Indicative biomarkers of Lewy body disease as predictors of treatment resistance in late-onset depression

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Late-onset depression (LOD) may indicate the prodromal phase of Lewy body disease (LBD) and is often associated with treatment resistance. However, the relationship between treatment resistance and indicative biomarkers of LBD is still unknown. This retrospective study investigated whether 123 I-ioflupane dopamine transporter single-photon emission computed tomography (DaT-SPECT) and 123 I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy can predict treatment resistance in hospitalized patients with LOD. The study included 79 inpatients diagnosed with LOD between October 2018 and September 2023 at a geriatric psychiatry ward. DaT-SPECT and MIBG cardiac scintigraphy were used to assess dopaminergic and autonomic function, respectively. Treatment resistance was defined as an inadequate response to antidepressant monotherapy, where cases require electroconvulsive therapy (ECT) analyzed as a distinct group. Logistic regression showed that DaT-SPECT abnormalities significantly predicted nonresponse to antidepressant monotherapy (OR = 4.70, p = 0.013). While oral sensory hallucinations, another clinical marker linked to dopaminergic dysfunction, did not significantly predict treatment response, MIBG cardiac scintigraphy findings enhanced predictive accuracy for severe cases requiring ECT. Additionally, the Cochran–Armitage test indicated that the likelihood of nonresponse to antidepressant monotherapy and the need for ECT increased significantly with a higher number of abnormal LBD biomarkers (z = 7.37, p = 0.007; z = 10.91, p < 0.001, respectively). These results suggest that neurodegenerative processes in the prodromal phase of LBD may contribute to treatment resistance in LOD. The combination of DaT-SPECT and MIBG cardiac scintigraphy improves early identification of treatment resistance, supporting more timely and personalized interventions for hospitalized patients with LOD.

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