Association of fractal dimension and other retinal vascular network parameters with cognitive performance and neuroimaging biomarkers: The Multi-Ethnic Study of Atherosclerosis (MESA).

INTRODUCTION: Retinal vascular network changes may reflect the integrity of the cerebral microcirculation, and may be associated with cognitive impairment. METHODS: Associations of retinal vascular measures with cognitive function and MRI biomarkers were examined amongst Multi-Ethnic Study of Atherosclerosis (MESA) participants in North Carolina who had gradable retinal photographs at Exams 2 (2002 to 2004, n = 313) and 5 (2010 to 2012, n = 306), and detailed cognitive testing and MRI at Exam 6 (2016 to 2018). RESULTS: After adjustment for covariates and multiple comparisons, greater arteriolar fractal dimension (FD) at Exam 2 was associated with less isotropic free water of gray matter regions (ß = -0.0005, SE = 0.0024, p = 0.01) at Exam 6, while greater arteriolar FD at Exam 5 was associated with greater gray matter cortical volume (in mm3 , ß = 5458, SE = 20.17, p = 0.04) at Exam 6. CONCLUSION: Greater arteriolar FD, reflecting greater complexity of the branching pattern of the retinal arteries, is associated with MRI biomarkers indicative of less neuroinflammation and neurodegeneration.

MicroRNA expression in extracellular vesicles as a novel blood-based biomarker for Alzheimer's disease.

INTRODUCTION: Brain cell-derived small extracellular vesicles (sEVs) in blood offer unique cellular and molecular information related to the onset and progression of Alzheimer's disease (AD). We simultaneously enriched six specific sEV subtypes from the plasma and analyzed a selected panel of microRNAs (miRNAs) in older adults with/without cognitive impairment. METHODS: Total sEVs were isolated from the plasma of participants with normal cognition (CN; n = 11), mild cognitive impairment (MCI; n = 11), MCI conversion to AD dementia (MCI-AD; n = 6), and AD dementia (n = 11). Various brain cell-derived sEVs (from neurons, astrocytes, microglia, oligodendrocytes, pericytes, and endothelial cells) were enriched and analyzed for specific miRNAs. RESULTS: miRNAs in sEV subtypes differentially expressed in MCI, MCI-AD, and AD dementia compared to the CN group clearly distinguished dementia status, with an area under the curve (AUC) > 0.90 and correlated with the temporal cortical region thickness on magnetic resonance imaging (MRI). DISCUSSION: miRNA analyses in specific sEVs could serve as a novel blood-based molecular biomarker for AD. HIGHLIGHTS: Multiple brain cell-derived small extracellular vesicles (sEVs) could be isolated simultaneously from blood. MicroRNA (miRNA) expression in sEVs could detect Alzheimer's disease (AD) with high specificity and sensitivity. miRNA expression in sEVs correlated with cortical region thickness on magnetic resonance imaging (MRI). Altered expression of miRNAs in sEVCD31 and sEVPDGFRß suggested vascular dysfunction. miRNA expression in sEVs could predict the activation state of specific brain cell types.

Impact of Socioeconomic Disadvantage and Diabetic Retinopathy Severity on Poor Ophthalmic Follow-Up in a Rural Vermont and New York Population.

OBJECTIVE: To investigate the impact of socioeconomic disadvantage and diabetic retinopathy severity on follow-up for vision care among people with diabetes mellitus (DM) residing in rural Vermont and northern New York State. METHODS: A retrospective chart review of people with DM who visited our academic eye clinic at least once between October 1, 2015, and March 31, 2016, was done. Of 1,466 unique patient visits, 500 were chosen for full chart review by simple random sampling. DM follow-up within 1 year was recommended for 331 adults. Data about prescribed and actual follow-up intervals were extracted. Regression models were used to identify factors associated with poor attendance at follow-up appointments. RESULTS: Sixty-eight [20.5%] patients had poor follow-up, defined as no ophthalmology visit within double the prescribed interval. Of these, 57 were not seen in follow-up by the end of study observation. Poor follow-up was greatest among socioeconomically disadvantaged patients, as defined by Medicaid enrollment (odds ratio [OR], 1.95; 95% CI, 1.07-3.56) in comparison to non-disadvantaged patients. Follow-up was better among those with moderate or worse diabetic retinopathy (OR, 0.38 95% CI, 0.20-0.70), and those with macular edema (OR, 0.19; 95% CI, 0.057-0.62). CONCLUSION: Medicaid insurance and better diabetic retinopathy status were associated with worse follow-up among our predominantly rural population of patients. Patients who did not follow-up within double the recommended interval were unlikely to follow-up at all. Interventions are needed to target those at highest risk for poor follow-up.