Retinal alterations in mild cognitive impairment and Alzheimer’s disease: an optical coherence tomography study

Ascaso, Francisco J.; Cruz, N; Modrego, Pedro J.; López-Antón, Raúl; Santabárbara, Javier; Pascual, Luis Fernando; Lobo, Antonio; Cristobal, Ja

doi:10.1007/s00415-014-7374-z

Cited by 157 publications

(205 citation statements)

References 42 publications

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“…In addition, one study using SD-OCT showed a diffuse reduction of the RNFL and GCL combined in AD [49], although the authors were not able to determinate which layer was most affected by AD. Later studies have demonstrated IPL thinning in AD patients [41,50,52,56,57]. This reduction of ganglion cell complex thickness (GC-IPL and RNFL layers) in AD occurs to a larger extent than that accounted for age-related GC-IPL loss alone (about 0.3 μm/ year) [54].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

“…In addition, invivo studies have shown reduced macular thickness and volume in patients with AD [44,[48][49][50][51][52][53][54].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

“…Retinal changes may be an early event in the course of AD, and retinal OCT may provide insights for assessing neurodegeneration in the brain [50].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

“…believed to reflect axonal loss, whereas macular volume reflects neuronal loss of RGC, since the neuronal bodies and dendrites are located in the ganglion cell/internal plexiform layer (GC-IPL), mostly in the macula lutea [50]. TD-OCT has been the most widely employed ocular imaging technique for assessment of optic nerve degeneration in AD [43][44][45][46][47], as well as for evaluating macular thinning in these patients [44].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

“…Whether or not a correlation exists between retinal changes and severity of dementia also remains a controversial issue. While most OCT studies did not show correlation between Minimal Mental State Examination (MMSE) and peripapillary RNFL thinning (Table 2), one TD-OCT study reported correlation between MMSE scores and macular volume [44], and more recent studies using SD-OCT have indeed reported a significant correlation between MMSE scores and RNFL thickness [50,66,72,76,77]. Studies comparing changes in RNFLT in MCI and AD (Table 2) have also yielded conflicting results, although the majority reported no statistically significant differences between MCI and AD patient groups [46,47,54,77].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

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Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo

Cunha

Moura-Coelho

Proença

et al. 2016

Graefes Arch Clin Exp Ophthalmol

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Alzheimer's disease (AD) is a prevalent, long-term progressive degenerative disorder with great social impact. It is currently thought that, in addition to neurodegeneration, vascular changes also play a role in the pathophysiology of the disease. Visual symptoms are frequent and are an early clinical manifestation; a number of psychophysiologic changes occur in visual function, including visual field defects, abnormal contrast sensitivity, abnormalities in color vision, depth perception deficits, and motion detection abnormalities. These visual changes were initially believed to be solely due to neurodegeneration in the posterior visual pathway. However, evidence from pathology studies in both animal models of AD and humans has demonstrated that neurodegeneration also takes place in the anterior visual pathway, with involvement of the retinal ganglion cells' (RGCs) dendrites, somata, and axons in the optic nerve. These studies additionally showed that patients with AD have changes in retinal and choroidal microvasculature. Pathology findings have been corroborated in in-vivo assessment of the retina and optic nerve head (ONH), as well as the retinal and choroidal vasculature. Optical coherence tomography (OCT) in particular has shown great utility in the assessment of these changes, and it may become a useful tool for early detection and monitoring disease progression in AD. The authors make a review of the current understanding of retinal and choroidal pathological changes in patients with AD, with particular focus on invivo evidence of retinal and choroidal neurodegenerative and microvascular changes using OCT technology.

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Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

“…In addition, invivo studies have shown reduced macular thickness and volume in patients with AD [44,[48][49][50][51][52][53][54].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

“…Retinal changes may be an early event in the course of AD, and retinal OCT may provide insights for assessing neurodegeneration in the brain [50].…”

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

Section: Pathological Changes In the Retina And Optic Nervementioning

confidence: 99%

See 3 more Smart Citations

Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo

Cunha

Moura-Coelho

Proença

et al. 2016

Graefes Arch Clin Exp Ophthalmol

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Retinal Imaging Findings in Carriers With PSEN1-Associated Early-Onset Familial Alzheimer Disease Before Onset of Cognitive Symptoms

