Associations Between Hippocampal Transverse Relaxation Time and Amyloid PET in Cognitively Normal Aging Adults.

Abstract

Background: Identifying early neuropathological changes in Alzheimer's disease (AD) is important for improving treatment efficacy. Among quantitative MRI measures, transverse relaxation time (T2) has been shown to reflect tissue microstructure relevant in aging and neurodegeneration; however, findings regarding T2 changes in both normal aging and AD have been inconsistent. The association between T2 and amyloid-beta (Aβ) accumulation, a hallmark of AD pathology, is also unclear, particularly in cognitively normal individuals who may be in preclinical stages of the disease.

Purpose: To investigate longitudinal hippocampal T2 changes in a cognitively normal cohort of older adults and their association with global Aβ accumulation.

Study type: Retrospective, longitudinal.

Subjects: 56 cognitively normal adults between 55 and 90 years of age (17 males and 39 females).

Field strength/sequence: 3 Tesla; multi-echo spin echo sequence for T2 mapping; 18F-florbetaben positron emission tomography for Aβ measurement.

Assessment: Bilateral hippocampal T2 and volume were extracted to relate to Aβ PET measurements. To understand variations in AD risk, participants were separated into Aβ-high and Aβ-low subgroups using a predetermined threshold.

Statistical tests: Linear mixed-effect models and general linear models were used. A p-value < 0.025 was considered significant to account for bilateral comparisons.

Results: Older age was associated with increased T2 in the bilateral hippocampus (left: β = 0.30, right: β = 0.25) and smaller hippocampal volume on the left (β = -0.12). In the Aβ-low subgroup, both longitudinal T2 increase rates (β = 0.65) in the left hippocampus and bilateral cross-sectional T2 (left: β = 0.64, right: β = 0.46) were positively correlated with Aβ PET, independent of hippocampal volume.

Data conclusion: This study provided in vivo evidence linking hippocampal T2 to Aβ accumulation in cognitively normal aging individuals, suggesting that quantitative T2 may be sensitive to microstructural changes accompanying early Aβ pathology, such as neuroinflammation, demyelination, and reduced tissue integrity.

Evidence level: 3.

Technical efficacy: Stage 2.