Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults

Val Lowe, Tyler J. Bruinsma, Heather J. Wiste, Hoon Ki Min, Stephen D. Weigand, Ping Fang, Matthew L. Senjem, Terry M Therneau, Bradley F Boeve, Keith Anthony Josephs, Mukesh Pandey, Melissa E Murray, Kejal M Kantarci, David T. Jones, Prashanthi D Vemuri, Jonathan Graff-Radford, Christopher G. Schwarz, Mary Margaret Machulda, Michelle M Mielke, Rosebud O Roberts & 3 others David S Knopman, Ronald Carl Petersen, Clifford R Jr. Jack

Research output: Contribution to journalArticle

Abstract

OBJECTIVE: To assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults. METHODS: Tau- and amyloid-PET were performed in 579 CU participants aged 50-98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A-) and normal/abnormal regional tau-PET (T+/T-). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30-49. RESULTS: Higher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A- and A+. CONCLUSIONS: Tau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.

Original languageEnglish (US)
Pages (from-to)e29-e39
JournalNeurology
Volume93
Issue number1
DOIs
StatePublished - Jul 2 2019

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Entorhinal Cortex
Temporal Lobe
Cognition
Amyloid
Brain
Neurofibrillary Tangles
Longitudinal Studies
Linear Models
Language
Population

ASJC Scopus subject areas

  • Clinical Neurology

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Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults. / Lowe, Val; Bruinsma, Tyler J.; Wiste, Heather J.; Min, Hoon Ki; Weigand, Stephen D.; Fang, Ping; Senjem, Matthew L.; Therneau, Terry M; Boeve, Bradley F; Josephs, Keith Anthony; Pandey, Mukesh; Murray, Melissa E; Kantarci, Kejal M; Jones, David T.; Vemuri, Prashanthi D; Graff-Radford, Jonathan; Schwarz, Christopher G.; Machulda, Mary Margaret; Mielke, Michelle M; Roberts, Rosebud O; Knopman, David S; Petersen, Ronald Carl; Jack, Clifford R Jr.

In: Neurology, Vol. 93, No. 1, 02.07.2019, p. e29-e39.

Research output: Contribution to journalArticle

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title = "Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults",
abstract = "OBJECTIVE: To assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults. METHODS: Tau- and amyloid-PET were performed in 579 CU participants aged 50-98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A-) and normal/abnormal regional tau-PET (T+/T-). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30-49. RESULTS: Higher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A- and A+. CONCLUSIONS: Tau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.",
author = "Val Lowe and Bruinsma, {Tyler J.} and Wiste, {Heather J.} and Min, {Hoon Ki} and Weigand, {Stephen D.} and Ping Fang and Senjem, {Matthew L.} and Therneau, {Terry M} and Boeve, {Bradley F} and Josephs, {Keith Anthony} and Mukesh Pandey and Murray, {Melissa E} and Kantarci, {Kejal M} and Jones, {David T.} and Vemuri, {Prashanthi D} and Jonathan Graff-Radford and Schwarz, {Christopher G.} and Machulda, {Mary Margaret} and Mielke, {Michelle M} and Roberts, {Rosebud O} and Knopman, {David S} and Petersen, {Ronald Carl} and Jack, {Clifford R Jr.}",
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T1 - Cross-sectional associations of tau-PET signal with cognition in cognitively unimpaired adults

AU - Lowe, Val

AU - Bruinsma, Tyler J.

AU - Wiste, Heather J.

AU - Min, Hoon Ki

AU - Weigand, Stephen D.

AU - Fang, Ping

AU - Senjem, Matthew L.

AU - Therneau, Terry M

AU - Boeve, Bradley F

AU - Josephs, Keith Anthony

AU - Pandey, Mukesh

AU - Murray, Melissa E

AU - Kantarci, Kejal M

AU - Jones, David T.

AU - Vemuri, Prashanthi D

AU - Graff-Radford, Jonathan

AU - Schwarz, Christopher G.

AU - Machulda, Mary Margaret

AU - Mielke, Michelle M

AU - Roberts, Rosebud O

AU - Knopman, David S

AU - Petersen, Ronald Carl

AU - Jack, Clifford R Jr.

PY - 2019/7/2

Y1 - 2019/7/2

N2 - OBJECTIVE: To assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults. METHODS: Tau- and amyloid-PET were performed in 579 CU participants aged 50-98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A-) and normal/abnormal regional tau-PET (T+/T-). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30-49. RESULTS: Higher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A- and A+. CONCLUSIONS: Tau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.

AB - OBJECTIVE: To assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults. METHODS: Tau- and amyloid-PET were performed in 579 CU participants aged 50-98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A-) and normal/abnormal regional tau-PET (T+/T-). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30-49. RESULTS: Higher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A- and A+. CONCLUSIONS: Tau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.

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