Acetate enables metabolic fitness and cognitive performance during sleep disruption

Cell Metabolism, Journal Year: 2024, Volume and Issue: 36(9), P. 1998 - 2014.e15

Published: Aug. 19, 2024

Language: Английский

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Locus coeruleus integrity and neuropsychiatric symptoms in a cohort of early‐ and late‐onset Alzheimer's disease

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 6351 - 6364

Published: July 25, 2024

Early-onset Alzheimer's disease (EOAD) shows a higher burden of neuropsychiatric symptoms than late-onset (LOAD). We aim to determine the differences in severity and locus coeruleus (LC) integrity between EOAD LOAD accounting for stage.

Language: Английский

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Reconstructed Cell-Type Specific Rhythms in Human Brain link Alzheimer's Pathology, Circadian Stress, and Ribosomal Disruption

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 26, 2025

Alzheimer's disease (AD) disrupts behavioral circadian rhythms, but its effects on molecular rhythms in the human brain are poorly understood. Using single-nucleus RNA sequencing from post-mortem cortical samples, we informatically estimated relative phases of 409 persons with and without AD dementia. We then reconstructed expression profiles across cell types. While core clock were preserved AD, many cell-type specific outputs disrupted. Rhythms ribosomal biogenesis oxidative phosphorylation dampened Similar losses gene observed APP/PS1 mice, which showed further reductions protein polysome-mediated translation after desynchrony. Exploratory computational modeling reveals that altered may contribute to increased variability seen patients. These findings reveal output brains affected patients, highlight disrupted as a feature AD.

Language: Английский

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Locus coeruleus tau validates and informs high-resolution MRI in aging and at earliest Alzheimer’s pathology stages

Acta Neuropathologica Communications, Journal Year: 2025, Volume and Issue: 13(1)

Published: Feb. 28, 2025

The locus coeruleus (LC) has been identified as a site that develops phosphorylated tau pathology earlier than cerebral cortex. We present data using high-resolution postmortem MRI and validated histopathology in controls the earliest Braak (BB) stages (BBI-BBII) LC. ex vivo provides 3D volume (quantitative), while histology reveals specificity severity burden (semi-quantitative). mapped our highly regionally specific LC onto reconstructions of same samples used (n = 11). noted significant structural subatrophy between BB 0 II (30.0% smaller volumes, p 0.0381), trend which primarily affected rostral-most (49.2% average volume, 0.0381). show on both neighboring dorsal raphe caudal (DRc), were assessed at multiple rostrocaudal levels with sensitive spatial matrices. observed accumulation I (37.6% increase, < 0.0001), may reflect change prior to presumptive cognitive impairment III. Tau was most severe middle portion (11.3% greater compared rostral LC, 0.0289) when including gradient DRc (58.2% decrease DRc, suggesting selective regional vulnerabilities nuclei. Our study represents rigorous approach investigating pathology, having sections per sublevel measure whole without missing slices histological only approach. Taken together, findings provide novel demonstrate occurring during preclinical AD stages, alongside will serve valuable references for imaging.

Language: Английский

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REM sleep quality is associated with balanced tonic activity of the locus coeruleus during wakefulness

Journal of Biomedical Science, Journal Year: 2025, Volume and Issue: 32(1)

Published: March 11, 2025

Abstract Background Animal studies established that the locus coeruleus (LC) plays important roles in sleep and wakefulness regulation. Whether it contributes to variability humans is not yet established. Here, we investigated if vivo activity of LC related quality Rapid Eye Movement (REM) sleep. Methods We assessed 34 healthy younger (~ 22y) 18 older 61y) individuals engaged bottom-up top-down cognitive tasks using 7-Tesla functional Magnetic Resonance Imaging (fMRI). further recorded their electroencephalogram (EEG) evaluate associations between fMRI measures REM EEG metrics. Results Theta oscillation energy during was positively associated with response task. In contrast, theta negatively Importantly, sigma oscillations power immediately preceding a episode Conclusions intensity transient change sleep, feature causally animal studies. The depend on task, suggesting balanced level tonic required for optimal expression findings may have implications high prevalence complaints reported aging disorders such as insomnia, Alzheimer’s, Parkinson’s disease, which play pivotal through

Language: Английский

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Detecting Sleep/Wake Rhythm Disruption Related to Cognition in Older Adults With and Without Mild Cognitive Impairment Using the myRhythmWatch Platform: Feasibility and Correlation Study

