Exploring Multimodal Ocular Imaging for Retinal Biomarkers of Alzheimer’s Disease, Frontotemporal Dementia, and Cognitively Normal Subjects

Background and ObjectivesAlzheimer’s disease (AD) and frontotemporal dementia (FTD) are difficult to reliably differentiate clinically. While their distinct pathologies may be captured by existing diagnostic modalities, these are expensive, time-consuming, and often inaccessible. Dementias are associated with visual dysfunctions, perhaps due to changes in the retina, a developmental outgrowth of the central nervous system. We explore the role of multimodal ocular imaging in the diagnosis of two dementias, AD and FTD.MethodsWe recruited 5 AD participants, 2 FTD participants, and 9 age-matched controls. Each participant underwent comprehensive ophthalmologic examination and imaging (optical coherence tomography (OCT), OCT-angiography (OCTA), wide-field fundus photography, near-infrared imaging, and fundus autofluorescence). Ocular findings were correlated with cerebral amyloid burden, as measured by [11C]PiB PET.ResultsOCT analysis identified a trend toward differences in retinal nerve fiber layer (RNFL) thicknesses among dementia subtypes (p = 0.064). AD eyes had increased RNFL thicknesses compared to FTD (p = 0.046) and control eyes (p = 0.046), and AD RNFL thickness was positively associated with amyloid burden (p = 0.037). OCTA fractal analysis revealed decreased vascular complexity within the retinal superficial vascular complex in AD compared to FTD eyes (p = 0.035). Lastly, fundus autofluorescence demonstrated increased signal intensity in AD eyes compared to control eyes (p = 0.046). However, these findings were not statistically significant following correction for multiple comparisons.DiscussionDespite identifying trends toward differences in retinal layer thicknesses unique to individuals with AD and FTD, our study suggests that changes in retinal thicknesses alone may not serve as reliable biomarkers for distinguishing between dementia subtypes. However, multiple ocular imaging modalities may be considered in conjunction with clinical presentation to aid in diagnosing and monitoring AD and FTD.Trial registrationThe study was prospectively registered on clinicaltrials.gov (NCT03699644) on October 9, 2018.