How aging concomitantly modulates the structural integrity of the brain and retina in healthy individuals remains an outstanding question. Given the strong bottom-up retinocortical connectivity, it is important to study how these structures co-evolve during healthy aging in order to unravel mechanisms that may affect the physiological integrity of both structures. For the 56 participants in the study, primary visual cortex (BA17), as well as frontal, parietal and temporal regions thicknesses were measured in T1-weighted magnetic resonance imaging (MRI), and retinal macular thickness (10 neuroretinal layers) was measured by optical coherence tomography (OCT) imaging. We investigated the statistical association of these measures and their age dependence. We found an age-related decay of primary visual cortical thickness that was significantly correlated with a decrease in global and multiple layer retinal thicknesses. The atrophy of both structures might jointly account for the decline of various visual capacities that accompany the aging process. Furthermore, associations with other cortical regions suggest that retinal status may index cortical integrity in general.

Background: It has been proposed that amyloid-β (Aβ) plays a causal role in Alzheimer’s disease (AD) by triggering a series of pathologic events—possibly including neuroinflammation—which culminate in progressive brain atrophy. However, the interplay between the two pathological molecular events and how both are associated with neurodegeneration is still unclear. Objective: We aimed to estimate the spatial inter-relationship between neurodegeneration, neuroinflammation and Aβ deposition in a cohort of in 20 mild AD patients and 17 healthy controls. Methods: We resorted to magnetic resonance imaging to measure cortical atrophy, using the radiotracer 11C-PK11195 PET to measure neuroinflammation levels and 11C-PiB PET to assess Aβ levels. Between-group comparisons were computed to explore AD-related changes in the three types of markers. To examine the effects of each one of the molecular pathologic mechanisms on neurodegeneration we computed: 1) ANCOVAs with the anatomic data, controlling for radiotracer uptake differences between groups and 2) voxel-based multiple regression analysis between-modalities. In addition, associations in anatomically defined regions of interests were also investigated. Results: We found significant differences between AD and controls in the levels of atrophy, neuroinflammation, and Aβ deposition. Associations between Aβ aggregation and brain atrophy were detected in AD in a widely distributed pattern, whereas associations between microglia activation and structural measures of neurodegeneration were restricted to few anatomically regions. Conclusion: In summary, Aβ deposition, as opposed to neuroinflammation, was more associated with cortical atrophy, suggesting a prominent role of Aβ in neurodegeneration at a mild stage of the AD.

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The retina may serve as putative window into neuropathology of synaptic loss in Alzheimer’s disease (AD). Here, we investigated synapse-rich layers versus layers composed by nuclei/cell bodies in an early stage of AD. In addition, we examined the associations between retinal changes and molecular and structural markers of cortical damage. We recruited 20 AD patients and 17 healthy controls (HC). Combining optical coherence tomography (OCT), magnetic resonance (MR), and positron emission tomography (PET) imaging, we measured retinal and primary visual cortex (V1) thicknesses, along with V1 amyloid β (Aβ) retention ([11C]-PiB PET tracer) and neuroinflammation ([11C]-PK11195 PET tracer). We found that V1 showed increased amyloid-binding potential, in the absence of neuroinflammation. Although thickness changes were still absent, we identified a positive association between the synapse-rich inner plexiform layer (IPL) and V1 in AD. This retinocortical interplay might reflect changes in synaptic function resulting from Aβ deposition, contributing to early visual loss.