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

Abstract

BackgroundLow muscle strength has been found in late adolescence in individuals diagnosed with Parkinson disease (PD) 30 y later. This study investigated whether this lower muscle strength also may translate into increased risks of falling and fracture before the diagnosis of PD.Methods and FindingsAmong all Swedish citizens aged ≥50 y in 2005, two nested case–control cohorts were compiled. In cohort I, individuals diagnosed with PD during 1988–2012 (n = 24,412) were matched with up to ten controls (n = 243,363), and the risk of fall-related injuries before diagnosis of PD was evaluated. In cohort II, individuals with an injurious fall in need of emergency care during 1988–2012 (n = 622,333) were matched with one control (n = 622,333), and the risk of PD after the injurious fall was evaluated. In cohort I, 18.0% of cases and 11.5% of controls had at least one injurious fall (p < 0.001) prior to PD diagnosis in the case. Assessed by conditional logistic regression analysis adjusted for comorbid diagnoses and education level, PD was associated with increased risks of injurious fall up to 10 y before diagnosis (odds ratio [OR] 1.19, 95% CI 1.08–1.31; 7 to <10 y before diagnosis) and hip fracture ≥15 y before diagnosis (OR 1.36, 95% CI 1.10–1.69; 15–26 y before diagnosis). In cohort II, 0.7% of individuals with an injurious fall and 0.5% of controls were diagnosed with PD during follow-up (p < 0.001). The risk of PD was increased for up to 10 y after an injurious fall (OR 1.18, 95% CI 1.02–1.37; 7 to <10 y after diagnosis). An important limitation is that the diagnoses were obtained from registers and could not be clinically confirmed for the study.ConclusionsThe increased risks of falling and hip fracture prior to the diagnosis of PD may suggest the presence of clinically relevant neurodegenerative impairment many years before the diagnosis of this disease.

Traumatic brain injury in the prodromal period of Parkinson's disease: A large epidemiological study using medicare data

“…These findings were consistent with our original hypothesis that undetected non-motor and motor symptoms may contribute to falls and hence TBI. Interestingly, the magnitude of the PD-TBI association for each of the five years was remarkably similar to risk estimates observed in a large population-based study comparing PD patients in their prodromal period to controls with regard to hip fractures 6 . It was unlikely that hip fractures were associated causally with PD, but rather a result of progressive symptoms that led to falls and subsequent trauma.…”

“…First, we verified that results were not altered by excluding the individuals who had delayed entry because their inclusion required us to assume that they had not experienced a TBI between study start time and their entry. Second, we excluded the three months prior to PD diagnosis/reference date because prior studies of PD suggested that traumas in this time period may have facilitated PD ascertainment, 6,14 and we also repeated this excluding a full year.…”

“…In a study of community dwelling individuals with early-stage PD, 48% reported at least one fall in a six month period 5 . During the prodromal PD period, individuals who will eventually be diagnosed with PD based on the classic motor signs may be at an increased risk of falls 6 . Because some falls may result in TBI 7 , it is not clear whether the known association between PD and TBI 6,8–14 is causal.…”

“…During the prodromal PD period, individuals who will eventually be diagnosed with PD based on the classic motor signs may be at an increased risk of falls 6 . Because some falls may result in TBI 7 , it is not clear whether the known association between PD and TBI 6,8–14 is causal. Although the possible mechanisms for falls during the prodromal period have not been elucidated, there is evidence to suggest that non-motor and motor symptoms are occurring in the years prior to PD diagnosis 15,16 .…”

Shared molecular and cellular mechanisms of premature ageing and ageing-associated diseases

“…Cellular ageing and deterioration as a driver in AADs explain the observation that in many AADs, not only the tissue primarily associated with the disease is affected, but other tissues simultaneously undergo functional decline 6,7 . The often overlooked functional decline across multiple organs in AADs is important for disease pathology and diagnosis, as non-primary tissue defects can be used as an independent disease predictor: for example, handgrip strength and hip fractures are indicators of CKD and preclinical Parkinson disease, respectively 8,9 . These observations indicate that cellular ageing is a universal principle underlying AADs.…”