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Retinopathy Can Signal Impending Cognitive Decline

In a group of healthy older women, retinopathy was associated with worsening cognitive function over 10 years and with larger ischemic lesion volumes on brain imaging….

The finding, said the researchers, “strengthens existing evidence that retinopathy as a marker of small vessel disease is a risk factor for cerebrovascular disease that may influence cognitive performance and related brain changes.”

Study author Mary Haan, DrPH, MPH, of the University of California, San Francisco noted that, “Screening for retinopathy may be useful in identifying those with pending cognitive decline.”

The findings, in women who were simultaneously enrolled in the Women’s Health Initiative Memory Study (WHIMS) and the WHI Sight Examination Study (WHISE), were published online last week. .

In a commentary, Rebecca F. Gottesman, MD, PhD, from Johns Hopkins University School of Medicine, Baltimore, Maryland, and Ge Li, MD, PhD, from University of Washington, Seattle, said the study findings “provide further support for a microvascular etiology for cognitive decline.”

The study included 511 women aged 65 years and older (mean age, 69 years). Dr. Haan and colleagues examined the link between retinopathy assessed using fundus photography between 2000 and 2002, cognitive performance over time (1996 to 2007) assessed with the modified Mini-Mental State Examination (3MSE), and white matter hyperintensities and lacunar infarcts in the basal ganglia as seen on magnetic resonance imaging (MRI).

Thirty-nine (7.6%) of the 511 women were classified as having retinopathy; of these 8 were mild, 15 had only microaneurysms, 2 were moderate, 1 was severe, and 13 were of other types (fibrous proliferation).

According to the investigators, the presence of retinopathy was associated with poorer 3MSE scores (mean difference, 1.01; SE = 0.43; P = .019) for 10 years. Women with retinopathy performed worse on both the vision-dependent (P = .036) and nonvision-dependent (P = .017) items over time.

The presence of retinopathy was also associated with greater ischemic volumes in the total brain (47% larger, P = .04) and the parietal lobe (68% larger, P = .01) but not with measures of regional brain atrophy.

The investigators note that retinopathy was significantly associated with cognitive scores and cerebral microvascular disease independent of the effect of hypertension and diabetes.

In response to the study results Dr. Gottesman and Dr. Li say this study “adds to the growing evidence of a causal association of small vessel disease and cognition, but most importantly, it further validates retinopathy as an early marker for brain small vessel disease in living persons.”

Given the shared microvascular mechanism behind retinopathy and subclinical lacunar infarcts and white matter disease, “this association is biologically plausible and has been supported by other studies,” the authors note. “In addition, cognitive dysfunction in older adults is usually due to vascular disease, degeneration, or a combination of both. These WHI data support a vascular etiology or at least a vascular contribution to cognitive impairment,” they write.

Retinal evaluation may also be a way to screen for an underlying vascular cause in individuals with evidence of cognitive impairment or dementia, they write. “More aggressive management of vascular risk factors might be indicated” in these individuals.

Neurology 2012;78:936-937, 942-94