Circadian rest‐activity rhythm and longitudinal brain changes underlying late‐life cognitive decline

Jeon, So Yeon; Byun, Min Soo; Yi, Dahyun; Jung, Gijung; Lee, Jun-Young; Kim, Yu Kyeong; Sohn, Chul‐Ho; Kang, Koung Mi; Lee, Yu Jin; Lee, Dong Young

doi:10.1111/pcn.13521

Cited by 3 publications

(2 citation statements)

References 60 publications

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“…Furthermore, the Rotterdam Study indicated earlier L5 onset with increased dementia risk in the next 2 years, which supports our findings. In contrast, several other studies have indicated that delayed acrophase is associated with cognitive decline or dementia 31,32 . Our study has the advantages of a large sample size and inclusion of a healthy elderly population excluding early‐onset dementia cases, providing sufficient statistical power for our analyses.…”

Section: Discussionmentioning

confidence: 97%

“…In contrast, several other studies have indicated that delayed acrophase is associated with cognitive decline or dementia. 31,32 Our study has the advantages of a large sample size and inclusion of a healthy elderly population excluding early-onset dementia cases, providing sufficient statistical power for our analyses. However, further systematic reviews and meta-analyses are needed to thoroughly investigate the association between circadian phase and incident dementia.…”

Section: Clinical Neurosciencesmentioning

confidence: 99%

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Associations between accelerometer‐measured circadian rest‐activity rhythm, brain structural and genetic mechanisms, and dementia

Liu,

Feng,

et al. 2024

Psychiatry Clin Neurosci

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AimKnowledge of how circadian rhythm influences brain health remains limited. We aimed to investigate the associations of accelerometer‐measured circadian rest‐activity rhythm (CRAR) with incident dementia, cognitive dysfunction, and structural brain abnormalities in the general population and underlying biological mechanisms.MethodsFifty‐seven thousand five hundred and two participants aged over 60 years with accelerometer data were included to investigate the association of CRAR with incidental dementia. Non‐parametric CRAR parameters were utilized, including activity level during active periods of the day (M10), activity level during rest periods of the day (L5), and the relative difference between the M10 and L5 (relative amplitude, RA). Associations of CRAR with cognitive dysfunction and brain structure were studied in a subset of participants. Neuroimaging‐transcriptomics analysis was utilized to identify the underlying molecular mechanisms.ResultsOver 6.86 (4.94–8.78) years of follow‐up, 494 participants developed dementia. The risk of incident dementia was associated with decreasing M10 (hazard ratio [HR] 1.45; 95% conference interval [CI], 1.28–1.64) and RA (HR 1.37; 95% CI, 1.28–1.64), increasing L5 (HR 1.14, 95% CI 1.07–1.21) and advanced L5 onset time (HR 1.12; 95% CI, 1.02–1.23). The detrimental associations were exacerbated by APOE ε4 status and age (>65 years). Decreased RA was associated with lower processing speed (Beta −0.04; SE 0.011), predominantly mediated by abnormalities in subcortical regions and white matter microstructure. The genes underlying CRAR‐related brain regional structure variation were enriched for synaptic function.ConclusionsOur study underscores the potential of intervention targeting at maintaining a healthy CRAR pattern to prevent dementia risk.

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Section: Discussionmentioning

confidence: 97%

Section: Clinical Neurosciencesmentioning

confidence: 99%

Associations between accelerometer‐measured circadian rest‐activity rhythm, brain structural and genetic mechanisms, and dementia

Liu,

Feng,

et al. 2024

Psychiatry Clin Neurosci

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Non-nutritive Sweetener Aspartame Disrupts Circadian Behavior and Causes Memory Impairment in Mice

Bai,

Zuo,

Zhao

et al. 2024

J. Agric. Food Chem.

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As a non-nutritive sweetener, aspartame is widely used in everyday life. However, its safety is highly controversial, especially its effects on neurobehavior. We evaluated the effects of chronic daily oral administration of aspartame-containing drinking water (at doses equivalent to 7−28% of the FDA-recommended human DIV) on memory and rhythm behaviors in mice and further investigated changes at the molecular level in the brains. Our results demonstrated that mice exposed to aspartame exhibited memory impairment. Disorders of hippocampal neurotransmitter metabolism and pathological damage may be responsible for the aspartame-induced memory impairment via inhibition of the BDNF/TrkB pathway. Furthermore, our findings suggested that disturbed clock gene expression in the hypothalamus after aspartame exposure led to altered rest−activity behavior, and this disruption of the circadian rhythm may exacerbate memory impairment. This study highlights the negative neurobehavioral effects of aspartame and provides valuable insights into its rational and safe use.

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Digital biomarkers for non-motor symptoms in Parkinson’s disease: the state of the art

Janssen Daalen,

van den Bergh,

Prins

et al. 2024

npj Digit. Med.

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Digital biomarkers that remotely monitor symptoms have the potential to revolutionize outcome assessments in future disease-modifying trials in Parkinson’s disease (PD), by allowing objective and recurrent measurement of symptoms and signs collected in the participant’s own living environment. This biomarker field is developing rapidly for assessing the motor features of PD, but the non-motor domain lags behind. Here, we systematically review and assess digital biomarkers under development for measuring non-motor symptoms of PD. We also consider relevant developments outside the PD field. We focus on technological readiness level and evaluate whether the identified digital non-motor biomarkers have potential for measuring disease progression, covering the spectrum from prodromal to advanced disease stages. Furthermore, we provide perspectives for future deployment of these biomarkers in trials. We found that various wearables show high promise for measuring autonomic function, constipation and sleep characteristics, including REM sleep behavior disorder. Biomarkers for neuropsychiatric symptoms are less well-developed, but show increasing accuracy in non-PD populations. Most biomarkers have not been validated for specific use in PD, and their sensitivity to capture disease progression remains untested for prodromal PD where the need for digital progression biomarkers is greatest. External validation in real-world environments and large longitudinal cohorts remains necessary for integrating non-motor biomarkers into research, and ultimately also into daily clinical practice.

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Circadian rest‐activity rhythm and longitudinal brain changes underlying late‐life cognitive decline

Cited by 3 publications

References 60 publications

Associations between accelerometer‐measured circadian rest‐activity rhythm, brain structural and genetic mechanisms, and dementia

Associations between accelerometer‐measured circadian rest‐activity rhythm, brain structural and genetic mechanisms, and dementia

Non-nutritive Sweetener Aspartame Disrupts Circadian Behavior and Causes Memory Impairment in Mice

Digital biomarkers for non-motor symptoms in Parkinson’s disease: the state of the art

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