Evelyne Bischof, MD, PhD

MD, PhD, MPH, FEFIM

Chief Associate Physician, Department of Internal Medicine and Medical Oncology at Renji Hospital of Shanghai Jiaotong University School of Medicine

Co-Founder and Vice President at Healthy Longevity Medicine Society

Director, Sheba Longevity Center at Sheba Medical Center


Dr. Bischof’s research focuses on oncology and multimorbidity in internal medicine, as well as healthy longevity medicine, artificial intelligence (AI) and digital health, precision medicine, biogerontology, and geronto-oncology. She has conducted research and clinical practice at the following institutions: University Hospital of Basel, Fudan University Shanghai Cancer Center, Zhongshan Hospital, Renji Hospital, and Shanghai East Hospital. Dr. Bischof is currently affiliated with the Centre of Healthy Aging, Universität Zürich, and previously was senior attending physician of internal medicine at the University Hospital Basel.

Learn more about the 50+ Atria Academy Fellows guiding a transformation in medicine

Learn more about the 50+ Atria Academy Fellows guiding a transformation in medicine

Pre-Draft Elbow Magnetic Resonance Imaging in Major League Baseball Pitchers.

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Date: 07/2024

Journal : Journal of shoulder and elbow surgery

Collaborators
Collaborators: Brandon J Erickson, Peter N Chalmers, John D'Angelo, Kevin Ma, Stephen Fealy, Frank S Alexander, Christopher S Ahmad

Prior to the Major League Baseball (MLB) draft, some pitchers undergo pre-draft magnetic resonance imaging (MRI). This study aimed to evaluate pre-draft elbow MRI on baseball pitchers who were entering the MLB draft to determine the presence or absence of pathology, the associations between these pathologies and UCL tears, and inter-observer reliability regarding common MRI pathology.

Surfer's neurapraxia - an uncommon surfing injury of the saphenous nerve.

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Date: 07/2024

Journal : The Physician and sportsmedicine

Collaborators
Collaborators: Kyle K Obana, David P Trofa, Christopher S Ahmad, William N Levine, Charles A Popkin

Surfer's neurapraxia is a rare surfing injury of the saphenous nerve secondary to persistent compression of the saphenous nerve along the medial thigh by the surfboard when paddling prone and while sitting upright on the board waiting for a wave. Symptoms may be nonspecific and consist of pain in the medial thigh with or without radiation along the saphenous nerve distribution (medial leg, medial ankle, medial arch of the foot). The saphenous nerve tension test can be utilized to reproduce the symptoms of surfer's neurapraxia. Treatment consists of conservative management while refractory cases may benefit from injection with local anesthetic. The authors propose the Obana Plan (WATER) for prevention of surfer's neurapraxia, consisting of Wetsuits, Abduction, Timing, Exercise, and Rest. Overall, surfer's neurapraxia is a benign condition that can be prevented and managed conservatively.

Assessing the state of obesity care: Quality, access, guidelines, and standards.

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Date: 08/2024

Journal : Obesity science & practice

Collaborators
Collaborators: Lee M Kaplan, Caroline M Apovian, Jamy D Ard, David B Allison, Louis J Aronne, Rachel L Batterham, Luca Busetto, Dror Dicker, Deborah B Horn, Aaron S Kelly, Jeffrey I Mechanick, Jonathan Q Purnell, Ximena Ramos-Salas,

An international panel of obesity medicine experts from multiple professional organizations examined patterns of obesity care and current obesity treatment guidelines to identify areas requiring updating in response to emerging science and clinical evidence.

Sex ratio and age of onset in AQP4 antibody-associated NMOSD: a review and meta-analysis.

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Date: 07/2024

Journal : Journal of neurology

Collaborators
Collaborators: Simon Arnett, Sin Hong Chew, Unnah Leitner, Jyh Yung Hor, Friedemann Paul, Michael R Yeaman, Michael Levy, Brian G Weinshenker, Brenda L Banwell, Kazuo Fujihara, Hesham Abboud, Irena Dujmovic Basuroski, Georgina Arrambide, Veronika E Neubrand, Chao Quan, Esther Melamed, Jacqueline Palace, Jing Sun, Nasrin Asgari, Simon A Broadley,

Aquaporin-4 (AQP4) antibody-associated neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system. We have undertaken a systematic review and meta-analysis to ascertain the sex ratio and mean age of onset for AQP4 antibody associated NMOSD. We have also explored factors that impact on these demographic data.

White Matter Hyperintensities Are Associated with Slower Gait Speed in Older Adults Without Dementia.

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Date: 07/2024

Journal : Neuro-degenerative diseases

Collaborators
Collaborators: Juan P Vazquez, Joe Verghese, Nir Barzilai, Sofiya Milman, Helena M Blumen

Slow gait speed is associated with poor health outcomes in aging, but the relationship between cerebral small vessel disease (CSVD) pathologies and gait speed in aging is not well understood. We investigated the relationships between cerebral small vessel disease (CSVD) imaging markers and gait speed during simple (normal pace walking (NPW)) and complex (walking-while talking (WWT)) as both measures are associated with shared health outcomes such as falls, frailty, disability, mortality, and dementia.

