Antemortem differential diagnosis of dementia pathology using structural MRI: Differential-STAND

Prashanthi Vemuri; Gyorgy Simon; Kejal Kantarci; Jennifer L. Whitwell; Matthew L. Senjem; Scott A. Przybelski; Jeffrey L. Gunter; Keith A. Josephs; David S. Knopman; Bradley F. Boeve; Tanis J. Ferman; Dennis W. Dickson; Joseph E. Parisi; Ronald C. Petersen; Clifford R. Jack

doi:10.1016/j.neuroimage.2010.12.073

Antemortem differential diagnosis of dementia pathology using structural MRI: Differential-STAND

Prashanthi Vemuri, Gyorgy Simon, Kejal Kantarci, Jennifer L. Whitwell, Matthew L. Senjem, Scott A. Przybelski, Jeffrey L. Gunter, Keith A. Josephs, David S. Knopman, Bradley F. Boeve, Tanis J. Ferman, Dennis W. Dickson, Joseph E. Parisi, Ronald C. Petersen, Clifford R. Jack

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65 Scopus citations

Abstract

The common neurodegenerative pathologies underlying dementia are Alzheimer's disease (AD), Lewy body disease (LBD) and frontotemporal lobar degeneration (FTLD). Our aim was to identify patterns of atrophy unique to each of these diseases using antemortem structural MRI scans of pathologically confirmed dementia cases and build an MRI-based differential diagnosis system. Our approach of creating atrophy maps using structural MRI and applying them for classification of new incoming patients is labeled Differential-STAND (Differential Diagnosis Based on Structural Abnormality in Neurodegeneration). Pathologically confirmed subjects with a single dementing pathologic diagnosis who had an MRI at the time of clinical diagnosis of dementia were identified: 48 AD, 20 LBD, 47 FTLD-TDP (pathology-confirmed FTLD with TDP-43). Gray matter density in 91 regions-of-interest was measured in each subject and adjusted for head size and age using a database of 120 cognitively normal elderly. The atrophy patterns in each dementia type when compared to pathologically confirmed controls mirrored known disease-specific anatomic patterns: AD-temporoparietal association cortices and medial temporal lobe; FTLD-TDP-frontal and temporal lobes and LBD-bilateral amygdalae, dorsal midbrain and inferior temporal lobes. Differential-STAND based classification of each case was done based on a mixture model generated using bisecting k-means clustering of the information from the MRI scans. Leave-one-out classification showed reasonable performance compared to the autopsy gold standard and clinical diagnosis: AD (sensitivity: 90.7%; specificity: 84%), LBD (sensitivity: 78.6%; specificity: 98.8%) and FTLD-TDP (sensitivity: 84.4%; specificity: 93.8%). The proposed approach establishes a direct a priori relationship between specific topographic patterns on MRI and ''gold standard'' of pathology which can then be used to predict underlying dementia pathology in new incoming patients.

Original language	English (US)
Pages (from-to)	522-531
Number of pages	10
Journal	NeuroImage
Volume	55
Issue number	2
DOIs	https://doi.org/10.1016/j.neuroimage.2010.12.073
State	Published - Mar 15 2011

Keywords

Alzheimer's disease
Frontotemporal lobar degeneration
Lewy body disease
MRI

ASJC Scopus subject areas

Neurology
Cognitive Neuroscience

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10.1016/j.neuroimage.2010.12.073

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Vemuri, P., Simon, G., Kantarci, K., Whitwell, J. L., Senjem, M. L., Przybelski, S. A., Gunter, J. L., Josephs, K. A., Knopman, D. S., Boeve, B. F., Ferman, T. J., Dickson, D. W., Parisi, J. E., Petersen, R. C., & Jack, C. R. (2011). Antemortem differential diagnosis of dementia pathology using structural MRI: Differential-STAND. NeuroImage, 55(2), 522-531. https://doi.org/10.1016/j.neuroimage.2010.12.073

