Parker, Kirby G.

Abstract Background Relationships of midlife inflammation with late‐life mobility and influences of chronic health conditions, race, and social determinants of health (SDoH) on these relationships are poorly understood. Methods Among 4758 community‐dwelling participants (41% men, 20% Black), high‐sensitivity C‐reactive protein (hsCRP) was measured over 20+ years: in midlife at study visit 2 (V2: 1990–1992, 47–68 years); at V4 (1996–1998, 53–74 years); and with concurrent late‐life 4‐m gait speed at V5 (2011–2013, 67‐88 years, mean 75 years). SDoH measures included race, the national‐rank area deprivation index, education, and income. We examined associations of late‐life gait speed with midlife hsCRP (V2 continuous and clinically high ≥3 mg/L), with 20‐year hsCRP history from midlife (V2–V5 average continuous hsCRP and clinically high ≥3 mg/L) and with inflammation accumulation (visits and years with high hsCRP). Regression models adjusted for demographic, cardiovascular, and SDoH measures; effect modification by the presence of other common chronic conditions (obesity, diabetes, hypertension) and race were examined, with and without accounting for SDoH. Results High midlife hsCRP was associated with slower late‐life gait speed, even among those without chronic conditions in midlife: −4.6 cm/s (95% CI: −6.4, −2.8). Importantly, sustained high hsCRP was associated with a 20‐year slowing of −10.0 cm/s (−14.9, −5.1) among those who never experienced obesity, diabetes, or hypertension over the 20‐year period. Associations were similar between Black participants, −3.8 cm/s (−6.9, −0.7) and White participants −3.3 (−4.5, −2.2) per interquartile range of midlife hsCRP; effect modifications by chronic conditions and race were unsupported throughout. Results were robust to accounting for SDoH or otherwise; however, worse SDoH was associated with higher inflammation and slower gait speed in both Black and White participants. Conclusions Inflammation in midlife may contribute to clinically meaningful late‐life slowing of gait speed, even among otherwise healthy‐appearing adults and regardless of race and socioeconomic disadvantage. Regular monitoring and interventions for inflammation may be warranted from midlife.

AbstractIntroductionSlower mobility is associated with mild cognitive impairment (MCI) and dementia. We examined the interaction of endurance with gait speed on prevalent MCI and dementia.MethodsCross‐sectional multinomial regression in the ARIC cohort (n = 2844 participants; 71 to 94 years; 44% men; 18% Black persons) with cognitive status (normal/MCI/dementia), 4 m gait speed, and endurance (2 minute walk [2MW]).ResultsFaster gait speed (up to but not above 1 m/s) and better 2MW were separately associated with lower dementia risk. Good performance in both (2MW = 200 m, gait speed = 1.2 m/s) was associated with 99% lower dementia (Relative Prevalence Ratio [RPR] = 0.01 [95% CI: 0.0 to 0.06]) and 73% lower MCI, RPR = 0.27 (0.15 to 0.48) compared to poor performance in both (2MW = 100 m, gait speed = 0.8 m/s). Models incorporating a gait speed‐by‐2MW interaction term outperformed gait speed‐only models (P < .001).DiscussionGait speed relationships with dementia diminish at faster gait speeds. Combining endurance with gait speed may yield more sensitive markers of MCI and dementia than gait speed alone.