Brain β-amyloid load approaches a plateau

Clifford R Jr. Jack, Heather J. Wiste, Timothy G. Lesnick, Stephen D. Weigand, David S Knopman, Prashanthi D Vemuri, Vernon S. Pankratz, Matthew L. Senjem, Jeffrey L. Gunter, Michelle M Mielke, Val Lowe, Bradley F Boeve, Ronald Carl Petersen

Research output: Contribution to journalArticle

174 Citations (Scopus)

Abstract

Objective: To model the temporal trajectory of β-amyloid accumulation using serial amyloid PET imaging. Methods: Participants, aged 70-92 years, were enrolled in either the Mayo Clinic Study of Aging (n = 246) or the Mayo Alzheimer's Disease Research Center (n = 14). All underwent 2 or more serial amyloid PET examinations. There were 205 participants classified as cognitively normal and 55 as cognitively impaired (47 mild cognitive impairment and 8 Alzheimer dementia). We measured baseline amyloid PET-relative standardized uptake values (SUVR) and, for each participant, estimated a slope representing their annual amyloid accumulation rate. We then fit regression models to predict the rate of amyloid accumulation given baseline amyloid SUVR, and evaluated age, sex, clinical group, and APOE as covariates. Finally, we integrated the amyloid accumulation rate vs baseline amyloid PET SUVR association to an amyloid PET SUVR vs time association. Results: Rates of amyloid accumulation were low at low baseline SUVR. Rates increased to a maximum at baseline SUVR around 2.0, above which rates declined - reaching zero at baseline SUVR above 2.7. The rate of amyloid accumulation as a function of baseline SUVR had an inverted U shape. Integration produced a sigmoid curve relating amyloid PET SUVR to time. The average estimated time required to travel from an SUVR of 1.5-2.5 is approximately 15 years. Conclusion: This roughly 15-year interval where the slope of the amyloid SUVR vs time curve is greatest and roughly linear represents a large therapeutic window for secondary preventive interventions.

Original languageEnglish (US)
Pages (from-to)890-896
Number of pages7
JournalNeurology
Volume80
Issue number10
DOIs
StatePublished - Mar 5 2013

Fingerprint

Amyloid
Brain
Plateau
Alzheimer Disease
Sigmoid Colon

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Brain β-amyloid load approaches a plateau. / Jack, Clifford R Jr.; Wiste, Heather J.; Lesnick, Timothy G.; Weigand, Stephen D.; Knopman, David S; Vemuri, Prashanthi D; Pankratz, Vernon S.; Senjem, Matthew L.; Gunter, Jeffrey L.; Mielke, Michelle M; Lowe, Val; Boeve, Bradley F; Petersen, Ronald Carl.

In: Neurology, Vol. 80, No. 10, 05.03.2013, p. 890-896.

Research output: Contribution to journalArticle

Jack, CRJ, Wiste, HJ, Lesnick, TG, Weigand, SD, Knopman, DS, Vemuri, PD, Pankratz, VS, Senjem, ML, Gunter, JL, Mielke, MM, Lowe, V, Boeve, BF & Petersen, RC 2013, 'Brain β-amyloid load approaches a plateau', Neurology, vol. 80, no. 10, pp. 890-896. https://doi.org/10.1212/WNL.0b013e3182840bbe
Jack, Clifford R Jr. ; Wiste, Heather J. ; Lesnick, Timothy G. ; Weigand, Stephen D. ; Knopman, David S ; Vemuri, Prashanthi D ; Pankratz, Vernon S. ; Senjem, Matthew L. ; Gunter, Jeffrey L. ; Mielke, Michelle M ; Lowe, Val ; Boeve, Bradley F ; Petersen, Ronald Carl. / Brain β-amyloid load approaches a plateau. In: Neurology. 2013 ; Vol. 80, No. 10. pp. 890-896.
@article{67c0035977054171b8c93a054eb25d3a,
title = "Brain β-amyloid load approaches a plateau",
abstract = "Objective: To model the temporal trajectory of β-amyloid accumulation using serial amyloid PET imaging. Methods: Participants, aged 70-92 years, were enrolled in either the Mayo Clinic Study of Aging (n = 246) or the Mayo Alzheimer's Disease Research Center (n = 14). All underwent 2 or more serial amyloid PET examinations. There were 205 participants classified as cognitively normal and 55 as cognitively impaired (47 mild cognitive impairment and 8 Alzheimer dementia). We measured baseline amyloid PET-relative standardized uptake values (SUVR) and, for each participant, estimated a slope representing their annual amyloid accumulation rate. We then fit regression models to predict the rate of amyloid accumulation given baseline amyloid SUVR, and evaluated age, sex, clinical group, and APOE as covariates. Finally, we integrated the amyloid accumulation rate vs baseline amyloid PET SUVR association to an amyloid PET SUVR vs time association. Results: Rates of amyloid accumulation were low at low baseline SUVR. Rates increased to a maximum at baseline SUVR around 2.0, above which rates declined - reaching zero at baseline SUVR above 2.7. The rate of amyloid accumulation as a function of baseline SUVR had an inverted U shape. Integration produced a sigmoid curve relating amyloid PET SUVR to time. The average estimated time required to travel from an SUVR of 1.5-2.5 is approximately 15 years. Conclusion: This roughly 15-year interval where the slope of the amyloid SUVR vs time curve is greatest and roughly linear represents a large therapeutic window for secondary preventive interventions.",
author = "Jack, {Clifford R Jr.} and Wiste, {Heather J.} and Lesnick, {Timothy G.} and Weigand, {Stephen D.} and Knopman, {David S} and Vemuri, {Prashanthi D} and Pankratz, {Vernon S.} and Senjem, {Matthew L.} and Gunter, {Jeffrey L.} and Mielke, {Michelle M} and Val Lowe and Boeve, {Bradley F} and Petersen, {Ronald Carl}",
year = "2013",
month = "3",
day = "5",
doi = "10.1212/WNL.0b013e3182840bbe",
language = "English (US)",
volume = "80",
pages = "890--896",
journal = "Neurology",
issn = "0028-3878",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Brain β-amyloid load approaches a plateau

