Melanopsin retinal ganglion cells and circadian dysfunction in Alzheimer's disease

    loading  Checking for direct PDF access through Ovid

Abstract

Purpose

To evaluate optic nerve and in particular melanopsin retinal ganglion cells (mRGCs) in relation to rest-activity rhythm in Alzheimer disease (AD).

Methods

Retinal nerve fiber layer (RNFL) thickness measurements by optical coherence tomography were performed in 21 AD and 74 age-matched controls. Actigraphic monitoring was performed in 16 AD patients and 10 age-matched controls. Non-parametric methods were applied to assess interdaily stability (IS), intradaily variability (IV) and relative amplitude (RA) of rest-activity rhythm. We also performed immunohistochemical analysis of mRGCs and axonal count on optic nerve cross-sections in 14 neuropathologically confirmed AD and 13 control post-mortem retinas.

Results

OCT evaluation showed reduced average (p=0.03) and superior (p=0.005) RNFL thickness in AD patients. Actigraphic monitoring demonstrated an increased IV (p=0.04) and reduced RA (p=0.04) in AD. Furthermore, AD patients were significantly less active during the day (p=0.03). Considering the patients with at least one circadian parameter outside the 2SD from the mean of controls, we found a significant correlation between IV, average (p=0.035), superior (p=0.045) and inferior (p=0.017) RNFL thickness. Melanopsin RGCs density was significantly reduced, independently from age, in AD retinas (p=0.003) and AD optic nerves showed variable degree of age-related axonal loss.

Conclusion

We demonstrated a subclinical optic nerve involvement in AD patients, both by OCT and histopathology. We also documented rest-activity circadian dysfunction in AD patients. Post-mortem investigation revealed loss of mRGCs and RGCs with a different pattern in AD. The reduction of mRGCs may contribute to circadian rhythm dysfunction in AD.

Related Topics

    loading  Loading Related Articles