Fractal motor activity regulation and sex differences in preclinical Alzheimer's disease pathology

Introduction: Degradation in fractal motor activity regulation (FMAR), a measure of multiscale self-similarity of motor control, occurs in aging and accelerates with clinical progression to Alzheimer's disease (AD). Whether FMAR changes occur during the pre-symptomatic phase of the disease in women and men remains unknown. Methods: FMAR was assessed in cognitively normal participants (n = 178) who underwent 7 to 14 days of home actigraphy. Preclinical AD pathology was determined by amyloid imaging-Pittsburgh compound B (PiB) and cerebrospinal fluid (CSF) phosphorylated-tau181 (p-tau) to amyloid beta 42 (Aβ42) ratio. Results: Degradation in daytime FMAR was overall significantly associated with preclinical amyloid plaque pathology via PiB+ imaging (beta coefficient β = 0.217, standard error [SE] = 0.101, P =.034) and increasing CSF tau181-Aβ42 ratio (β = 0.220, SE = 0.084, P =.009). In subset analysis by sex, the effect sizes were significant in women for PiB+ (β = 0.279, SE = 0.112, P =.015) and CSF (β = 0.245, SE = 0.094, P =.011) but not in men (both Ps >.05). These associations remained after inclusion of daily activity level, apolipoprotein E ε4 carrier status, and rest/activity patterns. Discussion: Changes in daytime FMAR from actigraphy appear to be present in women early in preclinical AD. This may be a combination of earlier pathology changes in females reflected in daytime FMAR, and a relatively underpowered male group. Further studies are warranted to test FMAR as an early noncognitive physiological biomarker that precedes the onset of cognitive symptoms.