Retinal layer thickness in preclinical Alzheimer's disease

Abstract

Purpose: There is urgent need for non-invasive diagnostic biomarkers in the preclinical phase of Alzheimer's Disease (AD). Several studies suggest that retinal thickness is reduced in AD. Here, we aim to test the diagnostic value of retinal thickness in preclinical AD, as defined by cognitively normal individuals with amyloid pathology on PET. Methods: One hundred and sixty five cognitively healthy monozygotic twins aged ≥ 60 were included from the Netherlands Twin Register taking part in the European Medical Information Framework for Alzheimer's Disease PreclinAD study. Participants underwent [ 18 F] flutemetamol PET that was visually rated for presence or absence of cortical amyloid beta (Ab). Binding potential (BP ND ) was calculated as continuous measure for Ab. Spectral Domain OCT was used to asses total and individual inner retinal layer thickness in the macular region (ETDRS circles) as well as peripapillary retinal nerve fibre layer (pRNFL) thickness. Differences between Ab+ and AbÀ individuals and associations between BP ND and retinal thickness were analyzed. Results: No differences were found in retinal layer thickness in the macula or pRNFL between Ab+ and AbÀ individuals. A positive associations between BP ND and macular total retinal thickness was observed in the inner ring (p = 0.018), but this was not statistically significant after correction for multiple testing (p = 0.144). Brain/eye parameters had moderate to high intra-twin correlations (p < 0.001) except visual rating score of Ab, which did not correlate (r = 0.21, p = 0.068). Conclusion: Variation in retinal thickness likely reflects genetic differences between individuals, but cannot discriminate between healthy and preclinical AD cases, making its use as biomarker in these early stages limited.

Anatomical and functional changes in the retina in patients with Alzheimer’s disease and mild cognitive impairment

“…Whether this can be interpreted as a higher susceptibility of the temporal sectors because of higher metabolic turnover is unclear and warrants further investigation. However, recently doubts have been raised whether retinal thickness alone is a suitable parameter for the early identification of preclinical AD patients (van de Kreeke et al 2019a). Thus, it has been hypothesized that functional parameters may be more sensitive than structural parameters alone (Liao et al 2018).…”

Advances in retina imaging as potential biomarkers for early diagnosis of Alzheimer’s disease

“…MCI had thinner mGC-IPL in the majority of sectors. Shao et al [ 64 ] 2018 pRNFL, GC-IPL AD MCI Thinning Almeida et al [ 65 ] 2019 pRNFL, mRNFL MCI Thinner mRNFL, mGC-IPL and mGCC Santos et al [ 66 ] 2018 pRNFL, mRNFL, GCL, IPL, OPL, INL, ONL Preclinical AD Thinner mRNFL, ONL and IPL López-Cuenca et al [ 67 ] 2020 pRNFL, mRNFL, GCL, IPL, INL, OPL, ONL, RPE Preclinical AD Thinner mRNFL, IPL, INL and OPL Snyder et al [ 68 ] 2016 pRNFL, mRNFL, GCL, IPL, INL, OPL, ONL, Preclinical AD Thicker IPL van de Kreeke et al [ 69 ] 2019 pRNFL, mRNFL, GCL, IPL, Preclinical AD No difference van de Kreeke et al [ 70 ] 2020 pRNFL, mRNFL, GCL, IPL, Preclinical AD No difference in the rate of change of any retinal layers OCT optical coherence tomography; AD Alzheimer’s disease; MCI mild cognitive impairment; pRNFL peripapillary retinal nerve fiber layer; mRNFL macular retinal nerve fiber layer; GCL ganglion cell layer; IPL inner plexiform layer; GC-IPL ganglion cell-inner plexiform layer; pGC-IPL peripapillary ganglion cell-inner plexiform layer; mGCC macular ganglion cell complex; INL inner nuclear layer; OPL outer plexiform layer; ONL outer nuclear layer; RPE retinal pigment epithelium …”

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 …”

“…The vast majority of studies compared patients with AD to healthy controls, while 25 studies 24 , 26–30 , 37 , 39 , 41 , 42 , 44 , 46–48 , 51 , 52 , 54 , 56 , 57 , 65 , 75 , 76 , 78 , 81 , 83 included an additional subset of patients with a diagnosis of MCI or subjective cognitive decline for comparison. Four studies also included subjects with preclinical AD, 32 , 35 , 40 , 53 defined as cognitively normal individuals who are positive for established AD biomarkers. Three studies also included patients with other forms of dementia, including Parkinson’s disease (PD), Lewy Body dementia (LBD), and unspecified non-AD dementia for comparison.…”