Abstract:Excessive gambling is recognized with dopamine agonist therapy, but the prevalence is unknown. We assessed the prevalence of excess gambling by specific prospective enquiry in Parkinson's disease patients attending six West Scotland movement disorder clinics. Of 388 patients taking anti-Parkinson medication, 17 (4.4%) developed pathological gambling, all of whom were prescribed dopamine agonists. Thus, 8% of patients taking dopamine agonists had pathological gambling. Pathological gambling is not uncommon, and patients should be made aware of this potential adverse effect. © 2006 Movement Disorder Society Key words: Parkinson's disease; dopamine agonists; pathological gambling Pathological gambling associated with anti-Parkinson therapy is considered rare. 1,2 Estimates of prevalence vary between 0.05% of 1,884 patients from a retrospective database review 3 to approximately 7% of 200 cases from face-to-face interview. 4 Systematic prospective review analyzing drug class and dosages has been suggested, in particular to assess relative risk among antiParkinson agents and was the purpose of the present study. PATIENTS AND METHODSConsecutive patients with a clinical diagnosis of idiopathic Parkinson's disease (PD) in six West Scotland movement disorder clinics were asked over a 3-month period about their interest in gambling. Patients were excluded if such enquiry was deemed inappropriate, e.g., in the presence of advanced dementia. Demographic data, anti-Parkinson medication, and gambling behavior (classed as pathological when Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were fulfilled) were recorded by semistructured interview. Type of gambling (e.g., lottery, Internet, horse racing) and weekly expenditure were also registered. Daily doses were recorded, using salt for pramipexole. Statistical analysis used GraphPad Prism (GraphPad Software, San Diego, CA) and Statistica (StatSoft, Tulsa, OK). Groups were compared by unmatched t tests for continuous parametric variables, Mann-Whitney tests for nonparametric data, and 2 tests for categorical variables. RESULTSOf 424 patients, 10 with advanced dementia were excluded. Of the remaining 414, mean age was 69 years (standard deviation [SD] 11; range, 35-93 years) and 61% were men. Twenty-six patients were diagnosed recently and not yet prescribed anti-Parkinson medication. Of the 388 prescribed anti-Parkinson therapy, 66 cases (17%) were taking dopamine agonists either as monotherapy (n ϭ 57; 15%) or with an adjunct (n ϭ 9; 2.3%); 174 (45%) were on levodopa-based treatment as monotherapy (n ϭ 128; 33%) or with an adjunct (n ϭ 46; 12%); 146 (38%) had a combination of dopamine agonist and L-dopa (with adjunct n ϭ 71; 18%), and 2 (0.5%) were on selegiline only. Of those 388 patients, 17 (4.4%) reported problematic excessive gambling that began after starting anti-Parkinson therapy. None of these cases had prior pathological gambling. The mean age of these 17 cases was 56 years (SD 7; range,, which was significantly younger than n...

Our findings are consistent with a number of published plasma Aβ studies and, although the prognostic value of individual measures in any given subject is limited, the diagnostic contribution of plasma Aβ may demonstrate utility when combined with a panel of peripheral biomarkers.

The formation of low-order oligomers of β-amyloid (Aβ) within the brain is widely believed to be a central component of Alzheimer's disease (AD) pathogenesis. However, despite advances in high-throughput and high-resolution techniques such as xMAP and mass spectrometry (MS), investigations into these oligomeric species have remained reliant on low-resolution Western blots and enzyme-linked immunosorbent assays. The current investigation compared Aβ profiles within human cortical tissue using sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis (PAGE), xMAP and surface enhanced laser desorption/ionization time-of-flight MS and found that whilst there was significant correlation across the techniques regarding levels of monomeric Aβ, only SDS-PAGE was capable of detecting dimeric isoforms of Aβ. The addition of synthetic di-tyrosine cross-linked Aβ(1-40)Met(35)(O) to the AD tissue demonstrated that the MS methodology was capable of observing dimeric Aβ at femto-molar concentrations, with no noticeable effect on monomeric Aβ levels. Focus turned to the association between SDS-PAGE and levels of observable dimeric Aβ within the AD brain tissue. These investigations revealed that increased levels of dimeric Aβ were observed with increasing concentrations of SDS in the sample buffer. This finding was subsequently confirmed using synthetic Aβ(1-42) and suggests that SDS was inducing the formation of dimeric Aβ. The findings that SDS promotes Aβ dimerization have significant implications for the putative role of low-order oligomers in AD pathogenesis and draw into question the utility of oligomeric Aβ as a therapeutic target.