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.