18F–FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer’s disease (AD) patients at the mild cognitive impairment (MCI) stage

Silvia Morbelli, Matteo Bauckneht, Dario Arnaldi, Agnese Picco, Matteo Pardini, Andrea Brugnolo, Ambra Buschiazzo, Marco Pagani, Nicola Girtler, Alberto Nieri, Andrea Chincarini, Fabrizio De Carli, Gianmario Sambuceti, Flavio Nobili

Research output: Contribution to journalArticle

Abstract

Purpose: We aimed to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in mild cognitive impairment due to Alzheimer’s disease (MCI-AD). Methods: We selected from the clinical database of our tertiary center memory clinic, eighty-two consecutive MCI-AD that underwent 18F–fluorodeoxyglucose (FDG) PET at baseline during the first diagnostic work-up and were followed up at least until their clinical conversion to AD dementia. The whole group of MCI-AD was compared in SPM8 with a group of age-matched healthy controls (CTR) to verify the presence of AD diagnostic-pattern; then the correlation between conversion time and brain metabolism was assessed to identify the prognostic-pattern. Significance threshold was set at p < 0.05 False-Discovery-Rate (FDR) corrected at peak and at cluster level. Each MCI-AD was then compared with CTR by means of a SPM single-subject analysis and grouped according to presence of AD diagnostic-pattern and prognostic-pattern. Kaplan-Meier-analysis was used to evaluate if diagnostic- and/or prognostic-patterns can predict speed of conversion to dementia. Results: Diagnostic-pattern corresponded to typical posterior hypometabolism (BA 7, 18, 19, 30, 31 and 40) and did not correlate with time to conversion, which was instead correlated with metabolic levels in right middle and inferior temporal gyri as well as in the fusiform gyrus (prognostic-pattern, BA 20, 21 and 38). At Kaplan-Meier analysis, patients with hypometabolism in the prognostic pattern converted to AD-dementia significantly earlier than patients not showing significant hypometabolism in the right middle and inferior temporal cortex (9 versus 19 months; Log rank p < 0.02, Breslow test: p < 0.003, Tarone-Ware test: p < 0.007). Conclusion: The present findings support the role of FDG PET as a robust progression biomarker even in a naturalist population of MCI-AD. However, not the AD-typical diagnostic-pattern in posterior regions but the middle and inferior temporal metabolism captures speed of conversion to dementia in MCI-AD since baseline. The highlighted prognostic pattern is a further, independent source of heterogeneity in MCI-AD and affects a primary-endpoint on interventional clinical trials (time of conversion to dementia).

Original languageEnglish
Pages (from-to)2073-2083
Number of pages11
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume44
Issue number12
DOIs
Publication statusPublished - Nov 1 2017

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Alzheimer Disease
Dementia
Temporal Lobe
Kaplan-Meier Estimate
Cognitive Dysfunction
Research Design
Age Groups
Biomarkers
Clinical Trials
Databases

Keywords

  • 18F–FDG PET
  • AD-biomarkers
  • Alzheimer’s disease
  • Mild cognitive impairment

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

18F–FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer’s disease (AD) patients at the mild cognitive impairment (MCI) stage. / Morbelli, Silvia; Bauckneht, Matteo; Arnaldi, Dario; Picco, Agnese; Pardini, Matteo; Brugnolo, Andrea; Buschiazzo, Ambra; Pagani, Marco; Girtler, Nicola; Nieri, Alberto; Chincarini, Andrea; De Carli, Fabrizio; Sambuceti, Gianmario; Nobili, Flavio.

In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 44, No. 12, 01.11.2017, p. 2073-2083.

Research output: Contribution to journalArticle

Morbelli, Silvia ; Bauckneht, Matteo ; Arnaldi, Dario ; Picco, Agnese ; Pardini, Matteo ; Brugnolo, Andrea ; Buschiazzo, Ambra ; Pagani, Marco ; Girtler, Nicola ; Nieri, Alberto ; Chincarini, Andrea ; De Carli, Fabrizio ; Sambuceti, Gianmario ; Nobili, Flavio. / 18F–FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer’s disease (AD) patients at the mild cognitive impairment (MCI) stage. In: European Journal of Nuclear Medicine and Molecular Imaging. 2017 ; Vol. 44, No. 12. pp. 2073-2083.
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abstract = "Purpose: We aimed to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in mild cognitive impairment due to Alzheimer’s disease (MCI-AD). Methods: We selected from the clinical database of our tertiary center memory clinic, eighty-two consecutive MCI-AD that underwent 18F–fluorodeoxyglucose (FDG) PET at baseline during the first diagnostic work-up and were followed up at least until their clinical conversion to AD dementia. The whole group of MCI-AD was compared in SPM8 with a group of age-matched healthy controls (CTR) to verify the presence of AD diagnostic-pattern; then the correlation between conversion time and brain metabolism was assessed to identify the prognostic-pattern. Significance threshold was set at p < 0.05 False-Discovery-Rate (FDR) corrected at peak and at cluster level. Each MCI-AD was then compared with CTR by means of a SPM single-subject analysis and grouped according to presence of AD diagnostic-pattern and prognostic-pattern. Kaplan-Meier-analysis was used to evaluate if diagnostic- and/or prognostic-patterns can predict speed of conversion to dementia. Results: Diagnostic-pattern corresponded to typical posterior hypometabolism (BA 7, 18, 19, 30, 31 and 40) and did not correlate with time to conversion, which was instead correlated with metabolic levels in right middle and inferior temporal gyri as well as in the fusiform gyrus (prognostic-pattern, BA 20, 21 and 38). At Kaplan-Meier analysis, patients with hypometabolism in the prognostic pattern converted to AD-dementia significantly earlier than patients not showing significant hypometabolism in the right middle and inferior temporal cortex (9 versus 19 months; Log rank p < 0.02, Breslow test: p < 0.003, Tarone-Ware test: p < 0.007). Conclusion: The present findings support the role of FDG PET as a robust progression biomarker even in a naturalist population of MCI-AD. However, not the AD-typical diagnostic-pattern in posterior regions but the middle and inferior temporal metabolism captures speed of conversion to dementia in MCI-AD since baseline. The highlighted prognostic pattern is a further, independent source of heterogeneity in MCI-AD and affects a primary-endpoint on interventional clinical trials (time of conversion to dementia).",
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T1 - 18F–FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer’s disease (AD) patients at the mild cognitive impairment (MCI) stage

