Accelerated Brain Atrophy, Microstructural Decline and Connectopathy in Age-Related Macular Degeneration

Stout, Jacques A.; Mahzarnia, Ali; Dai, Rui; Anderson, Robert J.; Cousins, Scott; Zhuang, Jie; Lad, Eleonora M.; Whitaker, Diane B.; Madden, David J.; Potter, Guy G.; Whitson, Heather E.; Badea, Alexandra

doi:10.3390/biomedicines12010147

Cited by 4 publications

References 112 publications

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Correlations between plasma markers and brain Aβ deposition across the AD continuum: Evidence from SILCODE

Yu,

Shi,

Zhou

et al. 2024

Alzheimer's & Dementia

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BACKGROUNDPrevious studies have found that Alzheimer's disease (AD)‐related plasma markers are associated with amyloid beta (Aβ) deposition, but the change of this association in different Aβ pathological stages remains unclear.METHODSData were obtained from the SILCODE. According to the standardized uptake value ratio (SUVR) and Aβ stage classification, correlation analysis was performed among plasma biomarkers, and voxel/SUVR values in the regions of interest (ROI) and clinical scale information, respectively. Mediation analysis was used to study the possible pathways.RESULTSThe proportion of cognitively normal (CN) and subjective cognitive decline (SCD) was the highest in stages A0 to 1, while in stages A2 to 4, the proportion of mild cognitive impairment (MCI) and AD increased. Plasma phosphorylated tau (p‐tau)181 and glial fibrillary acidic protein (GFAP) levels were significantly lower in stage A0 compared to the later phases. Two pathways demonstrated fully mediated effects: positron emission tomography (PET) SUVR–plasma p‐tau181–Mini‐Mental State Examination (MMSE) and PET SUVR–plasma GFAP–MMSE.DISCUSSIONThis study demonstrated the role of plasma biomarkers in the early stage of AD, especially in SCD, from both the clinical diagnosis and Aβ stage dimensions.Highlights Plasma ptau181 and GFAP level serve as indicators of early Alzheimer's disease and the pathologic Aβ staging classification. A possible ceiling effect of GFAP was observed in the mid‐to‐late stages of the AD course. This study confirms the role of AD plasma markers in promoting Aβ deposition at an early stage, particularly in females with subjective cognitive decline(SCD). The overlapping brain regions of plasma p‐tau181, GFAP, and neurofilament light for Aβ deposition in the brain in early AD were distributed across various regions, including the posterior cingulate gyrus, rectus gyrus, and inferior temporal gyrus.

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Correlations between plasma markers and brain Aβ deposition across the AD continuum: Evidence from SILCODE

Yu,

Shi,

Zhou

et al. 2024

Alzheimer's & Dementia

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Mapping the impact of age and APOE risk factors for late onset Alzheimer’s disease on long range brain connections through multiscale bundle analysis

Stout,

Anderson,

Mahzarnia

et al. 2024

Preprint

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Alzheimer’s disease currently has no cure and is usually detected too late for interventions to be effective. In this study we have focused on cognitively normal subjects to study the impact of risk factors on their long-range brain connections. To detect vulnerable connections, we devised a multiscale, hierarchical method for spatial clustering of the whole brain tractogram and examined the impact of age and APOE allelic variation on cognitive abilities and bundle properties including texture e.g., mean fractional anisotropy, variability, and geometric properties including streamline length, volume, and shape, as well as asymmetry. We found that the third level subdivision in the bundle hierarchy provided the most sensitive ability to detect age and genotype differences associated with risk factors. Our results indicate that frontal bundles were a major age predictor, while the occipital cortex and cerebellar connections were important risk predictors that were heavily genotype dependent, and showed accelerated decline in fractional anisotropy, shape similarity, and increased asymmetry. Cognitive metrics related to olfactory memory were mapped to bundles, providing possible early markers of neurodegeneration. In addition, physiological metrics such as diastolic blood pressure were associated with changes in white matter tracts. Our novel method for a data driven analysis of sensitive changes in tractography may differentiate populations at risk for AD and isolate specific vulnerable networks.

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Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration

Owsley,

McGwin,

Swain

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Purpose Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer–inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium–Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores ( P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.

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Accelerated Brain Atrophy, Microstructural Decline and Connectopathy in Age-Related Macular Degeneration

Cited by 4 publications

References 112 publications

Correlations between plasma markers and brain Aβ deposition across the AD continuum: Evidence from SILCODE

Correlations between plasma markers and brain Aβ deposition across the AD continuum: Evidence from SILCODE

Mapping the impact of age and APOE risk factors for late onset Alzheimer’s disease on long range brain connections through multiscale bundle analysis

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration

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