Combination of biomarkers: PET [18F]flutemetamol imaging and structural MRI in dementia and mild cognitive impairment

Lennart Thurfjell; Jyrki Lötjönen; Roger Lundqvist; Juha Koikkalainen; Hilkka Soininen; Gunhild Waldemar; David Brooks; Rik Vandenberghe

doi:10.1159/000335381

Combination of biomarkers: PET [18F]flutemetamol imaging and structural MRI in dementia and mild cognitive impairment

Lennart Thurfjell, Jyrki Lötjönen, Roger Lundqvist, Juha Koikkalainen, Hilkka Soininen, Gunhild Waldemar, David Brooks, Rik Vandenberghe

48 Citations (Scopus)

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 language	English
Journal	Neurodegenerative Diseases
Volume	10
Issue number	1-4
Pages (from-to)	246-9
Number of pages	4
ISSN	1660-2854
DOIs	https://doi.org/10.1159/000335381
Publication status	Published - Apr 2012

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@article{73cdc07bf47c40f0a9d6a874b02ded2e,

title = "Combination of biomarkers: PET [18F]flutemetamol imaging and structural MRI in dementia and mild cognitive impairment",

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.",

author = "Lennart Thurfjell and Jyrki L{\"o}tj{\"o}nen and Roger Lundqvist and Juha Koikkalainen and Hilkka Soininen and Gunhild Waldemar and David Brooks and Rik Vandenberghe",

note = "Copyright {\textcopyright} 2012 S. Karger AG, Basel.",

year = "2012",

month = apr,

doi = "10.1159/000335381",

language = "English",

volume = "10",

pages = "246--9",

journal = "Neurodegenerative Diseases",

issn = "1660-2854",

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}

TY - JOUR

T1 - Combination of biomarkers

T2 - PET [18F]flutemetamol imaging and structural MRI in dementia and mild cognitive impairment

AU - Thurfjell, Lennart

AU - Lötjönen, Jyrki

AU - Lundqvist, Roger

AU - Koikkalainen, Juha

AU - Soininen, Hilkka

AU - Waldemar, Gunhild

AU - Brooks, David

AU - Vandenberghe, Rik

PY - 2012/4

Y1 - 2012/4

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.

U2 - 10.1159/000335381

DO - 10.1159/000335381

M3 - Journal article

SN - 1660-2854

VL - 10

SP - 246

EP - 249

JO - Neurodegenerative Diseases

JF - Neurodegenerative Diseases

IS - 1-4

ER -

Combination of biomarkers: PET [18F]flutemetamol imaging and structural MRI in dementia and mild cognitive impairment

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