“The AAN Annual Meeting is an important opportunity for neurologists to share scientific and clinical advances shaping the care of patients with neurological disorders,” said Nancy Sicotte, MD, chair of the Department of Neurology at Cedars-Sinai. “Our physician-scientists are sharing information about the most important challenges in neurology—from improving treatments for chronic neurological diseases to strengthening communication and support for patients and families.”

Cedars-Sinai Experts Presenting Research at the Meeting

Alexis Simpkins, MD, PhD, director of Stroke Research and the Stroke RNA, Imaging, and Protein Predictors for Patient Tailored Treatment Program at Cedars-Sinai, will receive the DEI Changemaker Award, and she will chair the research hub at the meeting. She will also share information on women’s leadership in neurology and the history of neurology.

Andrew Blumenfeld, MD, a Cedars-Sinai neurologist specializing in headache disorders, will present research on the use of botulinum toxin, popularly known as Botox, for chronic migraine management, and he can discuss advances in migraine treatment.

Richard Lewis, MD, professor of Neurology, will present research on new therapies for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), a rare disorder in which the immune system damages the nerves, leading to weakness and numbness. He will also share results from late-stage clinical trials evaluating potential new CIDP treatments.

Paula Barreras, MD, assistant professor of Neurology and director of the Center of Excellence in Rare Neuroimmune Disorders at Cedars-Sinai, will discuss vascular causes of myelopathy, a frequent source of misdiagnosis in spinal cord disorders.

Jessica Besbris, MD, director of Neuropalliative Care and the Neurology Supportive Care Medicine Program, will discuss neuropalliative care, including ways neurologists can effectively and compassionately communicate about serious illnesses to their patients.

Yvette Bordelon, MD, PhD, director of the Cedars-Sinai Huntington’s Disease Society of America Partner Center of Excellence, will discuss gene therapy for Huntington’s disease, including new therapeutic developments, clinical applications of research and innovative technical advances.

Maranatha O. Ayodele, MD, assistant professor of Neurology, will moderate a session on cerebrovascular diseases and can discuss intracerebral hemorrhage and traumatic brain injuries.

Additional Cedars-Sinai Experts

Lisa Bateman, MD, director of the Surgical Epilepsy Program and professor of Neurology, can discuss epilepsy research and treatment advances.

Ilana E. Lasner, DO, assistant professor of Neurology, can discuss Alzheimer’s disease, Parkinson’s disease and migraines.

Marwa Kaisey, MD, associate professor of Neurology, will discuss disease-modifying therapies for multiple sclerosis.

Konrad Schlick, MD, Neurology Residency Program director, can discuss ischemic stroke management and neurology resident training.

Jodi Nelson, DO, assistant professor of Neurology, can discuss treating dementia and multiple sclerosis.

Contact

To arrange interviews with Cedars-Sinai experts, contact Kelsie Sandoval at Kelsie.sandoval@cshs.org or 562-631-1169.

The study shows that the same brain neurons are activated when we imagine something and when we perceive something. The research, led by Cedars-Sinai, is the first to provide a detailed understanding of the shared mechanism that underlies visual perception and creation of mental images in the human brain. It was published in the journal Science.

“We generate a mental image of an object that we have seen before by reactivating the brain cells we used to see it in the first place,” said Ueli Rutishauser, PhD, director of the Center for Neural Science and Medicine and professor of Neurosurgery, Neurology and Biomedical Sciences at Cedars-Sinai Health Sciences University, and the study’s joint senior author. “Our study revealed the code that we use to re-create the images.”

The findings provide a biological basis for visual imagination, a process that is also critical for creative arts.

“Further insight into this neural process has the potential to open pathways toward developing new therapies for post-traumatic stress disorder, obsessive-compulsive disorder, and other mental conditions that involve uncontrolled vivid imagery,” said Adam Mamelak, MD, director of the Functional Neurosurgery Program and professor of Neurosurgery at Cedars-Sinai, and co-author of the study.

To conduct the study, investigators asked 16 adults with epilepsy, who had electrodes temporarily implanted in their brains for diagnosing their seizures, to view a series of images of faces and objects. After viewing them, a subset of the participants were asked to imagine those same images from memory. Meanwhile, researchers recorded the electrical activity of hundreds of individual neurons in each participant’s brain.

When the patients viewed the images, neurons were activated in their fusiform gyrus, an area of the brain essential for high-level visual processing, particularly for faces. For 80% of the visually responsive neurons recorded in the study, the researchers uncovered the aspects of the images they reacted to, thereby revealing their neural code. When the patients later imagined the images, about 40% of these neurons reactivated using the same code, thereby recreating the pattern of activity that occurred during the initial viewing of the images.

“Advanced artificial intelligence tools were critical to our investigation at all stages,” said Varun Wadia, PhD, a postdoctoral scientist in Rutishauser’s laboratory and first author of the study. “We used deep visual neural networks to create numerical descriptions of objects so that we could understand the neurons’ code. We then verified the code by using generative AI to create never-before-seen images and correctly predict the brain’s responses to these images.”

The research builds on the work of Doris Y. Tsao, PhD, of the University of California, Berkeley, who is co-senior author on the study. She identified the neural code for object recognition in nonhuman primates. The current study reveals that the same neural code is present in humans and that it explains visual imagination.