Hypothalamic MRI-derived microstructure is associated with neurocognitive aging in humans.

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Date: 09/2024

Journal : Neurobiology of aging

Collaborators
Collaborators: Sandra Aleksic, Roman Fleysher, Erica F Weiss, Noa Tal, Timothy Darby, Helena M Blumen, Juan Vazquez, Kenny Q Ye, Tina Gao, Shira M Siegel, Nir Barzilai, Michael L Lipton, Sofiya Milman

The hypothalamus regulates homeostasis across the lifespan and is emerging as a regulator of aging. In murine models, aging-related changes in the hypothalamus, including microinflammation and gliosis, promote accelerated neurocognitive decline. We investigated relationships between hypothalamic microstructure and features of neurocognitive aging, including cortical thickness and cognition, in a cohort of community-dwelling older adults (age range 65-97 years, n=124). Hypothalamic microstructure was evaluated with two magnetic resonance imaging diffusion metrics: mean diffusivity (MD) and fractional anisotropy (FA), using a novel image processing pipeline. Hypothalamic MD was cross-sectionally positively associated with age and it was negatively associated with cortical thickness. Hypothalamic FA, independent of cortical thickness, was cross-sectionally positively associated with neurocognitive scores. An exploratory analysis of longitudinal neurocognitive performance suggested that lower hypothalamic FA may predict cognitive decline. No associations between hypothalamic MD, age, and cortical thickness were identified in a younger control cohort (age range 18-63 years, n=99). To our knowledge, this is the first study to demonstrate that hypothalamic microstructure is associated with features of neurocognitive aging in humans.

Cognitive reserve proxies are associated with age-related cognitive decline - Not age-related gait speed decline.

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Date: 09/2024

Journal : Neurobiology of aging

Collaborators
Collaborators: Helena M Blumen, Oshadi Jayakody, Emmeline Ayers, Nir Barzilai, Christian Habeck, Sofiya Milman, Yaakov Stern, Erica F Weiss, Joe Verghese

Cognition and gait share brain substrates in aging and dementia. Cognitive reserve (CR) allows individuals to cope with brain pathology and delay cognitive impairment and dementia. Yet, evidence for that CR is associated with age-related cognitive decline is mixed, and evidence for that CR is associated with age-related gait decline is limited. In 1,079 older (M Age = 75.4 years; 56.0% women) LonGenity study participants without dementia at baseline and up to 12 years of annual follow-up (M follow-up = 3.9 years, SD = 2.5 years), high CR inferred from cognitive (education years), physical (number of blocks walked per day; weekly physical activity days), and social (volunteering/working; living with someone) proxies were associated with slower rates of age-related decline in global cognition - not gait speed decline. Thus, cognitive, physical, and social CR proxies are associated with cognitive decline in older adults without dementia. The multifactorial etiology and earlier decline in gait than cognition may render it less modifiable by CR proxies later in life.

A deep catalogue of protein-coding variation in 983,578 individuals.

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Date: 07/2024

Journal : Nature

Collaborators
Collaborators: Kathie Y Sun, Xiaodong Bai, Siying Chen, Suying Bao, Chuanyi Zhang, Manav Kapoor, Joshua Backman, Tyler Joseph, Evan Maxwell, George Mitra, Alexander Gorovits, Adam Mansfield, Boris Boutkov, Sujit Gokhale, Lukas Habegger, Anthony Marcketta, Adam E Locke, Liron Ganel, Alicia Hawes, Michael D Kessler, Deepika Sharma, Jeffrey Staples, Jonas Bovijn, Sahar Gelfman, Alessandro Di Gioia, Veera M Rajagopal, Alexander Lopez, Jennifer Rico Varela, Jesús Alegre-Díaz, Jaime Berumen, Roberto Tapia-Conyer, Pablo Kuri-Morales, Jason Torres, Jonathan Emberson, Rory Collins, , , Michael Cantor, Timothy Thornton, Hyun Min Kang, John D Overton, Alan R Shuldiner, M Laura Cremona, Mona Nafde, Aris Baras, Gonçalo Abecasis, Jonathan Marchini, Jeffrey G Reid, William Salerno, Suganthi Balasubramanian

Rare coding variants that substantially affect function provide insights into the biology of a gene. However, ascertaining the frequency of such variants requires large sample sizes. Here we present a catalogue of human protein-coding variation, derived from exome sequencing of 983,578 individuals across diverse populations. In total, 23% of the Regeneron Genetics Center Million Exome (RGC-ME) data come from individuals of African, East Asian, Indigenous American, Middle Eastern and South Asian ancestry. The catalogue includes more than 10.4 million missense and 1.1 million predicted loss-of-function (pLOF) variants. We identify individuals with rare biallelic pLOF variants in 4,848 genes, 1,751 of which have not been previously reported. From precise quantitative estimates of selection against heterozygous loss of function (LOF), we identify 3,988 LOF-intolerant genes, including 86 that were previously assessed as tolerant and 1,153 that lack established disease annotation. We also define regions of missense depletion at high resolution. Notably, 1,482 genes have regions that are depleted of missense variants despite being tolerant of pLOF variants. Finally, we estimate that 3% of individuals have a clinically actionable genetic variant, and that 11,773 variants reported in ClinVar with unknown significance are likely to be deleterious cryptic splice sites. To facilitate variant interpretation and genetics-informed precision medicine, we make this resource of coding variation from the RGC-ME dataset publicly accessible through a variant allele frequency browser.

