Specific damages to olfactory‐related structures and their relation to episodic memory in Individuals at Risk of Alzheimer’s Disease.

Abstract

AbstractBackgroundOne of the major challenges in the diagnosis of Alzheimer’s disease (AD) is to increase the specificity of the early diagnosis. While episodic memory impairment is a sensitive marker of AD, other markers are needed to improve diagnostic specificity. A promising biomarker might be a cerebral atrophy of the central olfactory processing areas in the early stages of the disease since an impairment of olfactory identification is present at early clinical stages of AD. Our goal was to evaluate whether reduced grey matter volume (GMV) in the central olfactory processing regions could be observed in early and preclinical stages of AD. We also aimed to verify if GMV of central olfactory processing regions is associated with episodic memory performance.Method166 participants from the Consortium for the Early Identification of Alzheimer’s Disease‐Quebec (CIMA‐Q) (92 with subjective cognitive decline ‐ SCD, 40 with mild cognitive impairment ‐ MCI and 34 cognitively healthy controls) were included. We performed regions of interest (ROI) analysis using a mask of the regions that are activated during olfactory stimulation. We also extracted GMV outside ROIs, representing non‐olfactory areas of these regions, i.e., regions which do not respond to olfactory stimulation. Verbal episodic memory was assessed using a free word recall task from Memoria Word Recall test.ResultCompared to controls (p = .019) and participants with SCD (p = .003), participants with MCI exhibited a smaller total GMV of central olfactory processing regions, with a significant interaction effect between region and group (p = .004). Specifically, the piriform cortex, amygdala, entorhinal cortex, and left hippocampus were significantly smaller in individuals with MCI (p≤.05, corrected). In contrast, when comparing GMV outside ROIs between the three groups, there was no such interaction between region and group (p = .428). Additionally, GMV in the olfactory areas of the piriform cortex, amygdala, and left hippocampal gyrus was correlated with episodic memory performance, while GMV in the non‐olfactory areas of the left hippocampus and left parahippocampal gyrus was correlated with episodic memory performance (p≤.05, corrected).ConclusionThere is a specific neurodegeneration of limbic and medial‐temporal olfactory‐structures in MCI, GMV of these regions being related to cognitive performance.