“These findings support the idea that imagining and seeing share a common neural code and may have important implications for understanding psychiatric disorders marked by disruptions in mental imagery and reality discrimination,” said Hermon Gebrehiwet, DrPH, program officer at the National Institutes of Health.

Still to be determined are what triggers the neural reactivation the investigators found, and how memories lead to reactivation of just the right subset of neurons needed, the investigators said.

Other Cedars-Sinai authors include: C. M. Reed, J. M. Chung, and L. M. Bateman

Funding: The work was supported by the National Institutes of Health’s Brain Research Through Advancing Innovative Neurotechnologies® Initiative, or The BRAIN Initiative® (U01NS117839 to UR), the Howard Hughes Medical Institute (DYT), the Simons Foundation Collaboration on the Global Brain (UR and DYT) and the Chen Center for Systems Neuroscience at Caltech (DYT).

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The findings, stemming from two complementary studies published in Nature, could lead to therapies to protect the brain in neurological conditions like multiple sclerosis (MS).

Investigators focused on a group of brain cells called “CUX2 neurons.” Located on the outer layer of the brain, known as the cortex, CUX2 neurons are linked to brain communication, movement, thinking and memory. They are also linked to many neurological conditions, including MS, autism, epilepsy and Alzheimer’s disease.

In the first study, researchers found that CUX2 neurons are especially sensitive to damage caused by inflammation. In diseases like MS, the body’s immune system attacks the brain, leading to long-term damage. While MS has been thought to primarily affect white matter in the brain, this research shows that it could also damage particularly vulnerable CUX2 neurons in the gray matter.

This damage may help explain why people with MS can experience memory problems and cognitive decline as the disease progresses.

“The CUX2 neurons are like a ‘canary in the coal mine’ for the brain affected by MS,” said David Rowitch, MD, PhD, co-corresponding author of both studies, deputy director for Research at Guerin Children’s, and professor of Paediatrics at the University of Cambridge. “They are early warning signs of trouble. If we can protect these cells, we might be able to contain the damage before disease progresses.”

To better understand the workings of CUX2 neurons, investigators performed genetic sequencing of brain tissue from people with MS, and in laboratory mice that can model MS. Their study concluded that these neurons, when under stress, sustain much more DNA damage than neighboring brain cells do. Over time, this damage can lead to cell death.

In the second study, investigators found that CUX2 neurons use the molecule ATF4 to help repair their DNA. ATF4 and the molecules it regulates act like a switch that turns on genes that protect critical brain cells from DNA damage.

Even with these repair tools, the study found, CUX2 neurons remain at risk, especially during long-term inflammation. This may be one reason the condition of people with progressive MS continues to worsen even when treatments reduce inflammation.

“We were excited to find that these brain cells already have natural ways to repair themselves,” said Stephen Fancy, PhD, DVM, co-corresponding author of the study and professor in the departments of Neurology and Pediatrics at UCSF. “By uncovering how certain brain cells protect and repair themselves, we have taken a significant step toward developing treatments that could one day preserve brain function and quality of life.”

Through the studies, researchers found that there are several ways to switch on protective processes in the body that can help prevent damage. Further research is needed to bring the findings into clinical use, but they represent a step toward new approaches to treating brain diseases—one that focuses on limiting DNA damage, enhancing repair and bolstering the resilience of critical brain cells.

“Findings from these two studies represent an important milestone in our understanding of neurological disease pathways,” said Nancy Sicotte, MD, chair of the Department of Neurology and director of Multiple Sclerosis and Neuroimmunology at Cedars-Sinai. “This work is a testament to the dedication and innovation of our investigators, who continue to push the boundaries of science and drive discovery in pursuit of effective therapies for patients.”

Other authors who contributed to the first study include: Laura Morcom, Wenlong Xia, Zhaoyang Xu, Yashika Awasthi, Celine Geywitz, Matthew Ellis, Tomas Noli, Amel Zulji, Daniel Yamamoto, Gemma Girdler, Li Kai, Keying Zhu, Mingming Wei, Xiao-Yan Tang, Kimberly Hoi, Julio Gonzalez, Greg Duncan, Adrien Vaquie, Diana Gold, Riki Kawaguchi, Erdong Liu, Yu Sun, Denny Yang, Gregory Jordan, I-ling Lu, Staffan Holmqvist, Theresa Bartels, Katherine Ridley, Jennifer Choi, Santos Franco, Eric Huang, Ben Emery, Daniel Geschwind, Lucas Schirmer, Gabriel Balmus and Brian Popko.

Funding for the first study: This work was supported by funding from the European Research Council (Advanced Grant 789054 to D.H.R.; DecOmPress ERC StG, 950584 to L.S.), the Wellcome Trust (to D.H.R.), NIH (P01 NS083513 to D.H.R. and S.P.J.F.; R01NS128021 and R21NS133891 to S.P.J.F.; R01 NS124166 to S.J.F.; R01NS120981 to B.E.; 1R35NS137478 to B.P.), NIHR Cambridge Biomedical Research Centre (NIHR203312 to D.H.R.), Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to D.H.R., D.G. and B.P.), the US Department of Defence (MS230141 to S.P.J.F.), Alex’s Lemonade Stand Foundation (to S.P.J.F.), Race to Erase MS (to S.P.J.F.), the National MS Society (RFA-2203-39300 to L.S.; RG-2001-35775 to B.E.), the German Research Foundation (InCheck GRK 2727, Priority Program SPP 2395, NeuroFlame FOR 5705 to L.S.), the UK Dementia Research Institute (to G.B.), Therapeutic Innovation Networks (PNRR-III-C9-2022-I8 to G.B.), the Hertie Foundation (medMS MyLab, P1180016 to L.S.), an endowment from the Warren family (to B.E.), and a gift from the Spangler Foundation (to S.P.J.F.).

