Neuroanatomical predictors of L-DOPA response in older adults with psychomotor slowing and depression: A pilot study.

BACKGROUND: Declining function in dopamine circuits is implicated in normal aging and late-life depression (LLD). Dopamine augmentation recently has shown therapeutic promise, but predictors of response are unknown. METHODS: Depressed elders with slowed gait underwent baseline magnetic resonance imaging (MRI) and [11C]raclopride positron emission tomography (PET). Subjects then received open treatment with carbidopa/levodopa (L-DOPA) for three weeks. Linear regressions examined relationships between baseline MRI measures, [11C]raclopride binding, and behavioral outcomes. RESULTS: Among N = 16 participants aged 72.5 ± 6.8 years, higher left superior temporal gyrus volume was associated with higher processing speed at baseline, while cortical thinning in a processing speed network was associated with greater improvement following L-DOPA. Greater volume and cortical thickness in brain regions associated with mobility were associated with higher baseline gait speed. Higher baseline white matter hyperintensity volume predicted less post-L-DOPA improvement on dual task gait speed and IDS-SR scores. Higher [11C]raclopride binding in the associative striatum was associated with cortical thickness in some, but not all, processing speed brain regions, while higher binding in sensorimotor striatum was significantly associated with left caudate volume. LIMITATIONS: Limiting the conclusions drawn from this pilot study are the small sample size and open administration of L-DOPA. CONCLUSIONS: Greater baseline brain volumes and cortical thickness in regions supporting cognition and gait were associated with higher behavioral performance, while lower structural integrity was associated with increased responsivity to L-DOPA. If substantiated in larger studies, these findings could facilitate the targeting of dopaminergic treatments to those LLD patients most likely to respond.

Effects of L-DOPA Monotherapy on Psychomotor Speed and [11C]Raclopride Binding in High-Risk Older Adults With Depression.

BACKGROUND: A high-risk subgroup of older patients with depression has slowed processing and gait speeds. This study examined whether carbidopa/levodopa (L-DOPA) monotherapy increased dopamine availability, increased processing/gait speed, and relieved depressive symptoms. METHODS: Adult outpatients with depression >59 years old underwent baseline [11C]raclopride positron emission tomography followed by open L-DOPA for 3 weeks (1 week each of 150 mg, 300 mg, and 450 mg). Generalized estimating equations tested the pre- and post-L-DOPA differences in processing and gait speed measures, depressive symptoms, and reported side effects. The decrease in binding potential between the pre- and posttreatment scans indexed enhanced synaptic dopamine availability induced by L-DOPA treatment. RESULTS: Thirty-six subjects participated (age, 75.3 ± 7.5 years; 44.4% male). Significant, dose-dependent increases in processing and gait speed were observed with L-DOPA (450-mg dose: processing speed factor score effect size = 0.41, p = .001; dual-task gait speed effect size = 0.43, p = .002). [11C]raclopride decrease in binding potential was significantly different from 0 in sensorimotor (t24 = -4.85, p < .001) and associative striatum (t24 = -2.52, p = .019) but not in limbic striatum (t24 = 0.265, p = .793). Depressive symptoms decreased significantly on the Hamilton Rating Scale for Depression (effect size = -0.37, p = .002). Dropout rate was 8.3%, and nausea was the most frequently reported side effect. CONCLUSIONS: By enhancing availability of dopamine, L-DOPA improved processing and gait speed in older adults with depression and significantly decreased [11C]raclopride binding in selected striatal subregions.