Longitudinal morphometry of medial temporal lobe subregions in earlyAlzheimer’s disease

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AbstractBackgroundStructural MRI is frequently used to track Alzheimer’s disease (AD) progression in clinic, research, and pharmacological trials. It has been shown that established MRI‐derived measures lack diagnostic sensitivity particularly in early stages of AD. Here, we investigate if the utility of structural MRI for tracking early AD progression can be increased when focusing on subregions of the medial temporal lobe (MTL) which are known to exhibit earliest AD‐related neuropathological change.MethodWe used data from N = 143 participants enrolled in the DZNE Longitudinal Cognitive Impairment and Dementia Study (DELCODE). This included cognitively unimpaired participants who were either Aß‐negative (CU Aß‐; n = 67) or Aß‐positive (CU Aß+; n = 20), Aß+ participants with subjective cognitive decline (SCD Aß+; n = 38), and Aß+ participants with MCI (MCI Aß+; n = 18). Participants underwent annual assessments up to three years after baseline, including MRI (2.19 ± 0.86 follow‐ups) and a neuropsychological testing (2.18 ± 0.83 follow‐ups). Segmentations of MTL subregions were generated using a longiudinal, template‐based implementation of the Automated Segmentation of Hippocampal Subfields (ASHS; Yushkevich et al., 2015, Hum Brain Mapp.) algorithm (Figure 1). Linear mixed models were fitted to derive volumetric slopes and to test their relationship with longitudinal changes in Preclinical Alzheimer Cognitive Composite (PACC‐5) scores.ResultWe observed significant volume losses across diagnostic groups with the MCI Aß+ group exhibiting the fastest rates. Compared with the CU Aß‐ group, there were accelerated volume losses in the subiculum and dentate gyrus in the SCD Aß+ group and, additionally, in the entorhinal cortex and Brodmann areas 35 and 36 in the MCI Aß+ group. There was also a trend towards faster volume losses in the entorhinal cortex in the CU Aß+ group. Higher rates of MTL subregional volume losses, particularly in the cornu ammonis 1 subfield, were related to a faster decline on the PACC‐5 in the MCI Aß+ group. This effect remained significant when controlling for baseline volumes.ConclusionOur findings highlight the viability of subregional MTL morphometry for tracking earliest neurodegeneration and related cognitive decline due to AD.