Other authors who contributed to the second study include: Wenlong Xia, Laura Morcom, Zhaoyang Xu, I-Ling Lu, Qing Wang, Kimberly Hoi, Mingming Wei, Keying Zhu, Gregory Jordan, Xiao-Yan Tang, Julio Gonzalez, Vanesa Mattera, Sophia Panigrahi, Riki Kawaguchi, Ben Emery, Santos Franco, Daniel Geschwind and Brian Popko.

Funding for the second study: This work was supported by funding from the European Research Council Advanced Grant (789054 to D.H.R.), the Wellcome Trust (to D.H.R), NIH (P01 NS083513 to D.H.R., S.P.J.F; and R35 NS137478 to B.P.) and Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (to D.H.R., D. G, B. P.), and the NIHR Cambridge Biomedical Research Centre (NIHR203312). This work was supported by the NIH NINDS (R01 NS128021 and R21 NS133891 to S.P.J.F.), the U.S. Department of Defence (MS230141 to S.P.J.F.), Alex’s Lemonade Stand Foundation (to S.P.J.F.), Race to Erase MS (to S.P.J.F.), and a generous gift from the Spangler Foundation (to S.P.J.F.).

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

This condition not only can accelerate cognitive decline but is often mistaken for an underlying neurological condition—delaying proper diagnosis and treatment.

In a recent review published in the journal Alzheimer’s & Dementia, Cedars-Sinai researchers explored how UTI-induced delirium affects brain function, why individuals with dementia are especially vulnerable, and the critical need for early recognition and intervention.

“It’s a vicious cycle where dementia increases the risk of infection, and infection-related delirium accelerates cognitive decline,” said Shouri Lahiri, MD, principal investigator of the Critical Care Neurodegenerative Medicine Lab, director of the Neurosciences Critical Care Unit and Neurocritical Care Research at Cedars-Sinai, and senior author of the review.

Previous laboratory studies by Lahiri and his colleagues revealed that the immune system’s response to UTI-induced delirium—specifically the inflammatory protein interleukin-6—can cause changes in the brain. Blocking this pathway reversed delirium-like symptoms in mice.

Lahiri sat down with the Cedars-Sinai Newsroom to discuss UTIs as a potentially preventable and treatable contributor to cognitive decline and the importance of early recognition and swift treatment.

What is delirium, and how is it different from memory loss?

Delirium is a sudden change in thinking and awareness. It affects attention, judgment and short-term memory, and develops over hours or days.

Memory loss from conditions such as Alzheimer’s disease progresses slowly over time. Delirium, by contrast, is acute and usually triggered by a medical illness, such as a urinary tract infection, dehydration or infection elsewhere in the body.

Why can urinary tract infections cause confusion, especially in older adults?

Our research shows UTIs can cause acute brain dysfunction through inflammation. An infection in the bladder releases inflammatory signals into the bloodstream, which can affect the brain and disrupt normal function, leading to delirium.

Older adults are more vulnerable because their brains are often less resilient to physiological stress.

UTIs aren’t the only infections that can trigger this response. Any systemic infection, including pneumonia, gastrointestinal infections or skin infections, can provoke widespread inflammation that affects the brain and causes acute confusion.

Why are people with Alzheimer’s disease at higher risk for UTIs?

People with Alzheimer’s may have challenges upkeeping with hygiene and age-related hormonal changes that increase UTI risk. Alzheimer’s can also impair sensation and communication, making it harder for patients to recognize or report well-known UTI symptoms such as burning or urgency to urinate. As a result, infections may go untreated until they trigger delirium.

For people without dementia, delirium increases the risk of developing dementia by about threefold. Repeated episodes further raise that risk.

Why can a UTI make Alzheimer’s symptoms suddenly worse?

A UTI can cause a rapid cognitive decline that looks like a sudden worsening of Alzheimer’s disease. The key difference is timing. Alzheimer’s progresses gradually, while delirium causes an abrupt change from a person’s baseline.

We believe inflammation related to infection places added stress on an already vulnerable brain, which can worsen dementia symptoms and, in some cases, cause lasting damage.

Is delirium from a UTI reversible?

Early treatment offers the best chance for recovery. When UTIs are identified and quickly treated, delirium symptoms can improve or resolve. However, in some cases, cognitive effects can persist or become permanent. That’s why early recognition is critical.

Because UTIs don’t always cause obvious urinary symptoms, especially in older adults, we need to change the way we diagnose UTIs, using a mix of clinical observations and urinary and blood tests that show infection, to recognize when a UTI is behind sudden confusion.

How can caregivers tell the difference between Alzheimer’s progression and a UTI?

Sudden change is the biggest warning sign. Dementia generally does not cause abrupt declines. If someone with Alzheimer’s suddenly becomes much more confused, less alert or behaves very differently, that may signal delirium.

Other changes to look out for include changes in urination patterns, incontinence, pain, or changes in urine color or odor.

What can caregivers do to help prevent UTIs and delirium?

