Associations Between Retinal Microvascular Changes and Dementia, Cognitive Functioning, and Brain Imaging Abnormalities: A Systematic Review

Retinal microvascular changes can be visualized noninvasively and have been associated with cognitive decline and brain changes in relation to aging and vascular disease. We systematically reviewed studies, published between 1990 and November 2012, on the association between retinal microvascular changes and dementia, cognitive functioning, and brain imaging abnormalities, in the context of aging and vascular risk factors. In cross-sectional studies (k = 26), retinal microvascular changes were associated with the presence of dementia (range of odds ratios (ORs) 1.17;5.57), with modest decrements in cognitive functioning in nondemented people (effect sizes -0.25;0.03), and with brain imaging abnormalities, including atrophy and vascular lesions (ORs 0.94;2.95). Longitudinal studies were more sparse (k = 9) and showed no consistent associations between retinal microvascular changes and dementia or cognitive dysfunctioning 3 to 15 years later (ORs and hazard ratios 0.77;1.55). However, there were indications of prospective associations with brain imaging abnormalities ((ORs) 0.81;3.19). In conclusion, particularly in cross-sectional studies there is a correlation between retinal microvascular changes and dementia, cognitive impairment, and brain imaging abnormalities. Associations are strongest for more severe retinal microvascular abnormalities. Retinal microvascular abnormalities may offer an important window on the brain for etiological studies.

[1]  T. Wong,et al.  Visual impairment, age-related eye diseases, and cognitive function: the Singapore Malay Eye study. , 2012, Archives of ophthalmology.

[2]  R. Sergott.  Retinal microvascular abnormalities and cognitive decline: The ARIC 14-year follow-up study , 2010 .

[3]  George Mendelson,et al.  Book Reviews , 1995 .

[4]  Niels D Prins,et al.  Retinal vessel diameters and cerebral small vessel disease: the Rotterdam Scan Study. , 2006, Brain : a journal of neurology.

[5]  Beau B. Bruce,et al.  Hypertension-related eye abnormalities and the risk of stroke. , 2011, Reviews in neurological diseases.

[6]  R. Klein,et al.  Retinal Microvascular Signs, Cognitive Function, and Dementia in Older Person: The Cardiovascular Health Study , 2007, Stroke.

[7]  R. Klein,et al.  Retinal Microvascular Signs and Functional Loss in Older Persons: The Cardiovascular Health Study , 2011, Stroke.

[8]  B. Girard,et al.  Retinal microvascular abnormalities and incident stroke : the atherosclerosis risk in communities study. , 2008 .

[9]  R. Klein,et al.  Retinal Microvascular Abnormalities and Cognitive Impairment in Middle-Aged Persons: The Atherosclerosis Risk in Communities Study , 2002, Stroke.

[10]  Tien Yin Wong,et al.  Retinal microvascular changes and MRI signs of cerebral atrophy in healthy, middle-aged people , 2003, Neurology.

[11]  I. Deary,et al.  Diabetic Retinopathy and Cognitive Decline in Older People With Type 2 Diabetes , 2010, Diabetes.

[12]  P. Massin,et al.  Retinal microvascularisation abnormalities and cardiovascular risk. , 2009, Archives of cardiovascular diseases.

[13]  D. Moher,et al.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement , 2009, BMJ.

[14]  A. Hanley,et al.  Window to the brain: Can retinopathy be used to assess cognitive function , 2010, Brain injury.

[15]  R. Klein,et al.  Retinal vessel diameters and their associations with age and blood pressure. , 2003, Investigative ophthalmology & visual science.

[16]  Tien Yin Wong,et al.  Associations between findings on cranial magnetic resonance imaging and retinal photography in the elderly: the Cardiovascular Health Study. , 2006, American journal of epidemiology.

[17]  Paul Mitchell,et al.  The eye in hypertension , 2007, The Lancet.

[18]  Tien Yin Wong,et al.  Systemic associations of retinal microvascular signs: a review of recent population‐based studies , 2005, Ophthalmic & physiological optics : the journal of the British College of Ophthalmic Opticians.

[19]  J. Stam,et al.  Retinal arterial changes correlate with cerebral small-vessel disease , 2002, Neurology.

[20]  T. Wong,et al.  Retinal vascular fractal dimension is associated with cognitive dysfunction. , 2014, Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association.

[21]  Geert Jan Biessels,et al.  Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review. , 2008, European journal of pharmacology.

[22]  A. Hofman,et al.  Retinal vessel diameters and risk of stroke , 2006, Neurology.

[23]  I. Deary,et al.  Retinal microvascular abnormalities and cognitive dysfunction: a systematic review , 2008, British Journal of Ophthalmology.

[24]  R. Klein,et al.  Cerebral white matter lesions, retinopathy, and incident clinical stroke. , 2002, JAMA.

[25]  Gabriëlle H S Buitendijk,et al.  Retinopathy and risk of dementia , 2012, Neurology.

[26]  T. Wong,et al.  Retinal Microvasculature as a Model to Study the Manifestations of Hypertension , 2012, Hypertension.

