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

Abstract

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 P s > .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.

Circadian Rest–Activity Rhythms, Delirium Risk, and Progression to Dementia

“…We recently showed the same rhythm disturbances (lower normalized amplitude and higher IV) predicted incident AD and progression to AD from MCI; worsening cognition also correlated with decreasing amplitude and increasing IV 8 . At the same time, RAR disturbances were found to be associated with preclinical amyloid/tau pathology 9,11 . It is generally accepted that dementia is a significant risk factor for delirium, 2 and those with preclinical dementia may already be vulnerable to the stressors precipitating delirium.…”

“…Emerging evidence has shown that actigraphy‐derived RAR degrades with age and predicts cognitive decline, incident mild cognitive impairment (MCI), and Alzheimer disease (AD) 8–10 . In addition, disrupted RARs were found to be associated with amyloid/tau pathology even in cognitively intact humans 9,11 . The very same pathology has recently been implicated in delirium 12,13 .…”

Differential Fractal and Circadian Patterns in Motor Activity in Spontaneously Hypertensive Rats at the Stage of Prehypertension

“…In addition, iii) Δ𝛼 = 𝛼 1 -𝛼 2 was calculated as an overall measure for the breakdown of fractal patterns across the two regions. [42,43]…”

Influence of amyloid and diagnostic syndrome on non‐traditional memory scores in early‐onset Alzheimer's disease

“…Neuropsychological tests have traditionally served as the foundation for the detection and monitoring of Alzheimer's disease (AD) and related disorders (ADRD). 1,2 Depending on the type of neuropsychological test, digital analysis can provide additional scores based on speech quality, 3,4 acceleration of motion, 5 or timing measurements (e.g., during writing tasks 6 ).…”