Understanding the Clinical Utility of Low-Contrast Letter Acuity and RAN Tasks in Alzheimer Disease

Lauren Seidman

Alzheimer disease (AD) is a common neurodegenerative condition marked by a slow loss of cognitive function and memory. Amyloid plaques and neurofibrillary tangles build up in the brain in AD, resulting in the death of neurons and malfunctioning synapses. There are several reasons early AD identification is stressed, including the need for future planning, access to various therapies or interventions that may half the spread of illness, or the ability to enroll in clinical trials and research projects for cutting-edge approaches and preventive measures.

At the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, a group of reseachers from NYU Langone presented a study on the use of binocular visual measures of low-contrast letter acuity (LCLA) to distinguish patients with mild cognitive impairment due to AD and AD vs cognitively normal controls. The study, which included 75 participants (MCI: n = 31; AD: n = 10; controls: 34; age, 74 [±6] years), also used the Mobile Universal Lexicon Evaluation (MULES) and the Staggered Uneven Number (SUN) tests.

Led by Lauren Seidman, results showed that LCLA scores at 2.5% were significantly lower (worse) in MCI vs controls (28 vs 36 letters; P = .02); this was also similar for 1.25% (MCI: 5 letters vs 12 for controls; P = .004). MULES times were slower (worse) in MCI compared with controls using the tablet (75 sec for MCI vs. 60 for controls, p=0.03), and for AD vs. controls for both paper/pencil (152 vs. 59 sec, p=0.0001) and tablet (100 vs. 60 sec, p=0.003). Seidman, a second-year student at NYU’s Grossman School of Medicine, sat down at AAN to discuss her research, some of the major takeaways, and the clinical utility of rapid automatized naming tasks (RAN).

NeurologyLive: What were some of the greatest takeaways from the study?

Lauren Seidman: We looked specifically at three different tests, low contrast visual acuity and three RAN tasks, or rapid automatized naming tasks. One asks participants to name a bunch of pictures out loud in different contexts, and the other asks participants to read aloud numbers in different spatial orientations. We were really surprised and happy to see the low contrast visual acuity, and specifically the picture naming ran task, does a really good job of differentiating patients with mild cognitive impairment from normal aging controls. What's exciting about that result is that we're hoping to catch neurodegenerative changes early on so we can have patients enroll in relevant clinical trials and also start disease modifying therapies early.

How are the MULES and SUN used in clinical settings? Are there advantages/limitations to each?

We know that RAN tasks have been used for centuries. Our group recently employed an app called MICK that uses the MULES and SUN, but in a digitized format. We're hoping that improves the ease of use. Our group has used the MICK app in trials of concussion, research in sports sideline studies, and specifically in division one football and in youth hockey. We're seeing that this is a really feasible and good way to assess for concussion symptoms in sports patients. Our goal is to see, can we expand that to the aging population for Alzheimer disease and patients with mild cognitive impairment?

How can we build upon this data?

I think we're really excited about the ability of these simple tasks to track these complex cognitive changes. It would be a good idea to see if we can track disease progression using these binocular visual tests. Also, can we continue to measure cognitive decline using these tests to see if patients get worse or better using them. In addition, it would be a good idea to run a large-scale feasibility analysis to see if clinicians like using our app, the RAN tasks, and low contrast visual acuity in addition to the cognitive tests they already use.

As someone who’s still in medical school, how does it feel to be at AAN? What are your biggest takeaways?

It's been incredible to be here at ANN. I really appreciate the opportunity to connect with all my future colleagues in the field. The idea of brain health is something that I’m hearing a lot throughout. With this being the new frontier, we hear a lot about cardiac health, heart healthy foods, gut health, probiotics, as well as making brain health more mainstream and getting lay people excited about the research that we're all doing together.

Transcript edited for clarity. Click here for more coverage of AAN 2024.

REFERENCE
1. Seidman L, Hyman S, Galetta S, Masurkar A, Balcer L. Binocular visual function testing in an Alzheimer’s disease research cohort: low-contrast letter acuity and rapid automatized naming (RAN) tasks of MULES and SUN. Presented at: 2024 AAN Annual Meeting; April 13-18; Denver, CO. Abstract 005987