et al. 2021

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IMPORTANCE Individuals with autosomal dominant mutations for Alzheimer disease are valuable in determining biomarkers present prior to the onset of cognitive decline, improving the ability to diagnose Alzheimer disease as early as possible. Optical coherence tomography (OCT) has surfaced as a potential noninvasive technique capable of analyzing central nervous system tissues for biomarkers of Alzheimer disease.OBJECTIVE To evaluate whether OCT can detect early retinal alterations in carriers of the presenilin 1 (PSEN1 [OMIM 104311]) E280A mutation who are cognitively unimpaired. DESIGN, SETTING, AND PARTICIPANTSA cross-sectional imaging study conducted from July 13, 2015, to September 16, 2020, included 10 carriers of the PSEN1 E280A mutation who were cognitively unimpaired and 10 healthy noncarrier family members, all leveraged from a homogenous Colombian kindred. Statistical analysis was conducted from September 9, 2017, to September 16, 2020.MAIN OUTCOMES AND MEASURES Mixed-effects multiple linear regression was performed to compare the thickness values of the whole retina and individual retinal layers on OCT scans between mutation carriers and noncarriers. Simple linear-effects and mixed-effects multiple linear regression models were used to assess whether age was an effect modifier for PSEN1 mutation of amyloid β levels and retinal thickness, respectively. Fundus photographs were used to compare the number of arterial and venous branch points, arterial and venous tortuosity, and fractal dimension. RESULTSThis study included 10 carriers of the PSEN1 E280A mutation who were cognitively unimpaired (7 women [70%]; mean [SD] age, 36.3 [8.1] years) and 10 healthy noncarrier family members (7 women [70%]; mean [SD] age, 36.4 [8.2] years). Compared with noncarrier controls, PSEN1 mutation carriers who were cognitively unimpaired had a generalized decrease in thickness of the whole retina as well as individual layers detected on OCT scans, with the inner nuclear layer (outer superior quadrant, β = -3.06; P = .007; outer inferior quadrant, β = -2.60; P = .02), outer plexiform layer (outer superior quadrant, β = -3.44; P = .03), and outer nuclear layer (central quadrant, β = -8.61; P = .03; inner nasal quadrant, β = -8.39; P = .04; inner temporal quadrant, β = -9.39; P = .02) showing the greatest amount of statistically significant thinning. Age was a significant effect modifier for the association between PSEN1 mutation and amyloid β levels in cortical regions (β = 0.03; P = .001) but not for the association between PSEN1 mutation and retinal thickness. No statistical difference was detected in any of the vascular parameters studied.CONCLUSIONS AND RELEVANCE These findings suggest that OCT can detect functional and morphologic changes in the retina of carriers of familial Alzheimer disease who are cognitively unimpaired several years before clinical onset, suggesting that OCT findings and retinal vascular parameters may be biomarkers prior to the onset of cognitive decline.

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Association Between Retinal Layer Thickness and Cognitive Decline in Older Adults

et al. 2022

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IMPORTANCERetinal layer thickness is hypothesized to be related to cognitive function in patients with mild cognitive impairment (MCI) and Alzheimer disease (AD). However, longitudinal cohort studies of the healthy older population are scarce.OBJECTIVE To investigate the association between retinal layer thickness and cognitive impairment and future cognitive decline in a community-based population cohort.DESIGN, SETTING, AND PARTICIPANTS A total of 430 randomly sampled community-dwelling Korean individuals 60 years or older participated in the baseline assessment (mean [SD], 76.3 [6.6] years) 215 of whom completed a mean (SD) of 5.4 (0.6) years (range, 4.1-6.2 years) of follow-up. Using spectral-domain optical coherence tomography, the study team assessed the thickness of 6 retinal layers in the macular region, the peripapillary retinal nerve fiber layers (RNFLs), and the subfoveal choroid at baseline. EXPOSURES Age, sex, education, diabetes, hypertension, and apolipoprotein E4 gene status.MAIN OUTCOMES AND MEASURES Retinal layer thickness and cognitive function test scores were analyzed. RESULTSThis study included 430 participants (female, 208 [48.6%]). Baseline macular RNFL thickness was associated with baseline Consortium to Establish a Registry for Alzheimer's Disease (CERAD) score (coefficient [β] = 0.077; 95% CI, 0.054-0.100; P = .04 for total macular area) and Mini-Mental State Examination (MMSE) score (coefficient [β] = 0.082; 95% CI, 0.063-0.101; P = .03 for total macular area). A thinner baseline total macular RNFL thickness (lowest quartile, <231 μm) was associated with a larger decline in the CERAD and MMSE scores during the follow-up period (P = .003 and P = .01, respectively). Furthermore, participants with baseline total macular RNFL thickness below the lowest quartile cutoff value presented a greater decline in cognitive scores and a higher prevalence of cognitive impairment and Alzheimer disease than those with RNFL thickness above the lowest quartile cutoff value. CONCLUSIONS AND RELEVANCEIn this study, macular RNFL thickness could be used as a prognostic biomarker of long-term cognitive decline in adults 60 years or older. However, to confirm these results, further large-scale population-based studies should be performed.

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Retinal alterations in mild cognitive impairment and Alzheimer’s disease: an optical coherence tomography study

Cited by 157 publications

References 42 publications

Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo

Alzheimer’s disease: A review of its visual system neuropathology. Optical coherence tomography—a potential role as a study tool in vivo

Retinal Imaging Findings in Carriers With PSEN1-Associated Early-Onset Familial Alzheimer Disease Before Onset of Cognitive Symptoms

Association Between Retinal Layer Thickness and Cognitive Decline in Older Adults

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