Ganglion cell layer thinning in prodromal Alzheimer's disease defined by amyloid PET

Abstract

Introduction The objective of this study was to investigate and compare optic nerve and retinal layers in eyes of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) with paired control eyes using optical coherence tomography. Methods Sixty‐three eyes of 34 subjects, 12 eyes with AD and 51 eyes with MCI, positive to 11C‐labeled Pittsburgh Compound‐B with positron emission tomography (11C‐PiB PET/CT), and the same number of sex‐ and age‐paired control eyes underwent optical coherence tomography scanning analyzing retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), Bruch's membrane opening–minimum rim width (BMO‐MRW), inner plexiform layer (IPL), outer nuclear layer, and lamina cribrosa (LC). Results Compared with healthy controls, eyes of patients with positive 11C‐PiB PET/CT showed a significant thinning of RNFL (P < .028) and GCL (P < .014). IPL and outer nuclear layer also showed significant thinning in two (P < .025) and one location (P < .010), respectively. No significant differences were found when optic nerve measurements BMO‐MRW and LC were compared (P > .131 and P > .721, respectively). Temporal sector GCL, average RNFL, and temporal sector RNFL also exhibited significant thinning when MCI and control eyes were compared (P = .015, P = .005 and P = .050, respectively), and also the greatest area under the curve values (0.689, 0.647, and 0.659, respectively). GCL, IPL, and RNFL tend to be thinner in the AD group compared with healthy controls. Discussion Our study suggests that RNFL and GCL are useful for potential screening in the early diagnosis of AD. LC and BMO‐MRW appear not to be affected by AD.

Ganglion Cell Layer Thinning in Alzheimer’s Disease

“…However, the authors were not able to determinate which layer was most affected by AD due to poor segmentation OCT system. Lately, a number of studies suggested including RNFL in the GCIPL analysis in the macular area may influence the sensitivity for revealing GCL damage, so they measured GCIPL without including the RNFL, and found significant GCIPL thinning in AD [ 52 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 ] and MCI patients compared to HC [ 61 , 64 ].…”

“…Recently, our group have published an investigation about retinal damage in AD assessed by Spectralis OCT, reporting promising results. The study included highly characterized patients with detailed neurocognitive testing and positive to 11 C-labeled Pittsburgh Compound-B with positron emission tomography [ 64 ] analysis that could readily differentiate between participants with normal cognition from dementia due to AD. AD and MCI patients were recruited and compared among them and HC.…”

“…Besides, definition of MCI was used meeting research diagnostic criteria for probable AD MCI or with evidence of the AD pathophysiological process (in most cases defined by a positive amyloid-PET) following the recommendations of the National Institute on Aging-Alzheimer’s Association [ 70 ], but criteria should be consistent. In addition, all studies screened the eyes with the OCT technology after pupil dilation, except one [ 64 ], which might constitute a limitation. Finally, it is important to focus that his review revealed that limited research had focused exclusively on screening the eyes of study subjects with and with no cognitive decline using optical coherence tomography, neuropsychological tests, and in vivo neuroimaging techniques.…”

Evaluation of choroidal thickness in prodromal Alzheimer’s disease defined by amyloid PET

“…In an attempt to investigate CT in AD patients, we conducted a study which involved deeply characterized prodromal AD patients with detailed neurocognitive testing and PET imaging with 11 C-PiB. The present work is a logical extension of our previous publication about AD biomarkers, in which we suggested RNFL and RGCL as potential AD biomarkers in a near future [25]. Our main outcomes herein were CT thinning in different localizations comparing PiB+ patients (MCI stage and dementia stage) versus HC and a general trend toward CT thinning in MCI patients compared with HC, which became more pronounced in dementia.…”

“…We conducted a cross-sectional study including patients in the AD continuum (MCI and dementia) with positive 11 C-PiB PET/CT (MCI and AD) compared with cognitively healthy age-and gender-matched controls recruited consecutively from the Neurology and Ophthalmology departments of the University Hospital Marqués de Valdecilla (UHMV), between May 2016 and June 2018. The study cohort of the present submission overlaps with our previous work [25].…”