Amyloid-first and neurodegeneration-first profiles characterize incident amyloid PET positivity

Clifford R Jr. Jack, Heather J. Wiste, Stephen D. Weigand, David S Knopman, Val Lowe, Prashanthi D Vemuri, Michelle M Mielke, David T Jones, Matthew L. Senjem, Jeffrey L. Gunter, Brian E. Gregg, Vernon S. Pankratz, Ronald Carl Petersen

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118 Citations (Scopus)

Abstract

Objective: To estimate the incidence of and to characterize cognitive and imaging findings associated with incident amyloid PET positivity. Methods: Cognitively normal (CN) participants in the Mayo Clinic Study of Aging who had 2 or more serial imaging assessments, which included amyloid PET, FDG-PET, and MRI at each time point, were eligible for analysis (n 5 207). Twelve subjects with Alzheimer disease dementia were included for comparison. Results: Of the 123 CN participants who were amyloid-negative at baseline, 26 met criteria for incident amyloid PET positivity. Compared to the 69 subjects who remained stable amyloid-negative, on average these 26 did not differ on any imaging, demographic, or cognitive variables except amyloid PET (by definition) and task-free functional connectivity, which at baseline was greater in the incident amyloid-positive group. Eleven of the 26 incident amyloid-positive subjects had abnormal hippocampal volume, FDG-PET, or both at baseline. Conclusions: The incidence of amyloid PET positivity is approximately 13% per year among CN participants over age 70 sampled from a population-based cohort. In 15/26 (58%), incident amyloid positivity occurred prior to abnormalities in FDG-PET and hippocampal volume. However, 11/26 (42%) incident amyloid-positive subjects had evidence of neurodegeneration prior to incident amyloid positivity. These 11 could be subjects with combinations of preexisting non-Alzheimer pathophysiologies and tau-mediated neurodegeneration who newly entered the amyloid pathway. Our findings suggest that both "amyloid-first" and "neurodegeneration-first" biomarker profile pathways to preclinical AD exist.

Original languageEnglish (US)
Pages (from-to)1732-1740
Number of pages9
JournalNeurology
Volume81
Issue number20
DOIs
StatePublished - Nov 12 2013

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Amyloid
Positivity
Alzheimer Disease
Imaging
Incidence
Pathway
Biomarkers
Demography

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

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Amyloid-first and neurodegeneration-first profiles characterize incident amyloid PET positivity. / Jack, Clifford R Jr.; Wiste, Heather J.; Weigand, Stephen D.; Knopman, David S; Lowe, Val; Vemuri, Prashanthi D; Mielke, Michelle M; Jones, David T; Senjem, Matthew L.; Gunter, Jeffrey L.; Gregg, Brian E.; Pankratz, Vernon S.; Petersen, Ronald Carl.

In: Neurology, Vol. 81, No. 20, 12.11.2013, p. 1732-1740.

Research output: Contribution to journalArticle

Jack, Clifford R Jr. ; Wiste, Heather J. ; Weigand, Stephen D. ; Knopman, David S ; Lowe, Val ; Vemuri, Prashanthi D ; Mielke, Michelle M ; Jones, David T ; Senjem, Matthew L. ; Gunter, Jeffrey L. ; Gregg, Brian E. ; Pankratz, Vernon S. ; Petersen, Ronald Carl. / Amyloid-first and neurodegeneration-first profiles characterize incident amyloid PET positivity. In: Neurology. 2013 ; Vol. 81, No. 20. pp. 1732-1740.
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abstract = "Objective: To estimate the incidence of and to characterize cognitive and imaging findings associated with incident amyloid PET positivity. Methods: Cognitively normal (CN) participants in the Mayo Clinic Study of Aging who had 2 or more serial imaging assessments, which included amyloid PET, FDG-PET, and MRI at each time point, were eligible for analysis (n 5 207). Twelve subjects with Alzheimer disease dementia were included for comparison. Results: Of the 123 CN participants who were amyloid-negative at baseline, 26 met criteria for incident amyloid PET positivity. Compared to the 69 subjects who remained stable amyloid-negative, on average these 26 did not differ on any imaging, demographic, or cognitive variables except amyloid PET (by definition) and task-free functional connectivity, which at baseline was greater in the incident amyloid-positive group. Eleven of the 26 incident amyloid-positive subjects had abnormal hippocampal volume, FDG-PET, or both at baseline. Conclusions: The incidence of amyloid PET positivity is approximately 13{\%} per year among CN participants over age 70 sampled from a population-based cohort. In 15/26 (58{\%}), incident amyloid positivity occurred prior to abnormalities in FDG-PET and hippocampal volume. However, 11/26 (42{\%}) incident amyloid-positive subjects had evidence of neurodegeneration prior to incident amyloid positivity. These 11 could be subjects with combinations of preexisting non-Alzheimer pathophysiologies and tau-mediated neurodegeneration who newly entered the amyloid pathway. Our findings suggest that both {"}amyloid-first{"} and {"}neurodegeneration-first{"} biomarker profile pathways to preclinical AD exist.",
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AU - Jack, Clifford R Jr.

AU - Wiste, Heather J.

AU - Weigand, Stephen D.

AU - Knopman, David S

AU - Lowe, Val

AU - Vemuri, Prashanthi D

AU - Mielke, Michelle M

AU - Jones, David T

AU - Senjem, Matthew L.

AU - Gunter, Jeffrey L.

AU - Gregg, Brian E.

AU - Pankratz, Vernon S.

AU - Petersen, Ronald Carl

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AB - Objective: To estimate the incidence of and to characterize cognitive and imaging findings associated with incident amyloid PET positivity. Methods: Cognitively normal (CN) participants in the Mayo Clinic Study of Aging who had 2 or more serial imaging assessments, which included amyloid PET, FDG-PET, and MRI at each time point, were eligible for analysis (n 5 207). Twelve subjects with Alzheimer disease dementia were included for comparison. Results: Of the 123 CN participants who were amyloid-negative at baseline, 26 met criteria for incident amyloid PET positivity. Compared to the 69 subjects who remained stable amyloid-negative, on average these 26 did not differ on any imaging, demographic, or cognitive variables except amyloid PET (by definition) and task-free functional connectivity, which at baseline was greater in the incident amyloid-positive group. Eleven of the 26 incident amyloid-positive subjects had abnormal hippocampal volume, FDG-PET, or both at baseline. Conclusions: The incidence of amyloid PET positivity is approximately 13% per year among CN participants over age 70 sampled from a population-based cohort. In 15/26 (58%), incident amyloid positivity occurred prior to abnormalities in FDG-PET and hippocampal volume. However, 11/26 (42%) incident amyloid-positive subjects had evidence of neurodegeneration prior to incident amyloid positivity. These 11 could be subjects with combinations of preexisting non-Alzheimer pathophysiologies and tau-mediated neurodegeneration who newly entered the amyloid pathway. Our findings suggest that both "amyloid-first" and "neurodegeneration-first" biomarker profile pathways to preclinical AD exist.

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