Abstract
PurposeThere has been increasing interest in identifying non-invasive, imaging biomarkers for neurodegenerative disorders of the central nervous system (CNS). The aim of this proof-of-concept study was to investigate whether corneal sensory nerve and dendritic cell (DC) parameters, captured using in vivo confocal microscopy (IVCM), are altered in individuals with mild cognitive impairment (MCI) and Alzheimer’s disease (AD).MethodsFifteen participants were recruited from the Australian Imaging Biomarkers and Lifestyle (AIBL) study in Melbourne, VIC, Australia. The cohort consisted of cognitively normal (CN) individuals (n = 5), and those with MCI (n = 5) and AD (n = 5). Participants underwent a slit lamp examination of the anterior segment, followed by corneal imaging using laser-scanning in vivo confocal microscopy (IVCM) of the central and inferior whorl regions. Corneal DC density, field area, perimeter, circularity index, aspect ratio, and roundness were quantified using Image J. Quantitative data were derived for corneal nerve parameters, including nerve fiber length (CNFL), fiber density (CNFD), branch density (CNBD), and diameter.ResultsCorneal DC field area and perimeter were greater in individuals with MCI, relative to CN controls, in both the central and inferior whorl regions (p < 0.05 for all comparisons). In addition, corneal DCs in the whorl region of MCI eyes had lower circularity and roundness indices and a higher aspect ratio relative to CNs (p < 0.05 for all comparisons). DC density was similar across participant groups in both corneal regions. There was a trend toward lower quantitative parameters for corneal nerve architecture in the AD and MCI groups compared with CN participants, however, the inter-group differences did not reach statistical significance. Central corneal nerve diameters were similar between groups.ConclusionThis study is the first to report morphological differences in corneal DCs in humans with MCI. These differences were evident in both the central and mid-peripheral cornea, and in the absence of significant nerve abnormalities or a difference in DC density. These findings justify future large-scale studies to assess the utility of corneal IVCM and DC analysis for identifying early stage pathology in neurodegenerative disorders of the CNS.
Highlights
Alzheimer’s disease (AD) is the most common form of irreversible dementia; it is estimated to affect about 40 million people worldwide (Wu et al, 2017)
The aim of this study was to investigate whether sensory nerve and dendritic cells (DCs) parameters in both the central and mid-peripheral cornea, captured non-invasively using in vivo confocal microscopy (IVCM), are altered in individuals with AD and mild cognitive impairment (MCI)
The corneal IVCM procedure was well tolerated in all participants, with no adverse events
Summary
Alzheimer’s disease (AD) is the most common form of irreversible dementia; it is estimated to affect about 40 million people worldwide (Wu et al, 2017). Cerebrospinal fluid biomarkers and amyloid PET, which can detect earlier AD pathology, have revealed subtle subclinical pathological changes that occur before the clinical decline (Villemagne et al, 2011, 2013; Vos et al, 2013). These advanced procedures are impractical for routine use due to their cost and invasiveness. The United States National Institute of Aging and Alzheimer’s Association have emphasized a need to identify reliable biomarkers that can identify individuals at highest risk for cognitive decline or progression from MCI to AD (Albert et al, 2011). Developing accessible, non-invasive and sensitive biomarkers of early stage disease will provide an essential foundation for both investigating new treatments and enabling earlier disease intervention (Vos et al, 2013; Scheltens et al, 2016)
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