Paroxetine does not improve symptoms and impairs cognition in frontotemporal dementia: a double-blind randomized controlled trial

Rationale. Patients with frontal variant frontotemporal dementia (fvFTD) present with disinhibition, impulsiveness, apathy, altered appetite and stereotypic behaviors. A non-randomized clinical trial found improvement in these symptoms after treatment with a selective serotonin reuptake inhibitor (SSRI). Objectives. We aimed to subject a SSRI, paroxetine, to a more rigorous test of its efficacy using a double-blind, placebo-controlled experimental design. Methods. Ten subjects meeting the consensus criteria for FTD were entered into a double-blind, placebo-controlled crossover trial. Doses of paroxetine were progressively increased to 40 mg daily. The same regimen was used for placebo capsules. Subjects were assessed with a battery of cognitive tests in the sixth week of paroxetine and placebo treatment. At each assessment, caregivers were interviewed using the Neuropsychiatric Inventory and asked to complete the Cambridge Behavioral Inventory. Results. There were no significant differences on the Neuropsychiatric Inventory or the Cambridge Behavioral Inventory. Paroxetine caused a decrease in accuracy on the paired associates learning task, reversal learning and a delayed pattern recognition task. There were no changes on the decision-making task, in spatial span, spatial recognition, spatial working memory, digit span and verbal fluency. Conclusions. This study finds no evidence for the efficacy of paroxetine in the treatment of fvFTD. The results suggest that a chronic course of paroxetine may selectively impair paired associates learning, reversal learning and delayed pattern recognition. This pattern of deficits closely resembles that seen after tryptophan depletion. Results are discussed with respect to current theories on serotonergic modulation of orbitofrontal/ventromedial prefrontal cortex

Pseudo-neglect in Huntington's disease correlates with decreased angular gyrus density

Visuospatial attentional bias was examined in Huntington's disease (HID) patients with mild disease, asymptomatic gene-positive patients and controls. No group differences were found on the grey scales task (which is a non-motor task of visuospatial attentional bias), although patients' trinucleotide (CAG) repeat length correlated with increasing leftward bias. On the line bisection task, symptomatic patients made significantly larger leftward bisection errors relative to controls, who showed the normal slight degree of leftward error (pseudo-neglect). The asymptomatic group showed a trend for greater leftward error than controls. A subset of participants went on to have structural MRI, which showed a correlation between increased leftward error on the line bisection task and reduced density in the angular gyrus area (BA39) bilaterally. This finding is consistent with recent literature suggesting a critical role for the angular gyrus in the lateralization of visuospatial attention