Sectoral segmentation of retinal amyloid imaging in subjects with cognitive decline

Abstract

Introduction Despite advances in imaging retinal amyloidosis, a quantitative and topographical investigation of retinal amyloid beta burden in patients with cognitive decline has never been reported. Methods We used the specific amyloid‐binding fluorophore curcumin and laser ophthalmoscopy to assess retinal amyloid imaging (RAI) in 34 patients with cognitive decline. We automatically quantified retinal amyloid count (RAC) and area in the superotemporal retinal sub‐regions and performed correlation analyses with cognitive and brain volumetric parameters. Results RAC significantly and inversely correlated with hippocampal volume (HV; r = ‐0.39, P = .04). The proximal mid‐periphery (PMP) RAC and RA areas were significantly greater in patients with Montreal Cognitive Assessment (MOCA) score < 26 ( P = .01; Cohen d = 0.83 and 0.81, respectively). PMP showed significantly more RAC and area in subjects with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD) compared to cognitively normal ( P = .04; Cohen d = 0.83). Conclusion Quantitative RAI is a feasible technique and PMP RAC may predict HV. Future larger studies should determine RAI's potential as a biomarker of early AD.

Role of Retinal Amyloid-β in Neurodegenerative Diseases: Overlapping Mechanisms and Emerging Clinical Applications

“…The highest amyloid load has usually been observed in the hippocampus [ 4 ]. Due to the developmental, structural, and pathological connections between the retina and the CNS and the accessibility of the neuroretina for non-invasive imaging, recent studies have explored retinal Aβ as a potential biomarker for the assessment of cerebral Aβ and AD progression [ 29 , 30 , 31 , 32 , 33 , 34 ]. Through positron emission tomography (PET) imaging cerebral Aβ accumulation may be detected as early as 20 years before cognitive decline [ 30 , 35 ].…”

“…Post-mortem and in vivo human studies have also shown an association between retinal Aβ deposits and cerebral structural and functional changes [ 29 , 30 ]. In addition to a positive correlation between supertemporal retinal Aβ42 load and cerebral Aβ, worse neuropathy cortical assessment scores like neuritic plaque score and cerebral amyloid angiopathy (CAA) were correlated to increased retinal Aβ load in AD retinal whole mounts [ 30 , 39 ].…”

“…Aβ accumulations positively correlated between ultra-centrifuged homogenates of the hippocampus and the retina [ 54 ]. This relationship may explain why retinal Aβ count in the superotemporal retina subregions was inversely correlated with hippocampal volume for both MCI and AD patients in vivo [ 29 ]. To note, loss of hippocampal volume has been related to a decrease in executive dysfunction and memory impairment [ 55 , 56 ].…”

Color and contrast vision in mouse models of aging and Alzheimer’s disease using a novel visual-stimuli four-arm maze

“…Mounting evidence indicates that Alzheimer’s Disease (AD) affects the neurosensory retina, a CNS tissue and developmental outgrowth of the diencephalon 1 – 8 . The pathology of AD in the retina appears to mirror the disease in the brain 9 – 16 . Specifically, the retina of AD patients exhibits neuronal and pericyte cell loss along with retinal manifestation of AD pathological hallmarks—amyloid β-protein (Aβ) plaques and hyperphosphorylated tau (p-Tau) 9 – 13 , 16 – 27 .…”

“…The pathology of AD in the retina appears to mirror the disease in the brain 9 – 16 . Specifically, the retina of AD patients exhibits neuronal and pericyte cell loss along with retinal manifestation of AD pathological hallmarks—amyloid β-protein (Aβ) plaques and hyperphosphorylated tau (p-Tau) 9 – 13 , 16 – 27 . Similarly, numerous studies examining the retina of sporadic and transgenic animal models of AD have reported the existence of Aβ deposits and tauopathy that are linked with inflammation and neurodegeneration 9 , 14 , 15 , 28 – 41 .…”