Walking pace, handgrip strength, age, APOE genotypes, and new-onset dementia: the UK Biobank prospective cohort study

Abstract

Background The independent and additive associations of walking pace and grip strength on dementia risk and the potential modifying effects of age, APOE phenotypes, and other dementia risk factors on the walking pace and dementia relationships demand further clarification. We aimed to investigate the independent and additive relationships of walking pace and handgrip strength on the risk of new-onset dementia and examine the potentially modifying effects of age, APOE phenotypes, lifestyle factors, and family history of dementia in the relationships. Methods A total of 495,700 participants from the UK Biobank, who were free of dementia at baseline, were included in this study. Walking pace was self-defined as slow, average, or brisk. Handgrip strength was assessed by dynamometer and was divided into sex-specific quartiles. The APOE genotypes were determined by a combination variant of rs429358 and rs7412. Other dementia risk factors, including education, physical activity, hypertension, depression, diabetes, and family history of dementia, were also collected. The primary outcome was new-onset all-cause dementia. Results Over a median follow-up duration of 12.0 years, 3986 (0.8%) participants developed new-onset all-cause dementia. Compared with those with slow walking pace, participants with average (HR, 0.61; 95%CI: 0.55–0.68) or brisk (HR, 0.59; 95%CI: 0.52–0.67) walking pace had a significantly lower risk of new-onset all-cause dementia. Moreover, compared with those with both slow walking pace and lower handgrip strength (the first quartile), the lowest risk of new-onset all-cause dementia was observed in participants with both average or brisk walking pace and higher handgrip strength (the 2–4 quartiles) (HR, 0.45; 95%CI: 0.40–0.52). Notably, the negative relationship between walking pace and the risk of new-onset all-cause dementia was significantly reduced as APOE ε4 dosage increased (APOE ε4 dosages = 0 or 1: brisk vs. slow: HR, 0.55; 95%CI: 0.48–0.63; vs. APOE ε4 dosages = 2: brisk vs. slow: HR, 1.14; 95%CI: 0.77–1.68; P for interaction = 0.001) or age increased (< 58 [median]: brisk vs. slow: HR, 0.27; 95%CI: 0.18–0.41; vs. ≥ 58 years: brisk vs. slow: HR, 0.55; 95%CI: 0.48–0.63; P for interaction = 0.007). Conclusions Walking pace was inversely associated with new-onset dementia in the general population, especially in younger participants and those with lower APOE ε4 dosage. Participants with both faster walking pace and higher handgrip strength had the lowest risk of dementia, suggesting that maintaining both high handgrip strength and fast walking pace may be a more comprehensive strategy for preventing dementia risk.

APP in the Neuromuscular Junction for the Development of Sarcopenia and Alzheimer’s Disease

“…It is of interest to notice that a recent prospective cohort study, with 340,212 participants, suggests an association of an absolute 5 kg increment of grip strength with a lower risk of AD (HR 0.874) [19]. Another prospective cohort study, with 495,700 participants with a median 12 years followup, demonstrates that walking pace is inversely associated with new-onset dementia, particularly in young participants with lower APOEε4 dosage [20]. However, the mechanisms underlying the association between cognitive impairment and sarcopenia appear to be complicated.…”

Association of handgrip strength and walking pace with incident Parkinson's disease

“…Therefore, a combination of the two may be more relevant to health outcomes than use alone. 14,15 However, to date, the combined effect of grip strength and walking pace on the risk of PD has not been investigated.…”

“…Furthermore, from a physiological perspective, grip strength and walking pace may reflect different underlying physiological processes: Grip strength is more likely a measure of contraction strength, while walking pace integrates strength with other processes (e.g., balance and coordination). Therefore, a combination of the two may be more relevant to health outcomes than use alone 14,15 . However, to date, the combined effect of grip strength and walking pace on the risk of PD has not been investigated.…”

Establishing thresholds of handgrip strength based on mortality using machine learning in a prospective cohort of Chinese population

“…Handgrip strength (HGS) is an important indicator of physical function, and a biological marker of aging throughout the lifespan (4). Extensive studies have consistently demonstrated a robust correlation between low HGS and a range of adverse health outcomes, including hip fracture, nutrition deficiencies, new-onset chronic diseases and mortality risk (5)(6)(7)(8)(9). The measurement of HGS involves a simple and highly reproducible procedure utilizing a portable and relatively low-cost dynamometer, so it can be easily implemented in regions with limited advanced medical equipment (10).…”