Associations of sleep disorders with all-cause MCI/dementia and different types of dementia – clinical evidence, potential pathomechanisms and treatment options: A narrative review

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: March 22, 2024

Due to worldwide demographic change, the number of older persons in population is increasing. Aging accompanied by changes sleep structure, deposition beta-amyloid (Aß) and tau proteins vascular can turn into mild cognitive impairment (MCI) as well dementia. Sleep disorders are discussed both a risk factor for consequence MCI/dementia. Cross-sectional longitudinal population-based case–control studies revealed disorders, especially sleep-disorderded breathing (SDB) excessive or insufficient durations, factors all-cause Regarding different dementia types, SDB was associated with while insomnia/insufficient related an increased Alzheimer’s disease (AD). Scarce still inconsistent evidence suggests that therapy continuous positive airway pressure (CPAP) SDB, improve cognition patients without comorbid delay onset MCI/dementia previous impairment. potential pathomechanisms via which lead MCI/dementia, disturbed sleep, chronic deficit impair glymphatic clearance amyloid aggregation resulting brain structures responsible cognition. Orexins modulate Aß pathology. Their diurnal fluctuation suppressed fragmentation expression at point hippocampal atrophy, contributing progression Additionally, profile such inflammation, endothelial dysfunction atherosclerosis foster neurodegenerative There ample indicating structure aging also disorder Therefore, should be identified treated early.

Language: Английский

---

Breaking Ground: From CPAP Treatment to the First Medicine for OSA Patients with Obesity

Current Pulmonology Reports, Journal Year: 2025, Volume and Issue: 14(1)

Published: Jan. 11, 2025

Abstract Purpose of Review Pharmacologic alternatives in management obstructive sleep apnea (OSA) have been pursued for decades. Considering rapid development and promising findings recent years, we provide an overview novel agents treatment targets, ongoing trials, as well future perspectives. Recent Findings Several drugs demonstrate efficacy, though none is sufficient to cure the disease a monotherapy. Instead, main potential lies applying drug therapy specific subgroups or addition established treatments (e.g., positive airway pressure, oral appliance therapy). Glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists may be particularly beneficial obese OSA patients. As major breakthrough, terzipatide, GIP analog GLP-1 agonist, has become first FDA-approved EMA-sanctioned pharmacologic option individuals. Beyond this, alerting could help manage residual daytime sleepiness improve functioning. However, long-term studies on safety, adherence, effectiveness are scarce highlight certain limitations challenges. Summary Incorporating pharmaceuticals along conventional synergy benefit patients, but side-effects risk reduction related adverse outcomes over time yet assessed. Furthermore, guidelines/frameworks mapping out applicable targets needed.

Language: Английский

---

Pharmacological targeting of BMAL1 modulates circadian and immune pathways

Nature Chemical Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 25, 2025

Language: Английский

---

Factors Affecting Resilience and Prevention of Alzheimer's Disease and Related Dementias

Annals of Neurology, Journal Year: 2024, Volume and Issue: 96(4), P. 633 - 649

Published: Aug. 17, 2024

Alzheimer's disease (AD) is a devastating, age‐associated neurodegenerative disorder and the most common cause of dementia. The clinical continuum AD spans from preclinical to subjective cognitive decline, mild impairment, dementia stages (mild, moderate, severe). Neuropathologically, defined by accumulation amyloid β (Aβ) into extracellular plaques in brain parenchyma cerebral vasculature, abnormally phosphorylated tau that accumulates intraneuronally forming neurofibrillary tangles (NFTs). Development treatment approaches prevent or even reduce decline because has been slow compared other major causes death. Recently, United States Food Drug Administration gave full approval 2 different Aβ‐targeting monoclonal antibodies. However, this breakthrough modifying approach only applies limited subset patients there are stringent eligibility criteria. Furthermore, these do not progression disease, AD‐related pathologies, such as NFTs, directly targeted. A non‐mutually exclusive alternative address lifestyle interventions can help risk dementias (ADRD). It estimated addressing modifiable factors could potentially delay up 40% AD/ADRD cases. In review, we discuss some many may be associated with prevention and/or increasing resilience, well interact influence progression. [Color figure viewed at www.annalsofneurology.org ] ANN NEUROL 2024;96:633–649

Language: Английский

---

Stroke in the Time of Circadian Medicine

Circulation Research, Journal Year: 2024, Volume and Issue: 134(6), P. 770 - 790

Published: March 14, 2024

Time-of-day significantly influences the severity and incidence of stroke. Evidence has emerged not only for circadian governance over stroke risk factors, but also important determinants clinical outcome. In this review, we provide a comprehensive overview interplay between chronobiology cerebrovascular disease. We discuss regulation pathophysiological mechanisms underlying onset or tolerance as well in vascular dementia. This includes cell death mechanisms, metabolism, mitochondrial function, inflammation/immunity. Furthermore, present evidence supporting link disrupted rhythms increased susceptibility to propose that biochemical physiological pathways brain increase damage after sleep attenuate treatment effectiveness during active phase. review underscores importance considering biology understanding pathology choice dementia speculates patient's chronotype may be an factor developing precision following