Caregivers should make sure the person they’re taking care of maintains good hygiene and adequate hydration. Caregivers should also notify a physician if UTIs are recurrent, because treatments are available to reduce repeated episodes.

Also, being aware of sudden changes in mental status and seeking prompt medical care can make a significant difference.

Are UTIs linked to delirium in other neurological conditions?

Yes. Parkinson’s disease is a key example. Many people with Parkinson’s have difficulty fully emptying their bladder, which increases infection risk. UTIs can worsen Parkinson’s movement symptoms, just as they worsen cognition in Alzheimer’s disease.

What is your lab studying next?

We are studying new drugs that target inflammatory pathways involved in UTI-related brain dysfunction, with the goal of advancing them to clinical trials. We are also developing diagnostic approaches to better identify UTIs in patients who  don’t have the well-known urinary symptoms.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The study shows for the first time that Chlamydia pneumoniae can reach the retina—the tissue lining the back of the eye—where it triggers immune responses linked to inflammation, nerve cell death and cognitive decline.

“Seeing Chlamydia pneumoniae consistently across human tissues, cell cultures and animal models allowed us to identify a previously unrecognized link between bacterial infection, inflammation and neurodegeneration,” said Maya Koronyo-Hamaoui, PhD, professor of Neurosurgery, Neurology, and Biomedical Sciences at Cedars-Sinai Health Sciences University and the leading, senior author of the study. “The eye is a surrogate for the brain, and this study shows that retinal bacterial infection and chronic inflammation can reflect brain pathology and predict disease status, supporting retinal imaging as a noninvasive way to identify people at risk for Alzheimer’s.”

To conduct the study, researchers used advanced imaging, genetic testing and protein analysis to examine retinal tissue from 104 individuals, some with normal cognition, some with mild cognitive impairment and some with Alzheimer’s disease.

They found significantly higher levels of Chlamydia pneumoniae in the retinas and brains of people with Alzheimer’s disease than they found in people with normal cognition. The higher the bacterial levels detected, the more severe the brain changes and cognitive decline investigators found.

Higher levels of the bacterium were more common in people who carried the APOE4 gene variant, a known risk factor for Alzheimer’s disease.

Investigators also studied human neurons in the lab and in laboratory mice with Alzheimer’s disease. In both, infection with Chlamydia pneumoniae increased inflammation, nerve cell death and cognitive decline, showing the bacterium can accelerate disease processes. The infection also triggered production of amyloid-beta, the protein that accumulates in the brains of people with Alzheimer’s.

The findings were driven by co-first authors Bhakta Gaire, PhD, and Yosef Koronyo, MSc.

“This discovery raises the possibility of targeting the infection-inflammation axis to treat Alzheimer’s,” said Timothy Crother, PhD, co-corresponding author of the study and research professor at Cedars-Sinai Guerin Children's and the Department of Biomedical Sciences at Cedars‑Sinai.

The findings suggest that targeting chronic bacterial infection—and the inflammation it triggers—could represent a new treatment strategy. The research also supports potential use of the retina as a noninvasive way to help diagnose and monitor the disease.

Additional Cedars-Sinai authors include Bhakta Gaire, Yosef Koronyo, Jean-Philippe Vit, Alexandre Hutton, Lalita Subedi, Dieu-Trang Fuchs, Natalie Swerdlow, Altan Rentsendorj, Saba Shahin, Daisy Martinon, Edward Robinson, Alexander V. Ljubimov, Keith L. Black, Jesse Meyer, and Moshe Arditi.

Other authors include Julie A. Schneider, Lon S. Schneider, Debra Hawes, Stuart L. Graham, Vivek K. Gupta, and Mehdi Mirzaei.

Funding: This work has been supported by the NIH/NIA grants R01AG056478, R01AG055865, and AG056478-04S1 (M.K.H.), R01AG075998 (M.K.H. and T.R.C.), and Alzheimer’s Association grant AARG-NTF-21-846586 (T.R.C.). MKH is also supported by The Goldrich and Snyder Foundations. ER has been supported by The Ray Charles Foundation.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

“Astrocytes are critical responders to disease and disorders of the central nervous system—the brain and spinal cord,” said neuroscientist Joshua Burda, PhD, assistant professor of Biomedical Sciences and Neurology at Cedars-Sinai and senior author of the study. “We discovered that astrocytes far from the site of an injury actually help drive spinal cord repair. Our research also uncovered a mechanism used by these unique astrocytes to signal the immune system to clean up debris resulting from the injury, which is a critical step in the tissue-healing process.”

The investigators dubbed these astrocytes “lesion-remote astrocytes,” or LRAs, and identified several distinct LRA subtypes. Their study describes for the first time how one LRA subtype remotely senses and responds to tissue injury.

The spinal cord is a bundle of nerve tissue that runs from the brain down the back. At its center is gray matter, which contains the bodies of nerve cells and support cells called astrocytes. Surrounding it is white matter, made up of astrocytes and long nerve fibers that stretch up and down the cord to send signals between the brain and the rest of the body. Astrocytes help keep the nervous system healthy and ensure that these signals flow smoothly.

Spinal cord injuries damage nerve fibers, paralyzing parts of the body and disrupting sensory input such as touch and temperature. The severed fibers die off and become debris. In most other types of tissue in the body, inflammation takes place only at the site of injury. But because of the length of nerve fibers in the spinal cord, damage and inflammation extend far beyond the injury site.  

