The impact of amyloid-beta and tau on prospective cognitive decline in older individuals

Reisa A. Sperling, Elizabeth C. Mormino, Aaron P. Schultz, Rebecca Betensky, Kathryn V. Papp, Rebecca E. Amariglio, Bernard J. Hanseeuw, Rachel Buckley, Jasmeer Chhatwal, Trey Hedden, Gad A. Marshall, Yakeel T. Quiroz, Nancy J. Donovan, Jonathan Jackson, Jennifer R. Gatchel, Jennifer S. Rabin, Heidi Jacobs, Hyun Sik Yang, Michael Properzi, Dylan R. KirnDorene M. Rentz, Keith A. Johnson

Research output: Contribution to journalArticle

Abstract

Objectives: Amyloid-beta (Aβ) and tau pathologies are commonly observed among clinically normal older individuals at postmortem and can now be detected with in vivo neuroimaging. The association and interaction of these proteinopathies with prospective cognitive decline in normal aging and preclinical Alzheimer's disease (AD) remains to be fully elucidated. Methods: One hundred thirty-seven older individuals (age = 76.3 ± 6.22 years) participating in the Harvard Aging Brain Study underwent Aβ (11C-Pittsburgh compound B) and tau (18F-flortaucipir) positron emission tomography (PET) with prospective neuropsychological assessments following PET imaging (mean number of cognitive visits = 2.8 ± 1.1). Tau and Aβ PET measures were assessed in regions of interest (ROIs) as well as vertex-wise map analyses. Cognitive change was evaluated with Memory and Executive Function composites. Results: Higher levels of Aβ and tau were both associated with greater memory decline, but not with change in executive function. Higher cortical Aβ was associated with higher tau levels in all ROIs, independent of age, and very elevated levels of tau were observed primarily in clinically normal with elevated Aβ. A significant interaction between tau and Aβ was observed in both ROI and map-level analyses, such that rapid prospective memory decline was observed in participants who had high levels of both pathologies. Interpretation: Our results are consistent with the supposition that both Aβ and tau are necessary for memory decline in the preclinical stages of AD. These findings may be relevant for disambiguating aging and early cognitive manifestations of AD, and to inform secondary prevention trials in preclinical AD. Ann Neurol 2019;00:1–3 ANN NEUROL 2019;85:181–193.

Original languageEnglish (US)
Pages (from-to)181-193
Number of pages13
JournalAnnals of Neurology
Volume85
Issue number2
DOIs
StatePublished - Feb 1 2019

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Amyloid
Alzheimer Disease
Positron-Emission Tomography
Executive Function
Pathology
Neurobehavioral Manifestations
Episodic Memory
Secondary Prevention
Neuroimaging
Cognitive Dysfunction
Brain

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Sperling, R. A., Mormino, E. C., Schultz, A. P., Betensky, R., Papp, K. V., Amariglio, R. E., ... Johnson, K. A. (2019). The impact of amyloid-beta and tau on prospective cognitive decline in older individuals. Annals of Neurology, 85(2), 181-193. https://doi.org/10.1002/ana.25395

The impact of amyloid-beta and tau on prospective cognitive decline in older individuals. / Sperling, Reisa A.; Mormino, Elizabeth C.; Schultz, Aaron P.; Betensky, Rebecca; Papp, Kathryn V.; Amariglio, Rebecca E.; Hanseeuw, Bernard J.; Buckley, Rachel; Chhatwal, Jasmeer; Hedden, Trey; Marshall, Gad A.; Quiroz, Yakeel T.; Donovan, Nancy J.; Jackson, Jonathan; Gatchel, Jennifer R.; Rabin, Jennifer S.; Jacobs, Heidi; Yang, Hyun Sik; Properzi, Michael; Kirn, Dylan R.; Rentz, Dorene M.; Johnson, Keith A.

In: Annals of Neurology, Vol. 85, No. 2, 01.02.2019, p. 181-193.

Research output: Contribution to journalArticle

Sperling, RA, Mormino, EC, Schultz, AP, Betensky, R, Papp, KV, Amariglio, RE, Hanseeuw, BJ, Buckley, R, Chhatwal, J, Hedden, T, Marshall, GA, Quiroz, YT, Donovan, NJ, Jackson, J, Gatchel, JR, Rabin, JS, Jacobs, H, Yang, HS, Properzi, M, Kirn, DR, Rentz, DM & Johnson, KA 2019, 'The impact of amyloid-beta and tau on prospective cognitive decline in older individuals', Annals of Neurology, vol. 85, no. 2, pp. 181-193. https://doi.org/10.1002/ana.25395
Sperling, Reisa A. ; Mormino, Elizabeth C. ; Schultz, Aaron P. ; Betensky, Rebecca ; Papp, Kathryn V. ; Amariglio, Rebecca E. ; Hanseeuw, Bernard J. ; Buckley, Rachel ; Chhatwal, Jasmeer ; Hedden, Trey ; Marshall, Gad A. ; Quiroz, Yakeel T. ; Donovan, Nancy J. ; Jackson, Jonathan ; Gatchel, Jennifer R. ; Rabin, Jennifer S. ; Jacobs, Heidi ; Yang, Hyun Sik ; Properzi, Michael ; Kirn, Dylan R. ; Rentz, Dorene M. ; Johnson, Keith A. / The impact of amyloid-beta and tau on prospective cognitive decline in older individuals. In: Annals of Neurology. 2019 ; Vol. 85, No. 2. pp. 181-193.
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AU - Amariglio, Rebecca E.

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