Combination of Biomarkers: PET [18F]Flutemetamol Imaging and Structural MRI in Dementia and Mild Cognitive Impairment

L. Thurfjell, Jyrki Lötjönen, R. Lundqvist, Juha Koikkalainen, H. Soininen, G. Waldemar, D.J. Brooks, R. Vanderberghe

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Abstract

Background: The New National Institute on Aging-Alzheimer’s Association diagnostic guidelines for Alzheimer’s disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury. Objective: It was the aim of this study to compute hippocampus volume from MRI and a neocortical standard uptake value ratio (SUVR) from [18F]flutemetamol PET and investigate the performance of these biomarkers when used individually and when combined. Methods: Fully automated methods for hippocampus segmentation and for computation of neocortical SUVR were applied to MR and scans with the investigational imaging agent [18F]flutemetamol in a cohort comprising 27 AD patients, 25 healthy volunteers (HVs) and 20 subjects with amnestic mild cognitive impairment (MCI). Clinical follow-up was performed 2 years after the initial assessment. Results: Hippocampus volumes showed extensive overlap between AD and HV cases while PET SUVRs showed clear group clustering. When both measures were combined, there was a relatively compact cluster of HV scans and a less compact AD cluster. MCI cases had a bimodal distribution of SUVRs. [18F]Flutemetamol-positive MCI subjects showed a large variability in hippocampus volumes, indicating that these subjects were in different stages of neurodegeneration. Some [18F]flutemetamol-negative MCI scans had hippocampus volumes that were well below the HV range. Clinical follow-up showed that 8 of 9 MCI to AD converters came from the [18F]flutemetamol-positive group. Conclusion: Combining [18F]flutemetamol PET with structural MRI provides additional information for categorizing disease and potentially predicting shorter time to progression from MCI to AD, but this has to be validated in larger longitudinal studies.
Original languageEnglish
Pages (from-to)246-249
JournalNeurodegenerative Diseases
Volume10
Issue number1-4
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed
Event10th International Conference AD/PD - Barcelona, Spain
Duration: 9 Mar 201113 Mar 2011

Fingerprint

Dementia
Alzheimer Disease
Biomarkers
Hippocampus
Healthy Volunteers
National Institute on Aging (U.S.)
Cluster Analysis
Longitudinal Studies
Cognitive Dysfunction
flutemetamol
Guidelines
Wounds and Injuries

Keywords

  • [18F]Flutemetamol
  • Alzheimer's disease
  • mild cognitive impairment

Cite this

Thurfjell, L., Lötjönen, J., Lundqvist, R., Koikkalainen, J., Soininen, H., Waldemar, G., ... Vanderberghe, R. (2012). Combination of Biomarkers: PET [18F]Flutemetamol Imaging and Structural MRI in Dementia and Mild Cognitive Impairment. Neurodegenerative Diseases, 10(1-4), 246-249. https://doi.org/10.1159/000335381
Thurfjell, L. ; Lötjönen, Jyrki ; Lundqvist, R. ; Koikkalainen, Juha ; Soininen, H. ; Waldemar, G. ; Brooks, D.J. ; Vanderberghe, R. / Combination of Biomarkers : PET [18F]Flutemetamol Imaging and Structural MRI in Dementia and Mild Cognitive Impairment. In: Neurodegenerative Diseases. 2012 ; Vol. 10, No. 1-4. pp. 246-249.
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abstract = "Background: The New National Institute on Aging-Alzheimer’s Association diagnostic guidelines for Alzheimer’s disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury. Objective: It was the aim of this study to compute hippocampus volume from MRI and a neocortical standard uptake value ratio (SUVR) from [18F]flutemetamol PET and investigate the performance of these biomarkers when used individually and when combined. Methods: Fully automated methods for hippocampus segmentation and for computation of neocortical SUVR were applied to MR and scans with the investigational imaging agent [18F]flutemetamol in a cohort comprising 27 AD patients, 25 healthy volunteers (HVs) and 20 subjects with amnestic mild cognitive impairment (MCI). Clinical follow-up was performed 2 years after the initial assessment. Results: Hippocampus volumes showed extensive overlap between AD and HV cases while PET SUVRs showed clear group clustering. When both measures were combined, there was a relatively compact cluster of HV scans and a less compact AD cluster. MCI cases had a bimodal distribution of SUVRs. [18F]Flutemetamol-positive MCI subjects showed a large variability in hippocampus volumes, indicating that these subjects were in different stages of neurodegeneration. Some [18F]flutemetamol-negative MCI scans had hippocampus volumes that were well below the HV range. Clinical follow-up showed that 8 of 9 MCI to AD converters came from the [18F]flutemetamol-positive group. Conclusion: Combining [18F]flutemetamol PET with structural MRI provides additional information for categorizing disease and potentially predicting shorter time to progression from MCI to AD, but this has to be validated in larger longitudinal studies.",
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Thurfjell, L, Lötjönen, J, Lundqvist, R, Koikkalainen, J, Soininen, H, Waldemar, G, Brooks, DJ & Vanderberghe, R 2012, 'Combination of Biomarkers: PET [18F]Flutemetamol Imaging and Structural MRI in Dementia and Mild Cognitive Impairment', Neurodegenerative Diseases, vol. 10, no. 1-4, pp. 246-249. https://doi.org/10.1159/000335381

