Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia

David S. Knopman, Clifford R. Jack, Heather J. Wiste, Stephen D. Weigand, Prashanthi Vemuri, Val J. Lowe, Kejal Kantarci, Jeffrey L. Gunter, Matthew L. Senjem, Michelle M. Mielke, Mary M. Machulda, Rosebud O. Roberts, Bradley F. Boeve, David T. Jones, Ronald C. Petersen

Research output: Contribution to journalArticle

Abstract

Objective: To examine neurodegenerative imaging biomarkers in Alzheimer disease (AD) dementia from middle to old age. Methods: Persons with AD dementia and elevated brain β-Amyloid with Pittsburgh compound B (PiB)-PET imaging underwent [ 18 F]-fluorodeoxyglucose (FDG)-PET and structural MRI. We evaluated 3 AD-related neurodegeneration biomarkers: hippocampal volume adjusted for total intracranial volume (HVa), FDG standardized uptake value ratio (SUVR) in regions of interest linked to AD, and cortical thickness in AD-related regions of interest. We examined associations of each biomarker with age and evaluated age effects on cutpoints defined by the 90th percentile in AD dementia. We assembled an age-, sex-, and intracranial volume-matched group of 194 similarly imaged clinically normal (CN) persons. Results: The 97 participants with AD dementia (aged 49-93 years) had PiB SUVR ≥1.8. A nonlinear (inverted-U) relationship between FDG SUVR and age was seen in the AD group but an inverse linear relationship with age was seen in the CN group. Cortical thickness had an inverse linear relationship with age in AD but a nonlinear (flat, then inverse linear) relationship in the CN group. HVa showed an inverse linear relationship with age in both AD and CN groups. Age effects on 90th percentile cutpoints were small for FDG SUVR and cortical thickness, but larger for HVa. Conclusions: In persons with AD dementia with elevated PiB SUVR, values of each neurodegeneration biomarker were associated with age. Cortical thickness had the smallest differences in 90th percentile cutpoints from middle to old age, and HVa the largest differences.

Original languageEnglish (US)
Pages (from-to)691-698
Number of pages8
JournalNeurology
Volume87
Issue number7
DOIs
StatePublished - Aug 16 2016
Externally publishedYes

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Alzheimer Disease
Biomarkers
Fluorodeoxyglucose F18
Amyloid
Research Design

ASJC Scopus subject areas

  • Medicine(all)
  • Clinical Neurology

Cite this

Knopman, D. S., Jack, C. R., Wiste, H. J., Weigand, S. D., Vemuri, P., Lowe, V. J., ... Petersen, R. C. (2016). Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia. Neurology, 87(7), 691-698. https://doi.org/10.1212/WNL.0000000000002979

Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia. / Knopman, David S.; Jack, Clifford R.; Wiste, Heather J.; Weigand, Stephen D.; Vemuri, Prashanthi; Lowe, Val J.; Kantarci, Kejal; Gunter, Jeffrey L.; Senjem, Matthew L.; Mielke, Michelle M.; Machulda, Mary M.; Roberts, Rosebud O.; Boeve, Bradley F.; Jones, David T.; Petersen, Ronald C.

In: Neurology, Vol. 87, No. 7, 16.08.2016, p. 691-698.

Research output: Contribution to journalArticle

Knopman, DS, Jack, CR, Wiste, HJ, Weigand, SD, Vemuri, P, Lowe, VJ, Kantarci, K, Gunter, JL, Senjem, ML, Mielke, MM, Machulda, MM, Roberts, RO, Boeve, BF, Jones, DT & Petersen, RC 2016, 'Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia', Neurology, vol. 87, no. 7, pp. 691-698. https://doi.org/10.1212/WNL.0000000000002979
Knopman DS, Jack CR, Wiste HJ, Weigand SD, Vemuri P, Lowe VJ et al. Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia. Neurology. 2016 Aug 16;87(7):691-698. https://doi.org/10.1212/WNL.0000000000002979
Knopman, David S. ; Jack, Clifford R. ; Wiste, Heather J. ; Weigand, Stephen D. ; Vemuri, Prashanthi ; Lowe, Val J. ; Kantarci, Kejal ; Gunter, Jeffrey L. ; Senjem, Matthew L. ; Mielke, Michelle M. ; Machulda, Mary M. ; Roberts, Rosebud O. ; Boeve, Bradley F. ; Jones, David T. ; Petersen, Ronald C. / Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia. In: Neurology. 2016 ; Vol. 87, No. 7. pp. 691-698.
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abstract = "Objective: To examine neurodegenerative imaging biomarkers in Alzheimer disease (AD) dementia from middle to old age. Methods: Persons with AD dementia and elevated brain β-Amyloid with Pittsburgh compound B (PiB)-PET imaging underwent [ 18 F]-fluorodeoxyglucose (FDG)-PET and structural MRI. We evaluated 3 AD-related neurodegeneration biomarkers: hippocampal volume adjusted for total intracranial volume (HVa), FDG standardized uptake value ratio (SUVR) in regions of interest linked to AD, and cortical thickness in AD-related regions of interest. We examined associations of each biomarker with age and evaluated age effects on cutpoints defined by the 90th percentile in AD dementia. We assembled an age-, sex-, and intracranial volume-matched group of 194 similarly imaged clinically normal (CN) persons. Results: The 97 participants with AD dementia (aged 49-93 years) had PiB SUVR ≥1.8. A nonlinear (inverted-U) relationship between FDG SUVR and age was seen in the AD group but an inverse linear relationship with age was seen in the CN group. Cortical thickness had an inverse linear relationship with age in AD but a nonlinear (flat, then inverse linear) relationship in the CN group. HVa showed an inverse linear relationship with age in both AD and CN groups. Age effects on 90th percentile cutpoints were small for FDG SUVR and cortical thickness, but larger for HVa. Conclusions: In persons with AD dementia with elevated PiB SUVR, values of each neurodegeneration biomarker were associated with age. Cortical thickness had the smallest differences in 90th percentile cutpoints from middle to old age, and HVa the largest differences.",
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T1 - Age and neurodegeneration imaging biomarkers in persons with Alzheimer disease dementia

