High‑Resolution T2 MRI Volumetry of Medial Temporal Lobe Subregions Predicts Cognitive Decline Across the Alzheimer’s Disease Continuum

Atrophy of medial temporal lobe (MTL) subregions is an early biomarker of Alzheimer's disease (AD). This study aimed to examine the relationship between MTL subregion volumes and cognitive performance in patients across the AD continuum. We analyzed data from 276 participants using the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 74 cognitively normal (CN), 110 subjective memory complaints (SMC), 37 early mild cognitive impairment (EMCI), 35 late mild cognitive impairment (LMCI), and 20 AD participants. MTL subregions volumes were measusing high-resolution T2-weighted MRI, and analyses were adjusted for age, education, <i>APOE</i> ε4 status, and intracranial volume (ICV). Significant atrophy in regions such as the cornu ammonis (CA), dentate gyrus (DG), subiculum (SUB), entorhinal cortex (ERC), and Brodmann area 35 (BA35) was found in AD participants compared with other groups. In AD, poorer Alzheimer's Disease Assessment Scale - Cognitive Subscale 13 (ADAS-13) performance was associated with reduced CA, DG, BA35, and parahippocampal cortex (PHC) volumes. In LMCI, lower Mini-Mental State Examination (MMSE) scores were associated with atrophy in CA and SUB. Diminished Montreal Cognitive Assessment (MoCA) scores were linked to reduced ERC volumes in CN, as well as with atrophy in BA35, ERC and CA subfields among AD patients. In LMCI, poorer Trail Making Test, Part B performance (i.e., longer completion time) was related to smaller Brodmann area 36 (BA36), collateral sulcus (CS), and PHC subregion volumes, whereas in the AD, it was related to BA36 only. Poorer immediate memory recall in AD was associated with atrophy in CA, DG, while in early stages of MCI, poorer verbal learning scores correlated with atrophy in the CA, DG, BA35, SUB, and CS regions. Moreover, diminished Logical Memory Delayed Recall was associated with atrophy in the CA, BA35, and PHC subfields among AD subjects. These findings support the value of atrophy in MTL subregions as potential imaging markers for detecting and monitoring cognitive decline across the AD continuum.