Methylphenidate (‘Ritalin’) can Ameliorate Abnormal Risk-Taking Behavior in the Frontal Variant of Frontotemporal Dementia

Abstract

The frontal variant of frontotemporal dementia is a significant neurological condition worldwide. There exist few treatments available for the cognitive and behavioural sequelae of fvFTD. Previous research has shown that these patients display risky decision-making, and numerous studies have now demonstrated pathology affecting the orbitofrontal cortex. The present study uses a within-subjects, doubleblind, placebo-controlled procedure to investigate the effects of a single dose of methylphenidate (40 mg) upon a range of different cognitive processes including those assessing prefrontal cortex integrity. Methylphenidate was effective in 'normalizing' the decisionmaking behavior of patients, such that they became less risk taking on medication, although there were no significant effects on other aspects of cognitive function, including working memory, attentional set shifting, and reversal learning. Moreover, there was an absence of the normal subjective and autonomic responses to methylphenidate seen in elderly subjects. The results are discussed in terms of the 'somatic marker' hypothesis of impaired decision-making following orbitofrontal dysfunction.

The Roles of Dopamine and Serotonin in Decision Making: Evidence from Pharmacological Experiments in Humans

“…Dopaminergic agents also appear to improve decision making in adult clinical populations. Methylphenidate, in comparison with single placebo treatments, has been shown to reduce the heightened tendency to take risksFmanifested again as a tendency to wager more reward on previous choices being correct (Rahman et al, 1999)Fin patients with diagnoses of fronto-temporal dementia (Rahman et al, 2006). fMRI experiments with healthy subjects suggest that this effect reflects a shift in the distribution of activity toward amygdala and para-hippocampal sites in response to uncertainty (Schlosser et al, 2009).…”

“…Decision making has been a research target in substance and alcohol misuse disorders (Bechara et al, 2001;Ersche et al, 2008;Rogers et al, 1999b;Rogers and Robbins, 2001), unipolar depression and bipolar disorder (Chandler et al, 2009;Murphy et al, 2001), suicidaility (Dombrovski et al, 2010;Jollant et al, 2005), and impulsive personality disorders (Bazanis et al, 2002;Kirkpatrick et al, 2007). Adjunctive work has explored the idea that impairments in decision making can serve as markers for likely relapse (Adinoff et al, 2007;Bechara et al, 2001) and facilitate the exploration of therapeutic interventions (Rahman et al, 2006;Robbins and Arnsten, 2009). …”

Impulsivity and Risk Taking in Bipolar Disorder and Schizophrenia

“…For example, enhancing dopaminergic signaling in Parkinson's Disease with the D2/D3 agonist pramipexole has been shown to increase risk taking behavior on a lottery task, and this is mirrored by the increased rate of impulse control disorders found in Parkinson's Disease patients treated with dopaminergic agonists (Riba et al, 2008). In contrast, psychostimulants that enhance dopaminergic signaling (eg, amphetamine or methylphenidate) decrease risk-taking behaviors in frontotemporal dementia and ADHD (Dalley and Roiser, 2012;Rahman et al, 2005).…”

Pharmacological treatment of frontotemporal lobar degeneration: systematic review

“…27,29,30,32 Four quality B studies noted behavioral improvement without significant results, 12,28,34,36 two studies did not observe any significant behavioral change, 26,36 one study described behavioral worsening 33 and one study did not assess this aspect. 31 On the other hand, there were conflicting results from the studies that focused on the efficacy of treatment for cognitive impairment.…”

“…Seven quality B studies did not reveal any significant changes. [26][27][28]30,32,34 However, the Bromocriptine study showed a significant improvement in the mean time of utterance as compared to the placebo, 31 and one Memantine study found a significant increase in the total score of ADAS-Cog. 35 36 Two B studies did not evaluate cognitive functions.…”