AU - Knopman, David S.

AU - Jack, Clifford R.

AU - Wiste, Heather J.

AU - Weigand, Stephen D.

AU - Vemuri, Prashanthi

AU - Lowe, Val J.

AU - Kantarci, Kejal

AU - Gunter, Jeffrey L.

AU - Senjem, Matthew L.

AU - Mielke, Michelle M.

AU - Machulda, Mary M.

AU - Roberts, Rosebud O.

AU - Boeve, Bradley F.

AU - Jones, David T.

AU - Petersen, Ronald C.

PY - 2016/8/16

Y1 - 2016/8/16

N2 - Objective: To examine neurodegenerative imaging biomarkers in Alzheimer disease (AD) dementia from middle to old age. Methods: Persons with AD dementia and elevated brain β-Amyloid with Pittsburgh compound B (PiB)-PET imaging underwent [ 18 F]-fluorodeoxyglucose (FDG)-PET and structural MRI. We evaluated 3 AD-related neurodegeneration biomarkers: hippocampal volume adjusted for total intracranial volume (HVa), FDG standardized uptake value ratio (SUVR) in regions of interest linked to AD, and cortical thickness in AD-related regions of interest. We examined associations of each biomarker with age and evaluated age effects on cutpoints defined by the 90th percentile in AD dementia. We assembled an age-, sex-, and intracranial volume-matched group of 194 similarly imaged clinically normal (CN) persons. Results: The 97 participants with AD dementia (aged 49-93 years) had PiB SUVR ≥1.8. A nonlinear (inverted-U) relationship between FDG SUVR and age was seen in the AD group but an inverse linear relationship with age was seen in the CN group. Cortical thickness had an inverse linear relationship with age in AD but a nonlinear (flat, then inverse linear) relationship in the CN group. HVa showed an inverse linear relationship with age in both AD and CN groups. Age effects on 90th percentile cutpoints were small for FDG SUVR and cortical thickness, but larger for HVa. Conclusions: In persons with AD dementia with elevated PiB SUVR, values of each neurodegeneration biomarker were associated with age. Cortical thickness had the smallest differences in 90th percentile cutpoints from middle to old age, and HVa the largest differences.

AB - Objective: To examine neurodegenerative imaging biomarkers in Alzheimer disease (AD) dementia from middle to old age. Methods: Persons with AD dementia and elevated brain β-Amyloid with Pittsburgh compound B (PiB)-PET imaging underwent [ 18 F]-fluorodeoxyglucose (FDG)-PET and structural MRI. We evaluated 3 AD-related neurodegeneration biomarkers: hippocampal volume adjusted for total intracranial volume (HVa), FDG standardized uptake value ratio (SUVR) in regions of interest linked to AD, and cortical thickness in AD-related regions of interest. We examined associations of each biomarker with age and evaluated age effects on cutpoints defined by the 90th percentile in AD dementia. We assembled an age-, sex-, and intracranial volume-matched group of 194 similarly imaged clinically normal (CN) persons. Results: The 97 participants with AD dementia (aged 49-93 years) had PiB SUVR ≥1.8. A nonlinear (inverted-U) relationship between FDG SUVR and age was seen in the AD group but an inverse linear relationship with age was seen in the CN group. Cortical thickness had an inverse linear relationship with age in AD but a nonlinear (flat, then inverse linear) relationship in the CN group. HVa showed an inverse linear relationship with age in both AD and CN groups. Age effects on 90th percentile cutpoints were small for FDG SUVR and cortical thickness, but larger for HVa. Conclusions: In persons with AD dementia with elevated PiB SUVR, values of each neurodegeneration biomarker were associated with age. Cortical thickness had the smallest differences in 90th percentile cutpoints from middle to old age, and HVa the largest differences.

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