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Association between neuromelanin-sensitive MRI signal and psychomotor slowing in late-life depression


Late-life depression (LLD) is a prevalent and disabling condition in older adults that is often accompanied by slowed processing and gait speed. These symptoms are related to impaired dopamine function and sometimes remedied by levodopa (L-DOPA). In this study, we recruited 33 older adults with LLD to determine the association between a proxy measure of dopamine function—neuromelanin-sensitive magnetic resonance imaging (NM-MRI)—and baseline slowing measured by the Digit Symbol test and a gait speed paradigm. In secondary analyses, we also assessed the ability of NM-MRI to predict L-DOPA treatment response in a subset of these patients (N = 15) who received 3 weeks of L-DOPA. We scanned a further subset of these patients (N = 6) with NM-MRI at baseline and after treatment to preliminarily evaluate the effects of L-DOPA treatment on the NM-MRI signal. We found that lower baseline NM-MRI correlated with slower baseline gait speed (346 of 1807 substantia nigra–ventral tegmental area (SN-VTA) voxels, Pcorrected = 0.038), particularly in the more medial, anterior, and dorsal SN-VTA. Secondary analyses failed to show an association between baseline NM-MRI and treatment-related changes in gait speed, processing speed, or depression severity (all Pcorrected > 0.361); we however found preliminary evidence of increases in the NM-MRI signal 3 weeks post-treatment with L-DOPA compared to baseline (200 of 1807 SN-VTA voxels; Pcorrected = 0.046), although the small sample size of these preliminary analyses warrants caution in their interpretation and future replications. Overall, our findings indicate that NM-MRI is sensitive to variability in gait speed in patients with LLD, suggesting this non-invasive MRI measure may provide a promising marker for dopamine-related psychomotor slowing in geriatric neuropsychiatry.

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Fig. 1: Baseline NM-MRI CNR correlates with baseline gait speed.
Fig. 2: Secondary analyses of baseline NM-MRI CNR do not predict changes in gait speed after 3 weeks of L-DOPA treatment in region-of-interest or voxelwise analyses.
Fig. 3: NM-MRI CNR significantly increases after 3 weeks of L-DOPA treatment in an exploratory analysis.


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KW: conceptualization, data curation, formal analysis, methodology, software, visualization, writing—original draft, writing—review and editing. BKA: methodology, writing—original draft, writing—review and editing. EP: writing—original draft, writing—review and editing. CMC: methodology, software, writing—review and editing. GH: conceptualization, funding acquisition, methodology, resources, software, supervision, writing—original draft, writing—review and editing. BRR: conceptualization, funding acquisition, investigation, methodology, resources, supervision, writing—original draft, writing—review and editing.

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Correspondence to Guillermo Horga or Bret R. Rutherford.

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Wengler, K., Ashinoff, B.K., Pueraro, E. et al. Association between neuromelanin-sensitive MRI signal and psychomotor slowing in late-life depression. Neuropsychopharmacol. 46, 1233–1239 (2021).

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