MASLD Linked to Worse Depression Trajectories in Older Adults

Key Takeaways

• In community-dwelling older Australian adults in the ASPREE-derived cohort, baseline MASLD was associated with worse depressive symptom trajectories over follow-up.
• At baseline, 2998 of 9097 participants (33%) met the study definition of MASLD.
• Depressive symptom trajectories were 46% non-depressed, 38.2% subthreshold, 9.1% persistent, and 6.7% emerging, with non-depressed and subthreshold patterns making up most of the cohort.
• The association with persistent depressive symptoms appeared stronger in females and in participants with dyslipidemia.

Late-life depressive symptoms often overlap with metabolic illness, and whether metabolic dysfunction-associated steatotic liver disease (MASLD), the metabolically focused replacement term for nonalcoholic fatty liver disease, tracks with different long-term symptom patterns in older adults has remained unclear. In community settings, the clinical issue is whether symptoms remain mild, persist, or emerge over time rather than whether they are present at a single visit. Older adults in the ASPREE cohort in Australia provided a setting to examine those longer-term patterns.

In the ASPREE cohort report on MASLD and depressive symptom trajectories, investigators conducted a secondary analysis of longitudinal ASPirin in Reducing Events in the Elderly (ASPREE) data in Australian community-dwelling older adults, including 9097 participants with a valid baseline Fatty Liver Index (FLI). MASLD required an FLI of 60 or higher plus at least one cardiometabolic criterion after exclusion of excessive alcohol intake and steatogenic medication use, and participants below that threshold served as the comparator. Depressive symptoms were measured with the Centre for Epidemiologic Studies Depression Scale-10 (CES-D-10) and modeled into four trajectories over a median 4.6 years (IQR 0.1-7.1 years), with multinomial models adjusted for baseline sociodemographic, lifestyle, cognitive, medication, and morbidity factors. Because this analytic sample came from Australian ASPREE participants, the findings describe that setting rather than a directly U.S.-based population.

Four depressive symptom trajectories were identified: non-depressed, subthreshold depression, persistent depression, and emerging depression, with non-depressed and subthreshold patterns comprising most of the cohort. The paper reports MASLD was associated with persistent (RRR 1.43, 95% CI 1.22-1.67) and subthreshold (RRR 1.13, 95% CI 1.02-1.24) depressive-symptom trajectories versus non-depressed. The pattern centered on subthreshold and persistent symptoms rather than new emergence.

The subgroup pattern was not uniform across the cohort. Among females, persistent depression trajectory membership was associated with MASLD at RRR 1.69 (95% CI 1.37-2.08), while participants with dyslipidemia also showed elevated persistent and subthreshold patterns. Additional adjustment for social isolation, social support, and anthropometric measures did not materially change the main pattern, and the three-category MASLD sensitivity analysis retained significance mainly for the persistent trajectory.

These findings came from an observational secondary analysis and do not establish that MASLD causes depressive symptoms. MASLD classification relied on FLI plus cardiometabolic criteria rather than direct liver imaging or biopsy, and depression was captured as CES-D-10 symptom trajectories rather than diagnostic interviews for major depressive disorder. The analytic sample was limited to Australian ASPREE participants with valid baseline biochemistry and was predominantly White, which narrows the study context. The report also contained a discrepancy in sex distribution between sections, adding a local caution around demographic detail.

The authors concluded that baseline MASLD was associated with worse depressive symptom trajectories in community-dwelling older adults, with the pattern concentrated in subthreshold and persistent trajectories and appearing more pronounced in females and participants with dyslipidemia.

Clinician Questions

How was MASLD defined in older adults in the ASPREE depression-trajectory analysis?

MASLD required a Fatty Liver Index of 60 or higher plus at least one cardiometabolic criterion after exclusion of excessive alcohol intake and steatogenic medication use, and participants with FLI below 60 served as the comparator.

Which older adults were included in the MASLD and depressive symptom trajectory cohort?

The cohort consisted of Australian ASPREE participants with a valid and calculable baseline FLI drawn from the larger biobank sample; participants were older adults, around 75 years on average, and predominantly White, so applicability is most direct to a similar population.

What does an emerging depression trajectory mean in the MASLD analysis of older adults?

In this CES-D-10 model, the emerging trajectory referred to initially low depressive symptoms that increased over time, and baseline MASLD was not significantly associated with membership in that trajectory.