title: Retinal vascular fractals and cognitive impairment.
abstract: BACKGROUND
  Retinal microvascular network changes have been found in patients with age-related brain diseases such as stroke and dementia including Alzheimer's disease. We examine whether retinal microvascular network changes are also present in preclinical stages of dementia.
  
  
  METHODS
  This is a cross-sectional study of 300 Chinese participants (age: ≥60 years) from the ongoing Epidemiology of Dementia in Singapore study who underwent detailed clinical examinations including retinal photography, brain imaging and neuropsychological testing. Retinal vascular parameters were assessed from optic disc-centered photographs using a semiautomated program. A comprehensive neuropsychological battery was administered, and cognitive function was summarized as composite and domain-specific Z-scores. Cognitive impairment no dementia (CIND) and dementia were diagnosed according to standard diagnostic criteria.
  
  
  RESULTS
  Among 268 eligible nondemented participants, 78 subjects were categorized as CIND-mild and 69 as CIND-moderate. In multivariable adjusted models, reduced retinal arteriolar and venular fractal dimensions were associated with an increased risk of CIND-mild and CIND-moderate. Reduced fractal dimensions were associated with poorer cognitive performance globally and in the specific domains of verbal memory, visuoconstruction and visuomotor speed.
  
  
  CONCLUSIONS
  A sparser retinal microvascular network, represented by reduced arteriolar and venular fractal dimensions, was associated with cognitive impairment, suggesting that early microvascular damage may be present in preclinical stages of dementia.
authors.affiliation: Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore ; Department of NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore ; Department of Singapore Eye Research Institute, Singapore National Eye Center, Singapore.
authors.forename: Yi-Ting
authors.initials: YT
authors.lastname: Ong
authors.affiliation: Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore ; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore ; Department of Memory, Aging and Cognition Center, National University Health System, Singapore.
authors.forename: Saima
authors.initials: S
authors.lastname: Hilal
authors.affiliation: Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore ; Department of Singapore Eye Research Institute, Singapore National Eye Center, Singapore ; Department of Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Carol Yim-Lui
authors.initials: CY
authors.lastname: Cheung
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore ; Department of Memory, Aging and Cognition Center, National University Health System, Singapore.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore ; Department of Memory, Aging and Cognition Center, National University Health System, Singapore.
authors.forename: Christopher
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Neuroscience Clinic, Raffles Hospital, Singapore.
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Venketasubramanian
authors.affiliation: Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore ; Department of Singapore Eye Research Institute, Singapore National Eye Center, Singapore ; Department of Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Tien Yin
authors.initials: TY
authors.lastname: Wong
authors.affiliation: Department of Singapore Eye Research Institute, Singapore National Eye Center, Singapore ; Department of Memory, Aging and Cognition Center, National University Health System, Singapore ; Department of Office of Clinical Sciences, Duke-NUS Graduate Medical School, Singapore.
authors.forename: Mohammad Kamran
authors.initials: MK
authors.lastname: Ikram
keywords: Cognition; Cognitive impairment; Fractal dimension; Microvasculature; Retina