Diagnostic images for mild cognitive impairment reveal biomarker status and abnormal scene processing

Research on the impairment of episodic memory in Alzheimer's disease often focuses on the processes of memory rather than the content of the specific images being remembered. We recently showed that patients with mild cognitive impairment (MCI), Stage 3 of Alzheimer's disease, can memorize certain images quite well, suggesting that episodic memory is not uniformly impaired. Certain images, on the other hand, could not be memorized by MCI patients and were instead diagnostic for distinguishing MCI from healthy older adults. In this study, we investigate whether poor memory for diagnostic images is related to impaired neural processing in specific brain regions due to Alzheimer's biomarker pathology. 64 healthy controls and 48 MCI participants in the DELCODE dataset performed a visual scene memory task during fMRI, with CSF Alzheimer's disease biomarker data collected (i.e., amyloid and tau biomarkers). We found that diagnostic images have larger behavior-biomarker correlations for total tau, phospho-tau, Aβ42/Aβ40, Aβ42/phospho-tau compared to non-diagnostic images, suggesting that memory for these specific images are more affected by Alzheimer's disease pathology. The fMRI data revealed an interaction effect between group membership (healthy control / MCI) and image diagnosticity (diagnostic / non-diagnostic scene images), with MCI participants having higher activation in scene processing regions (parahippocampal place area, retrosplenial cortex and occipital place area) for diagnostic images than non-diagnostic images. In contrast, healthy controls showed no differences in processing between diagnostic and non-diagnostic images. These results suggest that MCI individuals may engage in inefficiently heightened encoding activation for these diagnostic images. Our results show that special "diagnostic" images exist that can reveal amyloid and tau pathology and differences in neural activity in scene regions. ### Competing Interest Statement The authors have declared no competing interest.