Low muscle strength in late adolescence may indicate the presence of subclinical motor deficits and predict a subsequent diagnosis of Parkinson’s disease, according to data published May 5 in Neurology. “The pattern of reduced muscle strength only in the upper extremities is of interest, as motor symptoms of Parkinson’s disease debut most commonly at these sites,” said Helena Gustafsson, MD, a postgraduate student in the Department of Community Medicine and Rehabilitation at Umeå University in Sweden.

A prodromal phase of unknown length precedes the clinical onset of Parkinson’s disease. Research has suggested associations between nonspecific symptoms such as constipation, depression, sleep disorders, and olfactory impairment and a diagnosis of Parkinson’s disease as long as 20 years later. Koller and Kase found reduced muscle strength in patients with early Parkinson’s disease in 1986.

The Swedish National Patient Register
To investigate the potential association between muscle strength and Parkinson’s disease later in life, Dr. Gustafsson and colleagues examined data for cohort of 1,317,713 Swedish men who had been conscripted at age 18 for compulsory military service between 1969 and 1996. All conscripts underwent two-day physical examinations during which isometric maximal muscle force was measured by knee extension, elbow flexion, and handgrip tests. Each muscle group was measured three times. If the third value was highest, the conscript was tested until the test value became stable.

The investigators identified diagnoses of Parkinson’s disease through December 31, 2012, in the study cohort using the participants’ personal identification numbers from the National Patient Register. Participants were followed up for a mean of 29 years. The researchers used linear regression models to test whether men diagnosed with Parkinson’s disease during follow-up had lower muscle strength at baseline than the rest of the cohort, after adjustment for confounders. They also used Cox proportional hazard models to investigate associations between variables assessed at baseline and the later risk of Parkinson’s disease.

Parents’ Diagnosis Influenced Strength
Dr. Gustafsson and colleagues found that participants with greater handgrip strength generally were heavier, taller, and more physically fit at conscription, and less educated 15 years later, than participants with less handgrip strength. A total of 977 men in the cohort were diagnosed with Parkinson’s disease during follow-up at a mean age of 50. Participants with a diagnosis of Parkinson’s disease were more likely to have a parent with the disease, compared with participants without this diagnosis.

Linear regression models adjusted for age, year of conscription, weight, and height indicated that participants diagnosed with Parkinson’s disease during follow-up had less handgrip strength (mean difference [MD] –10.1 N) and elbow flexion strength (MD –5.8 N) than participants without this diagnosis. The difference in knee extension strength (–3.9 N) was not significant. Further adjustments for other variables such as physical fitness, income, and education did not change the significance of the results.

When Dr. Gustafsson and colleagues adjusted Cox regression models for several variables, the lowest fifths of handgrip strength (hazard ratio [HR] 1.38) and elbow flexion strength (HR 1.34), but not knee extension strength (HR 1.24), were associated with an increased risk of Parkinson’s disease diagnosis during follow-up, compared with the highest fifth.

After the researchers adjusted for age, year of conscription, weight, and height, they found that men whose mothers had been diagnosed with Parkinson’s disease had less handgrip strength (MD –3.9 N) and elbow flexion strength (MD –2.7 N), but not knee extension strength (MD 0.9 N), than those whose mothers had not received this diagnosis. Handgrip strength (MD –4.6 N) and elbow flexion strength (MD –3.3 N) values, but not knee extension strength values (MD 0.8 N), were lower in men whose fathers had been diagnosed with Parkinson’s disease than in men whose fathers did not receive this diagnosis.

Exercise May Not Play a Role
The data suggest a genetic link between low muscle strength in young men and later risk of Parkinson’s disease. “As the differences in muscle strength were detected in late adolescence, it would be of interest, although difficult, to study whether these deficits are present already in childhood or perhaps even at birth,” said Dr. Gustafsson.

The investigators observed substantial relationships between physical fitness and muscle strength, but the associations between muscle strength and Parkinson’s disease were independent of physical fitness, and physical fitness was not associated with the risk of Parkinson’s disease. “Thus, exercise habits are unlikely to underlie the associations between Parkinson’s disease and muscle strength observed in this study,” said Dr. Gustafsson.

Findings May Be Sex-Specific
The strengths of Dr. Gustafsson’s study are its large population and long follow-up, said Cuiling Wang, PhD, Associate Professor in the Department of Epidemiology and Population Health at Albert Einstein College of Medicine in Bronx, New York, in an accompanying editorial. The large number of 977 incident cases of Parkinson’s disease is uncommon for this type of study. “Possibly as both a strength and as a cautionary note, the modest magnitude of association found here would be difficult to detect in smaller studies,” Dr. Wang added.

“The finding from this study needs to be interpreted with caution, as it might not be applicable to women or other races and ethnicities. However, it presents an intriguing hypothetical biomarker that prompts further study,” she concluded.

—Erik Greb

Does Low Muscle Strength Predict Parkinson’s Disease?