-4184
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Edison P, 2022, Brain Connectivity: A Comprehensive Journal in Clinical Neurology and Neuroscience, BRAIN CONNECTIVITY, Vol: 12, Pages: 3-5, ISSN: 2158-0014
Edison P, 2022, Call for Papers: Brain Connectivity., Brain Connect, Vol: 12
Edison P, 2022, Call for Papers: Brain Connectivity., Brain Connect
de Erausquin GA, Snyder H, Brugha TS, et al., 2022, Chronic neuropsychiatric sequelae of SARS-CoV-2: Protocol and methods from the Alzheimer's Association Global Consortium, ALZHEIMERS & DEMENTIA-TRANSLATIONAL RESEARCH & CLINICAL INTERVENTIONS, Vol: 8
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Leng F, Zhan Z, Sun Y, et al., 2022, Cerebrospinal Fluid sTREM2 Has Paradoxical Association with Brain Structural Damage Rate in Early- and Late-Stage Alzheimer's Disease, JOURNAL OF ALZHEIMERS DISEASE, Vol: 88, Pages: 117-126, ISSN: 1387-2877
Edison P, 2021, COVID-19, Network Dysfunction and Neurodegeneration, BRAIN CONNECTIVITY, Vol: 11, Pages: 785-787, ISSN: 2158-0014
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