Neuroanatomical heterogeneity drives divergent cognitive and motor trajectories in Parkinson's disease subtypes
Cognitive symptoms of Parkinson's disease (PD) may initially present subtly, often overshadowed by more noticeable motor symptoms. However, as PD progresses, predicting which individuals will experience significant cognitive decline becomes challenging due to variability, suggesting distinct PD...
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| Veröffentlicht in: | Journal of the neurological sciences 2025-01, Vol.468, p.123335, Article 123335 |
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| creator | Vijayakumari, Anupa A. Saadatpour, Leila Floden, Darlene Fernandez, Hubert Walter, Benjamin L. |
| description | Cognitive symptoms of Parkinson's disease (PD) may initially present subtly, often overshadowed by more noticeable motor symptoms. However, as PD progresses, predicting which individuals will experience significant cognitive decline becomes challenging due to variability, suggesting distinct PD subtypes with varying cognitive trajectories. This study aimed to identify early PD subtypes based on patterns of gray matter atrophy in brain regions associated with cognition and assess their distinct patterns of cognitive change over time. Recognizing PD primarily as a movement disorder, we also evaluated their motor symptoms.
We analyzed T1-weighted MRI data, cognitive, and motor scores from 114 de novo PD patients and 120 healthy controls. Multivariate gray matter volumetric distances (MGMV) across frontal, subcortical, parietal, temporal, and occipital regions were computed, and K-means clustering was used to identify PD subtypes. Subsequently, cognitive assessments were compared between subtypes at baseline and 48 months using linear mixed-effects models and reliable change indices. Motor-symptom changes were assessed using linear mixed-effects models.
Two PD subtypes were identified from baseline MRI. Subtype 1 showed significantly higher MGMV in frontal (p |
| doi_str_mv | 10.1016/j.jns.2024.123335 |
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We analyzed T1-weighted MRI data, cognitive, and motor scores from 114 de novo PD patients and 120 healthy controls. Multivariate gray matter volumetric distances (MGMV) across frontal, subcortical, parietal, temporal, and occipital regions were computed, and K-means clustering was used to identify PD subtypes. Subsequently, cognitive assessments were compared between subtypes at baseline and 48 months using linear mixed-effects models and reliable change indices. Motor-symptom changes were assessed using linear mixed-effects models.
Two PD subtypes were identified from baseline MRI. Subtype 1 showed significantly higher MGMV in frontal (p < 0.001) and subcortical (p < 0.001) regions, indicating atrophy. At 48 months, subtype 1 had poorer global cognitive performance than subtype 2 (p = 0.005) and faster progression of postural instability and gait disturbance (p = 0.04).
PD subtypes identified early by distinct frontal and subcortical atrophy patterns exhibited divergent trajectories of cognitive decline and worsening motor symptoms over time, underscoring the neuroanatomical heterogeneity that drives clinical variability in PD.
•Machine learning was applied to baseline MRI data to identify PD subtypes.•Each PD subtype demonstrated distinct cognitive and motor trajectories.•Our study highlights the need for personalized PD management.</description><identifier>ISSN: 0022-510X</identifier><identifier>ISSN: 1878-5883</identifier><identifier>EISSN: 1878-5883</identifier><identifier>DOI: 10.1016/j.jns.2024.123335</identifier><identifier>PMID: 39644799</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Aged ; Atrophy - pathology ; Brain - diagnostic imaging ; Brain - pathology ; Brain - physiopathology ; Cluster analysis ; Cognition - physiology ; Cognitive decline ; Cognitive Dysfunction - diagnostic imaging ; Cognitive Dysfunction - etiology ; Cognitive Dysfunction - pathology ; Cognitive Dysfunction - physiopathology ; Disease Progression ; Female ; Gray Matter - diagnostic imaging ; Gray Matter - pathology ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Neuroanatomical heterogeneity ; Parkinson Disease - classification ; Parkinson Disease - complications ; Parkinson Disease - diagnostic imaging ; Parkinson Disease - pathology ; Parkinson Disease - physiopathology ; Parkinson's disease ; Postural instability and gait disturbance progression</subject><ispartof>Journal of the neurological sciences, 2025-01, Vol.468, p.123335, Article 123335</ispartof><rights>2024 Elsevier B.V.</rights><rights>Copyright © 2024 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c235t-1512ee2769c170a34e919334d78fd6480ba9a5ff010b0780625e6968fd4dc13a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0022510X24004714$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39644799$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vijayakumari, Anupa A.</creatorcontrib><creatorcontrib>Saadatpour, Leila</creatorcontrib><creatorcontrib>Floden, Darlene</creatorcontrib><creatorcontrib>Fernandez, Hubert</creatorcontrib><creatorcontrib>Walter, Benjamin L.</creatorcontrib><title>Neuroanatomical heterogeneity drives divergent cognitive and motor trajectories in Parkinson's disease subtypes</title><title>Journal of the neurological sciences</title><addtitle>J Neurol Sci</addtitle><description>Cognitive symptoms of Parkinson's disease (PD) may initially present subtly, often overshadowed by more noticeable motor symptoms. However, as PD progresses, predicting which individuals will experience significant cognitive decline becomes challenging due to variability, suggesting distinct PD subtypes with varying cognitive trajectories. This study aimed to identify early PD subtypes based on patterns of gray matter atrophy in brain regions associated with cognition and assess their distinct patterns of cognitive change over time. Recognizing PD primarily as a movement disorder, we also evaluated their motor symptoms.
