Retinal thickness correlates with parietal cortical atrophy in early‐onset Alzheimer's disease and controls

Haan, Jurre den; Janssen, Sarah F.; Kreeke, Jacoba A. van de; Scheltens, Philip; Verbraak, Frank D.; Bouwman, Femke H.

doi:10.1016/j.dadm.2017.10.005

Cited by 81 publications

(63 citation statements)

References 36 publications

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“…Table 1 shows cohort characteristics. We included 50 AD patients and 38 control subjects from our retinal imaging [21] cohort with retinal vasculature imaging available. One AD case was excluded because of glaucoma.…”

Section: Resultsmentioning

confidence: 99%

Is retinal vasculature a biomarker in amyloid proven Alzheimer's disease?

Haan

Kreeke

Berckel

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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Introduction The retina is a potential source of noninvasive vascular biomarkers for Alzheimer's disease (AD). We assessed retinal microvasculature in well-characterized AD cases, taking ophthalmological confounders into account. Methods We included 48 amyloid-positive AD patients and 38 amyloid-negative cognitively normal control subjects. All participants underwent ophthalmological screening to exclude interfering ocular disease. Using a multimodal approach, we measured retinal vascular parameters, choroidal thickness, macular vascular density, and foveal avascular zone size. Results We found no disease effects on retinal vascular measures (all β′s < |0.15|, all P > .2), adjusted for confounders. Venular tortuosity was inversely associated with Fazekas score in control subjects (β −0.56, P < .01), while vessel density in the outer ring of the macula was inversely associated with Fazekas score in AD cases (β −0.64, P < .01). Discussion In conclusion, retinal vasculature did not discriminate patients with AD from control subjects, despite evident changes on clinical, neuroimaging, and cerebrospinal fluid biomarkers, challenging the use of retinal vasculature measurements as AD biomarker.

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Section: Resultsmentioning

confidence: 99%

Is retinal vasculature a biomarker in amyloid proven Alzheimer's disease?

Haan

Kreeke

Berckel

et al. 2019

Alz & Dem Diag Ass & Dis Mo

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“…In fact, recent reports have suggested that retina is an approachable window to neurodegenerative diseases (Yu et al, 2014;Thomson et al, 2015;den Haan et al, 2018) and in healthy brain aging (Liu et al, 2016;Casaletto et al, 2017). Accordingly, we identified that associations between retina and brain exist beyond the visual areas.…”

Section: Discussionmentioning

confidence: 72%

Is the Retina a Mirror of the Aging Brain? Aging of Neural Retina Layers and Primary Visual Cortex Across the Lifespan

Jorge

Canário

Quental

et al. 2020

Front. Aging Neurosci.

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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.

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“…Most current studies investigating the role of the eye in neurodegenerative disease, such as AD, focus on retinal biomarkers imaged by optical coherence tomography (OCT). For example, the retinal nerve fiber layer (RNFL) is thinner, the retinal volume is reduced, and the choroidal thickness is reduced in patients with mild cognitive impairment (MCI) and AD compared to cognitively normal (CN) controls [25][26][27][28][29][30][31][32][33][34][35][36][37][38]. A newer and more sophisticated version of the OCT, the optical coherence tomography angiography (OCTA), has shown significant changes to the superficial and deep capillary vascular plexus of the macula and changes to the foveal avascular zone in those with cognitive dysfunction and AD compared to CN controls [39][40][41][42][43][44][45][46][47][48][49].…”

Section: Discussionmentioning

confidence: 99%

Neurofilament light chain in the vitreous humor of the eye

et al. 2020

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Background Neurofilament light chain (NfL) is a promising biomarker of neurodegeneration in the cerebrospinal fluid and blood. This study investigated the presence of NfL in the vitreous humor and its associations with amyloid beta, tau, inflammatory cytokines and vascular proteins, apolipoprotein E (APOE) genotypes, Mini-Mental State Examination (MMSE) scores, systemic disease, and ophthalmic diseases. Methods This is a single-site, prospective, cross-sectional cohort study. Undiluted vitreous fluid (0.5–1.0 mL) was aspirated during vitrectomy, and whole blood was drawn for APOE genotyping. NfL, amyloid beta (Aβ), total Tau (t-Tau), phosphorylated Tau (p-Tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous were quantitatively measured by immunoassay. The main outcome measures were the detection of NfL levels in the vitreous humor and its associations with the aforementioned proteins. Linear regression was used to test the associations of NfL with other proteins, APOE genotypes, MMSE scores, and ophthalmic and systemic diseases after adjustment for age, sex, education level, and other eye diseases. Results NfL was detected in all 77 vitreous samples. NfL was not found to be associated with ophthalmic conditions, APOE genotypes, MMSE scores, or systemic disease (p > 0.05). NfL levels were positively associated with increased vitreous levels of Aβ40 (p = 7.7 × 10−5), Aβ42 (p = 2.8 × 10−4), and t-tau (p = 5.5 × 10−7), but not with p-tau181 (p = 0.53). NfL also had significant associations with inflammatory cytokines such as interleukin-15 (IL-15, p = 5.3 × 10−4), IL-16 (p = 2.2 × 10−4), monocyte chemoattractant protein-1 (MCP1, p = 4.1 × 10−4), and vascular proteins such as vascular endothelial growth factor receptor-1 (VEGFR1, p = 2.9 × 10−6), Vegf-C (p = 8.6 × 10−6), vascular cell adhesion molecule-1 (VCAM-1, p = 5.0 × 10−4), Tie-2 (p = 6.3 × 10−4), and intracellular adhesion molecular-1 (ICAM-1, p = 1.6 × 10−4). Conclusion NfL is detectable in the vitreous humor of the eye and significantly associated with amyloid beta, t-tau, and select inflammatory and vascular proteins in the vitreous. Additionally, NfL was not associated with patients’ clinical eye condition. Our results serve as a foundation for further investigation of NfL in the ocular fluids to inform us about the potential utility of its presence in the eye.

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Retinal thickness correlates with parietal cortical atrophy in early‐onset Alzheimer's disease and controls

Cited by 81 publications

References 36 publications

Is retinal vasculature a biomarker in amyloid proven Alzheimer's disease?

Is retinal vasculature a biomarker in amyloid proven Alzheimer's disease?

Is the Retina a Mirror of the Aging Brain? Aging of Neural Retina Layers and Primary Visual Cortex Across the Lifespan

Neurofilament light chain in the vitreous humor of the eye

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