0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Editorial |

Possible Role of Orexin in the Pathogenesis of Alzheimer Disease

Luigi Ferini-Strambi, MD, PhD1
[+] Author Affiliations
1Sleep Disorders Center, Division of Neuroscience, Ospedale San Raffaele, Università Vita-Salute, Milan, Italy
JAMA Neurol. 2014;71(12):1478-1480. doi:10.1001/jamaneurol.2014.2819.
Text Size: A A A
Published online

Extract

Alzheimer disease (AD) is a current and growing public health problem that really has minimally effective therapies. Even a modest reduction in the risk of AD would have a tremendous public health impact. Interestingly, sleep disturbances are multifaceted and represent an early component of AD. The severity of sleep disruption appears to parallel the severity of dementia.1

Moreover, phase delay and increased nocturnal activity seem to differentiate patients with AD from patients with other types of dementia.2 The numerous studies that have shown an altered circadian rest-activity in AD seem to indicate that sleep regulation may be related to the neurobiology of AD. It is known that accumulation of intracellular neurofibrillary tangles of tau proteins and extracellular β-amyloid (Aβ) plaques (strictly associated with brain interstitial fluid levels of Aβ) plays a central role in the pathogenesis of AD.3 Some authors using in vivo microdialysis in mice showed a correlation between interstitial Aβ amount and wakefulness (sleep deprivation) or orexin infusion.4 Orexin is a neurotransmitter that plays a fundamental role in the regulation of the sleep-wake cycle by increasing arousal levels and maintaining wakefulness. In the same study, the infusion of a dual orexin receptor antagonist was associated with a decrease of interstitial fluid Aβ amount. These findings suggest that chronic sleep deprivation (and high level of orexin) can play a role in the pathogenesis of AD. However, patients with narcolepsy-cataplexy (in whom orexin is lacking) are not protected against AD.5

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview

Figures

Tables

References

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

1,448 Views
1 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Articles Related By Topic
Related Collections
PubMed Articles
Jobs
JAMAevidence.com

Care at the Close of Life: Evidence and Experience
Alzheimer Disease: "It's OK, Mama, If You Want to Go, It's OK"

The Rational Clinical Examination: Evidence-Based Clinical Diagnosis
Supplemental Content

brightcove.createExperiences();