MR elastography-based slip interface imaging (SII) for functional assessment of myofascial interfaces: A feasibility study.

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Date: 08/2024

Journal : Magnetic resonance in medicine

Collaborators
Collaborators: Emi Hojo, Yi Sui, Xiang Shan, Keni Zheng, Phillip Rossman, Armando Manduca, Garret M Powell, Kai-Nan An, Kristin D Zhao, Brent A Bauer, Richard L Ehman, Ziying Yin

Abnormal adherence at functional myofascial interfaces is hypothesized as an important phenomenon in myofascial pain syndrome. This study aimed to investigate the feasibility of MR elastography (MRE)-based slip interface imaging (SII) to visualize and assess myofascial mobility in healthy volunteers.

The role of quality of life data as an endpoint for collecting real-world evidence within geroscience clinical trials.

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Date: 06/2024

Journal : Ageing research reviews

Collaborators
Collaborators: Girish Harinath, Sajad Zalzala, Andy Nyquist, Maartje Wouters, Anar Isman, Mauricio Moel, Eric Verdin, Matt Kaeberlein, Brian Kennedy, Evelyne Bischof

With geroscience research evolving at a fast pace, the need arises for human randomized controlled trials to assess the efficacy of geroprotective interventions to prevent age-related adverse outcomes, disease, and mortality in normative aging cohorts. However, to confirm efficacy requires a long-term and costly approach as time to the event of morbidity and mortality can be decades. While this could be circumvented using sensitive biomarkers of aging, current molecular, physiological, and digital endpoints require further validation. In this review, we discuss how collecting real-world evidence (RWE) by obtaining health data that is amenable for collection from large heterogeneous populations in a real-world setting can help speed up validation of geroprotective interventions. Further, we propose inclusion of quality of life (QoL) data as a biomarker of aging and candidate endpoint for geroscience clinical trials to aid in distinguishing healthy from unhealthy aging. We highlight how QoL assays can aid in accelerating data collection in studies gathering RWE on the geroprotective effects of repurposed drugs to support utilization within healthy longevity medicine. Finally, we summarize key metrics to consider when implementing QoL assays in studies, and present the short-form 36 (SF-36) as the most well-suited candidate endpoint.

Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

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Date: 07/2024

Journal : Alzheimer's & dementia : the journal of the Alzheimer's Association

Collaborators
Collaborators: Daniela Andriuta, Julie Ottoy, Myuri Ruthirakuhan, Ginelle Feliciano, Allison A Dilliott, Robert A Hegele, Fuqiang Gao, Paula M McLaughlin, Jennifer S Rabin, Madeline Wood Alexander, Christopher J M Scott, Vanessa Yhap, Courtney Berezuk, Miracle Ozzoude, Walter Swardfager, Julia Zebarth, M Carmela Tartaglia, Ekaterina Rogaeva, David F Tang-Wai, Leanne Casaubon, Sanjeev Kumar, Dar Dowlatshahi, Jennifer Mandzia, Demetrios Sahlas, Gustavo Saposnik, Corinne E Fischer, Michael Borrie, Ayman Hassan, Malcolm A Binns, Morris Freedman, Howard Chertkow, Elizabeth Finger, Andrew Frank, Robert Bartha, Sean Symons, Henrik Zetterberg, Richard H Swartz, Mario Masellis, Sandra E Black, Joel Ramirez,

We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases.

Diagnostic Accuracy of SPECT for Mild Traumatic Brain Injury: A Systematic Review and Meta-analysis.

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Date: 06/2024

Journal : Clinical nuclear medicine

Collaborators
Collaborators: Alex Koziarz, Frank Koziarz, Rui Shen, Prasaanthan Gopee-Ramanan, Sandra E Black, Daniel Worsley, Ian Y M Chan, David L Streiner, Katherine A Zukotynski

This study examines the diagnostic accuracy of brain perfusion SPECT for mild traumatic brain injury (mTBI).

Tau follows principal axes of functional and structural brain organization in Alzheimer's disease.

