Dysfunction of circadian and sleep rhythms in the early stages of Alzheimer's disease

Acta Physiologica, Год журнала: 2023, Номер 238(2)

Опубликована: Март 31, 2023

Abstract Dysfunction of circadian and sleep rhythms is an early feature many neurodegenerative diseases. Alzheimer's disease (AD) a progressive disorder resulting in cognitive psychiatric disturbances. Although it largely unclear whether dysfunctions contribute to the etiology AD or are consequence disease, there evidence that these conditions involved complex self‐reinforcing bidirectional relationship. According recent studies, dysregulation clock already occurs during asymptomatic stage could promote neurodegeneration. Thus, restoration preclinical may represent opportunity for intervention slow course.

Язык: Английский

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The rise of Parkinson’s disease is a global challenge, but efforts to tackle this must begin at a national level: a protocol for national digital screening and “eat, move, sleep” lifestyle interventions to prevent or slow the rise of non-communicable diseases in Thailand

Frontiers in Neurology, Год журнала: 2024, Номер 15

Опубликована: Май 13, 2024

The rising prevalence of Parkinson’s disease (PD) globally presents a significant public health challenge for national healthcare systems, particularly in low-to-middle income countries, such as Thailand, which may have insufficient resources to meet these escalating needs. There are also many undiagnosed cases early-stage PD, period when therapeutic interventions would the most value and least cost. traditional “passive” approach, whereby clinicians wait patients with symptomatic PD seek treatment, is inadequate. Proactive, early identification will allow timely interventions, digital technologies can be scaled up diagnosis cases. risk survey (TCTR20231025005) aims evaluate population screening platform identify Thai population. Recognizing long prodromal phase target demographic people aged ≥ 40 years, approximately 20 years before usual emergence motor symptoms. Thailand has highly rated system an established universal program citizens, making it ideal deploying using technology. Designed by multidisciplinary group experts, comprises 20-item questionnaire about symptoms along objective tests eight markers: voice vowel, sentences, resting postural tremor, alternate finger tapping, “pinch-to-size” test, gait balance, performance recorded mobile application smartphone’s sensors. Machine learning tools use collected data subjects at developing, or signs of, PD. This article describes selection validation items markers, results showing chosen parameters analysis methods robust, reliable, reproducible. could serve model similar strategies other non-communicable diseases Thailand.

Язык: Английский

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The Bidirectional Relationship between Sleep and Neurodegeneration: Actionability to Improve Brain Health

Clinical and Translational Neuroscience, Год журнала: 2024, Номер 8(1), С. 11 - 11

Опубликована: Фев. 2, 2024

Recently, it has become increasingly clear that there is a bidirectional relationship between sleep/circadian rhythms and neurodegeneration. Knowledge about this topic further improved after the description of glymphatic system, which mainly active during sleep. Changes in sleep circadian are present not only overt neurodegenerative diseases but also their early, prodromal, preclinical phases, supporting they precede (and contribute to) development This narrative review provides brief overview rhythm disruption neurodegeneration, highlights changes addresses future perspectives, particular, whether able to predict neurodegeneration potential actionability prevent or modulate diseases.

Язык: Английский

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Early‐onset dementia and risk of hip fracture and major osteoporotic fractures

Alzheimer s & Dementia, Год журнала: 2024, Номер 20(5), С. 3388 - 3396

Опубликована: Апрель 1, 2024

There is limited knowledge about early-onset dementia (EOD) on fracture risk.

Язык: Английский

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Blunted Melatonin Circadian Rhythm in Parkinson’s Disease: Express Bewilderment

Neurotoxicity Research, Год журнала: 2024, Номер 42(5)

Опубликована: Авг. 23, 2024

Язык: Английский

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Role of astrocytes in sleep deprivation: accomplices, resisters, or bystanders?