[27]  G. Hankey,et al.  Differential Associations of Cortical and Subcortical Cerebral Atrophy With Retinal Vascular Signs in Patients With Acute Stroke , 2010, Stroke.

[28]  A. Hofman,et al.  Retinal vascular caliber and risk of dementia , 2011, Neurology.

[29]  T. Wong,et al.  Retinal Microvascular Abnormalities and Cognitive Function in Latino Adults in Los Angeles , 2012, Ophthalmic epidemiology.

[30]  B. Yoon,et al.  Retinopathy as an indicator of silent brain infarction in asymptomatic hypertensive subjects , 2007, Journal of the Neurological Sciences.

[31]  J. Ioannidis,et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. , 2009, Journal of clinical epidemiology.

[32]  Janet B W Williams,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[33]  C. Tzourio,et al.  Vascular risk factors and dementia , 2009, Neurology.

[34]  Ryo Kawasaki,et al.  Retinal Microvascular Signs and 10-Year Risk of Cerebral Atrophy: The Atherosclerosis Risk in Communities (ARIC) Study , 2010, Stroke.

[35]  T. Sakurai,et al.  Factors associated with lower Mini Mental State Examination scores in elderly Japanese diabetes mellitus patients , 2008, Neurobiology of Aging.

[36]  R. Klein,et al.  Retinal microvascular abnormalities and subclinical magnetic resonance imaging brain infarct: a prospective study. , 2010, Brain : a journal of neurology.

[37]  Tien Yin Wong,et al.  Similarities and differences in early retinal phenotypes in hypertension and diabetes , 2011, Journal of hypertension.

[38]  R. Klein,et al.  Microvascular lesions in the brain and retina: The age, gene/environment susceptibility–Reykjavik study , 2009, Annals of neurology.

[39]  I. Deary,et al.  Association of retinal arteriolar dilatation with lower verbal memory: the Edinburgh Type 2 Diabetes Study , 2011, Diabetologia.

[40]  Rebecca M Reynolds,et al.  The Edinburgh Type 2 Diabetes Study: study protocol , 2008, BMC endocrine disorders.

[41]  W. Jagust,et al.  Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer's Disease Diagnostic and Treatment Centers , 1992, Neurology.

[42]  R. Hu.  Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) , 2003 .

[43]  Y. D. Reijmer,et al.  A 4 year follow-up study of cognitive functioning in patients with type 2 diabetes mellitus , 2009, Diabetologia.

[44]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[45]  D. Tranel,et al.  Neuropsychological assessment, 5th ed. , 2012 .

[46]  A. R. Sharrett,et al.  A Review of Population-Based Retinal Studies of the Microvascular Contribution to Cerebrovascular Diseases , 2007, Ophthalmic epidemiology.

[47]  V. Gudnason,et al.  Cerebral microbleeds, retinopathy, and dementia , 2010, Neurology.

[48]  R. Klein,et al.  Revised formulas for summarizing retinal vessel diameters , 2003, Current eye research.

[49]  M. Viergever,et al.  Microvascular Determinants of Cognitive Decline and Brain Volume Change in Elderly Patients with Type 2 Diabetes , 2010, Dementia and Geriatric Cognitive Disorders.

[50]  Jacob Cohen.  Statistical Power Analysis for the Behavioral Sciences , 1969, The SAGE Encyclopedia of Research Design.

[51]  T. Wong,et al.  Retinal Microvascular Signs and Cognitive Impairment , 2009, Journal of The American Geriatrics Society.

[52]  Vilmundur Gudnason,et al.  Retinal and Cerebral Microvascular Signs and Diabetes , 2008, Diabetes.

[53]  R. Klein,et al.  Retinal microvascular signs and disability in the Cardiovascular Health Study. , 2012, Archives of ophthalmology.

[54]  Tien Yin Wong,et al.  Hypertensive retinopathy signs as risk indicators of cardiovascular morbidity and mortality. , 2005, British medical bulletin.

[55]  K. Yaffe,et al.  Cognitive function and retinal and ischemic brain changes , 2012, Neurology.

[56]  F. Çatal,et al.  Relationship between Retinopathy and Cognitive Impairment among Hypertensive Subjects , 2004, European Neurology.

[57]  R Nick Bryan,et al.  Retinal Microvascular Abnormalities and MRI-Defined Subclinical Cerebral Infarction: The Atherosclerosis Risk in Communities Study , 2006, Stroke.

[58]  C. Thompson,et al.  Living beyond our physiological means: small vessel disease of the brain is an expression of a systemic failure in arteriolar function: a unifying hypothesis. , 2009, Stroke.

[59]  Vilmundur Gudnason,et al.  Diabetes, markers of brain pathology and cognitive function , 2014, Annals of neurology.

[60]  A. Algra,et al.  Metabolic and vascular determinants of impaired cognitive performance and abnormalities on brain magnetic resonance imaging in patients with type 2 diabetes , 2007, Diabetologia.

[61]  Tom MacGillivray,et al.  The association between retinal vascular network geometry and cognitive ability in an elderly population. , 2007, Investigative ophthalmology & visual science.