Combination of Biomarkers : PET [18F]Flutemetamol Imaging and Structural MRI in Dementia and Mild Cognitive Impairment. / Thurfjell, L.; Lötjönen, Jyrki; Lundqvist, R.; Koikkalainen, Juha; Soininen, H.; Waldemar, G.; Brooks, D.J.; Vanderberghe, R.

In: Neurodegenerative Diseases, Vol. 10, No. 1-4, 2012, p. 246-249.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Combination of Biomarkers

T2 - PET [18F]Flutemetamol Imaging and Structural MRI in Dementia and Mild Cognitive Impairment

AU - Thurfjell, L.

AU - Lötjönen, Jyrki

AU - Lundqvist, R.

AU - Koikkalainen, Juha

AU - Soininen, H.

AU - Waldemar, G.

AU - Brooks, D.J.

AU - Vanderberghe, R.

PY - 2012

Y1 - 2012

N2 - Background: The New National Institute on Aging-Alzheimer’s Association diagnostic guidelines for Alzheimer’s disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury. Objective: It was the aim of this study to compute hippocampus volume from MRI and a neocortical standard uptake value ratio (SUVR) from [18F]flutemetamol PET and investigate the performance of these biomarkers when used individually and when combined. Methods: Fully automated methods for hippocampus segmentation and for computation of neocortical SUVR were applied to MR and scans with the investigational imaging agent [18F]flutemetamol in a cohort comprising 27 AD patients, 25 healthy volunteers (HVs) and 20 subjects with amnestic mild cognitive impairment (MCI). Clinical follow-up was performed 2 years after the initial assessment. Results: Hippocampus volumes showed extensive overlap between AD and HV cases while PET SUVRs showed clear group clustering. When both measures were combined, there was a relatively compact cluster of HV scans and a less compact AD cluster. MCI cases had a bimodal distribution of SUVRs. [18F]Flutemetamol-positive MCI subjects showed a large variability in hippocampus volumes, indicating that these subjects were in different stages of neurodegeneration. Some [18F]flutemetamol-negative MCI scans had hippocampus volumes that were well below the HV range. Clinical follow-up showed that 8 of 9 MCI to AD converters came from the [18F]flutemetamol-positive group. Conclusion: Combining [18F]flutemetamol PET with structural MRI provides additional information for categorizing disease and potentially predicting shorter time to progression from MCI to AD, but this has to be validated in larger longitudinal studies.

AB - Background: The New National Institute on Aging-Alzheimer’s Association diagnostic guidelines for Alzheimer’s disease (AD) incorporate biomarkers in the diagnostic criteria and suggest division of biomarkers into two categories: Aβ accumulation and neuronal degeneration or injury. Objective: It was the aim of this study to compute hippocampus volume from MRI and a neocortical standard uptake value ratio (SUVR) from [18F]flutemetamol PET and investigate the performance of these biomarkers when used individually and when combined. Methods: Fully automated methods for hippocampus segmentation and for computation of neocortical SUVR were applied to MR and scans with the investigational imaging agent [18F]flutemetamol in a cohort comprising 27 AD patients, 25 healthy volunteers (HVs) and 20 subjects with amnestic mild cognitive impairment (MCI). Clinical follow-up was performed 2 years after the initial assessment. Results: Hippocampus volumes showed extensive overlap between AD and HV cases while PET SUVRs showed clear group clustering. When both measures were combined, there was a relatively compact cluster of HV scans and a less compact AD cluster. MCI cases had a bimodal distribution of SUVRs. [18F]Flutemetamol-positive MCI subjects showed a large variability in hippocampus volumes, indicating that these subjects were in different stages of neurodegeneration. Some [18F]flutemetamol-negative MCI scans had hippocampus volumes that were well below the HV range. Clinical follow-up showed that 8 of 9 MCI to AD converters came from the [18F]flutemetamol-positive group. Conclusion: Combining [18F]flutemetamol PET with structural MRI provides additional information for categorizing disease and potentially predicting shorter time to progression from MCI to AD, but this has to be validated in larger longitudinal studies.

KW - [18F]Flutemetamol

KW - Alzheimer's disease

KW - mild cognitive impairment

U2 - 10.1159/000335381

DO - 10.1159/000335381

M3 - Article

VL - 10

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EP - 249

JO - Neurodegenerative Diseases

JF - Neurodegenerative Diseases

SN - 1660-2854

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