Hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and Alzheimer’s dementia

Background: Alzheimer’s disease (AD) is characterized by progressive cognitive decline and specific brain atrophy patterns, primarily involving the medial temporal lobes. A number of studies have discussed hypothalamic involvement in AD with consecutive metabolic and/or autonomic disturbances yet on...

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Main Authors: Hannah Pecher, Melanie Storch, Frauke Beyer, Veronica Witte, Christian-Frank Baasner, Peter Schönknecht, Christopher M. Weise
Format: Article
Language:English
Published: Elsevier 2024-01-01
Series:NeuroImage: Clinical
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213158224001281
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author Hannah Pecher
Melanie Storch
Frauke Beyer
Veronica Witte
Christian-Frank Baasner
Peter Schönknecht
Christopher M. Weise
author_facet Hannah Pecher
Melanie Storch
Frauke Beyer
Veronica Witte
Christian-Frank Baasner
Peter Schönknecht
Christopher M. Weise
author_sort Hannah Pecher
collection DOAJ
description Background: Alzheimer’s disease (AD) is characterized by progressive cognitive decline and specific brain atrophy patterns, primarily involving the medial temporal lobes. A number of studies have discussed hypothalamic involvement in AD with consecutive metabolic and/or autonomic disturbances yet only few studies have investigated hypothalamic atrophy in AD and its early stages in particular. Methods: We applied semi-automated volumetry of the hypothalamus (HTH) in 3 T MRI in a sample N = 175 participants [age 74.9 ± 7.22; gender 85 m/90f; cognitively normal controls (CN; N = 56); amnestic mild cognitive impairment (MCI; N = 78); AD (N = 41)] from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). In addition, we used voxel-based morphometry (VBM), cortical thickness (CTH) analyses and source-based morphometry (SBM) derived networks of structural covariance to investigate brain structural covariance patterns of the HTH under consideration of diagnostic groups, β-amyloid (AB) positivity and apolipoprotein E (APOE) ε4 status. Results: Hypothalamic atrophy was observed in both early and advanced disease stages (i.e. hypothalamic volume CN > MCI > AD). VBM, CTH analysis and SBM revealed positive associations between hypothalamic volume (HV) and AD-vulnerable regions, largely corresponding to the Papez circuit and brain regions implicated in autonomic regulation, however, group differences regarding HTH structural covariance were not observed. Similar observations were made in carriers and non-carriers of the ε4 allele, yet more pronounced in ε4 carriers. Although not reaching significance, comparisons of AB positive vs. negative subjects indicated stronger HTH atrophy in biomarker positive participants. HV was not associated with body mass index or longitudinal weight change. Conclusions: Our findings support early structural changes of the HTH in AD. HV covaries with regional volumes of AD-vulnerable regions. This could point to secondary atrophy of the HTH following atrophy of the hippocampus and other structures of the Papez circuit in AD.
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spelling doaj-art-b40a95ecf2924325bcd9783262d6b9762025-08-20T02:49:00ZengElsevierNeuroImage: Clinical2213-15822024-01-014410368710.1016/j.nicl.2024.103687Hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and Alzheimer’s dementiaHannah Pecher0Melanie Storch1Frauke Beyer2Veronica Witte3Christian-Frank Baasner4Peter Schönknecht5Christopher M. Weise6Department of Neurology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), German; Department of Radiology, Bundeswehrkrankenhaus Berlin, Scharnhorststr. 13, 10115 Berlin, Germany; Corresponding author at: Hannah Pecher, Department of Radiology, Bundeswehrkrankenhaus Berlin, Scharnhorststr. 13, 10115 Berlin, Germany.Department of Psychiatry and Psychotherapy, University Hospital Leipzig, Semmelweisstr. 10, 04103 Leipzig, Germany; Department of Biology, University of Leipzig, 04103 Leipzig, GermanyDepartment of Neurology, Max Planck-Institute for Human Cognitive and Brain Sciences, and Cognitive Neurology, University of Leipzig Medical Center, Leipzig, GermanyDepartment of Neurology, Max Planck-Institute for Human Cognitive and Brain Sciences, and Cognitive Neurology, University of Leipzig Medical Center, Leipzig, GermanyDepartment of Neurology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), GermanMedical Faculty, Department of Psychiatry and Psychotherapy, University Hospital Leipzig, 04103 Leipzig, Germany; Out-Patient Department for Sexual-Therapeutic Prevention and Forensic Psychiatry, University Hospital Leipzig, 04103, Leipzig, Germany; Academic Saxon State Hospital Altscherbitz, 04435 Schkeuditz, GermanyDepartment of Neurology, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), GermanBackground: Alzheimer’s disease (AD) is characterized by progressive cognitive decline and specific brain atrophy patterns, primarily involving the medial temporal lobes. A number of studies have discussed hypothalamic involvement in AD with consecutive metabolic and/or autonomic disturbances yet only few studies have investigated hypothalamic atrophy in AD and its early stages in particular. Methods: We applied semi-automated volumetry of the hypothalamus (HTH) in 3 T MRI in a sample N = 175 participants [age 74.9 ± 7.22; gender 85 m/90f; cognitively normal controls (CN; N = 56); amnestic mild cognitive impairment (MCI; N = 78); AD (N = 41)] from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). In addition, we used voxel-based morphometry (VBM), cortical thickness (CTH) analyses and source-based morphometry (SBM) derived networks of structural covariance to investigate brain structural covariance patterns of the HTH under consideration of diagnostic groups, β-amyloid (AB) positivity and apolipoprotein E (APOE) ε4 status. Results: Hypothalamic atrophy was observed in both early and advanced disease stages (i.e. hypothalamic volume CN > MCI > AD). VBM, CTH analysis and SBM revealed positive associations between hypothalamic volume (HV) and AD-vulnerable regions, largely corresponding to the Papez circuit and brain regions implicated in autonomic regulation, however, group differences regarding HTH structural covariance were not observed. Similar observations were made in carriers and non-carriers of the ε4 allele, yet more pronounced in ε4 carriers. Although not reaching significance, comparisons of AB positive vs. negative subjects indicated stronger HTH atrophy in biomarker positive participants. HV was not associated with body mass index or longitudinal weight change. Conclusions: Our findings support early structural changes of the HTH in AD. HV covaries with regional volumes of AD-vulnerable regions. This could point to secondary atrophy of the HTH following atrophy of the hippocampus and other structures of the Papez circuit in AD.http://www.sciencedirect.com/science/article/pii/S2213158224001281Hypothalamic atrophyAlzheimer’s diseaseVolumetryStructural covariance networksMild cognitive impairment
spellingShingle Hannah Pecher
Melanie Storch
Frauke Beyer
Veronica Witte
Christian-Frank Baasner
Peter Schönknecht
Christopher M. Weise
Hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and Alzheimer’s dementia
NeuroImage: Clinical
Hypothalamic atrophy
Alzheimer’s disease
Volumetry
Structural covariance networks
Mild cognitive impairment
title Hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and Alzheimer’s dementia
title_full Hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and Alzheimer’s dementia
title_fullStr Hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and Alzheimer’s dementia
title_full_unstemmed Hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and Alzheimer’s dementia
title_short Hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and Alzheimer’s dementia
title_sort hypothalamic atrophy and structural covariance in amnestic mild cognitive impairment and alzheimer s dementia
topic Hypothalamic atrophy
Alzheimer’s disease
Volumetry
Structural covariance networks
Mild cognitive impairment
url http://www.sciencedirect.com/science/article/pii/S2213158224001281
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