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Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease

OBJECTIVE: Parkinson's disease (PD) episodic memory impairments are common; however, it is not known whether these impairments are due to hippocampal pathology. Hippocampal Lewy-bodies emerge by Braak stage 4, but are not uniformly distributed. For instance, hippocampal CA1 Lewy-body pathology...

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Autores principales: La, Christian, Linortner, Patricia, Bernstein, Jeffrey D., Ua Cruadhlaoich, Matthew A.I., Fenesy, Michelle, Deutsch, Gayle K., Rutt, Brian K., Tian, Lu, Wagner, Anthony D., Zeineh, Michael, Kerchner, Geoffrey A., Poston, Kathleen L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500913/
https://www.ncbi.nlm.nih.gov/pubmed/31054380
http://dx.doi.org/10.1016/j.nicl.2019.101824
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author La, Christian
Linortner, Patricia
Bernstein, Jeffrey D.
Ua Cruadhlaoich, Matthew A.I.
Fenesy, Michelle
Deutsch, Gayle K.
Rutt, Brian K.
Tian, Lu
Wagner, Anthony D.
Zeineh, Michael
Kerchner, Geoffrey A.
Poston, Kathleen L.
author_facet La, Christian
Linortner, Patricia
Bernstein, Jeffrey D.
Ua Cruadhlaoich, Matthew A.I.
Fenesy, Michelle
Deutsch, Gayle K.
Rutt, Brian K.
Tian, Lu
Wagner, Anthony D.
Zeineh, Michael
Kerchner, Geoffrey A.
Poston, Kathleen L.
author_sort La, Christian
collection PubMed
description OBJECTIVE: Parkinson's disease (PD) episodic memory impairments are common; however, it is not known whether these impairments are due to hippocampal pathology. Hippocampal Lewy-bodies emerge by Braak stage 4, but are not uniformly distributed. For instance, hippocampal CA1 Lewy-body pathology has been specifically associated with pre-mortem episodic memory performance in demented patients. By contrast, the dentate gyrus (DG) is relatively free of Lewy-body pathology. In this study, we used ultra-high field 7-Tesla to measure hippocampal subfields in vivo and determine if these measures predict episodic memory impairment in PD during life. METHODS: We studied 29 participants with PD (age 65.5 ± 7.8 years; disease duration 4.5 ± 3.0 years) and 8 matched-healthy controls (age 67.9 ± 6.8 years), who completed comprehensive neuropsychological testing and MRI. With 7-Tesla MRI, we used validated segmentation techniques to estimate CA1 stratum pyramidale (CA1-SP) and stratum radiatum lacunosum moleculare (CA1-SRLM) thickness, dentate gyrus/CA3 (DG/CA3) area, and whole hippocampus area. We used linear regression, which included imaging and clinical measures (age, duration, education, gender, and CSF), to determine the best predictors of episodic memory impairment in PD. RESULTS: In our cohort, 62.1% of participants with PD had normal cognition, 27.6% had mild cognitive impairment, and 10.3% had dementia. Using 7-Tesla MRI, we found that smaller CA1-SP thickness was significantly associated with poorer immediate memory, delayed memory, and delayed cued memory; by contrast, whole hippocampus area, DG/CA3 area, and CA1-SRLM thickness did not significantly predict memory. Age-adjusted linear regression models revealed that CA1-SP predicted immediate memory (beta[standard error]10.895[4.215], p < .05), delayed memory (12.740[5.014], p < .05), and delayed cued memory (12.801[3.991], p < .05). In the fully-adjusted models, which included all five clinical measures as covariates, only CA1-SP remained a significant predictor of delayed cued memory (13.436[4.651], p < .05). CONCLUSIONS: In PD, we found hippocampal CA1-SP subfield thickness estimated on 7-Tesla MRI scans was the best predictor of episodic memory impairment, even when controlling for confounding clinical measures. Our results imply that ultra-high field imaging could be a sensitive measure to identify changes in hippocampal subfields and thus probe the neuroanatomical underpinnings of episodic memory impairments in patients with PD.