Investigators looked at laboratory mice with spinal cord injury and found that LRAs play an important role in supporting nervous system repair. They saw strong evidence of the same mechanism in tissue samples from human patients with spinal cord injury.

The Burda Lab identified one LRA subtype that sends out a protein called CCN1 to signal to immune cells called microglia.

“One function of microglia is to serve as chief garbage collectors in the central nervous system,” Burda said. “After tissue damage, they eat up pieces of nerve fiber debris—which are very fatty and can cause them to get a kind of indigestion. Our experiments showed that astrocyte CCN1 signals the microglia to change their metabolism so they can better digest all that fat.”

Burda said this efficient debris clearing might have a role in the spontaneous recovery found in many patients with spinal cord injury. In the absence of the astrocyte-derived CCN1 protein, the investigators found that recovery is drastically impaired.

“If we remove astrocyte CCN1, the microglia eat, but they don't digest. They call in more microglia, which also eat but don't digest,” Burda said. “Big clusters of debris-filled microglia form, heightening inflammation up and down the spinal cord. And when that happens, the tissue doesn’t repair as well.”

When investigators looked at spinal cord tissue from human patients with multiple sclerosis, they found the same mechanism at work, Burda said. He added that these fundamental principles of tissue repair likely apply to any sort of injury of the brain or spinal cord.

“The role of astrocytes in central nervous system healing is remarkably understudied,” said David Underhill, PhD, chair of the Department of Biomedical Sciences. “This work strongly suggests that lesion-remote astrocytes offer a viable path for limiting chronic inflammation, enhancing functionally meaningful regeneration, and promoting neurological recovery after brain and spinal cord injury and in disease.”

Burda is now leading efforts to harness this CCN1 mechanism in spinal cord healing and to further investigate the role of astrocyte CCN1 in inflammatory neurodegenerative disease and in aging.  

Additional Cedars-Sinai authors include Sarah McCallum, Keshav B. Suresh, Timothy S. Islam, Manish K. Tripathi, Ann W. Saustad, Oksana Shelest, Aditya Patil, David Lee, Brandon Kwon, Katherine Leitholf, Inga Yenokian, Sophia E. Shaka, Jasmine Plummer, Vinicius F. Calsavara, and Simon R.V. Knott.

Other authors include Connor H. Beveridge, Palak Manchandra, Caitlin E. Randolph, Gordon P. Meares, Ranjan Dutta, Riki Kawaguchi, and Gaurav Chopra.

Funding: This work was supported by: the US National Institutes of Health (NIH) 5R01NS128094, R00NS105915, K99NS105915 (to J.E.B.), F31NS129372 (to K.S.), K99AG084864 (S.M.) R35 NS097303 and R01 NS123532 (RD), R01MH128866, U18TR004146, P30 CA023168 and ASPIRE Challenge and Reduction-to-Practice award (to G.C.); the Paralyzed Veterans Research Foundation of America (to J.E.B.); Wings for Life (to J.E.B.); Cedars-Sinai Center for Neuroscience and Medicine Postdoctoral Fellowship (to S.M.); American Academy of Neurology Neuroscience Research Fellowship (to S.M.); California Institute for Regenerative Medicine Postdoctoral Scholarship (to S.M.); The United States Department of Defense USAMRAA award W81XWH2010665 through the Peer Reviewed Alzheimer’s Research Program (to G.C.); The Arnold O. Beckman Postdoctoral Fellowship (to C.E.R.); The Purdue University Center for Cancer Research funded by NIH grant P30 CA023168 is also acknowledged.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

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The Cedars-Sinai Newsroom recently spoke with Jane Tavyev Asher, MD, director of the Division of Pediatric Neurology at Cedars-Sinai Guerin Children’s, about how screens affect children and teens differently depending on their age, and what parents can do to set healthy boundaries for screen time.

What is the recommended amount of screen time for children in different age groups?

Before the COVID-19 pandemic, the American Academy of Pediatrics had fairly strict guidelines: no screen time at all for children under age 2, and minimal exposure for ages 2 to 5. Ideally, screen time should be under an hour a day. For ages 5 to 11 and older, less than two hours per day.

Since the pandemic shifted much of our education and social lives online, we've had to adapt those guidelines a bit. Still, research continues to support limiting screen time to less than two hours a day for older children as well. Exceeding that amount has been associated with increased risks of anxiety, depression and other emotional challenges.

How can excessive screen time affect young children’s developing brains?

The general consensus among developmental pediatricians is that children under age 3 should have little to no screen exposure. That’s because their brains are in a critical stage of development, with key processes like myelination, the biological process that speeds up the nerve transmission to the brain, and neural pathway formation actively taking place.

When a young brain is exposed to too much screen time, it can overstimulate the visual cortex—the part of the brain that processes images—at the expense of the auditory cortex, which is vital for developing social skills and language. Ideally, we want their early learning to be grounded in real-world, interactive face-to-face experiences—not passive viewing.

How does screen time via social media impact brain development in teenagers?

Adolescence is a time when the brain is deeply focused on social development and seeking acceptance from peers. Before social media, that feedback loop was limited to in-person interactions with a small group of peers. But now, through apps and platforms, teens are exposed to a constant, amplified stream of approval or disapproval on a much larger scale.

That amplification can be harmful. It places undue stress on the adolescent brain, increasing the risk of social anxiety, low self-esteem and even depression.