We analyzed T1-weighted MRI data, cognitive, and motor scores from 114 de novo PD patients and 120 healthy controls. Multivariate gray matter volumetric distances (MGMV) across frontal, subcortical, parietal, temporal, and occipital regions were computed, and K-means clustering was used to identify PD subtypes. Subsequently, cognitive assessments were compared between subtypes at baseline and 48 months using linear mixed-effects models and reliable change indices. Motor-symptom changes were assessed using linear mixed-effects models.
Two PD subtypes were identified from baseline MRI. Subtype 1 showed significantly higher MGMV in frontal (p < 0.001) and subcortical (p < 0.001) regions, indicating atrophy. At 48 months, subtype 1 had poorer global cognitive performance than subtype 2 (p = 0.005) and faster progression of postural instability and gait disturbance (p = 0.04).
PD subtypes identified early by distinct frontal and subcortical atrophy patterns exhibited divergent trajectories of cognitive decline and worsening motor symptoms over time, underscoring the neuroanatomical heterogeneity that drives clinical variability in PD.
•Machine learning was applied to baseline MRI data to identify PD subtypes.•Each PD subtype demonstrated distinct cognitive and motor trajectories.•Our study highlights the need for personalized PD management.</description><subject>Aged</subject><subject>Atrophy - pathology</subject><subject>Brain - diagnostic imaging</subject><subject>Brain - pathology</subject><subject>Brain - physiopathology</subject><subject>Cluster analysis</subject><subject>Cognition - physiology</subject><subject>Cognitive decline</subject><subject>Cognitive Dysfunction - diagnostic imaging</subject><subject>Cognitive Dysfunction - etiology</subject><subject>Cognitive Dysfunction - pathology</subject><subject>Cognitive Dysfunction - physiopathology</subject><subject>Disease Progression</subject><subject>Female</subject><subject>Gray Matter - diagnostic imaging</subject><subject>Gray Matter - pathology</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Neuroanatomical heterogeneity</subject><subject>Parkinson Disease - classification</subject><subject>Parkinson Disease - complications</subject><subject>Parkinson Disease - diagnostic imaging</subject><subject>Parkinson Disease - pathology</subject><subject>Parkinson Disease - physiopathology</subject><subject>Parkinson's disease</subject><subject>Postural instability and gait disturbance progression</subject><issn>0022-510X</issn><issn>1878-5883</issn><issn>1878-5883</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMGOFCEURYnROD2jH-DGsNNNtQ-ooiCuzEQdk4m60MQdoeHVSNkFLVCT9N9Lp0eXboAH596EQ8gLBlsGTL6Zt3MsWw683zIuhBgekQ1To-oGpcRjsgHgvBsY_Lggl6XMACCV0k_JhdCy70etNyR9xjUnG21NS3B2T39ixZzuMGKoR-pzuMdCfVtzu6vUpbsYahupjZ4uqaZMa7YzunYKDQ2RfrX5V4glxVenZEFbkJZ1V48HLM_Ik8nuCz5_2K_I9w_vv13fdLdfPn66fnfbOS6G2rGBcUQ-Su3YCFb0qJkWovejmrzsFeystsM0AYMdjAokH1Bq2R5775iw4oq8Pvcecvq9YqlmCcXhfm8jprUYwXo5SC2ANZSdUZdTKRknc8hhsfloGJiTZzOb5tmcPJuz55Z5-VC_7hb0_xJ_xTbg7RnA9sn7gNkUFzA69CE3V8an8J_6PzdfkAY</recordid><startdate>20250115</startdate><enddate>20250115</enddate><creator>Vijayakumari, Anupa A.</creator><creator>Saadatpour, Leila</creator><creator>Floden, Darlene</creator><creator>Fernandez, Hubert</creator><creator>Walter, Benjamin L.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20250115</creationdate><title>Neuroanatomical heterogeneity drives divergent cognitive and motor trajectories in Parkinson's disease subtypes</title><author>Vijayakumari, Anupa A. ; Saadatpour, Leila ; Floden, Darlene ; Fernandez, Hubert ; Walter, Benjamin L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c235t-1512ee2769c170a34e919334d78fd6480ba9a5ff010b0780625e6968fd4dc13a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>Aged</topic><topic>Atrophy - pathology</topic><topic>Brain - diagnostic imaging</topic><topic>Brain - pathology</topic><topic>Brain - physiopathology</topic><topic>Cluster analysis</topic><topic>Cognition - physiology</topic><topic>Cognitive decline</topic><topic>Cognitive Dysfunction - diagnostic imaging</topic><topic>Cognitive Dysfunction - etiology</topic><topic>Cognitive Dysfunction - pathology</topic><topic>Cognitive Dysfunction - physiopathology</topic><topic>Disease Progression</topic><topic>Female</topic><topic>Gray Matter - diagnostic imaging</topic><topic>Gray Matter - pathology</topic><topic>Humans</topic><topic>Magnetic Resonance Imaging</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neuroanatomical heterogeneity</topic><topic>Parkinson Disease - classification</topic><topic>Parkinson Disease - complications</topic><topic>Parkinson Disease - diagnostic imaging</topic><topic>Parkinson Disease - pathology</topic><topic>Parkinson Disease - physiopathology</topic><topic>Parkinson's disease</topic><topic>Postural instability and gait disturbance progression</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vijayakumari, Anupa A.