Accelerated brain aging in prolonged grief disorder of later life: Influence of comorbid depression.

Prolonged Grief Disorder (PGD) in later life may involve volumetric patterns indicative of accelerated brain aging. This study examined whether structural brain age differs between individuals with PGD and those with integrated grief (IG), and whether it is associated with clinical severity. Chronically grieving older adults with PGD (n = 36) and IG (n = 56), equated on demographics and time since loss, underwent structural MRI. Machine learning-derived indices were computed for each participant: Brain Age Gap (SPARE-BAG), Alzheimer's disease-like atrophy (SPARE-AD), and five dominant brain aging patterns. Group differences and associations with symptom severity were assessed, along with moderation by age, cognitive status, medical burden, and current and past depression. Compared to IG, the PGD group showed significantly higher SPARE-BAG (t = 2.61, pcorrected = 0.021), SPARE-AD (t = 2.04, pcorrected = 0.045), and medial temporal lobe atrophy pattern (t = 3.44, pcorrected = 0.005). However, these findings were attenuated and no longer significant after accounting for comorbid depressive symptoms. In the PGD group, both SPARE scores positively correlated with grief and depressive symptom severity (pcorrected < 0.03). The SPARE-BAG-grief symptom association was moderated by younger age (z = -2.92, pFDR = 0.018) and higher depressive symptoms (z = 1.88, p = 0.061); SPARE-AD-depressive symptom correlation was moderated by past depression history (z = 2.64, pcorrected = 0.041). Adults with PGD exhibit structural brain patterns consistent with accelerated and AD-like aging. However, these findings were largely driven by comorbid depressive symptoms. The brain aging indices were associated with both grief and depressive symptom severity, highlighting the cumulative neurobiological burden associated with PGD and co-occurring depression and underscoring the need for integrative clinical approaches addressing both conditions.