title: Retinal vascular and structural changes are associated with amyloid burden in the elderly: ophthalmic biomarkers of preclinical Alzheimer's disease.
abstract: BACKGROUND
  Retinal imaging may serve as an alternative approach to monitor brain pathology in Alzheimer's disease (AD). In this study, we investigated the association between retinal vascular and structural changes and cerebral amyloid-β (Aβ) plaque load in an elderly cohort.
  
  
  METHODS
  We studied a total of 101 participants, including 73 elderly subjects (79 ± 5 years, 22 male) with no clinical diagnosis of AD but reporting some subjective memory change and an additional 28 subjects (70 ± 9 years, 16 male) with clinically established AD. Following a complete dilated ocular examination, the amplitude of retinal vascular pulsations and dynamic response, retinal nerve fibre layer thickness and retinal ganglion cell layer (RGCL) thickness were determined in all patients. Systemic blood pressure and carotid-to-femoral pulse wave velocity were measured. The elderly cohort also underwent magnetic resonance imaging and18F-florbetaben (FBB)-positron emission tomographic amyloid imaging to measure neocortical Aβ standardised uptake value ratio (SUVR), and this was used to characterise a 'preclinical' group (SUVR >1.4).
  
  
  RESULTS
  The mean FBB neocortical SUVR was 1.35 ± 0.3. The amplitude of retinal venous pulsations correlated negatively with the neocortical Aβ scores (p < 0.001), whereas the amplitude of retinal arterial pulsations correlated positively with neocortical Aβ scores (p < 0.01). RGCL thickness was significantly lower in the clinical AD group (p < 0.05).
  
  
  CONCLUSIONS
  The correlation between retinal vascular changes and Aβ plaque load supports the possibility of a vascular component to AD. Dynamic retinal vascular parameters may provide an additional inexpensive tool to aid in the preclinical assessment of AD.
authors.affiliation: Vision Science Group, Graduate School of Health (Orthoptics Discipline), University of Technology Sydney, 15 Broadway, Ultimo, NSW, 2007, Australia. mojtaba.golzan@uts.edu.au.|Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia. mojtaba.golzan@uts.edu.au.
authors.forename: S Mojtaba
authors.initials: SM
authors.lastname: Golzan
authors.affiliation: KaRa Institute of Neurological Diseases, Macquarie Park, NSW, 2113, Australia.|Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia.|Anglican Retirement Village, Sydney, NSW, Australia.|School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Goozee
authors.affiliation: Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
authors.forename: Dana
authors.initials: D
authors.lastname: Georgevsky
authors.affiliation: Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia.
authors.forename: Alberto
authors.initials: A
authors.lastname: Avolio
authors.affiliation: KaRa Institute of Neurological Diseases, Macquarie Park, NSW, 2113, Australia.|Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia.
authors.forename: Pratishtha
authors.initials: P
authors.lastname: Chatterjee
authors.affiliation: Australian e-Health Research Centre, CSIRO Health and Biosecurity, Herston, QLD, Australia.
authors.forename: Kaikai
authors.initials: K
authors.lastname: Shen
authors.affiliation: Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
authors.forename: Vivek
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia.
authors.forename: Roger
authors.initials: R
authors.lastname: Chung
authors.affiliation: ARC Centre of Excellence in Cognition and its Disorders, Department of Psychology, Macquarie University, Sydney, NSW, Australia.
authors.forename: Greg
authors.initials: G
authors.lastname: Savage
authors.affiliation: Macquarie Neurology, Macquarie University, Sydney, NSW, Australia.
authors.forename: Carolyn F
authors.initials: CF
authors.lastname: Orr
authors.affiliation: KaRa Institute of Neurological Diseases, Macquarie Park, NSW, 2113, Australia.|Department of Biomedical Sciences, Macquarie University, Sydney, NSW, Australia.|School of Psychiatry and Clinical Neurosciences, University of Western Australia, Perth, WA, Australia.
authors.forename: Ralph N
authors.initials: RN
authors.lastname: Martins
authors.affiliation: Department of Clinical Medicine, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW, Australia.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Graham
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging; D015331:Cohort Studies; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D009929:Organ Size; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000503:physiopathology; D012160:Retina / Q000000981:diagnostic imaging* / Q000503:physiopathology; D012171:Retinal Vessels / Q000000981:diagnostic imaging / Q000503:physiopathology*
keywords: Alzheimer’s disease; Early diagnosis; Retinal imaging; Vascular biomarkers