Outer Retina Thinning Distinguishes Frontotemporal Degeneration from Alzheimer’s Disease

Abstract

Purpose : Alzheimer’s disease (AD) is difficult to clinically distinguish from frontotemporal degeneration (FTD), an age-related dementia with distinct brain pathology. Up to 30% of clinically diagnosed FTD cases have a neuropathological diagnosis of AD. We previously found outer retina thinning in FTD patients compared to normal controls and hypothesized that outer retina thinning may distinguish FTD from AD.

Methods : Thirty-three FTD patients and 15 AD patients of similar age were consecutively enrolled from the UPenn FTD Center. All patients were diagnosed by neurologists using standard clinical criteria. Patients had a validated cerebrospinal fluid biomarker for AD (total tau:amyloid β 1-42) to confirm each diagnosis. Retinal structure was imaged with a standard spectral-domain optical coherence tomography (SD-OCT) (Spectralis, Heidelberg Engineering, Carlsbad, CA) protocol and layers segmented by a masked analyst with the Iowa Reference Algorithm (v3.6) for the ETDRS (Early Treatment Diabetic Retinopathy Study) grid. Retinal layer thicknesses were compared between eyes of FTD and AD patients using a generalized linear model that accounted for inter-eye correlation and adjusted for age, sex, and race. The false discovery rate was used to correct for multiple comparisons.

Results : After excluding eyes with poor image quality, glaucoma or optic nerve disease, high refractive error, or macular disease, 46 eyes from 27 FTD patients (mean age 66 years) and 20 eyes from 10 AD patients (mean age 61 years) were included. FTD patients compared to AD patients had a thinner outer retina (mean 130 vs. 142 μm, p=0.03), a thinner outer nuclear layer (90 vs. 100 μm, p=0.006), but a thicker outer plexiform layer (31 vs. 26 μm, p=0.03) (Table 1). The retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) were similar between FTD and AD (p>0.05, Table 1).

Conclusions : Outer retina thinning, detected by SD-OCT, may distinguish FTD from AD. The thicker outer plexiform layer in FTD patients may be from bipolar and horizontal cell dendrite sprouting as the outer nuclear layer thins. A difference in RNFL and GCL thicknesses was not seen between these two patient groups. Specific dementia brain pathologies may be associated with specific retinal abnormalities.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

 

*From the generalized estimating equations that account for inter-eye correlation; adjusted for age, sex, and race.