How do concerns about subjective cognitive decline in clinically healthy older adults relate to tau burden in brain regions of interest and global β-amyloid burden?
In this imaging study of 133 clinically healthy adults, subjective cognitive decline was associated with greater tau burden only in the entorhinal cortical region and, to a lesser extent, greater global β-amyloid levels; however, neither pathologic factor exerted an interactive influence on subjective cognitive decline.
Subjective cognitive decline is an important early indicator of abnormal tau and β-amyloid burden in clinically healthy adults with multiple underlying pathways; as such, multiple Alzheimer disease pathologic factors must be examined when considering the appearance of subjective cognitive decline in clinically healthy older adults.
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.
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.
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.
Buckley RF, Hanseeuw B, Schultz AP, Vannini P, Aghjayan SL, Properzi MJ, Jackson JD, Mormino EC, Rentz DM, Sperling RA, Johnson KA, Amariglio RE. Region-Specific Association of Subjective Cognitive Decline With Tauopathy Independent of Global β-Amyloid Burden. JAMA Neurol. 2017;74(12):1455–1463. doi:10.1001/jamaneurol.2017.2216
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