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CHICAGO -- Changes in the retinal vasculature may identify patients in the earliest stages of Alzheimer's disease, possibly well before the first symptoms appear, according to two studies reported here.

One study showed that patients with Alzheimer's disease had significantly reduced macular vessel density (VD) and perfusion density (PD) as compared with patients who had mild cognitive impairment (MCI) and with a group of healthy volunteers. The second study, involving participants in an Israeli registry of familial Alzheimer's disease, showed associations between brain-scan results, cognitive function, and retinal vasculature in asymptomatic individuals with a family history of Alzheimer's disease.

Both studies involved use of optical coherence tomography (OCT) to study changes in retinal blood vessels. The findings add to previous evidence suggesting associations between retinal changes and Alzheimer's disease, as reported at the American Academy of Ophthalmology meeting.

"Changes in the retinal microvasculature may mirror small-vessel cerebrovascular changes in Alzheimer's disease," Sharon Fekrat, MD, of Duke University Medical Center in Durham, North Carolina, and colleagues concluded in a poster presentation. "These parameters may serve as surrogate noninvasive biomarkers for the diagnosis of Alzheimer's disease. Future studies are needed to determine whether such tests will be able to detect progression of mild cognitive impairment to Alzheimer's disease."

Previous studies demonstrated associations between changes in retinal microvasculature and Alzheimer's disease. Authors of concluded that "retinal microvascular abnormalities may offer an important window on the brain for etiological studies." A study added to the evidence base, as OCT angiography (OCTA) showed retinal vascular abnormalities and altered retinal architecture in patients with normal cognition but preclinical Alzheimer's disease as determined by biomarker tests.

Fekrat and colleagues noted that OCTA-detected vascular remodeling "is increasingly recognized" in association with patients with MCI and Alzheimer's disease. To continue the line of investigation, they conducted a cross-sectional study involving 39 patients with Alzheimer's disease, 37 with MCI, and 133 healthy individuals ages ≥50.

In most cases, OCTA imaging was performed in both eyes of study participants. Additionally, all study participants had cognitive assessments by means of a validated questionnaire. The primary objective was to evaluate retinal microvasculature in the superficial capillary plexus (SCP) and compare findings in the three groups of study participants.

The primary outcome was VD and PD in the SCP, as defined by Early Treatment Diabetic Retinopathy Study (ETDRS) criteria.

The results showed that patients with Alzheimer's disease had significantly reduced VD and PD in both the ETDRS 3-mm circle and ETDRS 3-mm ring as compared with the healthy control group (P=0.015 to P=0.004). The Alzheimer's group also had significantly reduced macular thickness in several sections as compared with the control group (P=0.041 to P=0.004).

The same measures also were significantly reduced in the Alzheimer's subgroup compared with the MCI subgroup (P=0.004 to P=0.001). Additionally, the Alzheimer's subgroup had significantly reduced VD in the 6-mm circle (P=0.047) and a trend toward reduced PD (P=0.053).

The patients with MCI differed from the control group only with respect to temporal retinal nerve fiber layer, which was significantly reduced in the former group (P=0.04).

The Israeli study involved 195 participants in the Israel Registry of Alzheimer's Prevention; 138 had parents with Alzheimer's disease and 57 age-matched controls had parents without Alzheimer's disease. None of the offspring participants had symptoms of Alzheimer's disease.

The primary objective was to identify early retinal biomarkers for Alzheimer's disease, said Ygal Rotenstreich, MD, of Sheba Medical Center in Tel Hashomer in Israel.

The participants underwent retinal assessment by spectral domain OCT, cognitive assessments of executive function and episodic memory, and brain MRI. Results showed that patients with a parental history of Alzheimer's disease had increased left hippocampal volume, which was associated with thicker macular inner layers (P=0.028 to P=0.003). Additionally, better executive functioning was associated with increased macular inner layers (P=0.007 for total macular thickness). No significant associations existed in the control group for any of the retinal measurements.

"The associations between macular thickness, performance in memory, and hippocampal volumes are measurable in yet-asymptomatic subjects at risk for Alzheimer's disease," Rotenstreich's group concluded in a poster presentation. "Observations regarding different layers of the retina -- rather than the entire retinal thickness -- may provide added sensitivity and specificity in the prediction of Alzheimer's's disease."