Abstract
As more biomarkers for Alzheimer's disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1148-1160 |
| Number of pages | 13 |
| Journal | Brain : a journal of neurology |
| Volume | 142 |
| Issue number | 4 |
| DOIs | |
| State | Published - Apr 1 2019 |
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Keywords
- amyloid PET
- cortical thickness, memory
- flortaucipir PET
ASJC Scopus subject areas
- Clinical Neurology
Cite this
Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects. / Knopman, David S; Lundt, Emily S.; Therneau, Terry M; Vemuri, Prashanthi D; Lowe, Val; Kantarci, Kejal M; Gunter, Jeffrey L.; Senjem, Matthew L.; Mielke, Michelle M; Machulda, Mary Margaret; Boeve, Bradley F; Jones, David T; Graff-Radford, Jonathan; Albertson, Sabrina M.; Schwarz, Christopher; Petersen, Ronald Carl; Jack, Clifford R Jr.
In: Brain : a journal of neurology, Vol. 142, No. 4, 01.04.2019, p. 1148-1160.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Entorhinal cortex tau, amyloid-β, cortical thickness and memory performance in non-demented subjects
AU - Knopman, David S
AU - Lundt, Emily S.
AU - Therneau, Terry M
AU - Vemuri, Prashanthi D
AU - Lowe, Val
AU - Kantarci, Kejal M
AU - Gunter, Jeffrey L.
AU - Senjem, Matthew L.
AU - Mielke, Michelle M
AU - Machulda, Mary Margaret
AU - Boeve, Bradley F
AU - Jones, David T
AU - Graff-Radford, Jonathan
AU - Albertson, Sabrina M.
AU - Schwarz, Christopher
AU - Petersen, Ronald Carl
AU - Jack, Clifford R Jr.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - As more biomarkers for Alzheimer's disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.
AB - As more biomarkers for Alzheimer's disease and age-related brain conditions become available, more sophisticated analytic approaches are needed to take full advantage of the information they convey. Most work has been done using categorical approaches but the joint relationships of tau PET, amyloid PET and cortical thickness in their continuous distributions to cognition have been under-explored. We evaluated non-demented subjects over age 50 years in the Mayo Clinic Study of Aging, 2037 of whom had undergone 3 T MRI scan, 985 amyloid PET scan with 11C-Pittsburgh compound B (PIB) and MRI, and 577 PIB-PET, 18F-AV1451 flortaucipir PET and MRI. Participants received a nine-test cognitive battery. Three test scores (logical memory delayed recall, visual reproduction delayed recall and auditory verbal learning test delayed recall) were used to generate a memory composite z-score. We used Gradient Boosting Machine models to analyse the relationship between regional cortical thickness, flortaucipir PET signal, PIB-PET signal and memory z-scores. Age, education, sex and number of test exposures were included in the model as covariates. In this population-based study of non-demented subjects, most of the associations between biomarkers and memory z-scores accrued after 70 years of age. Entorhinal cortex exhibited the strongest associations between biomarkers and memory z-scores. Other temporal regions showed similar but attenuated associations, and non-temporal regions had negligible associations between memory z-scores and biomarkers. Entorhinal flortaucipir PET signal, PIB-PET signal and entorhinal cortical thickness were independently and additively associated with declining memory z-scores. In contrast to global PIB-PET signal where only very high amyloid-β levels were associated low memory z-scores, entorhinal flortaucipir PET signal just above background levels was associated with low memory z-scores. The lowest memory z-scores occurred with the confluence of elevated entorhinal flortaucipir PET signal and lower entorhinal cortical thickness.
KW - amyloid PET
KW - cortical thickness, memory
KW - flortaucipir PET
UR - http://www.scopus.com/inward/record.url?scp=85064285307&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85064285307&partnerID=8YFLogxK
U2 - 10.1093/brain/awz025
DO - 10.1093/brain/awz025
M3 - Article
C2 - 30759182
AN - SCOPUS:85064285307
VL - 142
SP - 1148
EP - 1160
JO - Brain
JF - Brain
SN - 0006-8950
IS - 4
ER -