Does the type of screen make a difference?

Yes, the type of screen can make a difference. A lot of what’s called “educational content” is often just labeled that way for marketing purposes, without clear evidence that it's truly educational. Watching content on a TV screen is generally safer—it’s farther from the eyes and doesn’t strain the neck or vision as much as phones or tablets.

Also, the platform matters. Streaming services like YouTube often auto-play endless content using algorithms to keep kids hooked. There’s no clear stopping point. In contrast, traditional TV typically airs for a set duration, which naturally limits screen time and reduces the risk of overconsumption.

How does screen-based learning in school affect brain development?

We’ve found that when students read something from a book, they tend to retain the information better than when they read the same content on a screen. We don’t fully understand why that is, but it does suggest that traditional learning methods still hold an important place.

That said, screens can be very helpful when used purposefully. For example, watching a video demonstration of a complex science experiment can be far more effective than trying to imagine it from a textbook. In classroom settings, it’s best when screens are used collectively, as part of a group lesson with discussion led by the teacher, rather than having each student isolate on their own individual device.

Are some children more vulnerable than others to the negative effects of too much screen time?

Yes, certain children are especially sensitive. Children with attention-deficit hyperactivity disorder, or ADHD, symptoms can become overstimulated by video games and may struggle even more with attention. Similarly, children experiencing anxiety or depression, or children who face social challenges may be more prone to negative effects from screen exposure, especially if they’re using it as an escape or replacement for in-person interaction.

In these cases, screen time should be monitored closely, and alternative, healthy outlets should be prioritized.

What are some practical tips for parents to set healthy screen time limits?

One of the most beneficial things parents can do is to ensure their children get at least two hours of physical activity each day, ideally outside. This supports not only their physical health but also their energy levels, focus and even vision.

Another important tip is to delay giving your child a smartphone for as long as possible. There’s a movement called “Wait Until 8th” that encourages parents to hold off until at least after eighth grade. The longer you can wait, the more time your child has to build a strong foundation of social and emotional development without the added pressures of smartphone use.

Read more on the Cedars-Sinai Blog: Does My Child Need Growth Hormone Therapy?  

Still, more than 90% of Alzheimer’s disease trials do not yield the hoped-for result, said Mitzi Gonzales, PhD, director of Translational Research in the Jona Goldrich Center for Alzheimer’s and Memory Disorders. There is still something to learn from each study, Gonzales said.

“Even trials that aren’t considered successful are incredibly important in shaping our scientific knowledge,” Gonzales said. “Trials that show us that one pathway isn’t working can push us in new directions.”

That was the case with recently published results of a trial Gonzales led testing a drug called rapamycin. In preclinical studies, rapamycin was associated with increased longevity and reduction in many age-related symptoms and conditions.

“Data from preclinical studies showed rapamycin reduced buildup of amyloid beta and tau proteins in the brain, which we know are associated with Alzheimer’s disease,” Gonzales said. “We were hoping to see similar results in humans.”

Instead, levels of amyloid and tau increased, Gonzales said.

“That result has raised its own scientific questions and led to some other avenues of research,” Gonzales said. “So it has been helpful for pushing us in new directions, including looking at whether it might be more effective in earlier-stage disease.”

Samples—such as blood and cerebrospinal fluid—taken during unsuccessful clinical trials can also lead to breakthroughs down the road, said Sarah Kremen, MD, director of the Neurobehavior Program.

“The pivotal A4 study tested a drug called solanezumab in cognitively normal people with elevated amyloid,” Kremen said. “The drug did not improve cognition or remove amyloid from the brain, but it was the first time that we'd ever studied anybody who was asymptomatic but at risk. It was a really big deal.”

Studies done with samples from that trial contributed to a larger body of work showing that a biomarker called pTau217 can be an early indicator of Alzheimer’s disease. And that marker is used in the first Food and Drug Administration-approved blood test for the accumulation of amyloid plaques in the brain, Kremen said.

Gonzales and Kremen noted the many reasons Alzheimer’s disease has proved so challenging, including its multiple likely causes, the fact that these factors are present for many years before the disease is detectable, and the complexity of the brain itself.

“The brain is not as well understood as other organs and the processes underlying neurodegenerative disease are complex,” Kremen said. “It will take time—and many more clinical trials—to unravel all the different mechanisms behind Alzheimer’s disease.”

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“We found that by using gene editing to boost ACE in immune cells called microglia, which we believe become exhausted in the brains of patients with Alzheimer’s disease, we supercharged those cells and seemed to restore them to full function,” said Warren Tourtellotte, MD, PhD, professor of Pathology and Laboratory Medicine, Neurology, Neurosurgery, and Biomedical Sciences at Cedars-Sinai, and senior author of the study. “This allowed the microglia to clear the brain of the amyloid plaques associated with symptoms of Alzheimer’s disease and to reverse neurodegeneration and cognitive decline.”

To perform their experiments, investigators used genetic engineering to develop laboratory mice that accumulated amyloid plaques in their brains and overexpressed ACE in their microglia.

“The overexpression of ACE had a profound effect on the Alzheimer’s-related brain changes in these mice,” Tourtellotte said. “Their brains had fewer amyloid plaques and damage to neurons, and the connections between them appeared to be rescued. In addition, when ACE was expressed in microglia in these mice their performance in learning and memory tests was markedly improved.”

