(P09-027-25) Conjunctival Microvascular Abnormalities, Brain White Matter Hyperintensity, and Homocysteine in Cognitively Impaired Older Adults: A Case-Control Study

Objectives: Elevated homocysteine (Hcy) is associated with impaired cognitive function and dementia in older adults. Previously, we have shown that Hcy is correlated with microvascular abnormalities in the white of the eye (bulbar conjunctiva). The objective of this study is to compare conjunctival microvascular abnormalities, brain white matter hyperintensities, and Hcy in older adults with and without cognitive impairment.

Methods: This is a case-control study of older adults (age 60-82y) diagnosed with (n=9) or without (n=18) mild cognitive impairment or Alzheimer's disease. Microvascular abnormalities were quantified as a severity index (SI) score based on 10 identifiable abnormalities in the bulbar conjunctival vasculature, imaged by computer-assisted intravital microscopy. Whole brain and periventricular white matter hyperintensities (wbWMH and pvWMH) were determined by 3T MRI (Siemens Prisma) using UBO Detector. Median values were compared between groups by Mann Whitney U analysis. Linear regression was used to assess the correlations between SI and WMH, controlling for age, sex and BMI.

Results: Median (range) values in the cognitively impaired group were lower for Montreal Cognitive Assessment scores [23 (11-25) vs 28 (26-30); p < 0.001] and higher for age [70y (66-76) vs 63y (60-82); p = 0.007], SI [6 (5-9) vs 3 (2-5); p < 0.001], wbWMH [3479 mm³ (445-38637 mm³) vs 855 mm³ (209-7195 mm³); p = 0.02] and pvWMH [2905 mm³ (371-25734 mm³) vs 739 mm³ (192-6625 mm³); p = 0.04]. The difference in SI (but not in wbWMH or pvWMH) between the groups remained significant after controlling for age, sex and BMI. SI was significantly correlated with both wbWMH and pvWMH (p < 0.04) when all subjects were combined. The associations between SI and wbWMH and pvWMH did not remain significant after controlling for age, sex and BMI.

Conclusions: Conjunctival microvascular abnormalities are elevated in older adults with cognitive impairment and may serve as a sensitive, peripheral biomarker of cognitive impairment and potentially as a surrogate for brain vascular health in older adults. Measurements of Hcy and its determinants (folate, B12, B6, creatinine) are in progress and will be compared between the groups and associations with SI and WMH will be assessed.

Funding Sources: Rutgers Center for Advanced Human Brain Imaging Research