Shift work may lead to accelerated cognitive decline, research suggests

Nearly a quarter of Americans don’t follow a traditional nine-to-five workday, with many—including nurses, firefighters and flight attendants—working evenings, nights or rotating shifts. These irregular work schedules can disrupt shift workers’ internal body clocks, making it difficult for their bodies to keep track of the time of day. Now, researchers at the Texas A&M University College of Medicine are studying how this disruption may affect long-term health and well-being.

David Earnest, PhD, and Karienn de Souza, PhD, were inspired by previous epidemiological research suggesting that changes in how our body clocks regulate 24-hour or circadian rhythms could have an effect on health and aging. According to Earnest, past clinical literature suggests that people with abnormal work or social schedules are more susceptible to an array of health disorders, including cardiovascular disease, diabetes and cancer.

Their most recent project, published in the Journal of Neuroinflammation, examines the potential link between shift work from ages 18–26—when people are most likely to engage in shift work—and health later in life, specifically related to memory and cognitive decline.

De Souza’s expertise lies in cognition and aging and Earnest’s is in how internal body clocks control circadian rhythms and sleep. When the team was discussing ways to expand on previous research, the idea for this novel project arose naturally.

“We were interested in following up on our previous observations examining associations between age-related changes in cognition and circadian rhythms to determine whether or not circadian rhythm dysregulation by itself is a long-term risk factor for accelerated cognitive decline later in life,” Earnest said.

To achieve their goal, the team utilized an experimental model that allowed them to isolate the specific effects of circadian rhythm and sleep dysregulation and avoid potential influence of other shift work-related comorbidities, like drinking, smoking and poor diet, on any resulting cognitive changes. During the study, the subjects used spatial tests of learning and memory. These tests measure the ability of the subject to navigate maze-based tasks and utilize spatial cues to reach the goal.

Spatial tests of learning and memory use a part of the brain called the hippocampus, which is responsible for converting short-term memory to long-term memory. This is significant because the hippocampus is typically affected in Alzheimer’s and other cognitive diseases. In this study, the researchers found that animals exposed to shifted light-dark cycles during early adulthood showed signs of dramatic cognitive decline by middle age—roughly equivalent to 50 years in humans—well before cognitive deficits typically emerge in older subjects, around 70 or older. The team believes the shift work-related alterations in circadian rhythms earlier in life have a long-term impact on the function of the hippocampus, accelerating cognitive aging.

Earnest’s earlier research indicated that similar alterations of circadian rhythms affect the regulation of immune cells and their inflammatory responses. Current analyses led by Karen Newell-Rogers, PhD from Texas A&M College of Medicine show that early circadian rhythm dysregulation in response to shift work-like cycles promotes pro-inflammatory activation of immune cells, leading to a persistent inflammatory condition. Similar changes in the activation of immune cells and neuroinflammatory processes have been linked to the development of Alzheimer’s and age-related dementia.

Although all the study subjects exposed to shift work-like cycles developed severe cognitive decline, this does not occur during normal aging, where only about half of the population experiences cognitive deficits, while the rest maintain unimpaired learning and memory. This distinction suggests that some individuals have factors in the brain that promote resilience against cognitive decline. This research may lead to the discovery of why some people are susceptible to cognitive aging, and others are not.

“If we ever hope to have treatments for Alzheimer’s disease—even if they’re not treatments, but prevention or lifestyle changes—we have to understand why those individuals are resilient,” Earnest said.

With the knowledge gained through this research, the team hopes to identify therapeutic interventions or other strategies for reducing dementia risk in individuals with a history of shift work and irregular sleep schedules. The next steps involve exploring how other parts of the body may contribute to inflammation related to cognitive decline. Specifically, the team hopes to examine the gut microbiome and its connection to the potential impact of shift work on cognitive decline later in life.

“I’ve published a lot of studies in my research career over last 35 years,” Earnest said. “But this might be some of the most significant research findings I’ve published in my life.”