Retinal microvascular abnormalities and cognitive decline

Background: Because retinal and cerebral arterioles share similar pathologic processes, retinal microvascular changes are expected to be markers of cerebral small vessel disease (SVD). To better understand the role of SVD in cognitive function, we investigated the relationship between retinal microvascular abnormalities and longitudinal changes in cognitive function in a community-based study. Methods: A total of 803 participants underwent 4 cognitive assessments between 1990–1992 and 2004–2006, using the Word Fluency (WF) test, Digit Symbol Substitution (DSS), and Delayed Word Recall as well as retinal photography in 1993–1995. Covariate adjusted random effects linear models for repeated measures were used to determine the associations of cognitive change with specific retinal vascular abnormalities. Results: Individuals with retinopathy showed declines in executive function and psychomotor speed, with 1) an average decline in WF of −1.64 words per decade (95% confidence interval [CI] −3.3, −0.02) compared to no decline in those without retinopathy +0.06 (95% CI −0.6, 0.8) and 2) a higher frequency of rapid decliners on the DSS test. Conclusion: Signs of retinal vascular changes, as markers of the cerebral microvasculature, are associated with declines in executive function and psychomotor speed, adding to the growing evidence for the role of microvascular disease in cognitive decline in the elderly.

[1]  P. Jenkins,et al.  Modulation of Cortisol Metabolism during Treatment of Acromegaly Is Independent of Body Composition and Insulin Sensitivity , 2001, Hormone Research in Paediatrics.

[2]  R. Klein,et al.  Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study. , 1999, Ophthalmology.

[3]  W. Markesbery,et al.  Cerebrovascular Pathology and Dementia in Autopsied Honolulu‐Asia Aging Study Participants , 2002, Annals of the New York Academy of Sciences.

[4]  M. Esiri,et al.  Neuropathological assessment of the lesions of significance in vascular dementia , 1997, Journal of neurology, neurosurgery, and psychiatry.

[5]  I. Deary,et al.  Retinal vascular image analysis as a potential screening tool for cerebrovascular disease: a rationale based on homology between cerebral and retinal microvasculatures , 2005, Journal of anatomy.

[6]  K. Jellinger,et al.  The enigma of vascular cognitive disorder and vascular dementia , 2007, Acta Neuropathologica.

[7]  A. Folsom,et al.  The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. , 1989, American journal of epidemiology.

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

[9]  M. Fernando,et al.  Neuropathology of Vascular Cognitive Impairment and Vascular Dementia , 2003, International Psychogeriatrics.

[10]  Emily Y. Chew,et al.  Nonproliferative Diabetic Retinopathy , 2008 .

[11]  A. Hofman,et al.  Silent brain infarcts and the risk of dementia and cognitive decline. , 2003, The New England journal of medicine.

[12]  M. Lezak Neuropsychological assessment, 3rd ed. , 1995 .

[13]  Ralph H. B. Benedict,et al.  Composite reliability and standard errors of measurement for a seven-subtest short form of the Wechsler Adult Intelligence Scale—Revised. , 1994 .

[14]  P. Box Cerebral small-vessel disease and decline in information processing speed, executive function and memory , 2006 .

[15]  R. Klein,et al.  Are retinal arteriolar abnormalities related to atherosclerosis?: The Atherosclerosis Risk in Communities Study. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[16]  N. Lassen,et al.  Multi-infarct dementia. A cause of mental deterioration in the elderly. , 1974, Lancet.

[17]  A. Fleisher,et al.  Clinical predictors of progression to Alzheimer disease in amnestic mild cognitive impairment , 2007, Neurology.

[18]  D. Knopman,et al.  A verbal memory test with high predictive accuracy for dementia of the Alzheimer type. , 1989, Archives of neurology.

[19]  Niels D Prins,et al.  Cerebral small-vessel disease and decline in information processing speed, executive function and memory. , 2005, Brain : a journal of neurology.

[20]  M. Dichgans,et al.  Retinal vascular abnormalities in CADASIL , 2004, Neurology.

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

[22]  Paul G. Ince,et al.  Vascular pathologies and cognition in a population-based cohort of elderly people , 2004, Journal of the Neurological Sciences.

[23]  S. Black,et al.  National Institute of Neurological Disorders and Stroke–Canadian Stroke Network Vascular Cognitive Impairment Harmonization Standards , 2006, Stroke.

[24]  L. Chambless,et al.  Self-reported transient ischemic attack and stroke symptoms: methods and baseline prevalence. The ARIC Study, 1987-1989. , 1996, American journal of epidemiology.

[25]  L. Berkman,et al.  Two Shorter Forms of the CES-D Depression Symptoms Index , 1993 .

[26]  T. Curtis,et al.  Arteriolar Involvement in the Microvascular Lesions of Diabetic Retinopathy: Implications for Pathogenesis , 2007, Microcirculation.

[27]  R. Klein,et al.  Retinal arteriolar diameters and elevated blood pressure: the Atherosclerosis Risk in Communities Study. , 1999, American journal of epidemiology.

[28]  M. Albert,et al.  Longitudinal change in cognitive performance among individuals with mild cognitive impairment. , 2007, Neuropsychology.

[29]  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.

[30]  Gunhild Waldemar,et al.  Differential impact of cerebral white matter changes, diabetes, hypertension and stroke on cognitive performance among non-disabled elderly. The LADIS study , 2007, Journal of Neurology, Neurosurgery, and Psychiatry.

[31]  Neurological Disorders National Institute of Neurological Disorders and Stroke FIVE-YEAR STRATEGIC PLAN ON MINORITY HEALTH DISPARITIES , 2002 .

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

[33]  I. Goto Pathological Studies on the Intracerebral and Retinal Arteries in Cerebrovascular and Noncerebrovascular Diseases , 1975, Stroke.

[34]  L. Berkman,et al.  Two shorter forms of the CES-D (Center for Epidemiological Studies Depression) depression symptoms index. , 1993, Journal of aging and health.

[35]  O Salonen,et al.  Cognitive profile of subcortical ischaemic vascular disease , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[36]  T. Tombaugh,et al.  Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming. , 1999, Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists.

[37]  W. M. van der Flier,et al.  Small Vessel Disease and General Cognitive Function in Nondisabled Elderly: The LADIS Study , 2005, Stroke.

[38]  P. Mitchell,et al.  Retinal Vascular Imaging: A New Tool in Microvascular Disease Research , 2008, Circulation. Cardiovascular imaging.

[39]  P. Scheltens,et al.  Small vessel versus large vessel vascular dementia , 2008, Journal of Neurology.

[40]  H. C. Chui,et al.  White matter lesions impair frontal lobe function regardless of their location , 2004, Neurology.

[41]  H S Markus,et al.  Brief cognitive assessment for patients with cerebral small vessel disease , 2005, Journal of Neurology, Neurosurgery & Psychiatry.

[42]  R. Klein,et al.  Three-year incidence and cumulative prevalence of retinopathy: the atherosclerosis risk in communities study. , 2007, American journal of ophthalmology.

[43]  Tien Yin Wong,et al.  Reliability of retinal photography in the assessment of retinal microvascular characteristics: the Atherosclerosis Risk in Communities Study. , 2002, American journal of ophthalmology.