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Date: 06/2024

Journal : Nature communications

Collaborators
Collaborators: Julie Ottoy, Min Su Kang, Jazlynn Xiu Min Tan, Lyndon Boone, Reinder Vos de Wael, Bo-Yong Park, Gleb Bezgin, Firoza Z Lussier, Tharick A Pascoal, Nesrine Rahmouni, Jenna Stevenson, Jaime Fernandez Arias, Joseph Therriault, Seok-Jun Hong, Bojana Stefanovic, JoAnne McLaurin, Jean-Paul Soucy, Serge Gauthier, Boris C Bernhardt, Sandra E Black, Pedro Rosa-Neto, Maged Goubran

Alzheimer's disease (AD) is a brain network disorder where pathological proteins accumulate through networks and drive cognitive decline. Yet, the role of network connectivity in facilitating this accumulation remains unclear. Using in-vivo multimodal imaging, we show that the distribution of tau and reactive microglia in humans follows spatial patterns of connectivity variation, the so-called gradients of brain organization. Notably, less distinct connectivity patterns ("gradient contraction") are associated with cognitive decline in regions with greater tau, suggesting an interaction between reduced network differentiation and tau on cognition. Furthermore, by modeling tau in subject-specific gradient space, we demonstrate that tau accumulation in the frontoparietal and temporo-occipital cortices is associated with greater baseline tau within their functionally and structurally connected hubs, respectively. Our work unveils a role for both functional and structural brain organization in pathology accumulation in AD, and supports subject-specific gradient space as a promising tool to map disease progression.

Persistent fatigue in post-acute COVID syndrome is associated with altered T1 MRI texture in subcortical structures: a preliminary investigation.

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Date: 07/2024

Journal : Behavioural brain research

Collaborators
Collaborators: Nathan W Churchill, Eugenie Roudaia, J Jean Chen, Allison Sekuler, Fuqiang Gao, Mario Masellis, Benjamin Lam, Ivy Cheng, Chris Heyn, Sandra E Black, Bradley J MacIntosh, Simon J Graham, Tom A Schweizer

Post-acute COVID syndrome (PACS) is a global health concern and is often associated with debilitating symptoms. Post-COVID fatigue is a particularly frequent and troubling issue, and its underlying mechanisms remain incompletely understood. One potential contributor is micropathological injury of subcortical and brainstem structures, as has been identified in other patient populations. Texture-based analysis (TA) may be used to measure such changes in anatomical MRI data. The present study develops a methodology of voxel-wise TA mapping in subcortical and brainstem regions, which is then applied to T1-weighted MRI data from a cohort of 48 individuals who had PACS (32 with and 16 without ongoing fatigue symptoms) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19. Both groups were assessed an average of 4-5 months post-infection. There were no significant differences between PACS and control groups, but significant differences were observed within the PACS groups, between those with and without fatigue symptoms. This included reduced texture energy and increased entropy, along with reduced texture correlation, cluster shade and profile in the putamen, pallidum, thalamus and brainstem. These findings provide new insights into the neurophysiological mechanisms that underlie PACS, with altered tissue texture as a potential biomarker of this debilitating condition.

Improved Outcomes When Home-Dose Carbidopa-Levodopa Is Continued in the Geriatric Emergency Department in Patients With Parkinson's Disease.

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Date: 07/2024

Journal : The Senior care pharmacist

Collaborators
Collaborators: Jaylan M Yuksel, Kelly R Ulen, Jay M Brenner, Sharon A Brangman, John Noviasky

Parkinson's disease (PD) is a debilitating condition that affects 1.8% of people 65 years of age and older. Patients with PD often require hospitalization and are frequently admitted through the emergency department (ED). Notably, their hospital durations tend to be lengthier compared with patients without PD. The primary outcome of this research was to compare the length of stay (LOS) of patients who received carbidopa-levodopa (CL) in the ED with those who did not. Secondary outcomes included 30-day-readmission rates and administration of injectable for agitation. In addition, the percentage of patients receiving CL before and after an information management technology (IMT) alert implementation was compared in a sub-analysis. Patients that received CL during their inpatient stay were identified by a database report in this retrospective study. Patients were excluded if they were not admitted through the ED, younger than 65 years of age, or admitted to the intensive care unit after the ED. There was a total of 266 in the control group and 217 patients in the intervention group. The intervention group had a significantly shorter LOS than the control group (3.29 vs 5.37 days; = 0.002), significantly less frequent 30-day readmissions ( = 0.032), and used fewer injectables for agitation ( = 0.035). The sub-analysis of the IMT alert revealed that prior to the alert's implementation, 28.5% of patients received CL in the ED; whereas post-alert, this percentage increased to 91.4% ( < 0.001). The results of this study found that the group of PD patients who received CL in the ED had shorter LOS, lower 30-day readmissions, and used less injectables for agitation compared with the group that did not receive CL in the ED. This improvement is possibly due to continuity of CL supply considering its short half-life and clinical importance for PD.

The Integration of Clinical Trials With the Practice of Medicine: Repairing a House Divided.