Frontiers in Cellular Neuroscience, Год журнала: 2023, Номер 17

Опубликована: Июнь 26, 2023

Sleep plays an essential role in all studied animals with a nervous system. However, sleep deprivation leads to various pathological changes and neurobehavioral problems. Astrocytes are the most abundant cells brain involved important functions, including neurotransmitter ion homeostasis, synaptic neuronal modulation, blood–brain barrier maintenance; furthermore, they associated numerous neurodegenerative diseases, pain, mood disorders. Moreover, astrocytes increasingly being recognized as vital contributors regulation of sleep-wake cycles, both locally specific neural circuits. In this review, we begin by describing regulating circadian rhythms, focusing on: (i) activity; (ii) metabolism; (iii) glymphatic system; (iv) neuroinflammation; (v) astrocyte–microglia cross-talk. review comorbidities deprivation-related Finally, discuss potential interventions targeting prevent or treat Pursuing these questions would pave way for deeper understanding cellular mechanisms underlying deprivation-comorbid

Язык: Английский

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New Editor‐in‐Chief for Acta Physiologica

Acta Physiologica, Год журнала: 2025, Номер 241(5)

Опубликована: Апрель 4, 2025

Язык: Английский

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Melatonin as a Chronobiotic/Cytoprotective Agent in REM Sleep Behavior Disorder

Brain Sciences, Год журнала: 2023, Номер 13(5), С. 797 - 797

Опубликована: Май 13, 2023

Dream-enactment behavior that emerges during episodes of rapid eye movement (REM) sleep without muscle atonia is a parasomnia known as REM disorder (RBD). RBD constitutes prodromal marker α-synucleinopathies and serves one the best biomarkers available to predict diseases such Parkinson disease, multiple system atrophy dementia with Lewy bodies. Most patients showing will convert an α-synucleinopathy about 10 years after diagnosis. The diagnostic advantage relies on prolonged time, its predictive power absence disease-related treatments could act confounders. Therefore, are candidates for neuroprotection trials delay or prevent conversion pathology abnormal α-synuclein metabolism. administration melatonin in doses exhibiting chronobiotic/hypnotic effect (less than mg daily) commonly used first line treatment (together clonazepam) RBD. At higher dose, may also be effective cytoprotector halt progression. However, allometric derived from animal studies (in 100 mg/day range) rarely employed clinically regardless demonstrated toxicity phase 1 pharmacological up normal volunteers. This review discusses application RBD: (a) symptomatic RBD; (b) possible disease-modifying α-synucleinopathies. To what degree has therapeutic efficacy prevention awaits further investigation, particular multicenter double-blind trials.

Язык: Английский

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Time for circadian medicine

Acta Physiologica, Год журнала: 2023, Номер 238(3)

