Evaluation of macular thickness and volume tested by optical coherence tomography as biomarkers for Alzheimer's disease in a memory clinic

Abstract

Building on previous studies that report thinning of the macula in Alzheimer's disease (AD) and mild cognitive impairment (MCI) patients, the use of optical coherence tomography (OCT) has been proposed as a potential biomarker for AD. However, other studies contradict these results. A total of 930 participants (414 cognitively healthy people, 192 with probable amnestic MCI, and 324 probable AD patients) from a memory clinic were consecutively included in this study and underwent a spectral domain OCT scan (Maestro, Topcon) to assess total macular volume and thickness. Macular width measurements were also taken in several subregions (central, inner, and outer rings) and in layers such as the retinal nerve fiber (RNFL) and ganglion cell (CGL). The study employed a design of high ecological validity, with adjustment by age, education, sex, and OCT image quality. AD, MCI, and control groups did not significantly vary with regard to volume and retinal thickness in different layers. When these groups were compared, multivariate-adjusted analysis disclosed no significant differences in total (p = 0.564), CGL (p = 0.267), RNFL (p = 0.574), and macular thickness and volume (p = 0.380). The only macular regions showing significant differences were the superior (p = 0.040) and nasal (p = 0.040) sectors of the inner macular ring. However, adjustment for multiple comparisons nullified this significance. These results are not supporting existing claims for the usefulness of macular thickness as a biomarker of cognitive impairment in a memory unit. OCT biomarkers for AD should be subject to further longitudinal testing. ; The authors thank the study participants and their families for their collaboration, and Topcon for its reliability as technological partnership. This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement N° 796706 awarded to MM; from Fundació ACE Institut Català de Neurociències Aplicades in Barcelona, Spain and from a donation of "La nit de l'Alzheimer", a charity dinner initiative that took place on August 8th 2016 as part of the "Festival Castell de Peralada". The neuro-ophthalmology exam devices were acquired with a grant EFSD/Lilly Mental Health and Diabetes 2013 Programme of the European Foundation for the Study of Diabetes (EFSD) awarded to the project "Retinal neurodegeneration in type 2 diabetes as biomarker of Alzheimer's disease" under the leadership of CH. The present work was performed as part of Domingo Sánchez Ruiz' doctoral program with title "Clinical Utility of OCT in diagnosing and monitoring of cognitive impairment" in the Department of Surgery and Morphological Sciences at Universitat Autonoma Barcelona (Barcelona, Spain).