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spelling pubmed-65009132019-05-10 Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease La, Christian Linortner, Patricia Bernstein, Jeffrey D. Ua Cruadhlaoich, Matthew A.I. Fenesy, Michelle Deutsch, Gayle K. Rutt, Brian K. Tian, Lu Wagner, Anthony D. Zeineh, Michael Kerchner, Geoffrey A. Poston, Kathleen L. Neuroimage Clin Regular Article OBJECTIVE: Parkinson's disease (PD) episodic memory impairments are common; however, it is not known whether these impairments are due to hippocampal pathology. Hippocampal Lewy-bodies emerge by Braak stage 4, but are not uniformly distributed. For instance, hippocampal CA1 Lewy-body pathology has been specifically associated with pre-mortem episodic memory performance in demented patients. By contrast, the dentate gyrus (DG) is relatively free of Lewy-body pathology. In this study, we used ultra-high field 7-Tesla to measure hippocampal subfields in vivo and determine if these measures predict episodic memory impairment in PD during life. METHODS: We studied 29 participants with PD (age 65.5 ± 7.8 years; disease duration 4.5 ± 3.0 years) and 8 matched-healthy controls (age 67.9 ± 6.8 years), who completed comprehensive neuropsychological testing and MRI. With 7-Tesla MRI, we used validated segmentation techniques to estimate CA1 stratum pyramidale (CA1-SP) and stratum radiatum lacunosum moleculare (CA1-SRLM) thickness, dentate gyrus/CA3 (DG/CA3) area, and whole hippocampus area. We used linear regression, which included imaging and clinical measures (age, duration, education, gender, and CSF), to determine the best predictors of episodic memory impairment in PD. RESULTS: In our cohort, 62.1% of participants with PD had normal cognition, 27.6% had mild cognitive impairment, and 10.3% had dementia. Using 7-Tesla MRI, we found that smaller CA1-SP thickness was significantly associated with poorer immediate memory, delayed memory, and delayed cued memory; by contrast, whole hippocampus area, DG/CA3 area, and CA1-SRLM thickness did not significantly predict memory. Age-adjusted linear regression models revealed that CA1-SP predicted immediate memory (beta[standard error]10.895[4.215], p < .05), delayed memory (12.740[5.014], p < .05), and delayed cued memory (12.801[3.991], p < .05). In the fully-adjusted models, which included all five clinical measures as covariates, only CA1-SP remained a significant predictor of delayed cued memory (13.436[4.651], p < .05). CONCLUSIONS: In PD, we found hippocampal CA1-SP subfield thickness estimated on 7-Tesla MRI scans was the best predictor of episodic memory impairment, even when controlling for confounding clinical measures. Our results imply that ultra-high field imaging could be a sensitive measure to identify changes in hippocampal subfields and thus probe the neuroanatomical underpinnings of episodic memory impairments in patients with PD. Elsevier 2019-04-18 /pmc/articles/PMC6500913/ /pubmed/31054380 http://dx.doi.org/10.1016/j.nicl.2019.101824 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Regular Article
La, Christian
Linortner, Patricia
Bernstein, Jeffrey D.
Ua Cruadhlaoich, Matthew A.I.
Fenesy, Michelle
Deutsch, Gayle K.
Rutt, Brian K.
Tian, Lu
Wagner, Anthony D.
Zeineh, Michael
Kerchner, Geoffrey A.
Poston, Kathleen L.
Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease
title Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease
title_full Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease
title_fullStr Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease
title_full_unstemmed Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease
title_short Hippocampal CA1 subfield predicts episodic memory impairment in Parkinson's disease
title_sort hippocampal ca1 subfield predicts episodic memory impairment in parkinson's disease
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500913/
https://www.ncbi.nlm.nih.gov/pubmed/31054380
http://dx.doi.org/10.1016/j.nicl.2019.101824
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