OBJECT AND SCENE MEMORY ARE DIFFERENTIALLY ASSOCIATED WITH CSF MARKERS OF ALZHEIMER’S DISEASE AND MRI VOLUMETRY

Abstract

Alzheimer's Disease (AD) is characterized by progressive tau-pathology in perirhinal and entorhinal cortices (ErC), hippocampus, parahippocampal cortex and the retrosplenial/posterior cingulate region (RsC/PCC). The latter also shows early amyloid plaque accumulation. While these regions form a network for complex objects-in-scene memories, there is a segregation of object memory into a perirhinal-entorhinal and scene-layout memory into a RsC/PCC-parahippocampal-entorhinal pathway. Here we investigated whether complex objects-in-scene memory, as opposed to isolated object or scene-layout memory is correlated with CSF levels of Aß42 and phospho-tau and MR volume and thickness measures. 204 participants (cognitively healthy, subjective memory complaints, mild cognitive impairment or early AD) of the DELCODE study of the DZNE performed a complex scene recognition memory task. CSF samples were available from 80 participants. 78 participants also performed a second task on mnemonic discrimination of objects (in the absence of scenes) and scenes (in the absence of objects). Of these 28 CSF samples were available. MR thickness measures were obtained from T1 and T2-weighted images using Freesurfer 6. Objects-in-scene recognition memory correlated with right and left PCC volume (p=0.005; p=0.047), right and left hippocampal volume (p=0.002; p=0.001), Aß42, phospho-tau and their ratio (p=0.002; p=0.002; p=0.000). Isolated object and scene discrimination correlated with left and right hippocampal volume (Scene: p=0.039; p=0.006; Object: p=0.011; p=0.001); scene memory correlated with right and object memory with both left and right ErC thickness (Scene: p=0.027; Object: p=0.024; p=0.031). A scene-minus-object difference score correlated with Aß42 levels indicating that decreasing levels of Aß42 were associated with selective decline of scene discrimination (p=0.034). When considering only healthy older adults, object discrimination relatively selectively correlated with right and left hippocampal volume (n=57; rp=0.022; p=0.005), left entorhinal thickness (p=0.042) and with phospho-tau levels (n=19; p=0.052). These data suggest that complex object-in-scene recognition captures variance caused by both tau and amyloid pathology. A domain-specific breakdown, however, indicates that tau-related variance tends to be captured by object discrimination whereas amyloid pathology is captured by scene discrimination performance. The findings are compatible with the possibility that object and scene discrimination track different stages of disease progression in AD.