Language: Английский

---

Alzheimer’s disease and sleep disorders: a bidirectional relationship

Neuroscience, Journal Year: 2024, Volume and Issue: 557, P. 12 - 23

Published: Aug. 11, 2024

Alzheimer's disease (AD) is the most prevalent dementia, pathologically featuring abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau, while sleep, divided into rapid eye movement sleep (REM) nonrapid (NREM), plays a key role in consolidating social spatial memory. Emerging evidence has revealed that disorders such as circadian disturbances disruption neuronal rhythm activity are considered both candidate risks consequence AD, suggesting bidirectional relationship between AD. This review will firstly grasp basic knowledge AD pathogenesis, then highlight macrostructural microstructural alteration along with progression, explain interaction Aβ which two critical neuropathological processes well neuroinflammation finally introduce several methods enhancement strategies to reduce AD-associated neuropathology. Although theories about relevant therapeutic mice have been developed recent years, human still limited. More studies on how effectively ameliorate pathology patients by what specific roles play needed.

Language: Английский

---

SLEEP DISORDERS AND RISK OF ALZHEIMER'S DISEASE: A TWO-WAY ROAD

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 102514 - 102514

Published: Sept. 1, 2024

Language: Английский

---

Exploring Potential Mechanisms of Sleep Disorders in Alzheimer’s Dementia: A Scoping Review

Cureus, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 3, 2025

Alzheimer's dementia (AD) is characterized by a progressive decline in behavioral and cognitive functions, with sleep disorders (SDs) increasingly recognized as one of the noncognitive symptoms. Sleep plays critical role brain, supporting learning memory, regulating synaptic plasticity, facilitating waste clearance. However, mechanisms underlying disturbances AD remain poorly understood. This review aims to explore these their potential relevance for clinicians managing AD. A systematic search was conducted across multiple sources databases, using keywords such "Alzheimer AND disorder", along terms related neurodegeneration disturbances. Of 1,511 records identified, 18 were included final analysis. The findings highlight several linking SDs, suggesting bidirectional relationship. These include (i) shared genetic factors; (ii) disruption glymphatic system; (iii) circadian system dysregulation; (iv) neuroinflammation; (v) abnormal functional connectivity between brain regions; (vi) atrophy regions involved memory sleep. In conclusion, relationship SDs complex bidirectional. not only precede onset but also worsen disease progresses. may, therefore, serve promising biomarker AD, targeting offering early therapeutic strategy

Language: Английский

---

Role of metabolic characteristics in the co-occurrence of insomnia, Alzheimer’s disease, and Parkinson’s disease: a Mendelian randomization study

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 6, 2025

There reportedly exists a significant comorbidity between insomnia and neurodegenerative diseases, such as Alzheimer's disease (AD) Parkinson's (PD), indicative of potential link to serum metabolic dysregulation. To elucidate shared pathophysiological mechanisms AD/PD, we performed comprehensive two-sample Mendelian randomization (MR) analyses, investigating 1,400 characteristics for their causal relationships with the risks insomnia, AD, widely defined AD (WDAD), PD. We employed publicly available genetic data; primary estimate was determined using inverse-variance weighting, supplemented by weighted median, simple mode, MR-PRESSO MR-Egger methods evaluate heterogeneity pleiotropy. The ratio N-palmitoyl-sphingosine N-palmitoyl-sphinganine is linked higher (OR = 1.137, 95% CI 1.015-1.273, p 0.026) 1.090, 1.005-1.183, 0.037). acetylcarnitine propionylcarnitine risk factor 1.190, 1.003-1.370, 0.016) but has protective effects against 0.868, 0.784-0.961, 0.006) WDAD 0.892, 0.817-0.973, 0.010). Glutamine conjugate C7H12O2 levels are associated reduced 0.863, 0.749-0.995, 0.042) PD 0.856, 0.746-0.981, 0.026). Our findings highlight crucial role in providing valuable insights into prospective therapeutic targets diagnostic markers.

Language: Английский

---

Statistical Complexity Analysis of Sleep Stages

Entropy, Journal Year: 2025, Volume and Issue: 27(1), P. 76 - 76

Published: Jan. 16, 2025

Studying sleep stages is crucial for understanding architecture, which can help identify various health conditions, including insomnia, apnea, and neurodegenerative diseases, allowing better diagnosis treatment interventions. In this paper, we explore the effectiveness of generalized weighted permutation entropy (GWPE) in distinguishing between different from EEG signals. Using classification algorithms, evaluate feature sets derived both standard (PE) GWPE to determine set performs classifying stages, demonstrating that significantly enhances stage differentiation, particularly identifying transition N1 REM sleep. The results highlight potential as a valuable tool neurophysiology improving disorders.

Language: Английский

---