Fractal regulation and incident Alzheimer's disease in elderly individuals

Abstract

Introduction:Healthy physiological systems exhibit fractal regulation (FR), generating similar fluctuation patterns in physiological outputs across different time scales. FR in motor activity is degraded in dementia, and the degradation correlates to cognitive decline. We tested whether degraded FR predicts Alzheimer’s dementia.Methods:FR in motor activity was assessed in 1097 nondemented older adults at baseline. Cognition was assessed annually for up to 11 years.Results:Participants with an FR metric at the 10th percentile in this cohort had a 1.8-fold Alzheimer’s disease risk (equivalent to the effect of being ~5.2 years older) and 1.3-fold risk for mild cognitive impairment (equivalent to the effect of being ~3.0 years older) than those at the 90th percentile. Consistently, degraded FR predicted faster cognitive decline. These associations were independent of physical activity, sleep fragmentation, and stability of daily activity rhythms.Discussion:FR may be a useful tool for predicting Alzheimer’s dementia.

More random motor activity fluctuations predict incident frailty, disability, and mortality

“…Altered fractal fluctuations of motor activity may represent sub-clinical information stemming from disruptions to multiple physiological functions, including cognition, psychiatric stability, coordination, and physical conditioning. This interpretation is supported by our previous findings that fractal motor activity regulation was degraded in dementia and associated with cognitive impairment (13,27,40), and the finding in this study that the associations between α 1 and frailty/disability/mortality were slightly weakened (but still statistically significant) when the composite motor function measure (incorporating many tests that involve cognition) was included in the model. Together, these findings support that fractal motor activity regulation provides additional valuable information about physiological function beyond total daily activity.…”

“…Recent human studies showed that the degradation of the fractal motor activity regulation at timescales < 2 h (smaller α 1 ) was associated with dysregulations in higher brain activities including mood and cognitive function (44)(45)(46)(47)(48)(49), indicating that the decrease of α 1 could be an omen of accelerated cognitive degeneration. This hypothesis was supported by our recent study showing that α 1 reduction predicted faster cognitive decline and increased risk for dementia (27). This hypothesis was further supported by our observed association between smaller baseline α 1 and increased risk of IADL disability, considering that the decline in IADL is likely to represent a decline in cognitive function.…”

“…As a hallmark of healthy physiology, fractal regulation is believed to represent the system adaptability and to reflect the complexity of physiological networks in which regulatory processes function interactively over a wide range of timescales (23)(24)(25)(26). Consistently, our recent study further showed that the degraded fractal motor activity regulation is associated with cognitive impairment and predicts the risk of developing Alzheimer's dementia in elderly individuals many years before the clinical onset of dementia (27). However, its value for predicting other adverse health consequences has not been fully explored.…”

The neural correlates of discrete gait characteristics in ageing: A structured review

“…This limits our understanding of the neural control of variability and asymmetry; measures within the variability domain particularly have a high prevalence within gait research as they can be used as markers of fall risk and cognitive decline (Montero-Odasso et al, 2012; Tian et al, 2017a), therefore it is crucial that we develop a greater understanding of their underlying mechanisms. Additionally, non-linear approaches to analysis, such as the fractal analysis of stride-to-stride fluctuations in walking, are of increasing interest and prevalence within human gait research as they take in to consideration the structure and complexity of these large data sets (Hu et al, 2009; Li et al, 2018). Studies within this review varied not only by the gait measurement tools, but by the number, speed and type (continuous or intermittent) of walks performed, limiting our interpretation of findings.…”

Actigraphy‐estimated sleep and 24‐hour activity rhythms and the risk of dementia

“…Yet, the association of earlier L5 onset with increased dementia risk in the next 2 years suggests a phase advance of nighttime inactivity as a prodromal feature of dementia and AD. Heterogeneity of activity rhythm findings in dementia risk, including ours, with regard to the direction of a prodromal phase shift 10 and use of different modeling strategies 11,51 should be further investigated.…”