Intracellular signal changes in the anterosuperior medial temporal lobe associated with early cognitive decline

Abstract

AbstractBackgroundHippocampal degeneration and loss of white matter integrity both play a role in AD pathology. The anterosuperior part of the medial temporal lobe (MTL) acts as a white matter connecting point between the fontal and temporal lobes. Loss of white matter integrity in tracts passing through this region has been associated with AD [1,2]. Our aim was to use diffusion MRI to investigate changes in microstructure of white matter tracts passing through this region corresponding with cognitive impairment.Method120 subjects from the ADNI 3 cohort with multi‐shell diffusion MRI were analyzed [3]. Tractography through the anterosuperior MTL (asMTL) tracts were performed using the Quantitative Imaging Toolkit (QIT), using HCP‐derived atlas data [4,5]. Three tracts were selected for analysis including the uncinate and inferior fronto‐occipital fasciculi and the anterior commissure. . Subjects with global clinical dementia rating of 0 (N=71) and 1 (N=39) were grouped as cognitively normal (CN) and mild cognitive impairment (MCI), respectively. Intracellular signal fraction, isotropic signal fraction (free water) were obtained using NODDI [6] and mean diffusivity were obtained using DTI [7] estimated using QIT. The association between cognitive impairment and imaging features were assessed using logistic regression with age, sex, and brain volume as covariates.ResultThe intracellular signal fraction was reduced to a significant extent bilaterally in the uncinate and inferior fronto‐occipital fasciculi and anterior commissure among MCI compared to CN individuals (Figure 2.a). No significant difference in isotropic signal was observed (Figure 2.b). We also observed significantly increased mean diffusivity among MCI bilaterally in the uncinate fasciculi and the anterior commissure and trended towards significance bilaterally in the inferior fronto‐occipital fasciculi (Figure 2.c).ConclusionWe found significant microstructural alteration in early cognitive decline in tracts passing through the asMTL region. Among these tracts, the left inferior fronto‐occipital fasciculus showed the largest microstructural changes (Cohen’s D=0.525721). Identifying early white matter changes could aid early diagnosis or disease progression monitoring, as it has been suggested that white matter atrophy precede symptom onset [2]. Results suggest that decreased intracellular signal fraction in these tracts passing through the asMTL as a potential driving factor of this increased diffusivity.