The next step in this line of research is to show that this same biology exists in human microglia, Tourtellotte said. While more studies are needed, these findings might eventually lead to creation of a cell-based therapy that would work either independently or along with other Alzheimer’s disease treatments.

“Scientific discovery is the key to developing treatments that will help us overcome Alzheimer’s disease, which affects more than 7 million people in the U.S. and those who love them,” said Nancy L. Sicotte, MD, chair of the Department of Neurology at Cedars-Sinai. “These findings, from the first pilot project to receive funding from the Jona Goldrich Center for Alzheimer’s and Memory Disorders at Cedars-Sinai, point to a promising new direction for future work and possible new treatments.”

Additional authors include Andrew R. Gomez, Hyae Ran Byun, Shaogen Wu, A. K. M. Ghulam Muhammad, Jasmine Ikbariyeh, Jaelin Chen, Alek Muro, Lin Li, Kenneth E. Bernstein, and Richard Ainsworth.

Funding: This study was supported by NIH grant nos. RF1-AG074365 and R01-AG074365 to W.G.T., NIH grant no. R01-AI164519 to K.E.B. and a Cedars-Sinai Goldrich Alzheimer’s Center grant to W.G.T. and K.E.B.

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The analysis of data on 1,201 Cedars-Sinai patients with Parkinson’s disease found:

• Patients who took nonsteroidal anti-inflammatory drugs, including ibuprofen and aspirin, were on average 8.6 years older at the onset of symptoms than patients who had not taken the medications.
• Patients who took statins to lower cholesterol were an average of 9.3 years older at symptom onset.
• Those taking beta blockers to reduce blood pressure averaged being 9.6 years older when their symptoms first appeared when compared with patients not exposed to these medications.

Parkinson’s disease, a degenerative brain condition, is associated with tremors, balance problems and slowed movement; an individual’s risk of developing it increases with age. Its cause is unknown, though genetics play a role in some cases.

“The medications we studied have common features that may explain their effect on Parkinson’s disease, including the ability to control inflammation,” said Michele Tagliati, MD, vice chair of the Department of Neurology and director of the Division of Movement Disorders at Cedars-Sinai and senior author of the study. “While additional studies are needed to monitor patients over time, this research suggests that the medications studied also help control the cellular stress response and brain inflammation, which may have a prominent role in delaying the development of Parkinson’s disease.”

Additional Cedars-Sinai authors include Camille Malatt, Helia Maghzi, Elliot Hogg, Echo Tan and Ishani Khatiwala.

Funding: This work was supported by the F. Widjaja Foundation.

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“Our model, called the Unified Structural and Functional Connectivity model, provides a step toward mapping how different parts of the brain functionally communicate,” said Wei Gao, PhD, director of Neuroimaging Research and professor of Biomedical Sciences at Cedars-Sinai and senior author of the study. “The model shows that certain structural pathways, especially in networks related to emotions, self-awareness, and sensory processing, are heavily used for brain communications. The model also enhances our understanding of how these interactions relate to cognitive function.”

The investigative team—led by Gao, study co-author Pascal Sati, PhD, director of the Neuroimaging Program and associate professor of Neurology, and first author Arzu Silemek, PhD, a postdoctoral fellow supervised by Gao and Sati—found that certain areas serve as crucial hubs, with a significant corridor facilitating overall brain connectivity. They believe this mapping of brain communication could inform future research on cognitive processes and neurodevelopmental disorders. Clinically, they suggested it could improve physicians’ diagnostic tools by providing insights into how structural changes affect brain function, potentially leading to better-targeted interventions for conditions such as Alzheimer’s disease and other cognitive disorders.

Additional author: Haitao Chen

Funding: This work was supported by the National Institutes of Health (R01DA042988 and R01DA043678) and by Cedars-Sinai Precision Medicine Initiative Award and institutional support (to W.G.).

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“In older adults, higher levels of amyloid beta and tau have been associated with poorer memory and cognition," said Mitzi Gonzales, PhD, director of Translational Research in the Jona Goldrich Center for Alzheimer’s and Memory Disorders at Cedars-Sinai and lead author of the study. “Our study found that this was also true in adults age 55 and younger—a period thought to be important for prevention. We also found higher levels in individuals with a higher genetic risk for Alzheimer's disease. Future studies should examine memory and cognitive changes over time and look at why some individuals remain mentally sharp despite having high levels of these proteins, to provide important clues about maintaining cognitive health over the lifespan.”

The findings highlight the importance of understanding the effects of amyloid beta and tau proteins on memory and thinking abilities at earlier ages. The work could also help focus dementia-prevention efforts in younger at-risk populations.

Additional authors: Adrienne O’Donnell, Saptaparni Ghosh, Emma Thibault, Georges El Fakhri, Sudha Seshadri, Jeremy Tanner, Claudia L. Satizabal, Charles S. Decarli, Keith A. Johnson, Alexa S. Beiser, Matthew Pase.

Funding: National Institutes of Health, Grant/Award Numbers: N01-HC-25195, HHSN268201500001I, 75N92019D00031; National Institute on Aging, Grant/Award Numbers: RF1AG059421, R01AG054076, R01AG049607, R01AG033090, R01AG066524, R01NS017950, R01AG077472, P30AG066546; National Health and Medical Research Council of Australia Investigator, Grant/Award Number: GTN2009264. 

