Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal Study

Abstract

Medial temporal lobe (MTL) atrophy is a key feature of Alzheimer's disease (AD), however, it also occurs in typical aging. To enhance the clinical utility of this biomarker, we need to better understand the differential effects of age and AD by encompassing the full AD-continuum from cognitively unimpaired (CU) to dementia, including all MTL subregions with up-to-date approaches and using longitudinal designs to assess atrophy more sensitively. Age-related trajectories were estimated using the best-fitted polynomials in 209 CU adults (aged 19–85). Changes related to AD were investigated among amyloid-negative (Aβ−) (n = 46) and amyloid-positive (Aβ+) (n = 14) CU, Aβ+ patients with mild cognitive impairment (MCI) (n = 33) and AD (n = 31). Nineteen MCI-to-AD converters were also compared with 34 non-converters. Relationships with cognitive functioning were evaluated in 63 Aβ+ MCI and AD patients. All participants were followed up to 47 months. MTL subregions, namely, the anterior and posterior hippocampus (aHPC/pHPC), entorhinal cortex (ERC), Brodmann areas (BA) 35 and 36 [as perirhinal cortex (PRC) substructures], and parahippocampal cortex (PHC), were segmented from a T1-weighted MRI using a new longitudinal pipeline (LASHiS). Statistical analyses were performed using mixed models. Adult lifespan models highlighted both linear (PRC, BA35, BA36, PHC) and nonlinear (HPC, aHPC, pHPC, ERC) trajectories. Group comparisons showed reduced baseline volumes and steeper volume declines over time for most of the MTL subregions in Aβ+ MCI and AD patients compared to Aβ− CU, but no differences between Aβ− and Aβ+ CU or between Aβ+ MCI and AD patients (except in ERC). Over time, MCI-to-AD converters exhibited a greater volume decline than non-converters in HPC, aHPC, and pHPC. Most of the MTL subregions were related to episodic memory performances but not to executive functioning or speed processing. Overall, these results emphasize the benefits of studying MTL subregions to distinguish age-related changes from AD. Interestingly, MTL subregions are unequally vulnerable to aging, and those displaying non-linear age-trajectories, while not damaged in preclinical AD (Aβ+ CU), were particularly affected from the prodromal stage (Aβ+ MCI). This volume decline in hippocampal substructures might also provide information regarding the conversion from MCI to AD-dementia. All together, these findings provide new insights into MTL alterations, which are crucial for AD-biomarkers definition.

Automated High-Definition MRI Processing Routine Robustly Detects Longitudinal Morphometry Changes in Alzheimer’s Disease Patients

“…Even though there is a ubiquitous and quite consistent trend of brain morphometry loss in wide parts of the cortex, the temporal lobe expressed the most significant effects even after multiple testing correction. Our findings are well in line with previous literature showing that the medial temporal lobe degenerates strongest in AD patients compared to typically aging subjects ( Jack et al, 1998 ; Chauveau et al, 2021 ). Here, we documented temporal tissue loss by more precise surface based morphometry and at a higher resolution of 360 cortical areas, which has become possible due to increased imaging quality in ADNI3 compared to previous ADNI studies ( Jack et al, 2008 ) and further developed software-aided image assessments.…”

Temporal pole volume is associated with episodic autobiographical memory in healthy older adults

“…Yet, our results suggest that typical aging may not sufficiently alter hippocampal volumes to allow detection of these relationships with hippocampal‐dependent tasks. Consistent with this idea, strong positive associations between hippocampal volumes and episodic memory scores have been observed for individuals with mild cognitive impairment and Alzheimer's disease, who often have more pronounced atrophy to the hippocampus than cognitively healthy older adults (Chauveau et al, 2021).…”

“…Significant age‐related reductions have also been observed in nearby parahippocampal white matter, which includes axons of the perforant pathway (Stoub et al, 2012). In terms of macrostructure, both anterior and posterior gray matter volumes shrink with age, but show slightly different trajectories, with the posterior region showing an earlier inflection point and steeper decline thereafter (Chauveau et al, 2021; Langnes et al, 2020). Different trajectories of atrophy may partially explain why other longitudinal findings have demonstrated more robust anterior hippocampal volume change over time in older age (Chen et al, 2010); the years sampled may disproportionately impact the rate of change observed.…”

Temporal and spatial variability of dynamic microstate brain-network in early Parkinson's disease

“…Besides, the function of temporal lobe has a certain relationship with memory and emotion [25]. Previous studies have shown that the temporal lobe is the response area of cognitive impairment in Alzheimer's disease and even dementia, and it reflects the cognitive function network [26,27]. Therefore, this work can further infer that the spatial variability of microstate D network in the left temporal lobe can effectively reflect the cognitive level of PD patients.…”