Binocular Visual Function Testing in an Alzheimer's Disease Research Center (ADRC) Cohort: Low-Contrast Letter Acuity and Rapid Automatized Naming (RAN) Tasks of MULES and SUN

Binocular vision testing, performed with both eyes uncovered, is useful for reflecting daily activities. Low-contrast letter acuity (LCLA), the Mobile Universal Lexicon Evaluation System (MULES, rapid picture naming) and the Staggered Uneven Number (SUN, rapid number naming) have been used successfully in studies of multiple sclerosis, concussion and Parkinson's disease. We determined the capacity for LCLA, MULES and SUN, to distinguish patients with mild cognitive impairment (MCI) due to Alzheimer's disease and Alzheimer's dementia (AD) vs. cognitively normal controls.

Binocular Visual Function Testing in an Alzheimer’s Disease Research Center Cohort: Low-Contrast Letter Acuity and Rapid Automatized Naming (RAN) Tasks of MULES and SUN Lauren Seidman, BS; Sara Hyman, BS; Scott N. Grossman, MD; Steven L. Galetta, MD; Arjun V. Masurkar, MD, PhD; Laura J. Balcer, MD, MSCE Vision in Alzheimer’s Disease • Disorders of visual processing or perception may be presenting features – often subtle • ~50% of brain’s pathways dedicated to vision • Symptoms and deficits are most often noted when using both eyes together • Binocular testing, performed with both eyes uncovered, captures visual function as is present for daily activities Low-Contrast Letter Acuity (LCLA) • Best known for assessing visual function in multiple sclerosis (MS) • Binocular testing captures treatment effects in MS trials, complements monocular measurements of structurefunction with OCT • Low-contrast vision relates to real-world aspects of vision, including facial recognition Rapid Automatized Naming (RAN) MULES: Mobile Universal Lexicon Evaluation System • Rapid naming of photographic images in context • Examines brain’s visual pathways and neural networks • Tests color perception, object identification, conceptual representation, phonology, articulation SUN: • Staggered Uneven Number Test • Rapid number naming Mobile Integrated Cognitive Kit (MICK) App • Digital tablet platform designed to administer MULES and SUN • Android and iOS test versions • Intent to be freely accessible to facilitate dissemination of the tests to clinical (and sideline) settings • Feasible for use in youth to adult age groups for concussion to date Purpose • Determine the capacity for low-contrast letter acuity and RAN tasks of MULES and SUN to distinguish patients with mild cognitive impairment (MCI) due to Alzheimer’s disease and Alzheimer’s dementia (AD) vs. cognitively normal controls • Examine feasibility for testing of MULES and SUN using MICK app platform for computerized tablet Participants • Alzheimer’s Disease Research Center (ADRC) • Convenience sample of patients and controls • MCI or AD by National Institute on Aging criteria • History of comorbid ocular conditions noted • Written informed consent of patient or proxy Results • N = 75 participants (31 MCI, 10 AD, 34 controls; age 74±6 years) • Low-contrast scores at 2.5% were lower in MCI vs. controls (28 vs. 36 letters, p=0.02, paired t-test); similar for 1.25% (5 vs. 12 letters, p=0.004) • MULES times slower in MCI vs. controls using tablet (75 vs. 60 sec, p=0.03), and for AD vs. controls for both paper/ pencil (152 vs. 59 sec, p=0.0001) and tablet versions (100 vs. 60 sec, p=0.003) • SUN times did not differ for MCI vs. controls, but better distinguished AD vs. controls for both paper/ pencil (84 vs. 56 sec p=0.0001) and tablet (85 vs. 60, p=0.003) Low-Contrast Acuity MULES and SUN Conclusions • Binocular low-contrast acuity, MULES and SUN have potential roles in MCI and AD in a manner similar to MS and are analogous to patient-specific measures such as cognition • These measures likely complement eye-specific tests • May promote identification of MCI for early participation in clinical trials and for disease-modifying therapies Why Binocular Testing? • Monocular vision: more likely a test of refraction rather than an assessment of neurologic function and how the brain processes inputs from both eyes • Binocular summation and inhibition both captured • Depth perception important to navigation of world • Reflects vision as is present for daily activities that are also affected by other aspects of cognition