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AS714 - Pilot study of sensitive and specific clinical biomarkers of B vitamin deficiency and relationship to AMD

AS714 - Pilot study of sensitive and specific clinical biomarkers of B vitamin deficiency and relationship to AMD

[This page is intended to provide a study summary, the sections of which are below. Please complete these sections, as applicable. The headings below are suggested headings. You can remove inapplicable sections, or add new ones relevant to your study]

Investigator Names and Contact Information

Julie Mares

Paul Jacques


We propose to conduct a pilot study to describe the relationship of blood markers for the status of vitamin B 12 and folate to the 15-year incidence of age-related macular degeneration (AMD) and other indicators of ocular health, in a subsample 200 women in the Carotenoids in Age-Related Eye Disease Study (CAREDS) cohort. To assess B12 status, we will use a combined index of B12 insufficiency biomarkers, which has demonstrated a higher sensitivity to identify individuals with vitamin B12 insufficiency than circulating levels of this vitamin, alone, in other study samples. We will determine whether women who developed clinically significant AMD over the fifteen years of follow-up had lower vitamin B 12 status than women with similar ages and AMD severity at baseline who did not develop clinically significant AMD. We will also determine whether B12 status based on a more sensitive and specific measure of a combined score differed among those who did and did not develop AMD, and the magnitude of that difference.

Specific Aims
Aim. To describe, for the first time, the relationships of scores on a combined index of three markers of subclinical B12 insufficiency to AMD status, in a matched case-control study.

These data will permit us to compute the power to detect relationships of the combined B12 index score to AMD, if one exists, in the larger cohort for AS 612 (modification 3). These data will also provide a comparison of the odds for AMD among women in high vs. low quantiles of the index, and of serum B12, and folate.

Exploratory Aim. To determine whether the status of folate, vitamin B12, and homocysteine (Hcy) are related, both alone and in the combined B12 index, to subclinical morphological indicators of retinal health, as assessed by SD-OCT in 100 participants who do not have AMD (and were selected as controls in Aim 1.)
  • Hypothesis 2a: Better folate, vitamin B12, and Hcy status , and scores on the combined index are related to the following morphological measures of retinal health, as assessed by SD-OCT:
    •  Greater total thickness of the retina in the center, inner and outer ETDRS subfields of the macula, and of the photoreceptor area at the center point
      • Ganglion cell complex (GCC) comprising the:
        • Inner-plexiform layer (IPL) made up of the ganglion cell dendrites
        • Ganglion cell layer (GCL) made up of the ganglion cell bodies
        • Retinal nerve fiber layer (RNFL) made up of the ganglion cell axons
      • Retinal nerve fiber layer around the optic nerve head
These aims will support an R01 application to study the relationship between blood markers for B vitamins and retinal neurodegeneration in the full CAREDS cohort of 2005 women, (as described in AS 612). See the Aims for AS 612 in section A.1). The summary statement on a previous NIH application submitted for AS 612 suggested that preliminary data in support of a relationship of the combined index of vitamin B12 status and AMD be provided within samples collected in this specific study population.