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“The retina, a layer of tissue at the back of the eye, is part of the central nervous system and is directly connected with the brain,” said Maya Koronyo-Hamaoui, PhD, professor of Neurosurgery, Neurology and Biomedical Sciences at Cedars-Sinai and senior author all three studies. “It has similar cell types and vascular structures to the brain, but is not shielded by bone, so it is more accessible to noninvasive imaging. Our latest research unearths new details about the eye-brain connection.”

Tau

Tau is a protein that helps stabilize the structure of nerve cells in the brain and the retina and is one of the key markers of Alzheimer’s disease. When tau disengages from nerve cells it can form tangles that interfere with cellular function and contribute to cognitive decline.

In a study published in the peer-reviewed journal Acta Neuropathologica, Koronyo-Hamaoui and fellow investigators compared retinal tissue from 45 patients diagnosed with Alzheimer’s-related cognitive impairment or dementia with tissue from 34 individuals with normal cognition or non-Alzheimer’s forms of dementia.

Investigators found that higher levels of abnormal tau in the retina corresponded to levels of tau in the brain, other brain changes related to Alzheimer’s disease, and cognitive decline.

Vessels and amyloid plaques

Clumps of a protein called beta-amyloid, also known as amyloid plaques, are another hallmark of Alzheimer’s disease.

In a study published in the peer-reviewed journal Acta Neuropathologica Communications, Koronyo-Hamaoui and co-investigators used leading-edge imaging and image-processing technology to compare amyloid plaques in the retinas of living patients who had early-stage cognitive impairment with those in individuals who had normal cognition.

Thirty-four patients underwent retinal and brain imaging, and cognitive testing. Analysis in 28 patients revealed two to three times as many plaques clustered near blood vessels in the retinas of patients with mild cognitive impairment or Alzheimer’s disease when compared with individuals with normal cognition. The numbers and position of the plaques correlated with cognitive decline and physical changes in the brain.

Diagnosis in development

Koronyo-Hamaoui’s team also published a review article in the peer-reviewed journal Progress in Retinal and Eye Research that detailed additional Alzheimer’s disease biomarkers that have been identified in the retina.

These include reduced blood flow, deposits of amyloid-beta proteins inside blood vessel walls, damage to the barrier that prevents harmful substances from entering retinal tissue, inflammation, and damage to nerve cells.

“Imaging technology now being developed will allow us to see these changes in patients in clinical settings,” said Keith L. Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai and co-author of these studies. “This technology, which is noninvasive and affordable, allows us to see changes in the cells and blood vessels in tremendous detail.”

Black and Koronyo-Hamaoui envision this technology as a tool to screen patients in primary care settings, with those who show features suggestive of Alzheimer’s disease referred for additional testing, such as a PET brain scan or cerebrospinal fluid or blood test. The technology could also assess disease progression and the effectiveness and safety of new treatments.

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This could lead to new applications for the therapy, allowing it to influence higher-level functions such as learning and memory.

“Deep brain stimulation has typically been used to overexcite or shut down all neurons in a target area,” said Costas Anastassiou, PhD, associate professor of Neurology, Neurosurgery and Biomedical Sciences at Cedars-Sinai and senior author of the study. “We found that by varying the shape of the electrical pulse waves we apply, we can selectively influence specific neuron types while leaving others unaffected.”

In the study, investigators applied electrical fields to individual cells in tissue samples from the visual cortex and the hippocampal regions of the brains of patients and laboratory mice. The investigators recorded the activity of excitatory and inhibitory neurons, which act as the gas pedal and brakes, respectively, in brain circuits.

Results showed that different electrical wave frequencies influenced the timing of spikes, which are changes in electrical voltage that travel down neuron fibers and are transmitted to other neurons. Anastassiou called spikes “the coin of communication between neurons.”

“We found that electrical frequencies that influenced one cell type did not necessarily influence another, and vice versa,” Anastassiou said. “Surprisingly, the effects on each cell type were the same in both brain areas we examined, and in both species—though more pronounced in humans than in mice.”

Given that previous research has found that higher-level functions in the brain require coordination and communication between different cell types, the ability to manipulate this communication could be of great importance, Anastassiou said.

“This study offers new understanding of how to stimulate the human brain to promote or suppress specific activity patterns, and could pave the way for new directions in basic research and clinical applications,” said Keith L. Black, MD, chair of the Department of Neurosurgery and the Ruth and Lawrence Harvey Chair in Neuroscience at Cedars-Sinai. “These results offer the possibility for electrical protocols that are more selective, more controlled, and allow for different parts of the brain neural network to be manipulated in different ways.”

Investigators are now working to determine the exact mechanisms required to produce various results in the brain, and to replicate their brain tissue experiments in living patients.

“This data supports the idea that electrical brain stimulation could be used in new ways that target specific groups of brain cells,” said Adam Mamelak, MD, director of the Functional Neurosurgery Program at Cedars-Sinai. “This gives us an exciting opportunity to imagine new uses for this therapy and the chance to address disorders involving learning and memory.” 

Other Cedars-Sinai authors involved in the study include Konstantinos Kozalakis, PhD.

Funding: This work was supported by National Institutes of Health grants R01 NS120300 and RO1 NS130126.

Conflict of interest: Anastassiou is listed as an inventor on a patent application related to this work.

Learn more on the Cedars-Sinai Blog: A Patient’s Journey With Deep Brain Stimulation