A Hypnic Hypothesis of Alzheimer's Disease

  title={A Hypnic Hypothesis of Alzheimer's Disease},
  author={Camilla N. Clark and Jason D. Warren},
  journal={Neuro-Degenerative Diseases},
  pages={165 - 176}
  • C. Clark, J. Warren
  • Published 26 April 2013
  • Biology, Psychology
  • Neuro-Degenerative Diseases
Background: Understanding the pathophysiology of Alzheimer's disease (AD) is of fundamental importance for improved diagnosis, monitoring and ultimately, treatment. Objective: A role for the sleep-wake cycle in the pathogenesis of AD has been proposed, but remains to be worked out in detail. Methods: Here we draw together several lines of previous work to outline a ‘hypnic hypothesis' of AD. Results: We propose that altered function of brainstem neurotransmitter pathways associated with sleep… 
The sleep-wake cycle and Alzheimer's disease: what do we know?
Possible mechanisms underlying the reciprocal relationship between the sleep-wake cycle and AD pathology and behavior are discussed, and current approaches to therapy for sleep disorders in AD are presented.
The Reciprocal Interaction Between Sleep and Alzheimer's Disease.
Research is highlighted describing a potentially reciprocal interaction between impaired sleep and circadian patterns and the accumulation of pathological signs and features in Alzheimer's disease, the most prevalent neurodegenerative disease in the elderly.
Sleep pattern: preventing factors for alzheimer disease.
It is found that improving of sleep quality can reduce the disease progression and delay its symptoms by having effects in neuropathology.
Sleep is related to neuron numbers in the ventrolateral preoptic/intermediate nucleus in older adults with and without Alzheimer's disease.
It is demonstrated that a paucity of galanin-immunoreactive intermediate nucleus neurons is accompanied by sleep fragmentation in older adults with and without Alzheimer's disease.
Does sleep disturbance affect the amyloid clearance mechanisms in Alzheimer's disease?
Evaluating the current evidence on the role of sleep deprivation in Aβ clearance metabolism discusses possible mechanisms underlying the bidirectional interaction between the sleep deprivation and A β clearance pathways.
Aberrant brain stem morphometry associated with sleep disturbance in drug-naïve subjects with Alzheimer’s disease
This study is the first to analyze an association between sleep disturbances and brain stem morphology in AD and lends support to the possibility that brain stem structural abnormalities might be important neurobiological mechanisms underlying sleep disturbances associated with AD.
Review Article Omental transplantation for neurodegenerative diseases
NDDs, are wrongly classified as neurodegenerative disorders because they are of ischemic origin caused by cerebral atherosclerosis, associated with vascular anomalies and/or envi- ronmental chemicals.
The Role of Sleep in Cognitive Function: The Value of a Good Night's Rest.
The literature of sleep, aging, cognition, and the impact of two common clinical conditions (obstructive sleep apnea and insomnia) on cognitive impairment is reviewed to integrate the separate mechanisms towards more generalized common pathways.


Dysfunctional Nucleus Tractus Solitarius: Its Crucial Role in Promoting Neuropathogentic Cascade of Alzheimer’s Dementia—A Novel Hypothesis
A novel nucleus tractus solitarius (NTS) vector hypothesis is presented that underpins several disparate biological mechanisms and neural circuits, and identifies relevant hallmarks of major presumptive causative factor(s) linked to the NTS, in older/aging individuals.
Disruption of the Sleep-Wake Cycle and Diurnal Fluctuation of β-Amyloid in Mice with Alzheimer’s Disease Pathology
It is suggested that changes in the sleep-wake cycle may be caused by Aβ accumulation, andSleep-wake behavior and diurnal fluctuation of Aβ in the central nervous system may be functional and biochemical indicators, respectively, of A β-associated pathology.
Voluntary Exercise Decreases Amyloid Load in a Transgenic Model of Alzheimer's Disease
It is demonstrated that exercise is a simple behavioral intervention sufficient to inhibit the normal progression of AD-like neuropathology in the TgCRND8 mouse model.
Parkinson's disease and Alzheimer's disease as disorders of the isodendritic core.
Animal studies should be able to show whether such treatment can delay secondary cell loss, and, together with human postmortem studies, whether the hypothesis that the primary lesion is a loss of isodendritic cells is correct.
Amyloid-β Dynamics Are Regulated by Orexin and the Sleep-Wake Cycle
It is found that brain interstitial fluid levels of Aβ were significantly correlated with wakefulness and negatively correlated with sleep, and chronic sleep restriction significantly increased, and a dual orexin receptor antagonist decreased, Aβ plaque formation in amyloid precursor protein transgenic mice.
Role of melatonin in Alzheimer-like neurodegeneration
The capacity of melatonin to prevent or ameliorate tau and Aβ pathology further enhances its potential in the prevention or treatment of AD.
Sleep/wake patterns In Alzheimer's disease: relationships with cognition and function
The results indicate that with advancing severity of the disease, sleep/wake patterns are disrupted in parallel with the disturbances in cognition and function that are the hallmarks of AD, and suggest that the neural substrates underlying each process degenerate at somewhat comparable rates.
Treatment of sleep disturbance in Alzheimer's disease.
It is suggested that sleep problems in AD are multi-factorial, and influenced by a variety of demographic, physical, psychiatric and situational factors that vary in how readily they can be modified and in how relevant they are to any individual case.
Activity Dependent Degeneration Explains Hub Vulnerability in Alzheimer's Disease
The assumption of excessive neuronal activity leading to degeneration provides a possible explanation for hub vulnerability in Alzheimer's disease, supported by the observed relation between connectivity and activity and the reproduction of several neurophysiologic hallmarks.