Background The deep gray matter nuclei (DGMN)—including the thalamus, caudate, putamen, and pallidum—are essential for cognitive, motor, and affective functions and are highly susceptible to age-related degeneration. However, the combined effects of aging and sex on DGMN volume, microstructure, and perfusion remain incompletely characterized. Methods Using data from 652 healthy adults (36–89 years) from the Human Connectome Project-Aging cohort, we examined volumetric and perfusion changes across the DGMN. High-resolution T1- and T2-weighted MRI and multi-delay pseudo-continuous arterial spin labeling (pCASL) were used to quantify normalized volume, T1/T2 ratio, cerebral blood flow (CBF), and arterial transit time (ATT) in DGMN regions after perivascular spaces were removed. Age-related trajectories were modeled using linear and quadratic regression, and differences between sexes were examined, with false discovery rate correction applied. Results Advancing age was associated with significant volumetric decline in all DGMN regions (p < 0.001), prolonged ATT, and reduced CBF, particularly in the caudate and thalamus. The T1/T2 ratio exhibited region-specific nonlinear trajectories, peaking in mid-adulthood and declining thereafter, reflecting its underlying age-related processes of demyelination and iron accumulation. Sex-stratified analyses suggested modest differences in T1/T2, ATT, and CBF trajectories; however, no significant age × sex interactions were observed after correction for multiple comparisons. DGMN volumes correlated negatively with ATT, while T1/T2 ratio correlated inversely with CBF, indicating more complex interactions between structure, tissue properties, and perfusion. Conclusions This large-scale quantitative MRI study delineates distinct age-related trajectories of DGMN over adult lifespan. Integrating volumetric, T1/T2 ratio, and multi-delay ASL metrics—while correcting for perivascular spaces—enhances sensitivity to subtle changes and provides normative benchmarks for detecting early neurodegenerative alterations.
Zhang et al. (Tue,) studied this question.