</creatorcontrib><creatorcontrib>Saadatpour, Leila</creatorcontrib><creatorcontrib>Floden, Darlene</creatorcontrib><creatorcontrib>Fernandez, Hubert</creatorcontrib><creatorcontrib>Walter, Benjamin L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of the neurological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vijayakumari, Anupa A.</au><au>Saadatpour, Leila</au><au>Floden, Darlene</au><au>Fernandez, Hubert</au><au>Walter, Benjamin L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Neuroanatomical heterogeneity drives divergent cognitive and motor trajectories in Parkinson's disease subtypes</atitle><jtitle>Journal of the neurological sciences</jtitle><addtitle>J Neurol Sci</addtitle><date>2025-01-15</date><risdate>2025</risdate><volume>468</volume><spage>123335</spage><pages>123335-</pages><artnum>123335</artnum><issn>0022-510X</issn><issn>1878-5883</issn><eissn>1878-5883</eissn><abstract>Cognitive symptoms of Parkinson's disease (PD) may initially present subtly, often overshadowed by more noticeable motor symptoms. However, as PD progresses, predicting which individuals will experience significant cognitive decline becomes challenging due to variability, suggesting distinct PD subtypes with varying cognitive trajectories. This study aimed to identify early PD subtypes based on patterns of gray matter atrophy in brain regions associated with cognition and assess their distinct patterns of cognitive change over time. Recognizing PD primarily as a movement disorder, we also evaluated their motor symptoms.
We analyzed T1-weighted MRI data, cognitive, and motor scores from 114 de novo PD patients and 120 healthy controls. Multivariate gray matter volumetric distances (MGMV) across frontal, subcortical, parietal, temporal, and occipital regions were computed, and K-means clustering was used to identify PD subtypes. Subsequently, cognitive assessments were compared between subtypes at baseline and 48 months using linear mixed-effects models and reliable change indices. Motor-symptom changes were assessed using linear mixed-effects models.
Two PD subtypes were identified from baseline MRI. Subtype 1 showed significantly higher MGMV in frontal (p < 0.001) and subcortical (p < 0.001) regions, indicating atrophy. At 48 months, subtype 1 had poorer global cognitive performance than subtype 2 (p = 0.005) and faster progression of postural instability and gait disturbance (p = 0.04).
PD subtypes identified early by distinct frontal and subcortical atrophy patterns exhibited divergent trajectories of cognitive decline and worsening motor symptoms over time, underscoring the neuroanatomical heterogeneity that drives clinical variability in PD.
•Machine learning was applied to baseline MRI data to identify PD subtypes.•Each PD subtype demonstrated distinct cognitive and motor trajectories.•Our study highlights the need for personalized PD management.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>39644799</pmid><doi>10.1016/j.jns.2024.123335</doi></addata></record> |
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| subjects | Aged Atrophy - pathology Brain - diagnostic imaging Brain - pathology Brain - physiopathology Cluster analysis Cognition - physiology Cognitive decline Cognitive Dysfunction - diagnostic imaging Cognitive Dysfunction - etiology Cognitive Dysfunction - pathology Cognitive Dysfunction - physiopathology Disease Progression Female Gray Matter - diagnostic imaging Gray Matter - pathology Humans Magnetic Resonance Imaging Male Middle Aged Neuroanatomical heterogeneity Parkinson Disease - classification Parkinson Disease - complications Parkinson Disease - diagnostic imaging Parkinson Disease - pathology Parkinson Disease - physiopathology Parkinson's disease Postural instability and gait disturbance progression |
| title | Neuroanatomical heterogeneity drives divergent cognitive and motor trajectories in Parkinson's disease subtypes |
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