Perturbations in the Body’s Internal Clock Linked to Greater Risk of Parkinson’s, Study Finds

Older men who have a weak or irregular circadian rhythm — the body’s internal clock that controls the sleep-wake cycle — are approximately three-times more likely to develop Parkinson’s disease later in life, compared to those who have regular activity-rest cycles, a study has found.

According to researchers, more studies are needed to determine if alterations in circadian rhythms could be an early risk factor for the disease.

Findings were reported in the study, “Association of Circadian Abnormalities in Older Adults With an Increased Risk of Developing Parkinson Disease,” published in the journal JAMA Neurology.

Disruptions in circadian rhythms are common in older individuals, particularly those with neurodegenerative disorders, like Parkinson’s.

However, until recently, it was still unknown if disruptions in circadian rhythms could precede the onset of Parkinson’s.

A new study carried out by researchers at the UC San Francisco Weill Institute for Neurosciences and their colleagues has now uncovered that perturbations (disturbances) in the body’s internal clock may be an early sign of the disease setting in years before a formal diagnosis can be made.

“In this latest study we found that even small changes in circadian rhythm in older men were associated with a greater likelihood of getting Parkinson’s down the line,” Kristine Yaffe, MD, said in an UCSF news story. Yaffe is the Roy and Marie Scola Endowed Chair and vice chair of the Department of Psychiatry at UCSF, a member of the UCSF Memory and Aging Center, and senior author of the study.

In the study, which was part of the larger Osteoporotic Fractures in Men Study (MRoS), investigators gathered and analyzed 11-year follow-up data from 2,930 men with an average age of 76.3 years at the start of the study.

None of the men participating in the study had been diagnosed with Parkinson’s before enrolling, and all were living independently.

Their overall health status was evaluated at the start of the study, and regularly monitored during follow-up through visits and questionnaires.

During the study, all men were asked to wear an actigraph — a watch-like device that can be used to monitor several parameters of rest and activity cycles — for a minimum of three separate periods of 24 hours.

Assessed parameters included amplitude (rhythm strength), mesor (average activity), robustness (how closely rhythms followed a 24-hour curve pattern), and acrophase (a measure of advance or delay of the 24-hour cycle).

Statistical analyses then were used to evaluate possible associations between the different circadian rhythm parameters recorded by the actigraph and the risk of Parkinson’s later in life.

Of the 2,930 men included in the study, 78 (2.7%) developed  Parkinson’s at some point during follow-up.

Statistical analyses showed that men with weaker or irregular circadian rhythms — those with low amplitude, mesor, or robustness — were approximately three times more likely to develop Parkinson’s later in life, compared to those who had stronger or regular activity-rest cycles.

This link between circadian rhythms and Parkinson’s risk held true even after investigators adjusted data to account for night-time sleep disturbances, including loss of sleep, being unable to fall asleep, sleep apnea, and leg movement during sleep.

The association was slightly weakened — but maintained — after they excluded from the analysis cases of men who were diagnosed with Parkinson’s within a period of two years of entering the study.

Unlike the other three circadian rhythm parameters, acrophase was found not to be linked to a higher risk of Parkinson’s.

“Our results suggest that the reduced amplitude and/or robustness of the rhythms rather than disrupted timing (acrophase) are most indicative of a subsequent risk of PD [Parkinson’s disease], independent of nighttime sleep disturbances,” the researchers wrote.

“Future studies are needed to explore underlying mechanisms and to determine whether circadian disruption itself might contribute to the development of PD. If confirmed to be a risk factor for PD, then circadian rhythmicity could be a promising intervention target and will open new opportunities for the prevention and management of PD,” they concluded.