Erik Erhardt , Anna Horner , Nicholas Shaff , Chris Wertz , Stephanie Nitschke , Andrei Vakhtin , Andrew Mayer , John Adair , Janice Knoefel , Gary Rosenberg , Kathleen Poston , Gerson Suarez Cedeno , Amanda Deligtisch , Sarah Pirio Richardson , Sephira Ryman
{"title":"帕金森病患者的纵向海马亚区、CSF生物标志物和认知","authors":"Erik Erhardt , Anna Horner , Nicholas Shaff , Chris Wertz , Stephanie Nitschke , Andrei Vakhtin , Andrew Mayer , John Adair , Janice Knoefel , Gary Rosenberg , Kathleen Poston , Gerson Suarez Cedeno , Amanda Deligtisch , Sarah Pirio Richardson , Sephira Ryman","doi":"10.1016/j.prdoa.2023.100199","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>Hippocampal atrophy is an indicator of emerging dementia in PD, though it is unclear whether cerebral spinal fluid (CSF) Abeta-42, t-tau, or alpha-syn predict hippocampal subfield atrophy in a <em>de novo</em> cohort of PD patients. To examine whether levels of CSF alpha-synuclein (alpha-syn), beta-amyloid 1–42 (Abeta-42)<sub>,</sub> or total-tau (t-tau) are associated with hippocampal subfield volumes over time.</p></div><div><h3>Methods</h3><p>We identified a subset of Parkinson’s Progression Markers Initiative (PPMI) <em>de novo</em> PD patients with longitudinal T1-weighted imaging (baseline plus at least two additional visits across 12, 24, and 48 months) and CSF biomarkers available at baseline. We performed cross-sectional, regression, and linear mixed model analyses to evaluate the baseline and longitudinal CSF biomarkers, hippocampal subfields, and cognition. A false discovery rate (FDR) was used to correct for multiple comparisons.</p></div><div><h3>Results</h3><p>88 PD-CN and 21 PD-MCI had high quality longitudinal data. PD-MCI patients exhibited reduced bilateral CA1 volumes relative to PD-CN, though there were no significant differences in CSF biomarkers between these groups. Relationships between CSF biomarkers and hippocampal subfields changed over time, with a general pattern that lower CSF Abeta-42, higher t-tau and higher alpha-syn were associated with smaller hippocampal subfields, primarily in the right hemisphere.</p></div><div><h3>Conclusion</h3><p>We replicated prior reports that demonstrated reduced CA1 volumes in PD-MCI in a <em>de novo</em> PD cohort. CSF biomarkers were associated with individual subfields, with evidence that the increased CSF t-tau was associated with smaller subiculum volumes at baseline and over time, though there was no clear indication that the subfields associated with cognition (CA1 and HATA) were associated with CSF biomarkers.</p></div>","PeriodicalId":33691,"journal":{"name":"Clinical Parkinsonism Related Disorders","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Longitudinal hippocampal subfields, CSF biomarkers, and cognition in patients with Parkinson disease\",\"authors\":\"Erik Erhardt , Anna Horner , Nicholas Shaff , Chris Wertz , Stephanie Nitschke , Andrei Vakhtin , Andrew Mayer , John Adair , Janice Knoefel , Gary Rosenberg , Kathleen Poston , Gerson Suarez Cedeno , Amanda Deligtisch , Sarah Pirio Richardson , Sephira Ryman\",\"doi\":\"10.1016/j.prdoa.2023.100199\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Objective</h3><p>Hippocampal atrophy is an indicator of emerging dementia in PD, though it is unclear whether cerebral spinal fluid (CSF) Abeta-42, t-tau, or alpha-syn predict hippocampal subfield atrophy in a <em>de novo</em> cohort of PD patients. To examine whether levels of CSF alpha-synuclein (alpha-syn), beta-amyloid 1–42 (Abeta-42)<sub>,</sub> or total-tau (t-tau) are associated with hippocampal subfield volumes over time.</p></div><div><h3>Methods</h3><p>We identified a subset of Parkinson’s Progression Markers Initiative (PPMI) <em>de novo</em> PD patients with longitudinal T1-weighted imaging (baseline plus at least two additional visits across 12, 24, and 48 months) and CSF biomarkers available at baseline. We performed cross-sectional, regression, and linear mixed model analyses to evaluate the baseline and longitudinal CSF biomarkers, hippocampal subfields, and cognition. A false discovery rate (FDR) was used to correct for multiple comparisons.</p></div><div><h3>Results</h3><p>88 PD-CN and 21 PD-MCI had high quality longitudinal data. PD-MCI patients exhibited reduced bilateral CA1 volumes relative to PD-CN, though there were no significant differences in CSF biomarkers between these groups. Relationships between CSF biomarkers and hippocampal subfields changed over time, with a general pattern that lower CSF Abeta-42, higher t-tau and higher alpha-syn were associated with smaller hippocampal subfields, primarily in the right hemisphere.</p></div><div><h3>Conclusion</h3><p>We replicated prior reports that demonstrated reduced CA1 volumes in PD-MCI in a <em>de novo</em> PD cohort. CSF biomarkers were associated with individual subfields, with evidence that the increased CSF t-tau was associated with smaller subiculum volumes at baseline and over time, though there was no clear indication that the subfields associated with cognition (CA1 and HATA) were associated with CSF biomarkers.</p></div>\",\"PeriodicalId\":33691,\"journal\":{\"name\":\"Clinical Parkinsonism Related Disorders\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical Parkinsonism Related Disorders\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S2590112523000178\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Parkinsonism Related Disorders","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2590112523000178","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Longitudinal hippocampal subfields, CSF biomarkers, and cognition in patients with Parkinson disease
Objective
Hippocampal atrophy is an indicator of emerging dementia in PD, though it is unclear whether cerebral spinal fluid (CSF) Abeta-42, t-tau, or alpha-syn predict hippocampal subfield atrophy in a de novo cohort of PD patients. To examine whether levels of CSF alpha-synuclein (alpha-syn), beta-amyloid 1–42 (Abeta-42), or total-tau (t-tau) are associated with hippocampal subfield volumes over time.
Methods
We identified a subset of Parkinson’s Progression Markers Initiative (PPMI) de novo PD patients with longitudinal T1-weighted imaging (baseline plus at least two additional visits across 12, 24, and 48 months) and CSF biomarkers available at baseline. We performed cross-sectional, regression, and linear mixed model analyses to evaluate the baseline and longitudinal CSF biomarkers, hippocampal subfields, and cognition. A false discovery rate (FDR) was used to correct for multiple comparisons.
Results
88 PD-CN and 21 PD-MCI had high quality longitudinal data. PD-MCI patients exhibited reduced bilateral CA1 volumes relative to PD-CN, though there were no significant differences in CSF biomarkers between these groups. Relationships between CSF biomarkers and hippocampal subfields changed over time, with a general pattern that lower CSF Abeta-42, higher t-tau and higher alpha-syn were associated with smaller hippocampal subfields, primarily in the right hemisphere.
Conclusion
We replicated prior reports that demonstrated reduced CA1 volumes in PD-MCI in a de novo PD cohort. CSF biomarkers were associated with individual subfields, with evidence that the increased CSF t-tau was associated with smaller subiculum volumes at baseline and over time, though there was no clear indication that the subfields associated with cognition (CA1 and HATA) were associated with CSF biomarkers.