Nonvascular retinal imaging markers of preclinical Alzheimer's disease.
BACKGROUND
In patients with Alzheimer's disease (AD) and mild cognitive impairment, structural changes in the retina (i.e., reduced thicknesses of the ganglion cell and retinal nerve fiber layers and inclusion bodies that appear to contain beta-amyloid protein [Ab]) have been previously reported. We sought to explore whether anatomic retinal changes are detectable in the preclinical stage of AD.


METHODS
A cross-sectional study (as part of an ongoing longitudinal cohort study) involving 63 cognitively normal adults, all of whom have a parent with AD and subjective memory complaints. We compared neocortical amyloid aggregation (florbetapir PET imaging) to retinal spectral domain optical coherence tomography (SD-OCT) markers of possible disease burden. Retinal biomarkers, including the number and surface area of retinal inclusion bodies and the thickness of retinal neuronal layers, were compared across groups with high vs. low neocortical beta-amyloid load.


RESULTS
The surface area of inclusion bodies increased as a function of cortical amyloid burden. Additionally, there was a trend toward a selective volume increase in the inner plexiform layer (IPL; a layer rich in cholinergic activity) of the retina in Aβ+ relative to Aβ- participants, and IPL volume was correlated with the surface area of retinal inclusion bodies.


CONCLUSIONS
These initial results suggest that retinal imaging may be a potential cost-effective and noninvasive technique that can be used to identify those at-risk for AD. Layer-specific changes in the IPL and their association with surface area of inclusion bodies are discussed as a possible reflection of early inflammatory processes associated with cholinergic disruption and concurrent Ab accumulation in the neocortex.
Department of Neurology, Warren Alpert Medical School of Brown University, Providence, RI, USA; Lifespan Clinical Research Center, Rhode Island Hospital, Providence, RI, USA.
Peter J
PJ
Snyder
Lifespan Clinical Research Center, Rhode Island Hospital, Providence, RI, USA; Neuro-Ophthalmology Unit, Department of Ophthalmology, Warren Alpert Medical School of Brown University, Providence, RI, USA.
Lenworth N
LN
Johnson
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia.
Yen Ying
YY
Lim
Lifespan Clinical Research Center, Rhode Island Hospital, Providence, RI, USA; Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA.
Cláudia Y
CY
Santos
Lifespan Clinical Research Center, Rhode Island Hospital, Providence, RI, USA; Department of Psychiatry and Human Behavior, Warren Alpert Medical School of Brown University, Providence, RI, USA.
Jessica
J
Alber
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Melbourne, Victoria, Australia; Cogstate Ltd., Melbourne, Victoria, Australia.
Paul
P
Maruff
Heidelberg Engineering, Inc., Franklin, MA, USA.
Brian
B
Fernández
Acetylcholine; Alzheimer's disease; Biomarkers; Cholinergic hypothesis; Inner plexiform layer; OCT; Optical Coherence Tomography; Preclinical AD; Retina