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Date: 07/2024

Journal : JAMA

Collaborators
Collaborators: Derek C Angus, Alison J Huang, Roger J Lewis, Amy P Abernethy, Robert M Califf, Martin Landray, Nancy Kass, Kirsten Bibbins-Domingo,

Optimal health care delivery, both now and in the future, requires a continuous loop of knowledge generation, dissemination, and uptake on how best to provide care, not just determining what interventions work but also how best to ensure they are provided to those who need them. The randomized clinical trial (RCT) is the most rigorous instrument to determine what works in health care. However, major issues with both the clinical trials enterprise and the lack of integration of clinical trials with health care delivery compromise medicine's ability to best serve society.

Evidence for a novel neuronal mechanism driving Alzheimer's disease, upstream of amyloid.

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Date: 07/2024

Journal : Alzheimer's & dementia : the journal of the Alzheimer's Association

Collaborators
Collaborators: Sara Garcia Ratés, María-Salud García-Ayllón, Neus Falgàs, Sharon A Brangman, Margaret M Esiri, Clive W Coen, Susan Adele Greenfield

This perspective offers an alternative to the amyloid hypothesis in the etiology of Alzheimer's disease (AD). We review evidence for a novel signaling mechanism based on a little-known peptide, T14. T14 could drive neurodegeneration as an aberrantly activated process of plasticity selective to interconnecting subcortical nuclei, the isodendritic core, where cell loss starts at the pre-symptomatic stages of the disease. Each of these cell groups has the capacity to form T14, which can stimulate production of p-Tau and β-amyloid, suggestive of an upstream driver of neurodegeneration. Moreover, results in an animal AD model show that antagonism of T14 with a cyclated variant, NBP14, prevents formation of β-amyloid, and restores cognitive function to that of wild-type counterparts. Any diagnostic and/or therapeutic strategy based on T14-NBP14 awaits validation in clinical trials. However, an understanding of this novel signaling system could bring much-needed fresh insights into the progression of cell loss underlying AD. HIGHLIGHTS: The possible primary mechanism of neurodegeneration upstream of amyloid. Primary involvement of selectively vulnerable subcortical nuclei, isodendritic core. Bioactive peptide T14 trophic in development but toxic in context of mature brain. Potential for early-stage biomarker to detect Alzheimer's disease. Effective therapeutic halting neurodegeneration, validated already in 5XFAD mice.

A synergistic workspace for human consciousness revealed by Integrated Information Decomposition.

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Date: 07/2024

Journal : eLife

Collaborators
Collaborators: Andrea I Luppi, Pedro A M Mediano, Fernando E Rosas, Judith Allanson, John Pickard, Robin L Carhart-Harris, Guy B Williams, Michael M Craig, Paola Finoia, Adrian M Owen, Lorina Naci, David K Menon, Daniel Bor, Emmanuel A Stamatakis

How is the information-processing architecture of the human brain organised, and how does its organisation support consciousness? Here, we combine network science and a rigorous information-theoretic notion of synergy to delineate a 'synergistic global workspace', comprising gateway regions that gather synergistic information from specialised modules across the human brain. This information is then integrated within the workspace and widely distributed via broadcaster regions. Through functional MRI analysis, we show that gateway regions of the synergistic workspace correspond to the human brain's default mode network, whereas broadcasters coincide with the executive control network. We find that loss of consciousness due to general anaesthesia or disorders of consciousness corresponds to diminished ability of the synergistic workspace to integrate information, which is restored upon recovery. Thus, loss of consciousness coincides with a breakdown of information integration within the synergistic workspace of the human brain. This work contributes to conceptual and empirical reconciliation between two prominent scientific theories of consciousness, the Global Neuronal Workspace and Integrated Information Theory, while also advancing our understanding of how the human brain supports consciousness through the synergistic integration of information.

Psilocybin desynchronizes the human brain.

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Date: 07/2024

Journal : Nature

Collaborators
Collaborators: Joshua S Siegel, Subha Subramanian, Demetrius Perry, Benjamin P Kay, Evan M Gordon, Timothy O Laumann, T Rick Reneau, Nicholas V Metcalf, Ravi V Chacko, Caterina Gratton, Christine Horan, Samuel R Krimmel, Joshua S Shimony, Julie A Schweiger, Dean F Wong, David A Bender, Kristen M Scheidter, Forrest I Whiting, Jonah A Padawer-Curry, Russell T Shinohara, Yong Chen, Julia Moser, Essa Yacoub, Steven M Nelson, Luca Vizioli, Damien A Fair, Eric J Lenze, Robin Carhart-Harris, Charles L Raison, Marcus E Raichle, Abraham Z Snyder, Ginger E Nicol, Nico U F Dosenbach

