Newswise — Recent research conducted by UVA Health reveals that heightened light sensitivity might play a role in the phenomenon known as "sundowning" in Alzheimer's patients. Sundowning refers to the worsening of symptoms late in the day and is often accompanied by sleep disruptions, which are believed to contribute to the progression of the disease.
These new findings shed light on the disruptions of the biological clock observed in Alzheimer's patients, offering significant potential for the development of treatments and symptom management. Caregivers frequently face challenges due to the irregular sleep patterns resulting from altered "circadian rhythms," the body's natural daily cycle, in Alzheimer's patients. The study suggests that employing light therapy could be a promising approach to effectively managing these disturbances. Such interventions may offer hope for improving the well-being of both patients and caregivers in the fight against Alzheimer's disease.
Moreover, gaining a deeper comprehension of how Alzheimer's impacts the biological clock could have significant implications for disease prevention. Research indicates that poor sleep quality in adulthood is a risk factor for Alzheimer's, as the brain uses rest to naturally clear itself of amyloid beta proteins, which are believed to contribute to harmful tangles in Alzheimer's.
According to Thaddeus Weigel, a researcher working alongside Heather Ferris, MD, PhD, from the University of Virginia School of Medicine's Division of Endocrinology and Metabolism, circadian disruptions have long been recognized in Alzheimer's disease, but their underlying causes have remained elusive. The recent study highlights changes in light sensitivity as a fresh and intriguing potential explanation for some of the circadian symptoms observed in Alzheimer's patients. Understanding this connection could pave the way for innovative approaches to address and possibly prevent the disease.
Alzheimer's, the most prevalent form of dementia, affects approximately 50 million individuals worldwide. Its defining characteristic is a gradual decline in memory function, reaching a point where patients may even forget their own loved ones. Besides memory loss, patients can experience various other symptoms, including restlessness, aggression, impaired judgment, and a constant sense of searching. These symptoms often intensify during the evening and nighttime, a phenomenon commonly referred to as "sundowning."
To gain deeper insights into the impact of Alzheimer's on the biological clock, Ferris and her team utilized a mouse model of the disease. They induced a state of "jet lag" in the mice by altering their exposure to light and subsequently analyzed its effect on their behavior. Remarkably, the Alzheimer's mice exhibited distinct responses compared to regular mice under the same conditions. This research provides valuable clues to better comprehend the connection between Alzheimer's and circadian rhythms, potentially leading to improved approaches for managing and treating the disease.
According to the scientists' findings, the mice with Alzheimer's exhibited a significantly quicker adaptation to a six-hour time change compared to the control mice. This accelerated adjustment is suspected to be a consequence of their heightened sensitivity to changes in light. Normally, our biological clocks gradually synchronize with light cues, but when we experience significant time zone changes during travel, we encounter jet lag because our bodies need time to adapt. However, in the case of Alzheimer's mice, this adaptation occurred unusually rapidly.
Initially, the researchers speculated that this swift adjustment might be due to brain inflammation, referred to as "neuroinflammation." To explore this possibility, they focused on immune cells called microglia, which have shown promise in the development of improved Alzheimer's treatments. However, the scientists ultimately ruled out this hypothesis, as they found that microglia did not significantly influence the mice's adaptation speed. Nevertheless, it's worth noting that targeting microglia may still hold potential benefits for other reasons related to Alzheimer's treatment and management.
Significantly, the researchers from UVA also eliminated another possible factor: "mutant tau," an abnormal protein known to form tangles in the Alzheimer's brain. Surprisingly, the presence of these tangles did not influence the mice's adaptation either.
Based on their findings, the scientists concluded that the retina likely plays a crucial role in the heightened light sensitivity observed in Alzheimer's. This discovery opens up a promising avenue for researchers to explore as they strive to develop innovative approaches for treating, managing, and preventing the disease. Understanding the involvement of the retina in light sensitivity could lead to new and effective strategies to tackle Alzheimer's and its associated symptoms.
According to Ferris, the data strongly indicate that regulating the type and timing of light exposure could play a crucial role in mitigating circadian disruptions in Alzheimer's disease. The researchers believe that this valuable insight will pave the way for the development of light therapies aimed at slowing down the progression of Alzheimer's. By using targeted light interventions, they hope to provide individuals with effective tools to manage the disease and improve the overall quality of life for those affected.
The researchers have published their findings in the scientific journal Frontiers in Aging Neuroscience. The research team consisted of Weigel, Cherry L. Guo, Ali D. Güler and Ferris. The team members have no financial interest in the work.
The research was supported by the National Institutes of Health, grants K08DK097293, T32GM139787 and R35 GM140854; the Owens Family Foundation; and the Commonwealth of Virginia’s Alzheimer’s and Related Diseases Research Fund.
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