Vemuri, P, Simon, G, Kantarci, K , Whitwell, JL, Senjem, ML, Przybelski, SA, Gunter, JL, Josephs, KA , Knopman, DS , Boeve, BF , Ferman, TJ , Dickson, DW, Parisi, JE, Petersen, RC & Jack, CR 2011, 'Antemortem differential diagnosis of dementia pathology using structural MRI: Differential-STAND', NeuroImage, vol. 55, no. 2, pp. 522-531. https://doi.org/10.1016/j.neuroimage.2010.12.073

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title = "Antemortem differential diagnosis of dementia pathology using structural MRI: Differential-STAND",

abstract = "The common neurodegenerative pathologies underlying dementia are Alzheimer's disease (AD), Lewy body disease (LBD) and frontotemporal lobar degeneration (FTLD). Our aim was to identify patterns of atrophy unique to each of these diseases using antemortem structural MRI scans of pathologically confirmed dementia cases and build an MRI-based differential diagnosis system. Our approach of creating atrophy maps using structural MRI and applying them for classification of new incoming patients is labeled Differential-STAND (Differential Diagnosis Based on Structural Abnormality in Neurodegeneration). Pathologically confirmed subjects with a single dementing pathologic diagnosis who had an MRI at the time of clinical diagnosis of dementia were identified: 48 AD, 20 LBD, 47 FTLD-TDP (pathology-confirmed FTLD with TDP-43). Gray matter density in 91 regions-of-interest was measured in each subject and adjusted for head size and age using a database of 120 cognitively normal elderly. The atrophy patterns in each dementia type when compared to pathologically confirmed controls mirrored known disease-specific anatomic patterns: AD-temporoparietal association cortices and medial temporal lobe; FTLD-TDP-frontal and temporal lobes and LBD-bilateral amygdalae, dorsal midbrain and inferior temporal lobes. Differential-STAND based classification of each case was done based on a mixture model generated using bisecting k-means clustering of the information from the MRI scans. Leave-one-out classification showed reasonable performance compared to the autopsy gold standard and clinical diagnosis: AD (sensitivity: 90.7%; specificity: 84%), LBD (sensitivity: 78.6%; specificity: 98.8%) and FTLD-TDP (sensitivity: 84.4%; specificity: 93.8%). The proposed approach establishes a direct a priori relationship between specific topographic patterns on MRI and ''gold standard'' of pathology which can then be used to predict underlying dementia pathology in new incoming patients.",

keywords = "Alzheimer's disease, Frontotemporal lobar degeneration, Lewy body disease, MRI",

author = "Prashanthi Vemuri and Gyorgy Simon and Kejal Kantarci and Whitwell, {Jennifer L.} and Senjem, {Matthew L.} and Przybelski, {Scott A.} and Gunter, {Jeffrey L.} and Josephs, {Keith A.} and Knopman, {David S.} and Boeve, {Bradley F.} and Ferman, {Tanis J.} and Dickson, {Dennis W.} and Parisi, {Joseph E.} and Petersen, {Ronald C.} and Jack, {Clifford R.}",

note = "Funding Information: This work was supported completely by Mayo ADRC pilot grant and NIH grants R01 AG11378, K23 AG030935, R01 AG15866, P50 AG16574, U01 AG06786, Robert H. Smith Family Foundation Research Fellowship, Alexander Family Alzheimer's Disease Research Professorship and Opus building grant NIH C06 RR018898.",

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doi = "10.1016/j.neuroimage.2010.12.073",

language = "English (US)",

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AU - Vemuri, Prashanthi

AU - Simon, Gyorgy

AU - Kantarci, Kejal

AU - Whitwell, Jennifer L.

AU - Senjem, Matthew L.

AU - Przybelski, Scott A.

AU - Gunter, Jeffrey L.

AU - Josephs, Keith A.

AU - Knopman, David S.

AU - Boeve, Bradley F.

AU - Ferman, Tanis J.

AU - Dickson, Dennis W.

AU - Parisi, Joseph E.

AU - Petersen, Ronald C.

AU - Jack, Clifford R.