A single dose of psilocybin, a psychedelic that acutely causes distortions of space-time perception and ego dissolution, produces rapid and persistent therapeutic effects in human clinical trials. In animal models, psilocybin induces neuroplasticity in cortex and hippocampus. It remains unclear how human brain network changes relate to subjective and lasting effects of psychedelics. Here we tracked individual-specific brain changes with longitudinal precision functional mapping (roughly 18 magnetic resonance imaging visits per participant). Healthy adults were tracked before, during and for 3 weeks after high-dose psilocybin (25 mg) and methylphenidate (40 mg), and brought back for an additional psilocybin dose 6-12 months later. Psilocybin massively disrupted functional connectivity (FC) in cortex and subcortex, acutely causing more than threefold greater change than methylphenidate. These FC changes were driven by brain desynchronization across spatial scales (areal, global), which dissolved network distinctions by reducing correlations within and anticorrelations between networks. Psilocybin-driven FC changes were strongest in the default mode network, which is connected to the anterior hippocampus and is thought to create our sense of space, time and self. Individual differences in FC changes were strongly linked to the subjective psychedelic experience. Performing a perceptual task reduced psilocybin-driven FC changes. Psilocybin caused persistent decrease in FC between the anterior hippocampus and default mode network, lasting for weeks. Persistent reduction of hippocampal-default mode network connectivity may represent a neuroanatomical and mechanistic correlate of the proplasticity and therapeutic effects of psychedelics.

Longitudinal experiences of Canadians receiving compassionate access to psilocybin-assisted psychotherapy.

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Date: 07/2024

Journal : Scientific reports

Collaborators
Collaborators: Sara de la Salle, Hannes Kettner, Julien Thibault Lévesque, Nicolas Garel, Shannon Dames, Ryan Patchett-Marble, Soham Rej, Sara Gloeckler, David Erritzoe, Robin Carhart-Harris, Kyle T Greenway

Recent clinical trials have found that the serotonergic psychedelic psilocybin effectively alleviates anxiodepressive symptoms in patients with life-threatening illnesses when given in a supportive environment. These outcomes prompted Canada to establish legal pathways for therapeutic access to psilocybin, coupled with psychological support. Despite over one-hundred Canadians receiving compassionate access since 2020, there has been little examination of these 'real-world' patients. We conducted a prospective longitudinal survey which focused on Canadians who were granted Section 56 exemptions for legal psilocybin-assisted psychotherapy. Surveys assessing various symptom dimensions were conducted at baseline, two weeks following the session (endpoint), and optionally one day post-session. Participant characteristics were examined using descriptive statistics, and paired sample t-tests were used to quantify changes from baseline to the two-week post-treatment endpoint. Eight participants with Section 56 exemptions (four females, M = 52.3 years), all with cancer diagnoses, fully completed baseline and endpoint surveys. Significant improvements in anxiety and depression symptoms, pain, fear of COVID-19, quality of life, and spiritual well-being were observed. Attitudes towards death, medical assistance in dying, and desire for hastened death remained unchanged. While most participants found the psilocybin sessions highly meaningful, if challenging, one reported a substantial decrease in well-being due to the experience. These preliminary data are amongst the first to suggest that psilocybin-assisted psychotherapy can produce psychiatric benefits in real-world patients akin to those observed in clinical trials. Limited enrollment and individual reports of negative experiences indicate the need for formal real-world evaluation programs to surveil the ongoing expansion of legal access to psychedelics.

Psychotomimetic compensation versus sensitization.

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Date: 08/2024

Journal : Pharmacology research & perspectives

Collaborators
Collaborators: Ari Brouwer, Robin L Carhart-Harris, Charles L Raison

It is a paradox that psychotomimetic drugs can relieve symptoms that increase risk of and cooccur with psychosis, such as attention and motivational deficits (e.g., amphetamines), pain (e.g., cannabis) and symptoms of depression (e.g., psychedelics, dissociatives). We introduce the ideas of psychotomimetic compensation and psychotomimetic sensitization to explain this paradox. Psychotomimetic compensation refers to a short-term stressor or drug-induced compensation against stress that is facilitated by engagement of neurotransmitter/modulator systems (endocannabinoid, serotonergic, glutamatergic and dopaminergic) that mediate the effects of common psychotomimetic drugs. Psychotomimetic sensitization occurs after repeated exposure to stress and/or drugs and is evidenced by the gradual intensification and increase of psychotic-like experiences over time. Theoretical and practical implications of this model are discussed.

Hypersensitivity to BK channel opening in persistent post-traumatic headache.

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Date: 06/2024

Journal : The journal of headache and pain

Collaborators
Collaborators: Haidar M Al-Khazali, Rune H Christensen, David W Dodick, Basit Ali Chaudhry, Anna G Melchior, Rami Burstein, Håkan Ashina

Large conductance  calcium-activated potassium (BK) channels have been implicated in the neurobiological underpinnings of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BK channel opener) could induce migraine-like headache in persons with PPTH.

Functional impairment of chronic migraine with medication overuse: Secondary analysis from the Medication Overuse Treatment Strategy (MOTS) trial.

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Date: 06/2024

Journal : Headache

Collaborators
Collaborators: Samantha C Shao, Joseph Hentz, Patti Shank, Michael Leonard, David W Dodick, Todd J Schwedt

Chronic migraine exerts substantial negative impacts on daily functioning. Efforts to manage impaired functioning may result in medication overuse, which contributes to the worsening profile and chronification of migraine. The Migraine Functional Impact Questionnaire (MFIQ) is a recently developed measure assessing the impact of migraine on physical, social, and emotional function.

