Visual Sensory Binding is Associated with CSF Neurogranin in Cognitively Healthy Older Adults

Abstract

AbstractBackgroundCognitive tasks that require conjunctive binding – i.e., the integration of distinct features into a coherent representation – are sensitive to AD even in the preclinical stage. To further explore the sensitivity and utility of conjunctive binding tasks, we examined the association of visual sensory binding with novel CSF biomarkers of neurodegeneration in cognitively healthy older adults.MethodTwo versions of a visual search paradigm were used to compare sensory conjunctive binding under conditions that differ in terms of the demands placed on cross‐cortical interactions. In these tasks, the binding of motion direction (up/down or left/right) must be integrated with either luminance contrast (black or white; within stream binding) or isoluminant color (red or green; across‐stream binding). We examined the association of cross‐cortical sensory binding efficiency (the difference in overall median response time between the color and luminance conditions) with CSF biomarkers of AD pathology (Aß42/Aß40 and p‐tau 181) and synapse function (neurogranin, NPTX2, and SNAP25) in N = 32 cognitively healthy older adults (mean age = 74.6, SD = 5.5; mean Dementia Rating Scale score (max score: 144) = 139.9, SD = 2.9).ResultBivariate correlations revealed that cross‐cortical sensory binding efficiency was significantly associated with neurogranin (r = .36; p<.05) but not with Aß42 (r = .08; p = .68), p‐tau 181 (r = .25; p = .17), NPTX2 (r = .04; p = .82), or SNAP25 (r = .16; p = .41). In multiple regression analyses, neurogranin remained significantly associated with binding efficiency (ß = .46; p = .02) after controlling for age (ß = .03; p = .87), sex/gender (ß = .17; p = .33), and Aß42/Aß40 (ß = .30; p = .14). The addition of p‐tau 181 (ß = .45; p = .12) to this model slightly attenuated the association between neurogranin and binding (ß = .27; p = .24).ConclusionIn cognitively healthy older adults, efficiency of cross‐cortical conjunctive binding on a visual search task was significantly associated with CSF neurogranin, a post‐synaptic protein that is abundant in dendritic spines. Increased CSF neurogranin signifies synaptic degeneration and is specific to AD. Results suggest that visual sensory binding is a cognitive marker that is sensitive to changes in synaptic function in older adults who perform normally on traditional neuropsychological measures. Follow‐up investigation will determine if visual sensory binding efficiency is predictive of cognitive decline and subsequent dementia.