Neurodegeneration in cortical circuits vulnerable to early Alzheimer’s disease (AD) disrupts projections between distinct but functionally related cortical regions resulting in a functional disconnection syndrome. Therefore, conjunctive binding (i.e., combining distinct sensory features into a coherent representation) that requires cross-cortical interaction may be particularly sensitive to early AD pathology. We evaluated the potential utility of performance within a novel visual sensory binding paradigm as a behavioral marker of preclinical AD.

N=123 cognitively unimpaired older adults (55 men, 68 women) with normal color vision were recruited from the UCSD Alzheimer’s Disease Research Center. Overall mean age=79.1 years, education=17.0 years, and Dementia Rating Scale score=139.6 (max=144).

We developed a unique visual search paradigm that assesses sensory binding under conditions that place differential demands on cross-cortical interactions. In this task, a target’s motion (up-and-down or left-and-right) must be integrated with either its luminance contrast (black or white) or its isoluminant color (red or green). Participants search for a target stimulus (e.g., red dot moving up-and-down) among distractor stimuli that share the target’s features (e.g., green dots moving up-and-down and red dots moving left-and-right). Thus, the target stimulus cannot be identified by either motion direction or color information alone; rather, the conjunction of motion direction and color/luminance information must be integrated to accurately detect the target. Search displays consist of 1, 3, or 5 stimuli. A target stimulus is present on half of the trials (with 0, 2, or 4 distractors). Participants press a response key when a target is detected in the display. Reaction time (RT) is recorded. Each condition (color-motion, luminance-motion) is presented separately as a single continuous block of 108 trials. Because color-motion integration places greater demands than luminance-motion integration on cross-cortical binding, binding efficiency is calculated as the ratio of the slopes for RT across set-size 1-3-5 on the color vs. luminance conditions.

Plasma levels of P-tau181, a biomarker of AD pathology, were determined by the National Centralized Repository for Alzheimer’s Disease using Quanterix(v2). Plasma P-tau181>4.09 pg/mL determined AD biomarker positivity.

N=40 participants were plasma P-tau181 positive. Analyses of covariance comparing AD biomarker-positive and AD biomarker-negative groups while controlling for age, education, sex, and the sex by biomarker group interaction showed that AD biomarker positivity was the only factor significantly associated with sensory binding efficiency (F[1,117]=7.59; p<.01).  RT slowed significantly more as set size increased in the color condition than in the luminance condition for AD biomarker-positive participants, whereas RT slope across set size was similar in the luminance and color conditions for the AD biomarker-negative participants. In contrast, age (F[1,117]=17.45; p<.001), education (F[1,117]=7.03; p<.01), and sex (F[1,117]=21.57; p<.001) were highly significant predictors of overall RT (collapsed across condition), but AD biomarker positivity was not (F[1,117]=1.31; p=.25).

AD biomarker-positive cognitively unimpaired older adults performed significantly worse than biomarker-negative controls on a novel task requiring visual sensory binding that engages cross-cortical interaction. Thus, this task may be useful as a novel behavioral marker of preclinical AD. Follow-up investigations will determine if visual sensory binding efficiency predicts cognitive decline and subsequent dementia.