N1 - Funding Information: This work was supported completely by Mayo ADRC pilot grant and NIH grants R01 AG11378, K23 AG030935, R01 AG15866, P50 AG16574, U01 AG06786, Robert H. Smith Family Foundation Research Fellowship, Alexander Family Alzheimer's Disease Research Professorship and Opus building grant NIH C06 RR018898.

PY - 2011/3/15

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N2 - The common neurodegenerative pathologies underlying dementia are Alzheimer's disease (AD), Lewy body disease (LBD) and frontotemporal lobar degeneration (FTLD). Our aim was to identify patterns of atrophy unique to each of these diseases using antemortem structural MRI scans of pathologically confirmed dementia cases and build an MRI-based differential diagnosis system. Our approach of creating atrophy maps using structural MRI and applying them for classification of new incoming patients is labeled Differential-STAND (Differential Diagnosis Based on Structural Abnormality in Neurodegeneration). Pathologically confirmed subjects with a single dementing pathologic diagnosis who had an MRI at the time of clinical diagnosis of dementia were identified: 48 AD, 20 LBD, 47 FTLD-TDP (pathology-confirmed FTLD with TDP-43). Gray matter density in 91 regions-of-interest was measured in each subject and adjusted for head size and age using a database of 120 cognitively normal elderly. The atrophy patterns in each dementia type when compared to pathologically confirmed controls mirrored known disease-specific anatomic patterns: AD-temporoparietal association cortices and medial temporal lobe; FTLD-TDP-frontal and temporal lobes and LBD-bilateral amygdalae, dorsal midbrain and inferior temporal lobes. Differential-STAND based classification of each case was done based on a mixture model generated using bisecting k-means clustering of the information from the MRI scans. Leave-one-out classification showed reasonable performance compared to the autopsy gold standard and clinical diagnosis: AD (sensitivity: 90.7%; specificity: 84%), LBD (sensitivity: 78.6%; specificity: 98.8%) and FTLD-TDP (sensitivity: 84.4%; specificity: 93.8%). The proposed approach establishes a direct a priori relationship between specific topographic patterns on MRI and ''gold standard'' of pathology which can then be used to predict underlying dementia pathology in new incoming patients.

AB - The common neurodegenerative pathologies underlying dementia are Alzheimer's disease (AD), Lewy body disease (LBD) and frontotemporal lobar degeneration (FTLD). Our aim was to identify patterns of atrophy unique to each of these diseases using antemortem structural MRI scans of pathologically confirmed dementia cases and build an MRI-based differential diagnosis system. Our approach of creating atrophy maps using structural MRI and applying them for classification of new incoming patients is labeled Differential-STAND (Differential Diagnosis Based on Structural Abnormality in Neurodegeneration). Pathologically confirmed subjects with a single dementing pathologic diagnosis who had an MRI at the time of clinical diagnosis of dementia were identified: 48 AD, 20 LBD, 47 FTLD-TDP (pathology-confirmed FTLD with TDP-43). Gray matter density in 91 regions-of-interest was measured in each subject and adjusted for head size and age using a database of 120 cognitively normal elderly. The atrophy patterns in each dementia type when compared to pathologically confirmed controls mirrored known disease-specific anatomic patterns: AD-temporoparietal association cortices and medial temporal lobe; FTLD-TDP-frontal and temporal lobes and LBD-bilateral amygdalae, dorsal midbrain and inferior temporal lobes. Differential-STAND based classification of each case was done based on a mixture model generated using bisecting k-means clustering of the information from the MRI scans. Leave-one-out classification showed reasonable performance compared to the autopsy gold standard and clinical diagnosis: AD (sensitivity: 90.7%; specificity: 84%), LBD (sensitivity: 78.6%; specificity: 98.8%) and FTLD-TDP (sensitivity: 84.4%; specificity: 93.8%). The proposed approach establishes a direct a priori relationship between specific topographic patterns on MRI and ''gold standard'' of pathology which can then be used to predict underlying dementia pathology in new incoming patients.

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Antemortem differential diagnosis of dementia pathology using structural MRI: Differential-STAND

Abstract

Keywords

ASJC Scopus subject areas

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