ReviewAlzheimer's & dementia : the journal of the Alzheimer's Association2026
Wake-promoting neuromodulators in Alzheimer's disease: Implications for sleep and brain clearance.
Review in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Sleep Disturbance Correlates with Cognitive Impairment Partly via Plasma p-Tau217: ADNI Cross-Sectional Evidence and P301L Mouse Mechanistic Observations.International journal of molecular sciences · 2026Article
- Subcortical correlates of sleep in aging and Alzheimer's disease: anBrain communications · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Neuromodulatory subcortical systems (NSS) regulate arousal, cognition, and sleep-wake transitions through widespread influence on cortical and subcortical networks. Increasing evidence links dysfunction of these systems to the pathogenesis of Alzheimer's disease (AD). Degeneration and dysregulation of NSS occurs during the preclinical phase of AD, preceding the onset of cognitive decline. Alterations of NSS are implicated in sleep disruption and impair sleep-dependent cerebrospinal fluid (CSF) clearance via the glymphatic system, a process involved in removing amyloid beta and other neurotoxic proteins. This review synthesizes current evidence linking wake-promoting neuromodulators-norepinephrine, histamine, and orexin-to AD pathology, with an emphasis on their convergent effects on sleep regulation and brain fluid dynamics. We propose that NSS dysfunction may drive a self-reinforcing cycle of disrupted sleep, impaired glymphatic clearance, and neurodegeneration, underscoring the need to better understand this relationship to inform pharmacological interventions slowing or preventing AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.