This pilot, double-blind, placebo-controlled, randomized, escalating dose trial explored the safety and efficacy of tideglusib, an inhibitor of glycogen synthase kinase-3, in Alzheimer's disease (AD) patients. Thirty mild-moderate AD patients on cholinesterase inhibitor treatment were administered escalating doses (400, 600, 800, 1,000 mg) of tideglusib or placebo (ratio 2 : 1) for 4, 4, 6, and 6 weeks, respectively. The primary objective was to evaluate the safety and tolerability of tideglusib with strict criteria for drug escalation or withdrawal. Mini-Mental Status Examination (MMSE), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog+), word fluency, Geriatric Depression Scale (GDS), and a final Global Clinical Assessment (GCA) were assessed as secondary objectives. Treatment was well tolerated. Adverse events were as frequent in active and placebo groups, except for some moderate, asymptomatic, and fully reversible increases (>2.5 × ULN) of serum transaminases in 6 active cases (p = 0.001). Tideglusib produced positive trends in MMSE, ADAS-cog, GDS, and GCA without statistical significance in this small sample. Responders in MMSE were significantly higher in the active group (p = 0.05). Patients escalated up to 1000 mg/day had a benefit of 1.68 points in the MMSE and 4.72 points in the ADAS-cog+ when compared to placebo. This small pilot study provides valuable safety and efficacy estimates for the treatment of AD patients with tideglusib, currently being confirmed in a larger clinical trial. Due to escalating doses and the small sample size, this trial provides insufficient evidence to support or reject a benefit of tideglusib in AD.

Cued recall deficits are most closely associated with CSF biomarkers indicative of AD in subjects with MCI. This novel finding complements results from prospective clinical studies and provides further empirical support for cued recall as a specific indicator of prodromal AD, in line with recently proposed research criteria.

In this report, we present the results of a multicenter study to test analytic and diagnostic performance of soluble forms of amyloid precursor proteins a and b (sAPPa and sAPPb) in the cerebrospinal fluid (CSF) of patients with different forms of dementing conditions. CSF samples were collected from 188 patients with early dementia (mini-mental state examinationX20 in majority of cases) and mild cognitive impairment (MCI) in 12 gerontopsychiatric centers, and the clinical diagnoses were supported by neurochemical dementia diagnostic (NDD) tools: CSF amyloidb peptides, Tau and phospho-Tau. sAPPa and sAPPb were measured with multiplexing method based on electrochemiluminescence. sAPPa and sAPPb CSF concentrations correlated with each other with very high correlation ratio (R = 0.96, P < 0.001). We observed highly significantly increased sAPPa and sAPPb CSF concentrations in patients with NDD characteristic for Alzheimer's disease (AD) compared to those with NDD negative results. sAPPa and sAPPb highly significantly separated patients with AD, whose diagnosis was supported by NDD findings (sAPPa: cutoff, 117.4 ng ml À1 , sensitivity, 68%, specificity, 85%, P < 0.001; sAPPb: cutoff, 181.8 ng ml À1 , sensitivity, 75%, specificity, 85%, P < 0.001), from the patients clinically assessed as having other dementias and supported by NDD untypical for AD. We conclude sAPPa and sAPPb might be regarded as novel promising biomarkers supporting the clinical diagnosis of AD.

There is a broad reduction of alpha4beta2*-nAChR availability in patients with PD without clinically manifest dementia or depression compared with healthy volunteers. Reduced alpha4beta2*-nAChR binding in patients with PD within the subcortical and cortical regions is associated with the severity of mild cognitive or depressive symptoms. These results provide novel in vivo evidence for a role of the cholinergic neurotransmission in psychiatric comorbidity of PD.

A method is proposed for three-dimensional (3-D) texture analysis of magnetic resonance imaging brain datasets. It is based on extended, multisort co-occurrence matrices that employ intensity, gradient and anisotropy image features in a uniform way. Basic properties of matrices as well as their sensitivity and dependence on spatial image scaling are evaluated. The ability of the suggested 3-D texture descriptors is demonstrated on nontrivial classification tasks for pathologic findings in brain datasets.