Objective:

To investigate functional consequences of preclinical Tau deposition measured by a second-generation Tau tracer and using task-based functional magnetic resonance imaging scans (tb-fMRI) during two episodic memory tasks that are most vulnerable to Alzheimer’s disease (AD).

Background:

Interest in brain network functionality during the preclinical phase of AD is growing. Although the negative BOLD response (NBR) is often overlooked, it has been reported that aging with or without Aβ deposition is related to reduction in NBR from the default mode network (DMN). However, the relationship between Tau and NBR remains under investigation.

Design/Methods:

This cross-sectional study includes 188 cognitively unimpaired older adults (≥60 years and Blind MoCA > 17) undergoing Tau-PET (MK6240) and amyloid-PET (Florbetaben) scans. Aβ and Tau positivity were determined by two neuroradiologists. We used two episodic memory tasks; logical memory and paired associates; during fMRI scanning. The primary outcome was DMN deactivation measured by NBR which was z-scored based on a young group as the normative reference group. After removing outliers (3xIQR), we compared Aβ and Tau negative group (A-T-) with A-T+ and A+T-, using t-tests, adjusting for age, sex, education, and framewise displacement.

Results:

After removing outliers and individuals with missing fMRI task, sample sizes were 95 (A-T-), 25 (A-T+), and 9 (A+T-) for paired associates and 92 (A-T-), 27 (A-T+), and 7 (A+T-) for logical memory. We excluded A+T+ individuals to investigate the effects of Tau and Aβ independently.  Across both tasks, the A-T+ group showed significantly lower NBR magnitude than A-T- (logical memory: t=2.35, p=0.02; paired asociate: t=1.97, p=0.05). We observed no significant effect of Aβ on NBR (logical memory: t=-0.28, p=0.78; paired asociates: t=0.11, p=0.91).

Conclusions:

These findings suggest that the DMN deactivation is attenuated with preclinical Tau deposition. Future studies should focus on the clinical translation of DMN deactivation during preclinical AD using episodic memory tasks.