A study measuring daily rest-activity rhythms in older adults with no cognitive impairment found that weaker, more fragmented daily rhythms were associated with smaller memory-related brain regions and, in subsequent follow-ups, faster brain atrophy.
The study , led by researchers at the Johns Hopkins Bloomberg School of Public Health in collaboration with scientists at the National Institute on Aging Intramural Research Program, is thought to be the first to assess how circadian rest-activity rhythms in middle-aged and older adults are linked to changes in the volume of brain regions over time, and to study these effects by age.
Circadian rhythms—guided by the brain’s internal 24-hour clock that regulates everything from sleep to digestion—shift as we age. For decades, sleep and circadian scientists have used data collected over several days from wrist-worn accelerometers to characterize 24-hour rest-activity rhythms, which can serve as a proxy for circadian rhythms. Disruptions in circadian rest-activity rhythms have been associated with a greater risk of Alzheimer’s disease and related dementias.
Understanding circadian rest-activity rhythms in relation to cognitive and brain health outcomes can help researchers predict risks for cognitive decline and identify interventions such as bright-light therapy that could help maintain and strengthen rest-activity patterns.
For their study, the researchers followed 344 cognitively healthy adults age 50 and older. Participants were asked to wear wrist accelerometers for up to a week to track 24-hour rest/activity rhythms over successive days and nights. The devices tracked movement and inactivity or “rest”—which could include sedentary activities such as sitting and reading a book or eating a meal—as well as daytime napping and nighttime sleep; participants also kept nap/sleep logs.
All participants had MRI scans of brain regions typically affected by Alzheimer’s—the parahippocampal gyrus, hippocampus, and amygdala—at the study visits during which they were provided with accelerometers. About two-thirds of participants had follow-up MRI brain scans in one or more follow-up visits over the next year.
As dementia develops, key brain regions involved in memory and emotion often shrink. The study found that participants with signs of stronger, less fragmented rest-activity rhythms had larger volumes of the hippocampus and parahippocampus—two key memory-associated brain regions—and, over time, showed less shrinkage of the amygdala, a brain region important for emotions and emotion-linked memories.
The study also found that some associations between less fragmented rhythms and less brain shrinkage were strongest among the oldest participants—a finding that suggests that circadian rhythm disruption may become increasingly relevant to brain health later in life.
The study appears April 14 in Alzheimer's & Dementia: The Journal of the Alzheimer's Association .
“These findings add to evidence that a weaker, more fragmented rest-activity rhythm can be an early sign of adverse neurological changes, and might also contribute to the underlying neurodegenerative process,” says study senior author Adam Spira , PhD, professor in the Bloomberg School’s Department of Mental Health.
The study’s co-first authors were Marc Kaizi-Lutu, a PhD student in the Department of Mental Health at the Bloomberg School, and Daniel Callow , PhD, an assistant professor of Psychiatry and Behavioral Sciences at Johns Hopkins University School of Medicine.
Participants in the study were part of a larger, National Institute on Aging Intramural Research Program-funded project known as the Baltimore Longitudinal Study of Aging, which has been ongoing since 1958. The sample for the study comprised 344 adults, with an average age of about 73, who showed no signs of cognitive impairment, and whose records included the relevant MRI and rest-activity rhythm data. The data were adjusted to take into account subjects’ ages and other relevant factors.
The researchers looked at how participants’ brain volumes changed over follow-up periods averaging about a year. These analyses linked more consistent, less fragmented rest-activity rhythms to less shrinkage over time of the amygdala, a brain region affected in Alzheimer’s.
The follow-up MRI scans also revealed results linking more fragmented rest-activity rhythms to faster-increasing volumes of empty spaces in the brain called ventricles—which expand when the brain itself is shrinking. This link was stronger among older participants. A similar age-related link was seen for more fragmented rest-activity rhythms and faster volume loss of “gray matter”—a collective term for brain cells.
“It’s possible that there is a spiral of neurodegeneration and circadian disruption, and it gets more intense as the individual ages, which may be why we see this clearer relationship among the older participants,” Kaizi-Lutu says.
The study has several limitations. Study participants were highly educated and cognitively unimpaired at the start of the study, which may limit generalizability to the broader population. In addition, the researchers did not consider how new health conditions that developed during the study might have affected results.
The authors note that more research that follows participants for years is needed to understand how much rest-activity rhythms change over time and how these changes affect the brain.
“ Circadian Rest/Activity Rhythms and Change in MRI-Derived Brain Volumes: Differences by Age in a Cognitively Healthy Sample ” was co-authored by Marc Kaizi-Lutu, Daniel Callow, Jill Rabinowitz, Brendan Lucey, Yang An, Mark Wu, Vadim Zipunnikov, Arnold Bakker, Christos Davatzikos, Eleanor Simonsick, Keenan Walker, Luigi Ferrucci, Susan Resnick, and Adam Spira.
Support for the research was provided by the National Institute on Aging (R01AG050507, R01AG075883), the Intramural Research Program of the National Institutes of Health, and the Department of Health and Human Services (HHSN-260-2004-00012C).
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