Adults with PGD exhibit structural brain patterns consistent with accelerated and AD-like aging, but these findings were largely driven by comorbid depressive symptoms.
Key Findings
Results
Individuals with Prolonged Grief Disorder showed significantly higher brain age gap compared to those with integrated grief.
PGD group (n=36) and integrated grief group (n=56) were equated on demographics and time since loss
SPARE-BAG comparison: t=2.61, pcorrected=0.021
Groups underwent structural MRI with machine learning-derived brain age indices
These findings were attenuated and no longer significant after accounting for comorbid depressive symptoms
Results
Individuals with PGD showed significantly higher Alzheimer's disease-like atrophy patterns compared to those with integrated grief.
SPARE-AD comparison: t=2.04, pcorrected=0.045
Medial temporal lobe atrophy pattern was also significantly elevated: t=3.44, pcorrected=0.005
These findings were attenuated and no longer significant after accounting for comorbid depressive symptoms
Past depression history moderated the SPARE-AD-depressive symptom correlation: z=2.64, pcorrected=0.041
Results
Brain age and AD-like atrophy scores positively correlated with both grief and depressive symptom severity within the PGD group.
Both SPARE-BAG and SPARE-AD positively correlated with grief and depressive symptom severity in the PGD group (pcorrected<0.03)
The SPARE-BAG-grief symptom association was moderated by younger age: z=-2.92, pFDR=0.018
The SPARE-BAG-grief symptom association was also moderated by higher depressive symptoms: z=1.88, p=0.061
The SPARE-AD-depressive symptom correlation was moderated by past depression history: z=2.64, pcorrected=0.041
Results
Comorbid depressive symptoms accounted for the structural brain differences observed between the PGD and integrated grief groups.
Group differences in SPARE-BAG, SPARE-AD, and medial temporal lobe atrophy pattern were no longer significant after accounting for comorbid depressive symptoms
Findings highlight the cumulative neurobiological burden associated with PGD and co-occurring depression
Moderation analyses examined age, cognitive status, medical burden, and current and past depression as potential moderators
Authors conclude findings underscore the need for integrative clinical approaches addressing both PGD and comorbid depression
Methods
Five dominant brain aging patterns were computed alongside overall brain age gap and AD-like atrophy indices using machine learning.
Machine learning-derived indices included SPARE-BAG (Brain Age Gap), SPARE-AD (Alzheimer's disease-like atrophy), and five dominant brain aging patterns
Structural MRI was used as the imaging modality
Group differences and associations with symptom severity were assessed with corrections for multiple comparisons
Moderation by age, cognitive status, medical burden, and current and past depression was examined
Hwang G, Blair N, Claesges S, Reynolds C, Davatzikos C, Goveas J. (2026). Accelerated brain aging in prolonged grief disorder of later life: Influence of comorbid depression.. Journal of affective disorders. https://doi.org/10.1016/j.jad.2026.121387