Photophobia Contributes to Migraine-Associated Disability and Reduced Work Productivity: Results From the American Registry for Migraine Research (ARMR).

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Date: 06/2024

Journal : Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society

Collaborators
Collaborators: Zachary Leibovit-Reiben, Gina Dumkrieger, David W Dodick, Kathleen Digre, Catherine D Chong, Meesha Trivedi, Todd J Schwedt

Photosensitivity, often called "photophobia" in the migraine literature, is a common and bothersome symptom for most people during their migraine attacks. This study aimed to investigate the association of photophobia severity with work productivity, activity impairment, and migraine-associated disability using data from a large cohort of patients with migraine who were enrolled into the American Registry for Migraine Research (ARMR).

Physical enhancement of older adults using hyperbaric oxygen: a randomized controlled trial.

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Date: 07/2024

Journal : BMC geriatrics

Collaborators
Collaborators: Amir Hadanny, Efrat Sasson, Laurian Copel, Malka Daniel-Kotovsky, Eldad Yaakobi, Erez Lang, Gregory Fishlev, Nir Polak, Mony Friedman, Keren Doenyas, Shachar Finci, Yonatan Zemel, Yair Bechor, Shai Efrati

Aging is associated with a progressive decline in the capacity for physical activity. The objective of the current study was to evaluate the effect of an intermittent hyperbaric oxygen therapy (HBOT) protocol on maximal physical performance and cardiac perfusion in sedentary older adults.

Nutritional and Inflammatory Aspects of Low Parathyroid Hormone in Maintenance Hemodialysis Patients-A Longitudinal Study.

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Date: 06/2024

Journal : Journal of renal nutrition : the official journal of the Council on Renal Nutrition of the National Kidney Foundation

Collaborators
Collaborators: Shani Zilberman-Itskovich, Baker Algamal, Ada Azar, Shai Efrati, Ilia Beberashvili

Low serum parathyroid hormone (PTH) is an accepted marker for adynamic bone disease which is characterized by increased morbidity and mortality in maintenance hemodialysis (MHD) patients. In light of the known cross-sectional associations between PTH and malnutrition-inflammation syndrome, we aimed to examine the longitudinal associations between PTH with changes in nutritional and inflammatory parameters and clinical outcomes in MHD patients with low PTH.

Estimated Pulse-Wave Velocity and Magnetic Resonance Imaging Markers of Cerebral Small-Vessel Disease in the NOMAS.

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Date: 07/2024

Journal : Journal of the American Heart Association

Collaborators
Collaborators: Taylor A Ariko, Botagoz Aimagambetova, Hannah Gardener, Jose Gutierrez, Mitchell S V Elkind, Clinton B Wright, Weizhao Zhao, Tatjana Rundek

Pulse-wave velocity is a measure of arterial stiffness and a risk factor for cardiovascular disease. Recently, an estimated pulse-wave velocity (ePWV) was introduced that was predictive of increased risk of cardiovascular disease. Our objective was to determine whether ePWV was associated with cerebral small-vessel disease on magnetic resonance imaging.

Epidemiologic Features of Recovery From SARS-CoV-2 Infection.

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Date: 06/2024

Journal : JAMA network open

Collaborators
Collaborators: Elizabeth C Oelsner, Yifei Sun, Pallavi P Balte, Norrina B Allen, Howard Andrews, April Carson, Shelley A Cole, Josef Coresh, David Couper, Mary Cushman, Martha Daviglus, Ryan T Demmer, Mitchell S V Elkind, Linda C Gallo, Jose D Gutierrez, Virginia J Howard, Carmen R Isasi, Suzanne E Judd, Alka M Kanaya, Namratha R Kandula, Robert C Kaplan, Gregory L Kinney, Anna M Kucharska-Newton, Daniel T Lackland, Joyce S Lee, Barry J Make, Yuan-I Min, Joanne M Murabito, Arnita F Norwood, Victor E Ortega, Kelley Pettee Gabriel, Bruce M Psaty, Elizabeth A Regan, Daniela Sotres-Alvarez, David Schwartz, James M Shikany, Bharat Thyagarajan, Russell P Tracy, Jason G Umans, Ramachandran S Vasan, Sally E Wenzel, Prescott G Woodruff, Vanessa Xanthakis, Ying Zhang, Wendy S Post

Persistent symptoms and disability following SARS-CoV-2 infection, known as post-COVID-19 condition or "long COVID," are frequently reported and pose a substantial personal and societal burden.

Ischemic Stroke with Comorbid Cancer Has Specific miRNA-mRNA Networks in Blood That Vary by Ischemic Stroke Mechanism.

