Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal Study
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 cognitivel...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2021.750154/full |
| _version_ | 1818585261907378176 |
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| author | Léa Chauveau Elizabeth Kuhn Cassandre Palix Francesca Felisatti Valentin Ourry Valentin Ourry Vincent de La Sayette Gaël Chételat Robin de Flores |
| author_facet | Léa Chauveau Elizabeth Kuhn Cassandre Palix Francesca Felisatti Valentin Ourry Valentin Ourry Vincent de La Sayette Gaël Chételat Robin de Flores |
| author_sort | Léa Chauveau |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T08:34:16Z |
| format | Article |
| id | doaj.art-352465536b4447bcb5e26fe57d87f59b |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-16T08:34:16Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-352465536b4447bcb5e26fe57d87f59b2022-12-21T22:37:48ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652021-10-011310.3389/fnagi.2021.750154750154Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal StudyLéa Chauveau0Elizabeth Kuhn1Cassandre Palix2Francesca Felisatti3Valentin Ourry4Valentin Ourry5Vincent de La Sayette6Gaël Chételat7Robin de Flores8U1237 PhIND, Inserm, Caen-Normandie University, GIP Cyceron, Caen, FranceU1237 PhIND, Inserm, Caen-Normandie University, GIP Cyceron, Caen, FranceU1237 PhIND, Inserm, Caen-Normandie University, GIP Cyceron, Caen, FranceU1237 PhIND, Inserm, Caen-Normandie University, GIP Cyceron, Caen, FranceU1237 PhIND, Inserm, Caen-Normandie University, GIP Cyceron, Caen, FranceU1077 NIMH, Inserm, Caen-Normandie University, École Pratique des Hautes Études, Caen, FranceU1077 NIMH, Inserm, Caen-Normandie University, École Pratique des Hautes Études, Caen, FranceU1237 PhIND, Inserm, Caen-Normandie University, GIP Cyceron, Caen, FranceU1237 PhIND, Inserm, Caen-Normandie University, GIP Cyceron, Caen, FranceMedial 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.https://www.frontiersin.org/articles/10.3389/fnagi.2021.750154/fullmedial temporal lobe (MTL)Alzheimer's diseaseagingepisodic memorystructural magnetic resonance imagingmild cognitive impairment |
| spellingShingle | Léa Chauveau Elizabeth Kuhn Cassandre Palix Francesca Felisatti Valentin Ourry Valentin Ourry Vincent de La Sayette Gaël Chételat Robin de Flores Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal Study Frontiers in Aging Neuroscience medial temporal lobe (MTL) Alzheimer's disease aging episodic memory structural magnetic resonance imaging mild cognitive impairment |
| title | Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal Study |
| title_full | Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal Study |
| title_fullStr | Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal Study |
| title_full_unstemmed | Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal Study |
| title_short | Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal Study |
| title_sort | medial temporal lobe subregional atrophy in aging and alzheimer s disease a longitudinal study |
| topic | medial temporal lobe (MTL) Alzheimer's disease aging episodic memory structural magnetic resonance imaging mild cognitive impairment |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2021.750154/full |
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