AU - Morbelli, Silvia

AU - Bauckneht, Matteo

AU - Arnaldi, Dario

AU - Picco, Agnese

AU - Pardini, Matteo

AU - Brugnolo, Andrea

AU - Buschiazzo, Ambra

AU - Pagani, Marco

AU - Girtler, Nicola

AU - Nieri, Alberto

AU - Chincarini, Andrea

AU - De Carli, Fabrizio

AU - Sambuceti, Gianmario

AU - Nobili, Flavio

PY - 2017/11/1

Y1 - 2017/11/1

N2 - Purpose: We aimed to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in mild cognitive impairment due to Alzheimer’s disease (MCI-AD). Methods: We selected from the clinical database of our tertiary center memory clinic, eighty-two consecutive MCI-AD that underwent 18F–fluorodeoxyglucose (FDG) PET at baseline during the first diagnostic work-up and were followed up at least until their clinical conversion to AD dementia. The whole group of MCI-AD was compared in SPM8 with a group of age-matched healthy controls (CTR) to verify the presence of AD diagnostic-pattern; then the correlation between conversion time and brain metabolism was assessed to identify the prognostic-pattern. Significance threshold was set at p < 0.05 False-Discovery-Rate (FDR) corrected at peak and at cluster level. Each MCI-AD was then compared with CTR by means of a SPM single-subject analysis and grouped according to presence of AD diagnostic-pattern and prognostic-pattern. Kaplan-Meier-analysis was used to evaluate if diagnostic- and/or prognostic-patterns can predict speed of conversion to dementia. Results: Diagnostic-pattern corresponded to typical posterior hypometabolism (BA 7, 18, 19, 30, 31 and 40) and did not correlate with time to conversion, which was instead correlated with metabolic levels in right middle and inferior temporal gyri as well as in the fusiform gyrus (prognostic-pattern, BA 20, 21 and 38). At Kaplan-Meier analysis, patients with hypometabolism in the prognostic pattern converted to AD-dementia significantly earlier than patients not showing significant hypometabolism in the right middle and inferior temporal cortex (9 versus 19 months; Log rank p < 0.02, Breslow test: p < 0.003, Tarone-Ware test: p < 0.007). Conclusion: The present findings support the role of FDG PET as a robust progression biomarker even in a naturalist population of MCI-AD. However, not the AD-typical diagnostic-pattern in posterior regions but the middle and inferior temporal metabolism captures speed of conversion to dementia in MCI-AD since baseline. The highlighted prognostic pattern is a further, independent source of heterogeneity in MCI-AD and affects a primary-endpoint on interventional clinical trials (time of conversion to dementia).

AB - Purpose: We aimed to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in mild cognitive impairment due to Alzheimer’s disease (MCI-AD). Methods: We selected from the clinical database of our tertiary center memory clinic, eighty-two consecutive MCI-AD that underwent 18F–fluorodeoxyglucose (FDG) PET at baseline during the first diagnostic work-up and were followed up at least until their clinical conversion to AD dementia. The whole group of MCI-AD was compared in SPM8 with a group of age-matched healthy controls (CTR) to verify the presence of AD diagnostic-pattern; then the correlation between conversion time and brain metabolism was assessed to identify the prognostic-pattern. Significance threshold was set at p < 0.05 False-Discovery-Rate (FDR) corrected at peak and at cluster level. Each MCI-AD was then compared with CTR by means of a SPM single-subject analysis and grouped according to presence of AD diagnostic-pattern and prognostic-pattern. Kaplan-Meier-analysis was used to evaluate if diagnostic- and/or prognostic-patterns can predict speed of conversion to dementia. Results: Diagnostic-pattern corresponded to typical posterior hypometabolism (BA 7, 18, 19, 30, 31 and 40) and did not correlate with time to conversion, which was instead correlated with metabolic levels in right middle and inferior temporal gyri as well as in the fusiform gyrus (prognostic-pattern, BA 20, 21 and 38). At Kaplan-Meier analysis, patients with hypometabolism in the prognostic pattern converted to AD-dementia significantly earlier than patients not showing significant hypometabolism in the right middle and inferior temporal cortex (9 versus 19 months; Log rank p < 0.02, Breslow test: p < 0.003, Tarone-Ware test: p < 0.007). Conclusion: The present findings support the role of FDG PET as a robust progression biomarker even in a naturalist population of MCI-AD. However, not the AD-typical diagnostic-pattern in posterior regions but the middle and inferior temporal metabolism captures speed of conversion to dementia in MCI-AD since baseline. The highlighted prognostic pattern is a further, independent source of heterogeneity in MCI-AD and affects a primary-endpoint on interventional clinical trials (time of conversion to dementia).

KW - 18F–FDG PET

KW - AD-biomarkers

KW - Alzheimer’s disease

KW - Mild cognitive impairment

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