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Thursday, February 18, 2016

Frailty, falls, and hip fractures may be early predictors of Parkinson’s Disease

Thursday 18 February 2016

New research suggests that people who develop Parkinson’s Disease are at increased risk of falling and injuring themselves in the years leading up to their diagnosis

 X-ray showing a hip replacement. Image by Voisin/ Phanie/ Rex Features

People who are prone to falling and injuring and injuring themselves in middle age are at significantly increased risk of developing Parkinson’s Disease decades later, according to a new study by researchers in Sweden. The findings, published earlier this month in the open access journal PLoS Medicine, suggest that frailty – and especially an increased risk of falling and fracturing one’s hip – could be a marker for degenerative brain changes, which may occur decades before disease symptoms appear, and possibly aid in early diagnosis.
Parkinson’s Disease is a progressive neurodegenerative disease characterised by the death of dopamine-producing neurons in a region of the midbrain called the substantia nigra. This causes the three main symptoms of tremor, muscle rigidity, and slow movements, which typically appear at around 60 years of age, and progress at varying rates. Although widely considered to be a movement disorder, Parkinson’s is also associated with cognitive impairments, which in severe cases can develop into full-blown dementia.
Last year, Peter Nordström of Umeå University and his colleagues published the results of a large population study, in which they examined the medical records of all the approximately 1.35 million Swedish men conscripted at age 18 for compulsory military service between the years of 1969 and 1996. Looking specifically at measures of muscle strength, they found that those who scored lowest on handgrip and elbow flexion strength at the time of conscription were significantly more likely to develop Parkinson’s 30 years later.
The researchers therefore speculated that the reduced muscle strength they observed in adolescents who went on develop Parkinson’s in later life might indicate neuro-muscular deficits that increase the risk of falls and fractures long before a diagnosis of Parkinson’s.
To investigate, they again turned to the Swedish National Patient Register, and compared the medical records of more than 24,000 people, aged 50 and over and diagnosed with Parkinson’s between 1988 and 2012, with those of more than 243,000 matched controls, and the records of 622,000 patients admitted to accident and emergency departments with an injurious fall during the same period with those the same number of matched controls who had not.
Analysing these records, they find that 18% of the Parkinson’s patients had at least one injurious fall, and 7.8% had fractured a hip, up to 10 years before diagnosis, compared to 11% and 3.2% of the age-matched controls, respectively. In the second cohort, they find that 0.7% of those who had experienced an injurious fall were subsequently diagnosed with Parkinson’s, compared to 0.5% of those who had not.
The differences may seem small, but the large number of participants involved makes them meaningful. Overall, the risk of experiencing an injurious fall increased dramatically in the years leading up to diagnosis. The association with hip fractures was even stronger, with Parkinson’s patients being at significantly increased risk for more than 15 years before diagnosis, and almost twice as likely to suffer a fractured hip in the four years preceding diagnosis.
Nordström and his colleagues believe theirs is the first long-term study to assess the risk of injurious falls prior to the clinical onset of Parkinson’s Disease. They point out, however, that diagnoses of dementia, depression, and diabetes were also more common in the Parkinson’s patients than in the controls, and that all of these may also contribute to an increased risk of falling prior to diagnosis. They also note that their results are limited by a reliance on medical records, as opposed to clinically confirmed diagnoses. They also failed to take information about smoking and educational achievement, both of which are known to modify risk for Parkinson’s, into account.
Roxanne Sterniczuka neuropsychologist at Dalhousie University in Nova Scotia, who studies theinks between dementia, sleep and frailty, points out another potentially important confounding factor. “They don’t appear to have controlled for the effects of physical activity or exercise, which is one of the most important neuroprotective factors for healthy aging,” she says. “It’s well established that lack of physical activity is a strong risk factor for neurodegeneration, and lack of exercise is directly linked to lower bone density and muscle mass, which in turn increases risk of falls and subsequently fractures.”
Sterniczuk adds that while the results warrant further study, an increased risk of injurious falls may not be enough for accurate and early diagnosis. “Each person has a unique threshold for the onset of disease, and it’s theorized that we become more frail as deficits accumulate, so that eventually our defense mechanisms will be overridden and disease will take over,” she explains. “We know that other changes, such as a worsening sense of smell and sleep disturbances, can occur up to 20 years prior to a Parkinson’s diagnosis, so it’s possible that combining these deficits, including a history of falls and fractures, may serve as a valid preclinical diagnostic measure, and could aid the development of novel interventions at the earliest stages of the disease.”

References

Nyström, H., et al. (2016). Risk of Injurious Fall and Hip Fracture up to 26 y before the Diagnosis of Parkinson Disease: Nested Case–Control Studies in a Nationwide Cohort. PLoS Med. 13(2): e1001954. DOI: 10.1371/journal.pmed.1001954 [Full text]
Gustafsson, H., et al. (2015). Low muscle strength in late adolescence and Parkinson disease later in life. Neurology84: 1862–1869. DOI: 10.1212/WNL.0000000000001534 [Full text]
https://www.theguardian.com/science/neurophilosophy/2016/feb/18/frailty-falls-and-hip-fractures-may-be-early-predictors-of-parkinsons-disease?

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