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. 2021 Sep 25;13(1):161.
doi: 10.1186/s13195-021-00903-7.

The circadian rest-activity pattern predicts cognitive decline among mild-moderate Alzheimer's disease patients

Adriano D S Targa #  1   2 , Iván D Benítez #  1   2 , Faridé Dakterzada  3 , John Fontenele-Araujo  4 , Olga Minguez  1 , Henrik Zetterberg  5   6   7 , Kaj Blennow  7   8 , Ferran Barbé  1   2 , Gerard Piñol-Ripoll  9
Affiliations

The circadian rest-activity pattern predicts cognitive decline among mild-moderate Alzheimer's disease patients

Adriano D S Targa et al. Alzheimers Res Ther. .

Abstract

Background: Alterations in circadian rhythms are present in the presymptomatic stage of Alzheimer's disease (AD), possibly contributing to its pathogenesis. However, it is unknown whether such alterations are associated with worse outcomes once individuals are diagnosed with symptomatic disease. We aimed to evaluate the association between the circadian rest-activity pattern and AD-related features in patients with mild-moderate AD.

Methods: We assessed the circadian rest-activity pattern of consecutive patients with mild-moderate AD through actigraphy for 14 days. Cerebrospinal fluid was obtained to determine the levels of important pathological markers including amyloid-beta protein (Aβ42), phosphorylated tau (P-tau), total tau (T-tau), and neurofilament light (NF-L). Neuropsychological evaluation was conducted at the beginning of the study and after 12 months of follow-up. Linear regression models were performed considering the global population and Aβ42+ patients only.

Results: The cohort included 100 patients with mild-moderate AD. The median age [p25;p75] was 76.0 [73.0;80.0] years and 63.0% were female. Older age (effect size [SE] of 0.324 [0.096]; p = 0.001) and male sex (0.780 [0.193]; p = 0.001) were associated with increased fragmentation and decreased synchronization of the rhythm, respectively. After adjusting for age, sex, and season of the year, increased levels of T-tau (effect size [95% CI] of 0.343 [0.139 to 0.547]; p = 0.001) and NF-L (0.444 [0.212 to 0.676]; p = 0.001) were associated with a higher amplitude of the rest-activity rhythm. Increased fragmentation of the rhythm at baseline was associated with greater cognitive decline after one year of follow-up independent of age, sex, T-tau/Aβ42 ratio, educational level, and season of the year (- 0.715 [- 1.272 to - 0.157]; p = 0.013). Similar findings were obtained considering only the Aβ42+ patients.

Conclusions: Our results suggest a potential role of the circadian rest-activity pattern in predicting the cognitive decline of patients with mild-moderate AD. Further studies are warranted to confirm these findings and to elucidate whether there is causality among the observed associations.

Keywords: Alzheimer’s disease; Circadian rest-activity pattern; Cognitive decline; Intradaily variability; Neurofilament light.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Baseline characteristics according to the circadian rest-activity pattern. The color-filled symbols represent statistically significant associations. ApoEε4-, apolipoprotein E carrier; BMI, body mass index; CI, confidence interval; WASO, time spent awake after sleep onset
Fig. 2
Fig. 2
Cognitive decline according to the fragmentation of the rest-activity rhythm considering the global population or Aβ42+ patients only. Intradaily variability was log-transformed to normalize its distribution. MMSE, Mini-mental state examination
See this image and copyright information in PMC

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