Frailty identified as risk factor for Parkinson’s disease in study

Frailty, genetic variants linked to 3X higher risk of neurodegenerative condition

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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People with physical frailty have a nearly twofold higher risk of developing Parkinson’s disease than those who aren’t frail, according to an analysis of 12-year data from a U.K. study.

Being frail and carrying several genetic variants linked to Parkinson’s further enhanced the chances of developing the neurodegenerative disease — a three times higher risk.

“These findings indicate that physical frailty is a potential risk factor for PD [Parkinson’s disease] and the assessment and management of frailty might have clinical significance in the at-risk population,” the researchers wrote in “Physical Frailty, Genetic Predisposition, and Incident Parkinson Disease,” which was published in JAMA Neurology.

Physical frailty refers to a decline in physical function associated with a higher vulnerability to poor outcomes. Some core features of frailty, such as age-related fatigue, slow walking, weak handgrip strength, are also characteristics of Parkinson’s.

Frailty is common among people with Parkinson’s and increased frailty has been linked to more severe motor and nonmotor symptoms. There’s limited evidence on the association between frailty and developing Parkinson’s over time, however, leading researchers at the Huazhong University of Science and Technology, China, to analyze data from the UK Biobank, a large, prospective study that enrolled and followed more than 500,000 middle-aged and older adults across the U.K.

A total of 314,998 participants (mean age, 56.1; 49.1% men; all white) were included. Those who had Parkinson’s or dementia at the study’s start (baseline), who developed these conditions within two years, or had no frailty or genetic data were excluded.

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Frailty as Parkinson’s risk factor

Physical frailty was assessed using the Fried frailty phenotype that comprises five criteria — unintentional weight loss, weakness or poor handgrip strength, self-reported exhaustion, slow walking speed, and low physical activity.

Those who met up to two criteria were classified as having pre-frailty. Those meeting three or more criteria were classified as having frailty.

At baseline, 135,885 (43.1%) met the criteria for pre-frailty and 10,877 (3.5%) for frailty, while 168,236 (53.4%) did not have frailty. Pre-frail and frail people tended to be older (mean age 56.3-57.9 vs. 55.9) and more commonly were women (52.1-59.2% vs. 49.4%) than participants who weren’t frail.

Those with pre-frailty or frailty also tended to be smokers and more deprived, had higher body mass index (a ratio between weight and height), and presented a higher number of long-term health conditions.

During a mean follow-up of 12.3 years — corresponding to 3,860,420 person-years — 1,916 people were diagnosed with Parkinson’s. Person-years is a measure of the number of people participating in the study and the amount of time they were followed. For example, 100,000 person-years refers to data gathered from 100,000 patients followed for a year.

After adjusting for several potential influencing factors, the researchers found that pre-frail people had a 26% significantly higher risk of developing Parkinson’s and frailty was linked to a nearly twofold higher risk (87% higher).

While 41.9 cases of Parkinson’s per 100,000 person-years were seen among non-frail participants, this increased to 55.5 for those with pre-frailty and 99.6 for those with frailty.

The findings resulted in an absolute rate difference of 1.6 per 100,000 person-years for pre-frail people and 5.1 for frail participants relative to non-frail people.

Exhaustion, slow walking, low handgrip strength, and low physical activity were significantly associated with a greater risk of developing Parkinson’s, between 12-41%, further analyses of frailty criteria showed. No significant link was detected for weight loss.

Meeting a greater number of frailty criterium was associated with a significantly higher risk of Parkinson’s, with each additional criterium increasing the chances by 21%.

Effect of genetics on Parkinson’s, frailty

The researchers also investigated whether a polygenic risk score (PRS) — the sum of several genetic variants that contribute to the disease — affected the association between frailty and the disease. The PRS was comprised of 44 genetic variants previously identified as genetic risk factors for Parkinson’s in white people. The team divided the PRS into low, intermediate, and high.

Frail participants with high PRS showed the highest Parkinson’s risk — three times higher — compared with non-frail participants with low PRS.  Non-frail people had a 42-55% lower risk of Parkinson’s relative to frail participants across all PRS.

In addition, “the significant association between frailty and PD was more pronounced in participants with more long-term conditions,” the researchers wrote.

“We demonstrated a significant association of pre-frailty and frailty with the incidence of PD over 12 years of follow-up,” they wrote, adding this “association was modified by the genetic risk of PD, where the highest risk of PD was observed in those with frailty and high genetic risk.”

“Integrating frailty assessment into the primary prevention of PD may favor the identification of high-risk individuals,” the researchers wrote.