Neurochemical dementia diagnostics (NDD) can significantly improve the clinically based categorization of patients with early dementia disorders, and the cerebrospinal fluid (CSF) concentrations of amyloid b peptides ending at the amino acid position of 42 (Abx-42 and Ab1-42) are widely accepted biomarkers of Alzheimer's disease (AD). However, in subjects with constitutively high-or low-CSF concentrations of total Ab peptides (tAb), the NDD interpretation might lead to erroneous conclusions as these biomarkers seem to correlate better with the total Ab load than with the pathological status of a given patient in such cases. In this multicenter study, we found significantly increased CSF concentrations of phosphorylated Tau (pTau181) and total Tau in the group of subjects with high CSF Abx-40 concentrations and decreased Abx-42/x-40 concentration ratio compared with the group of subjects with low CSF Abx-40 and normal Ab ratio (p < 0.001 in both cases). Furthermore, we observed significantly decreased Ab ratio (p < 0.01) in the group of subjects with APOE e4 allele compared with the group of subjects without this allele. Surprisingly, patients with low-Abx-40 and the decreased Ab ratio characterized with decreased pTau181 (p < 0.05), and unaltered total Tau compared with the subjects with high Abx-40 and the Ab ratio in the normal range. We conclude that the amyloid b concentration ratio should replace the 'raw' concentrations of corresponding Ab peptides to improve reliability of the neurochemical dementia diagnosis.

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.

We report on a study comparing different systems for the diagnosis of attention deficit hyperactivity disorder (ADHD) in adulthood. Recruited for evaluation were 168 patients referred to our ADHD outpatient unit. We used the Diagnostic and Statistical Manual of Mental Disorders 4th edn. (DSM-IV), International Classification of Diseases 10th edn. (ICD-10), and Utah criteria for diagnostic assessment and the Wender Utah rating scale, ADHD Self Report (ADHD-SR), and Wender Reimherr Adult Attention Deficit Disorder Rating Scale as psychopathological assessment tools. We present basic psychometric data of the Wender-Reimherr Interview (WRI). Internal consistency was determined as 0.82 (alpha). The inter-rater reliability was 1.0 (kappa coefficient) regarding ADHD diagnoses, and the ICC was 0.98 referring to the WRI total scores. The convergent validity with the ADHD-SR was 0.65 (Spearman coefficient). In 126 of 168 patients an ADHD diagnosis was made according to at least one of the three systems. The DSM-IV diagnostic set led to 119 ADHD diagnoses. As compared with the two other systems, this is about the minimum level for an ADHD diagnosis. All of the 87 ADHD diagnoses according to ICD-10 were covered by DSM-IV. The ICD-10 had no independent psychopathological items and therefore offered no additional points for the diagnostic procedure than the DSM-IV. The situation regarding Utah criteria is different. These criteria contain seven psychopathological domains: inattention, hyperactivity, disorganisation, impulsivity, affective lability, overreactivity, and hot temper. They can be assessed by use of the WRI. Ninety-three of 168 patients were diagnosed as having ADHD according to the Utah concept, which is much lower than with the DSM-IV. The particular definition of the disorder by the Utah criteria resulted in seven patients having only a Utah diagnosis but no DSM-IV diagnosis. Thus we are in a position to say that the Utah criteria have a relatively high level for making an ADHD diagnosis but in certain cases move beyond the DSM-IV. Of the patients 56% had ADHD diagnoses according to all three classification instruments. Examining the factor structure of the ADHD psychopathology represented by seven WRI and three ADHD-SR subscales, we found a two-factor solution explaining for 63% of the variance. Factor 1 was designated by impulsivity, affective lability, hyperactivity, and hot temper; factor 2 consisted of inattention, disorganisation, and overreactivity.

Disturbed copper (Cu) homeostasis may be associated with the pathological processes in Alzheimer's disease (AD). In the present report, we evaluated the efficacy of oral Cu supplementation in the treatment of AD in a prospective, randomized, double-blind, placebo-controlled phase 2 clinical trial in patients with mild AD for 12 months. Sixty-eight subjects were randomized. The treatment was well-tolerated. There were however no significant differences in primary outcome measures (Alzheimer's Disease Assessment Scale, Cognitive subscale, Mini Mental Status Examination) between the verum [Cu-(II)-orotate-dihydrate; 8 mg Cu daily] and the placebo group. Despite a number of findings supporting the hypothesis of environmental Cu modulating AD, our results demonstrate that oral Cu intake has neither a detrimental nor a promoting effect on the progression of AD.

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