Опубликована: Май 22, 2023

Circadian medicine developed from chronobiology, which deals with temporal processes in biological systems. Humans have an internal circadian clock that it is genetically determined, synchronized the environment by light and food, controls myriad time-of-day-dependent physiological each cell of our body.1, 2 In 2017, Rosbash, Hall Young received Nobel Prize Physiology or Medicine for elucidating molecular mechanism clock. addition, incidence symptoms many diseases vary time day. Shift work other environmental factors disrupting are associated common diseases. Vice versa, various maladies perturb rhythms, such as sleep–wake cycle. Chronobiology allows us to study relationships mechanistically, example genetic models. The evidence now overwhelming: An intact, well-synchronized crucial health. Modern shift work, travel across zones, irregular diet, pollution social jetlag on rise 24/7 society increase risk disease misaligning Moreover, pathologies, rhythms disturbed, thus a disrupted may also be symptom disease. Because multiple feedbacks, disruption linked kind self-enforcing vicious cycle.3 Fortunately, these correlations gradually being recognized, new discipline “circadian medicine” established aims use translate this knowledge benefit patients. increasingly promoted high-profile medical journals4-6 standard books7 centres clinics emerging around world. There already first great successes, example, chronotherapy cancer8 rheumatoid arthritis9 or—just recently—in development novel diagnostic tools.10, 11 comprises three fundamental aspects, we called triad medicine: detecting clock, targeting exploiting clock.12 (i) Detecting means part precision through tools allow personalized interventions tailored status For objective biomarker tests been recently proposed require blood tissue samples only single few points, diagnosing larger cohorts.11, 13 increasing wearables telemedicine will enable live readout future, becoming very important preventive medicine. (ii) Targeting improvement re-synchronization Such can look different, therapy, dark hormone melatonin, time-restricted eating (TRE) zeitgeber, especially clocks peripheral organs exercise. Also, initial studies underway directly target using drugs. Underlying all approaches hypothesis strengthening realigning reduces accelerates recovery (iii) Exploiting usage about time-of-day adapted treatment regimens procedures. drugs, those short half-lives body, exhibit dependent difference their effects side effects, still largely ignored clinical practice. 75% pharmacological administration was explicitly evaluated outcome, variation drug efficacy toxicity demonstrated.4 reviews presented special issue address aspects They do so perspective different patterns, because there likely overarching principles reciprocal relationship between system disorders disease, uncovering requires broad transdisciplinary research. This attempts fact includes review articles conditions well options approaches. Our current impact pathologies vice versa addressed, ways strategies treating them presented. Finally, one addresses challenge data integration analysis questions projects, intersecting theme field whole.14 Despite deliberately chosen breadth subject matter, main areas focused on: immunology, energy metabolism neuropsychiatry. immunology goes back over 50 years, when reported circulating lymphocyte counts oscillate healthy humans manner endotoxin susceptibility mice depends exposure time. Since then, hundreds experimental epidemiological rodents shown regulates immunity at almost levels (e.g., migration myeloid lymphoid cells, cytokine secretion, differentiation maturation leukocyte subsets) regulation (for comprehensive reviews, see Refs. [15-17]). leads abnormal Th17 resulting higher autoimmune encephalomyelitis (EAE), mouse model MS.18 It note sleep per se increases organism's resistance infection deprivation impairs immune functions.19 Therefore, often not easy determine whether compromised direct result dysregulation indirectly caused insufficient sleep. 2019, National Institutes Health (NIH) recognized developments hosted interdisciplinary workshop titled “Sleep Insufficiency, Misalignment, Immune Response” discuss state recent findings field, thereby stimulating translational approaches.20 issue, interplay potential discussed context inflammatory arthritis sclerosis21 lung inflammation22 Alzheimer's disease.23 interaction metabolic functions complex intensively studied levels.24 became clear early systemic control mediated sophisticated central metabolically relevant tissues (liver, adipose tissue, muscle, pancreas, adrenal, etc.). With discovery nutrients metabolites, turn, act powerful zeitgebers clocks, malnutrition food intake wrong times disruptions system, idea born TRE could used approach restore normal (especially tissues). Indeed, shows significant parameters mice, but humans, occurs strict attention paid reduce caloric intake. timed nutritional cues improve health covered several articles, non-alcoholic fatty liver disease,25 sclerosis,21 obesity26 intensive care unit patients.22 exercise zeitgeber its effect myokine microRNA release type diabetes patients discussed.27 master mammals located suprachiasmatic nuclei anterior hypothalamus entrained via retinal innervations. Before oscillators, chronobiology usually neurobiology departments. Many neurodegenerative processes,28, 29 Parkinson's Huntington's psychiatric major depressive disorder, bipolar schizophrenia30, 31) brain failure neurocognitive disturbances delirium32) characterized substantial changes including rhythm frequently precede cognitive decline, they postulated predictors On hand, neural circuits regulate vulnerable neurodegeneration damage, consequence Thus, rhythm, neurological bidirectional. Uncovering fundamentals provide opportunities identify targets prevention debilitating focus neuropsychiatric disease,33 disease,23 delirium,22 psychosis,34 addiction.35 summary, series demonstrate ubiquity influence contributing identification link pathology organ prerequisite developing testing evidence-based application—concepts successes here. vision future integrate firmly into guidelines that, patient, aspect always taken account and, if necessary, included plan. has facets sustain development, need advanced. author consultant Stanford University shareholder BodyClock GmbH.

Язык: Английский

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REM Behavior Disorder: Implications for PD Therapeutics

Current Neurology and Neuroscience Reports, Год журнала: 2023, Номер 23(11), С. 727 - 734

Опубликована: Окт. 13, 2023

Язык: Английский

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