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Date: 06/2024

Journal : Annals of neurology

Collaborators
Collaborators: Bodie Knepp, Babak B Navi, Fernando Rodriguez, Lisa M DeAngelis, Mitchell S V Elkind, Costantino Iadecola, Carla P Sherman, Scott T Tagawa, Ashish Saxena, Allyson J Ocean, Heather Hull, Glen Jickling, Frank R Sharp, Bradley P Ander, Boryana Stamova

Approximately half of ischemic strokes (IS) in cancer patients are cryptogenic, with many presumed cardioembolic. We evaluated whether there were specific miRNA and mRNA transcriptome architectures in peripheral blood of IS patients with and without comorbid cancer, and between cardioembolic versus noncardioembolic IS etiologies in comorbid cancer.

Forecasting the Economic Burden of Cardiovascular Disease and Stroke in the United States Through 2050: A Presidential Advisory From the American Heart Association.

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Date: 06/2024

Journal : Circulation

Collaborators
Collaborators: Dhruv S Kazi, Mitchell S V Elkind, Anne Deutsch, William N Dowd, Paul Heidenreich, Olga Khavjou, Daniel Mark, Michael E Mussolino, Bruce Ovbiagele, Sonali S Patel, Remy Poudel, Ben Weittenhiller, Tiffany M Powell-Wiley, Karen E Joynt Maddox,

Quantifying the economic burden of cardiovascular disease and stroke over the coming decades may inform policy, health system, and community-level interventions for prevention and treatment.

Management of the Vasomotor Symptoms of Menopause: Twofers in Your Clinical Toolbox.

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Date: 07/2024

Journal : Mayo Clinic proceedings

Collaborators
Collaborators: Juliana M Kling, Cynthia A Stuenkel, Stephanie S Faubion

The number of midlife women transitioning into menopause is substantial, with more than 1 million women in the United States entering menopause each year. Vasomotor symptoms (VMS), mood and sleep disturbances, and sexual problems are common during the menopause transition yet often go untreated. Menopausal hormone therapy is the most effective treatment of VMS, and the benefits typically outweigh the risks for women without contraindications who are younger than 60 years or within 10 years from menopause onset. For women who cannot or choose not to use hormone therapy, nonhormone prescription options exist to treat VMS. Many of these therapies have secondary benefits beyond VMS relief. For example, whereas paroxetine is Food and Drug Administration approved to treat VMS, it can also help with depressive and anxiety symptoms. The aim of this paper is to summarize prescription treatments of VMS and their secondary benefits for other common symptoms experienced by midlife women. The tools presented will help clinicians caring for midlife women provide individualized, comprehensive care with the goal of improving their quality of life during the menopause transition and beyond.

Hormonal Contraception and Sexual Function: A Review, Clinical Insights, and Management Considerations.

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Date: 06/2024

Journal : Obstetrics and gynecology clinics of North America

Collaborators
Collaborators: Mariam Saadedine, Stephanie S Faubion

Most sexually active women of reproductive age have used contraception, with hormonal methods constituting approximately 40% of contraceptive choices. Among these hormonal options, combined oral contraceptives stand out as the most selected. Within this same demographic, sexual issues are prevalent. Although specific hormonal contraceptives have been implicated in sexual dysfunction among these women, the correlation lacks consistency across studies and varies between different types of hormonal contraception. This article assesses the available literature on the associations between various hormonal contraceptive methods and sexual function and provides practical management insights.

Risks and benefits of hormone therapy after menopause for cognitive decline and dementia: A conceptual review.

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Date: 06/2024

Journal : Maturitas

Collaborators
Collaborators: Walter A Rocca, Kejal Kantarci, Stephanie S Faubion

The effects on the brain of hormone therapy after the onset of menopause remain uncertain. The effects may be beneficial, neutral, or harmful. We provide a conceptual review of the evidence.

Menopause in the workplace: Challenges, impact, and next steps.

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Date: 07/2024

Journal : Maturitas

Collaborators
Collaborators: Nancy Safwan, Mariam Saadedine, Chrisandra L Shufelt, Ekta Kapoor, Juliana M Kling, Rajeev Chaudhry, Stephanie S Faubion

Menopause is a natural part of a woman's life that coincides with a time when many women play significant roles in the workforce. Menopause symptoms, such as hot flashes, fatigue, and difficulty with concentration and memory, can have a negative effect on work productivity and efficiency.

Artificial intelligence-based screening for cardiomyopathy in an obstetric population: A pilot study.

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Date: 06/2024

Journal : Cardiovascular digital health journal

Collaborators
Collaborators: Demilade Adedinsewo, Andrea Carolina Morales-Lara, Heather Hardway, Patrick Johnson, Kathleen A Young, Wendy Tatiana Garzon-Siatoya, Yvonne S Butler Tobah, Carl H Rose, David Burnette, Kendra Seccombe, Mia Fussell, Sabrina Phillips, Francisco Lopez-Jimenez, Zachi I Attia, Paul A Friedman, Rickey E Carter, Peter A Noseworthy

Cardiomyopathy is a leading cause of pregnancy-related mortality and the number one cause of death in the late postpartum period. Delay in diagnosis is associated with severe adverse outcomes.