JMIR Aging, Journal Year: 2025, Volume and Issue: 8, P. e67294 - e67294

Published: April 7, 2025

Abstract Background Consumer wearable devices could, in theory, provide sufficient accelerometer data for measuring the 24-hour sleep/wake risk factors dementia that have been identified prior research. To our knowledge, no study older adults has demonstrated feasibility and acceptability of accessing consumer to compute rhythm measures. Objective We aimed establish characterizing measures using gathered from Apple Watch with without mild cognitive impairment (MCI), examine correlations these neuropsychological test performance. Methods Of 40 enrolled (mean [SD] age 67.2 [8.4] years; 72.5% female), 19 had MCI 21 disorder (NCD). Participants were provided devices, oriented software (myRhythmWatch or myRW), asked use system a week. The primary outcome was whether participants collected enough assess (ie, ≥3 valid continuous days). extracted standard nonparametric extended-cosine based metrics. Neuropsychological tests gauged immediate delayed memory (Hopkins Verbal Learning Test) as well processing speed set-shifting (Oral Trails Parts A B). Results All meet providing (≥3 days) mean (SD) recording length somewhat shorter group at 6.6 (1.2) days compared NCD 7.2 (0.6) days. Later activity onset times associated worse performance ( β =−.28). More fragmented rhythms =.40). Conclusions Using Watch-based myRW gather raw is feasible MCI. Sleep/wake variables generated this correlated function, suggesting future studies can approach evaluate novel, scalable, factor characterization targeted therapy approaches.

Language: Английский

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Sleep and Arousal Hubs and Ferromagnetic Ultrafine Particulate Matter and Nanoparticle Motion Under Electromagnetic Fields: Neurodegeneration, Sleep Disorders, Orexinergic Neurons, and Air Pollution in Young Urbanites

Toxics, Journal Year: 2025, Volume and Issue: 13(4), P. 284 - 284

Published: April 8, 2025

Air pollution plays a key role in sleep disorders and neurodegeneration. Alzheimer’s disease (AD), Parkinson’s (PD), and/or transactive response DNA-binding protein TDP-43 neuropathology have been documented children young adult forensic autopsies the metropolitan area of Mexico City (MMC), along with disorders, cognitive deficits, MRI brain atrophy seemingly healthy populations. Ultrafine particulate matter (UFPM) industrial nanoparticles (NPs) reach urbanites’ brains through nasal/olfactory, lung, gastrointestinal tract, placental barriers. We Fe UFPM/NPs neurovascular units, as well lateral hypothalamic nucleus orexinergic neurons, thalamus, medullary, pontine, mesencephalic reticular formation, pinealocytes. quantified ferromagnetic materials arousal hubs examined their motion behavior to low magnetic fields MMC autopsy samples from nine 25 adults AD, PD, neuropathology. Saturated isothermal remanent magnetization curves at 50–300 mT were associated UFPM/NP accumulation sleep/awake 30–50 µT (DC fields) exposure. Brain exposed anthropogenic PM found be sensitive fields, behaviors that potentially linked early development progression fatal neurodegenerative diseases disorders. Single-domain orexin system, arousal, sleep, autonomic regions, are neurodegeneration, behavioral impairment, need identify higher risk monitor environmental UFPM NP emissions exposures fields. Ubiquitous ferrimagnetic particles field threat global health.

Language: Английский

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Rest‐activity rhythm characteristics associated with lower cognitive performance and Alzheimer's disease biomarkers in midlife women

Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring, Journal Year: 2025, Volume and Issue: 17(2)

Published: April 1, 2025

Abstract INTRODUCTION Disrupted rest‐activity rhythms (RARs) have been linked to poorer cognitive function and Alzheimer's disease (AD) biomarkers. Here we extend this work midlife women, who commonly experience menopause‐related sleep problems. METHODS One hundred ninety‐four postmenopausal participants underwent a neuropsychological evaluation, 72 h of wrist actigraphy generating RAR variables, blood draw measure AD biomarkers: phosphorylated tau (p‐tau181, p‐tau231) amyloid beta (Aβ40, Aβ42). RESULTS Lower interdaily stability (IS) relative amplitude (RA) higher variability (IV) least active 5 (L5) were associated with worse processing speed, independent sleep. Adjustment for significantly attenuated the associations RA memory. was p‐tau231 level, Further adjustment factors modestly accounted between RAR, measures, DISCUSSION Weaker particularly RA, functions, biomarkers levels, possibly linking pathology in women. Highlights rhythm robustness fragmentation speed. levels tau‐231. Menopause did not attenuate association function.

Language: Английский

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REM sleep quality is associated with balanced tonic activity of the locus coeruleus during wakefulness

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: July 16, 2024

Objective: Animal studies established that the locus coeruleus (LC) plays important roles in sleep and wakefulness regulation. Whether it contributes to variability humans is not yet established. Here, we investigated if vivo activity of LC related quality Rapid Eye Movement (REM) sleep. Methods: We assessed 34 healthy younger (~22y) 18 older (~61y) individuals engaged bottom-up top-down cognitive tasks using 7-Tesla functional Magnetic Resonance Imaging (fMRI). further recorded their electroencephalogram (EEG) evaluate associations between fMRI measures REM EEG metrics. Results: Theta oscillation energy during was positively associated with response task. In contrast, theta negatively Importantly, sigma oscillations power immediately preceding a episode Interpretation: intensity transient change sleep, feature causally animal studies. The depend on task, suggesting balanced level tonic required for optimal expression findings may have implications high prevalence complaints reported aging disorders such as insomnia, Alzheimers, Parkinsons disease, which play pivotal through

Language: Английский

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