Nonvascular retinal imaging markers of preclinical Alzheimer's disease

Abstract

IntroductionIn patients with Alzheimer's disease (AD) and mild cognitive impairment, structural changes in the retina (i.e., reduced thicknesses of the ganglion cell and retinal nerve fiber layers and inclusion bodies that appear to contain beta-amyloid protein [Ab]) have been previously reported. We sought to explore whether anatomic retinal changes are detectable in the preclinical stage of AD.MethodsA cross-sectional study (as part of an ongoing longitudinal cohort study) involving 63 cognitively normal adults, all of whom have a parent with AD and subjective memory complaints. We compared neocortical amyloid aggregation (florbetapir PET imaging) to retinal spectral domain optical coherence tomography (SD-OCT) markers of possible disease burden. Retinal biomarkers, including the number and surface area of retinal inclusion bodies and the thickness of retinal neuronal layers, were compared across groups with high vs. low neocortical beta-amyloid load.ResultsThe surface area of inclusion bodies increased as a function of cortical amyloid burden. Additionally, there was a trend toward a selective volume increase in the inner plexiform layer (IPL; a layer rich in cholinergic activity) of the retina in Aβ+ relative to Aβ− participants, and IPL volume was correlated with the surface area of retinal inclusion bodies.DiscussionThese initial results suggest that retinal imaging may be a potential cost-effective and noninvasive technique that can be used to identify those at-risk for AD. Layer-specific changes in the IPL and their association with surface area of inclusion bodies are discussed as a possible reflection of early inflammatory processes associated with cholinergic disruption and concurrent Ab accumulation in the neocortex.

Retinal thickness in Alzheimer's disease: A systematic review and meta‐analysis

“…In contrast, an increase of IPL thickness was reported in a recent study of Snyder et al. in preclinical AD [47]. Future research may use segmentation to identify the alterations of specific retinal layers in AD and its preclinical and prodromal stages.…”

“…Interestingly, they found a decrease in macular thickness while peripapillary thickness was unchanged, suggesting macular before peripapillary degeneration. In contrast, an increase of IPL thickness was reported in a recent study of Snyder et al in preclinical AD [47]. Future research may use segmentation to identify the alterations of specific retinal layers in AD and its preclinical and prodromal stages.…”

Revolution of Alzheimer Precision Neurology. Passageway of Systems Biology and Neurophysiology

“…A significant 2.1-fold increase in retinal amyloid index (RAI), a quantitative measure developed to assess numerical value of amyloid burden in the retina of living patients, was revealed in AD patients versus matched controls (Figure 7L–M) [485]. Recent studies applying non-invasive retinal imaging in live AD patients, which detected NFL thinning [466, 477], increased inclusion bodies [554, 555], reduced blood flow, microvasculature alterations, and oxygen saturation in arterioles and venules [479, 556, 557], and importantly, hallmark Aβ deposits [485], are encouraging first steps towards the development of practical tools for predicting disease risk and progression. Since the retina in other ND such as multiple sclerosis, ischemic stroke, and Parkinson’s disease also exhibits pathophysiological processes similar to those detected in the brain [501, 558–561], retinal imaging may also facilitate differential diagnosis for different proteinopathies, neurodegenerative and neurological diseases.…”

Retinal changes in the Tg-SwDI mouse model of Alzheimer’s disease

“…Due to the tremendous necessity to quickly diagnose AD and the high cost of other diagnostic techniques, such as positron emission tomography (Franzco et al, 2017) and magnetic resonance imaging (Kusne et al, 2016), researchers have begun employing numerous visual tests to detect differences in the eyes of individuals suffering from AD, as compared to healthy controls (Berisha et al, 2007; Moschos et al, 2012; Frost et al, 2013; Coppola et al, 2015; Snyder et al, 2016). All these data combined have yielded very important findings.…”

“…All these data combined have yielded very important findings. AD is linked to thicker retinal inner plexiform layer (IPL) (Snyder et al, 2016), thinner retinal NFL (Danesh-Meyer et al, 2006; Iseri et al, 2006; Paquet et al, 2007; Kesler et al, 2011; Gao et al, 2015; Thomson et al, 2015), a reduced number in ganglion cell axons (Blanks et al, 1996b; Danesh-Meyer et al, 2006), narrowing of retinal veins with decreased blood flow (Berisha et al, 2007), higher number of astrocytes in the NFL (Blanks et al, 1996a, 1996b), Aβ accumulation in GCL, NFL, IPL, outer retina (Alexandrov et al, 2011; Koronyo-Hamaoui et al, 2011) and lens (Goldstein et al, 2003), reduced amplitude and increased implicit times in ganglion cell responses (Katz et al, 1989; Trick et al, 1989; Krasodomska et al, 2010; Moschos et al, 2012), increased levels of inflammatory marker complement factor H in the retina (Alexandrov et al, 2011), and abnormalities in eye fixation, saccadic and pursuit movements (Chang et al, 2014; Shakespeare et al, 2015). …”