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Cited by 173Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden

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Buckley, Rachel F., Hanseeuw, Bernard, Schultz, Aaron P., Vannini, Patrizia, Aghjayan, Sarah L., Properzi, Michael J., Jackson, Jonathan D., Mormino, Elizabeth C. +4 more·2017·JAMA Neurology
DOI 10.1001/jamaneurol.2017.2216PMC PMC5774633
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Abstract

Importance: The ability to explore associations between reports of subjective cognitive decline (SCD) and biomarkers of early Alzheimer disease (AD) pathophysiologic processes (accumulation of neocortical β-amyloid [Aβ] and tau) provides an important opportunity to understand the basis of SCD and AD risk. Objective: To examine associations between SCD and global Aβ and tau burdens in regions of interest in clinically healthy older adults. Design, Setting, and Participants: This imaging substudy of the Harvard Aging Brain Study included 133 clinically healthy older participants (Clinical Dementia Rating Scale global scores of 0) participating in the Harvard Aging Brain Study who underwent cross-sectional flortaucipir F 18 (previously known as AV 1451, T807) positron emission tomography (FTP-PET) imaging for tau and Pittsburgh compound B carbon 11-labeled PET (PiB-PET) imaging for Aβ. The following 2 regions for tau burden were identified: the entorhinal cortex, which exhibits early signs of tauopathy, and the inferior temporal region, which is more closely associated with AD-related pathologic mechanisms. Data were collected from June 11, 2012, through April 7, 2016. Main Outcomes and Measures: Subjective cognitive decline was measured using a previously published method of z-transforming subscales from the Memory Functioning Questionnaire, the Everyday Cognition battery, and a 7-item questionnaire. The Aβ level was measured according to a summary distribution volume ratio of frontal, lateral temporal and parietal, and retrosplenial PiB-PET tracer uptake. The FTP-PET measures were computed as standardized uptake value ratios. Linear regression models focused on main and interactive effects of Aβ, entorhinal cortical, and inferior temporal tau on SCD, controlling for age, sex, educational attainment, and Geriatric Depression Scale score. Results: Of the 133 participants, 75 (56.3%) were women and 58 (43.6%) were men; mean (SD) age was 76 (6.9) years (range, 55-90 years). Thirty-nine participants (29.3%) exhibited a high Aβ burden. Greater SCD was associated with increasing entorhinal cortical tau burden (β = 0.35; 95% CI, 0.19-.52; P < .001) and Aβ burden (β = 0.24; 95% CI, 0.08-.40; P = .005), but not inferior temporal tau burden (β = 0.10; 95% CI, -0.08 to 0.28; P = .27). This association between entorhinal cortical tau burden and SCD was largely unchanged after accounting for Aβ burden (β = 0.36; 95% CI, 0.15-.58; P = .001), and no interaction influenced SCD (β = -0.36; 95% CI, -0.34 to 0.09; P = .25). An exploratory post hoc whole-brain analysis also indicated that SCD was predominantly associated with greater tau burden in the entorhinal cortex. Conclusions and Relevance: Subjective cognitive decline is indicative of accumulation of early tauopathy in the medial temporal lobe, specifically in the entorhinal cortex, and to a lesser extent, elevated global levels of Aβ. Our findings suggest multiple underlying pathways that motivate SCD that do not necessarily interact to influence SCD endorsement. As such, multiple biological factors must be considered when assessing SCD in clinically healthy older adults.

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Authors
Buckley, R. F., Hanseeuw, B., Schultz, A. P., Vannini, P., Aghjayan, S. L., Properzi, M. J., Jackson, J. D., Mormino, E. C., Rentz, D. M., Sperling, R. A., Johnson, K. A., & Amariglio, R. E.
Affiliations
  • Harvard University (US)
  • Cliniques Universitaires Saint-Luc (BE)
  • Massachusetts General Hospital (US)
  • Brigham and Women's Hospital (US)
Corresponding author
Amariglio, Rebecca E.
ORCID
Venue
JAMA Neurology
Publisher
American Medical Association (AMA)
Published
2017-12-01
Volume
74
Issue
12
Pages
1455
ISSN
2168-6149 (ISSN-L)
DOI
10.1001/jamaneurol.2017.2216
PMC
PMC5774633
OpenAlex
W2763250779
Cited by
173
References
61
Citations by year
2026: 8 · 2025: 17 · 2024: 25 · 2023: 12 · 2022: 21 · 2021: 20 · 2020: 20 · 2019: 31 · 2018: 18 · 2017: 1
FWCI
15.73
Type
journal article
Language
en
Open access
Locations
  • JAMA Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • Digital Access to Libraries (submittedVersion)
Funders
  • National Institutes of Health (1s10rr021110-01a1, 1s10rr023043-01)
  • National Institute on Aging (K24AG035007, K01AG048287, R01AG046396, K23AG044431, P50AG005134, K01AG051718, P01AG036694)
  • National Institute of Biomedical Imaging and Bioengineering (P41EB015896)
  • National Center for Research Resources (S10-RR-023043, S10‐RR‐021110, S10RR023401)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
Keywords
subjective cognitive decline, Alzheimer's disease, tauopathy, amyloid-beta, entorhinal cortex, inferior temporal cortex, flortaucipir PET, Pittsburgh compound B PET, healthy older adults, preclinical Alzheimer's disease, neurodegeneration, geriatric depression, sex differences
MeSH terms
Aged, Aged, 80 and over, Aniline Compounds, Brain, Carbolines, Cross-Sectional Studies, Female, Frontal Lobe, Humans, Male, Middle Aged, Parietal Lobe, Phenanthrolines, Surveys and Questionnaires, Temporal Lobe, Thiazoles, Amyloid beta-Peptides, tau Proteins, Entorhinal Cortex, Radiopharmaceuticals, Neocortex, Tauopathies, Positron-Emission Tomography, Diagnostic Self Evaluation, Cognitive Dysfunction

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