Optic nerve involvement in relation to rest-activity circadian rhythm in Alzheimer's disease

Abstract

 

Purpose

 

Optic nerve involvement and circadian rhythm disturbances are reported in Alzheimer's disease (AD). We aimed at characterizing optic nerve involvement with particular reference to rest-activity rhythm dysfunction in AD

 

Methods

 

Ophthalmologic evaluation and retinal nerve fiber layer (RNFL) thickness measurements by optical coherence tomography (Stratus OCT) were performed in 21 AD patients (age (71.24±10.54 ys) and 74 age-matched controls (age 69.1±8.1). Actigraphic monitoring for 7 days was performed in 16 AD patients (age 70.25±10.2) and 10 controls (age 65.8±7.5). Non-parametric methods were applied to assess interdaily stability (IS), intradaily variability (IV) and relative amplitude (RA) of rest-activity rhythm. Sleep minutes and sleep efficiency were also retrieved. Multivariate analysis was performed to investigate the effect of age and gender on RNFL and actigraphic measurements. Age significantly correlated with average RNFL thickness (p=0.013). Thus, for OCT parameters differences between patients and controls were assessed by ANCOVA using age as covariate. Differences in actigraphic parameters were assessed by unpaired t-test (p<0.05). Correlation analysis was performed with Pearson test

 

Results

 

OCT evaluation demonstrated reduced average (p=0.03) and superior (p=0.005) RNFL thickness in AD patients compared to controls. Stratification of AD patients in mild and moderate AD, according to MMSE score, showed a significant reduction of the superior RNFL thickness only in moderate AD patients (p=0.028). Actigraphic monitoring demonstrated a tendency towards an increased IV, a significantly reduced relative amplitude (RA) (p=0.043) and a significant reduction of sleep efficiency (p<0.001) in AD patients compared to controls. AD patients were also less active during the wake period (p=0.031). No significant correlation was detected between OCT measurements and actigraphic data. However, considering only patients with at least one circadian parameter outside 2SD from the mean of controls, we found a significant correlation between IV and average (p=0.035), superior (p=0.045) and inferior (p=0.017) RNFL thickness

 

Conclusions

 

We demonstrated subclinical optic nerve pathology with a glaucoma-like pattern, correlated to abnormal rest-activity circadian rhythm in a subgroup of AD patients. These findings point to a possible role of optic nerve neurodegeneration in circadian dysfunction of AD

 

Keywords: 458 circadian rhythms • 613 neuro-ophthalmology: optic nerve • 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)