Cognitive Opening

[Laila Berri]

Acognitive opening is a concept in social movement theory defined as a moment in which a catalytic event, sometimes a personal crisis or socioeconomic pressure, makes a person receptive to new ways of thinking because life changes challenge previously accepted beliefs, prompting a re-assessment of world views.[1][2]

It is described as a potential stage towards radicalization.[3][4] The catalytic event can be personal, such as a death in the family or a crime,[5] or broader, such as being confronted by discrimination, socioeconomic crisis, or political repression directly as an individual or as a member of a group.[6]

The nearly 20,000-square-foot Brain Aging and Memory Hub is located on the newly renovated fifth floor of UAB Callahan Eye Hospital.

Photography: Andrea MabryThe University of Alabama at Birmingham celebrated the opening of the UAB Brain Aging and Memory Hub on Friday, April 19. The effort was made possible by the UAB Health System and the UAB Marnix E. Heersink School of Medicine.

Memory disorders are often complex conditions and require a team approach, including neurologists, nurses and nurse practitioners, nurse care managers, pharmacy specialists, and social workers and counselors. The new Brain Aging and Memory Hub will increase collaboration and streamline efforts from prevention to research, to clinical care.

Ronald Lazar, Ph.D., director of the Division of Neuropsychology and UAB Evelyn F. McKnight Brain Institute, and his team look forward to advancing brain aging and cognitive decline research and care in the new hub.

Update: At the time of this announcement, RECOVER-VITAL had activated trial sites and had begun enrollment. As of September 5, 2023 RECOVER-NEURO clinical trial sites have been activated and are enrolling.

RECOVER is a large, nationwide research program designed to understand, treat and prevent long COVID, which is marked by long-term symptoms following infection by SARS-CoV-2, the virus that causes COVID-19. The initial stage of the initiative involved launching large, observational, multi-site studies examining and following people through their experience with COVID-19 to learn why some people develop long-term symptoms while others recover completely. These studies are ongoing and have recruited more than 24,000 participants to date. Researchers also are analyzing 60 million electronic health records and conducting more than 40 pathobiology studies on how COVID-19 affects different body tissues and organs. Data gleaned from these efforts helped shape the development of the phase 2 clinical trials, which test the safety and effectiveness of treatments typically in groups of 100-300 participants.

RECOVER-VITAL will initially focus on a treatment targeting SARS-CoV-2 persistence, which could occur if the virus stays in the body and causes the immune system to not function properly or damage to the organs. The first intervention will test a longer dose regimen of the antiviral PAXLOVID (nirmatrelvir and ritonavir) than is used for treating acute COVID to see if it improves the symptoms of patients with long COVID. PAXLOVID is provided by Pfizer, Inc., New York City, and is currently approved for the treatment of mild-to-moderate COVID-19 in adults who are at high risk for progression to severe COVID-19, including hospitalization or death. The first trial sites have been activated and are enrolling.

RECOVER-NEURO will examine accessible interventions for cognitive dysfunction related to long COVID, including brain fog, memory problems and difficulty with attention, thinking clearly and problem solving. Interventions under this protocol will include a web-based brain training program called BrainHQ, developed by Posit Science Corporation in San Francisco, that has been used to improve cognitive function; PASC-Cognitive Recovery, a web-based goal management training program, developed by Mount Sinai Health System, New York City, that has been used to improve executive function; and a device used for home-based transcranial direct current stimulation developed by Soterix Medical, Inc., Woodbridge, New Jersey, which has been demonstrated to help brain activity and blood flow. Trial sites are currently being activated.

RECOVER-SLEEP will test interventions for changes in sleep patterns or ability to sleep after having COVID-19. A trial for hypersomnia, or excessive daytime sleepiness, will test two wakefulness-promoting drugs compared to a placebo control. A second trial for sleep disturbances, such as problems falling or staying asleep, will test other interventions designed to improve sleep quality to learn if these interventions may help regulate sleep patterns in adults with long COVID.

RECOVER-AUTONOMIC will examine interventions to help treat symptoms associated with problems in the autonomic nervous system, which controls a range of bodily functions including heart rate, breathing and digestive system activity. The initial trial will focus on postural orthostatic tachycardia syndrome (POTS), a disorder with a number of symptoms including irregular heartbeat, dizziness and fatigue, and will have multiple study arms. The first arm will evaluate a treatment used for immune diseases versus placebo. The second arm will evaluate a drug currently used to treat chronic heart failure in people with an elevated heart rate versus placebo. Participants within each arm will then be randomized to receive either more intensive coordinated care that does not involve additional medication, or usual care.

All trials are designed to individually and collectively accelerate the identification of safe and effective treatments for some of the most debilitating symptoms of long COVID. Study interventions were reviewed by teams of scientists and patient representatives and approved by NIH leadership based on ideas submitted through a May 2022 request for applications.

RECOVER is committed to enrolling a study population that is inclusive and representative of the communities most affected by long COVID. Study sites will partner with local communities to raise awareness about long COVID and offer opportunities to participate in the RECOVER clinical trials. Researchers developed the trials with extensive feedback from patient representatives, experts in the symptom areas and proposed interventions, and after reviewing hundreds of proposals.

Trials will continue to launch and enroll participants on a rolling basis. Enrollment will take place at clinical research sites located throughout the United States. A track record for enrolling diverse participants was a key criterion for site selection. These trials will follow a traditional clinical trial recruitment strategy in that sites will contact their patients and residents in their local communities to enroll in the trials.

HHS Long COVID Coordination: This work is a part of the National Research Action Plan, a broader government-wide effort in response to the Presidential Memorandum directing the Secretary for the Department of Health and Human Services to mount a full and effective response to long COVID. Led by Assistant Secretary for Health Admiral Rachel Levine, the Plan and its companion Services and Supports for Longer-term Impacts of COVID-19 report lay the groundwork to advance progress in the prevention, diagnosis, treatment, and provision of services for individuals experiencing long COVID.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

In this open-label trial, participants with mild AD underwent MRI-guided FUS sonication to open the BBB in β-amyloid positive regions of the hippocampus, EC, frontal lobe, and parietal lobe. Participants underwent 3 separate FUS treatment sessions performed 2 weeks apart. Outcome assessments included safety, imaging, neurological, cognitive, and florbetaben β-amyloid PET.

This study is the largest cohort of participants with mild AD who received FUS treatment, and has the longest follow-up to date. Safety was demonstrated in conjunction with reversible and repeated BBB opening in multiple cortical and deep brain locations, with a concomitant reduction of β-amyloid. There was no apparent cognitive worsening beyond expectations up to 1 year after FUS treatment, suggesting that the BBB opening treatment in multiple brain regions did not adversely influence AD progression. Further studies are needed to determine the clinical significance of these findings. FUS offers a unique opportunity to decrease amyloid plaque burden as well as the potential to deliver targeted therapeutics to multiple brain regions in patients with neurodegenerative disorders.

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