Daily steps and health outcomes: Implications for persons with Parkinson's disease

Emerging evidence suggests that greater levels of physical activity are associated with a lower risk of developing Parkinson's disease (PD). ¹ Recently, the Lancet Public Health published a systematic review and meta-analysis on the potential benefits of physical activity for health outcomes. They demonstrated that accumulating 7000 steps per day, as compared to 2000 steps, is associated with a substantially reduced risk of all-cause mortality, cardiovascular disease, dementia and other health outcomes in adults aged 18 and older. ² The dose-response curve appeared to plateau at around 7000 steps per day, suggesting that those who achieved even greater numbers of step counts per day did not enjoy much greater health benefits. However, subgroup analyses of all-cause mortality suggest that older adults continued to achieve risk reduction beyond this threshold, potentially allowing for greater benefits above 7000 steps per day for older adults. The analysis included a large sample of over 160.000 participants in total, drawn exclusively from studies that used objectively measured step counts in a free-living environment. Therefore, these findings represent real-world daily activity patterns. This work constitutes an important scientific advancement because it adds robust evidence on the relationship between step count and health benefits. However, some caution is warranted, since source data came from observational studies, which are prone to reverse causality. This begs the question whether low physical activity is truly a risk factor of disease or –­alternatively– an early disease manifestation. ³ Randomized controlled trials (RCTs) are warranted to distinguish these two explanations.

This issue of reverse causality applies especially to neurodegenerative diseases, many of which have a pre-diagnostic phase that spans well over a decade. During this time, affected individuals already develop symptoms that can reduce levels of physical activity. ⁴ In particular, individuals with PD commonly experience apathy, slower movements, greater variability in step quality and mild instability several years prior to their diagnosis. ⁵ Observational studies in the PD field have consistently shown an inverse association between physical activity—both low- and high-intensity—and PD risk. ⁶ These findings are in line with those reported in the Lancet Public Health mentioned in this letter. However, similar to the data underlying the meta-analysis by Ding and colleagues, the evidence in the PD field is also derived exclusively from observational studies, and therefore potentially prone to reverse causation.

To answer this important question, we need RCTs that randomize participants on different step count targets and examine its effect on the prevention of clinical manifestations of a disease. For PD, the first-of-its-kind RCT that randomizes on step count targets is the Slow-SPEED-NL study (NCT06193252), which was launched in June 2024. This trial aims to determine whether increasing daily step counts in individuals with prodromal features of PD can postpone the onset of clinical manifestations of PD. The trial includes participants with an isolated REM-sleep behavior disorder, a well-established prodrome of PD. ⁷ Participants are randomized to either a smartphone-guided physical activity intervention or an active control group. The study leverages both passive and active digital outcomes to longitudinally monitor intermediate motor- and non-motor prodromal outcomes and investigates the biological impact of physical activity through blood- and imaging biomarkers. The trial also takes into account the risk of falling among those who reach excessive daily step counts, which was highlighted in the meta-analysis by Ding and colleagues, by excluding individuals who already exceed 10,000 steps per day.

Importantly, the Slow-SPEED-NL trial is part of a broader international series of trials, with parallel studies soon to be launched in the United States (in persons with a genetically defined risk of developing PD; clinicaltrials.gov NCT06993142), United Kingdom (in persons with prodromal PD defined as hyposmia based on abnormal scores on the University of Pennsylvania Smell Identification Test 40-item smell test; clinicaltrials.gov NCT06600438) and Austria and Germany (in persons with RBD ⁸ ). These complementary trials will include populations with additional PD risk factors, including hyposmia and genetic predisposition, thereby expanding the generalizability and impact of the findings. These trials will help to confirm whether higher daily step counts elicit true biological effects to prevent the development of clinically manifest PD.