Visual Contrast Sensitivity as a Novel Biomarker for Neurodegeneration in Early Alzheimer's Disease, Mild Cognitive Impairment, and Older Adults with Cognitive Complaints

Background: Patients with Alzheimer's disease (AD) have been reported to show visual impairments, including deficits in contrast sensitivity assessed using frequency doubling technology (FDT), but it is unclear how early such changes can be detected. The goal of the present study was to assess contrast sensitivity in early and preclinical stages of AD and to determine the relationship to other biomarkers including MRI-based atrophy measurements. Methods: Participants (n = 77) included those with mild AD (n = 9), amnestic mild cognitive impairment (MCI, n = 27), older adults with informant-verified cognitive complaints but no significant psychometric impairment (CC, n = 16), and healthy elderly controls (HC, n = 25) from two academic medical centers. Assessment included detailed neuropsychological and clinical evaluations and 3T structural MRI scans. Visual contrast sensitivity was assessed separately for both eyes using the FDT-2 (Welch Allyn, Syracuse, NY) in 55 visual field regions. Voxel-based morphometry (VBM) was used to extract grey matter density (GMD) maps. Summary statistics detailing alterations in contrast sensitivity (mean deviation, MD; pattern standard deviation, PSD), 110 threshold measures from 55 retinal regions of each eye, and demographic and cognitive performance variables were compared between groups using ANCOVA, covaried for age at exam, gender, and years of education. The relationships between global GMD, MD, and PSD were assessed using SPM5. Results: Significant differences across groups were detected in FDT-2 measures of overall and local contrast sensitivity, including both MD and PSD, and in 36 right eye retinal regions and 48 left eye retinal regions (p < 0.05 to p < .0001, Figure 1). AD and MCI patients demonstrated the greatest reduction in contrast sensitivity relative to HCs, with CC participants showing an intermediate level of impairment. MD and PSD were significantly related to hippocampal GMD in the left and bilateral hippocampi, respectively (p < 0.01 (unc.), Figure 2). Conclusions: Contrast sensitivity, as measured by the FDT-2 system, is reduced in patients with AD and MCI and may represent a novel and complementary biomarker for detecting and monitoring AD-related neurodegeneration. [Copyright Elsevier B.V.]