Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline

Abstract

BackgroundAlzheimer's disease (AD) pathology precedes symptoms and its detection can identify atrisk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß 42 (A) and tau (T) ratio. MethodsAs part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression. ResultsMean age (± standard deviation) in the CH-PAT group (n = 27; 75.2 ± 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 ± 7.9 years). Mean RNFL (standard error) was

Optical Coherence Tomography in Patients with Alzheimer’s Disease: What Can It Tell Us?

“…Sixty-one (86%) studies used a form of neurocognitive testing (eg Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), etc. ), 17–34 , 36–44 , 46 , 47 , 49–80 56 (79%) relied on clinical diagnosis by experts based on criteria such as the DSM-IV or NINCDS-ADRDA, 18 , 20 , 21 , 24 , 26–34 , 36 , 39 , 41–44 , 46–52 , 54–57 , 62–64 , 66–88 29 (41%) utilized neuroimaging techniques (eg magnetic resonance imaging (MRI), computed tomography (CT) scan, or PET), 18 , 19 , 21–23 , 25 , 29–31 , 33 , 34 , 37 , 39–41 , 44 , 46 , 48 , 49 , 51 , 53 , 56 , 57 , 60 , 61 , 66 , 68 , 75 , 79 and 13 (18%) used immunohistochemical staining for biomarkers tau and amyloid. 21–23 , 25 , 31 , 32 , 34 , 35 , 37 , 39 , 50 , 51 , 61 …”

“…Finally, OCT/OCTA findings have been shown to be associated with other objective tools for AD diagnosis such as cortical atrophy, immunohistochemical staining, and results of neurocognitive testing, which strengthens the case for their application as diagnostic tools. 17–19 , 22 , 23 , 31 , 32 , 40 , 45 , 48 , 55 , 59 , 64 , 87 …”

“…However, it is reassuring that the vast majority of studies included in this review either reported or attempted to account for potentially confounding factors (eg age, sex, or race) in the statistical analysis. 17–68 , 70–88 Also, a majority of the studies were cross-sectional or retrospective, thus limiting causal inference; and only a small number were prospective. 32 , 76 , 79 , 88 However, none of the studies to date have looked at changes in microvascular structure of AD or MCI patients over time in OCTA.…”

“…Sixty-one (86%) studies used a form of neurocognitive testing (eg Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), etc. ), [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][36][37][38][39][40][41][42][43][44]46,47, 56 (79%) relied on clinical diagnosis by experts based on criteria such as the DSM-IV or NINCDS-ADRDA, 18,20,21,24,[26][27][28][29][30][31][32][33][34]36,39,[41][42][43][44][46][47][48]…”

“…In just the past three years, there has been an explosion in research investigating the use of OCT and OCTA for the evaluation of AD, with over 35 new studies published and investigation of a number of novel parameters. 17–54 In the following review, we summarize the proposed ocular manifestations of AD observed by OCT and OCTA in the recent literature and explore their potential for evaluating retinal and optic nerve pathology to enable earlier detection of Alzheimer’s disease.…”