AU - Jack, Clifford R Jr.

AU - Wiste, Heather J.

AU - Lesnick, Timothy G.

AU - Weigand, Stephen D.

AU - Knopman, David S

AU - Vemuri, Prashanthi D

AU - Pankratz, Vernon S.

AU - Senjem, Matthew L.

AU - Gunter, Jeffrey L.

AU - Mielke, Michelle M

AU - Lowe, Val

AU - Boeve, Bradley F

AU - Petersen, Ronald Carl

PY - 2013/3/5

Y1 - 2013/3/5

N2 - Objective: To model the temporal trajectory of β-amyloid accumulation using serial amyloid PET imaging. Methods: Participants, aged 70-92 years, were enrolled in either the Mayo Clinic Study of Aging (n = 246) or the Mayo Alzheimer's Disease Research Center (n = 14). All underwent 2 or more serial amyloid PET examinations. There were 205 participants classified as cognitively normal and 55 as cognitively impaired (47 mild cognitive impairment and 8 Alzheimer dementia). We measured baseline amyloid PET-relative standardized uptake values (SUVR) and, for each participant, estimated a slope representing their annual amyloid accumulation rate. We then fit regression models to predict the rate of amyloid accumulation given baseline amyloid SUVR, and evaluated age, sex, clinical group, and APOE as covariates. Finally, we integrated the amyloid accumulation rate vs baseline amyloid PET SUVR association to an amyloid PET SUVR vs time association. Results: Rates of amyloid accumulation were low at low baseline SUVR. Rates increased to a maximum at baseline SUVR around 2.0, above which rates declined - reaching zero at baseline SUVR above 2.7. The rate of amyloid accumulation as a function of baseline SUVR had an inverted U shape. Integration produced a sigmoid curve relating amyloid PET SUVR to time. The average estimated time required to travel from an SUVR of 1.5-2.5 is approximately 15 years. Conclusion: This roughly 15-year interval where the slope of the amyloid SUVR vs time curve is greatest and roughly linear represents a large therapeutic window for secondary preventive interventions.

AB - Objective: To model the temporal trajectory of β-amyloid accumulation using serial amyloid PET imaging. Methods: Participants, aged 70-92 years, were enrolled in either the Mayo Clinic Study of Aging (n = 246) or the Mayo Alzheimer's Disease Research Center (n = 14). All underwent 2 or more serial amyloid PET examinations. There were 205 participants classified as cognitively normal and 55 as cognitively impaired (47 mild cognitive impairment and 8 Alzheimer dementia). We measured baseline amyloid PET-relative standardized uptake values (SUVR) and, for each participant, estimated a slope representing their annual amyloid accumulation rate. We then fit regression models to predict the rate of amyloid accumulation given baseline amyloid SUVR, and evaluated age, sex, clinical group, and APOE as covariates. Finally, we integrated the amyloid accumulation rate vs baseline amyloid PET SUVR association to an amyloid PET SUVR vs time association. Results: Rates of amyloid accumulation were low at low baseline SUVR. Rates increased to a maximum at baseline SUVR around 2.0, above which rates declined - reaching zero at baseline SUVR above 2.7. The rate of amyloid accumulation as a function of baseline SUVR had an inverted U shape. Integration produced a sigmoid curve relating amyloid PET SUVR to time. The average estimated time required to travel from an SUVR of 1.5-2.5 is approximately 15 years. Conclusion: This roughly 15-year interval where the slope of the amyloid SUVR vs time curve is greatest and roughly linear represents a large therapeutic window for secondary preventive interventions.

UR - http://www.scopus.com/inward/record.url?scp=84876209795&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84876209795&partnerID=8YFLogxK

U2 - 10.1212/WNL.0b013e3182840bbe

DO - 10.1212/WNL.0b013e3182840bbe

M3 - Article

C2 - 23446680

AN - SCOPUS:84876209795

VL - 80

SP - 890

EP - 896

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 10

ER -