Alzheimer’s disease and primary open angle glaucoma may share nailfold capillary abnormalities

Abstract

Purpose : Alzheimer’s disease (AD) and primary open angle glaucoma (POAG) are common neurodegenerative diseases without known causes. Superactivated platelets which may cause hemorrhages occur in AD (J Neuro 254:545,2007) and in POAG (IOVS 55;531,2014). Recently we observed a significantly elevated number of nailfold (NF) hemorrhages in POAG (IOVS 56:7021,2015). The purpose is to examine the NF capillary in patients with AD and mild cognitive impairment (MCI) as well as POAG and controls.

Methods : Subjects were recruited from five sites after Institutional Review Board approval. Inclusive criteria were 70 to 90 years of age. Exclusion criteria were connective tissue disease and blood diathesis. NF video microscopy was performed on 10 AD/MCI subjects with a global clinical dementia rating ≥0.5, 56 POAG patients and 46 controls. All controls had IOP< 21 mm Hg OU and a cup-disc ratio of ≤0.6. All POAG patients had manifest visual field loss on standard automated perimetric tests. All AD/MCI patients denied a history of glaucoma. Masked observers graded NF capillary videos for the presence of hemorrhages, dilated capillary loops (>50μm), and avascular areas (>200μm). Intraobserver and interobserver agreement was high. ANOVA with post-hoc Tukey’s correction was used for statistical analysis.

Results : The mean age was comparable: 78.4±7.7 (AD/MCI), 76.5±4.5 (POAG) vs. 73.9±5.2 (control) years. NF hemorrhages were present in 100% of AD/MCI, 86% of POAG compared to 24% of controls. The mean number of hemorrhages per 100 capillaries in AD/MCI was 2.41±2.3 (p<0.001 compared to control), in POAG was 2.06 ±2.0 (p<0.001 compared to controls) and 0.42 ±0.8 in controls. Dilated capillaries were present in 60% of AD/MCI, 45% of POAG and 35% of control subjects (p=0.2). Avascular zones were observed in 30% AD/MCI, 13% POAG, and 4% controls (p=0.1).

Conclusions : Both AD/MCI and POAG patients had significantly more NF hemorrhages compared to controls, supporting the notion that microvascular abnormalities exist in these patients. Since the NF hemorrhages are transient biomarkers lasting less than 7 days, the outcomes of therapeutic interventions to prevent the NF hemorrhages or treatments geared at AD can be readily determined by video microscopy. The etiology of these peripheral microvascular findings requires further studies, but these findings offer an exciting new lead to microvascular disease in AD/MCI and POAG.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.