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The present family investigation has shown that genes within the MHS are mainly responsible for the development of psoriasis or psoriasis-associated arthritic lesions (peripheral arthritis and sacroiliitis). We have hypothetically discussed the possibility that multiple genes, all located within the MHS, act in concert to increase the risk of developing disease to very high levels. This implies that at least two MHS linked genes act in complementary fashion for the development of disease, these genes seem to be able to operate both in the cis and in the trans position. One of these genes would be situated in the chromosomal portion of the MHS which carries the HLA-D locus. Families with a high incidence of disease would show inheritance according to the cis position of genes, when it can be shown that most of the carriers of the specific disease-associated haplotype are affected by disease, whereas in other families, complementarity between two distinct HLA haplotypes with genes acting in the trans position would result in disease.

In Sweden, as in many other industrial countries, the majority of patients with symptoms of dementia are initially evaluated by a general practitioner (GP), and many do not receive a follow-up assessment by a specialist. Accordingly, GPs play a vital role in identifying patients with possible dementia and undertaking additional diagnostic procedures. Currently, however, the ability of most GPs to perform assessments for dementia is limited. It is important that tests to confirm the presence of dementia be performed uniformly, irrespective of the specialty of the examining physician. Once a diagnosis of dementia has been established and appropriate living arrangements for the patient have been made, the GP should continue to monitor the patient's health status. In Sweden, "dementia teams" of health care professionals have been successful in providing a consistently high level of care to patients with dementia, reducing the incidence of hospitalization for acute illness.

The epsilon4 allele of APOE is a risk factor for Alzheimer disease (AD). By analysis of a large cohort of AD patients (n = 563) and control subjects (n = 118), it is shown that the epsilon4 allele is strongly associated with reduced CSF levels of beta-amyloid (1-42) (Abeta42) in both AD (p10(-9)) and control (p = 0.0012) populations. As no associations of APOE variants with other indexes of AD severity were observed, this effect may reflect a fundamental involvement of ApoE in Abeta metabolism.

Classification and registration of diseases is necessary in order to monitor the proliferation of diseases in a population. Despite the presence of an international framework for classification of diseases (ICD 10) which has been approved by the Swedish authorities, the guidelines provided are not observed in the area of dementia diseases. Different diagnoses can be used to describe the same condition, and "dementia unspecified" is sometimes employed when a specified diagnosis could have been used. In order to refine consensus regarding the use of different diagnoses in the dementia field, representatives for the Swedish University hospitals and medical faculties propose a unified description of a limited number of dementia diagnoses.

Tau protein and the 42-amino acid form of beta-amyloid (Abeta42) measured in cerebrospinal fluid (CSF) have been proposed as potential biochemical diagnostic markers for Alzheimer disease. For the introduction of these assays in clinical practice, adequate reference values are of importance.CSF samples were obtained from 231 neurologically and psychiatrically healthy individuals, 21-93 years of age, all with a MiniMental State examination score of 28 or above. Standardized ELISAs were used to measure tau and Abeta42 in CSF. Following IFCC recommendations, we used a rank-based method; the 0.90 and 0.10 fractiles were estimated to establish reference values for CSF-tau and CSF-Abeta42, respectively. Putative confounding factors, such as the influence of the passage of proteins from peripheral blood to CSF, influence of dysfunction of the blood-brain barrier, and freezing and thawing of CSF, were investigated.A correlation with age was found for CSF-tau (r = 0.60; P0.001). Therefore, separate reference values for different age groups were established for CSF-tau:300 ng/L in the group 21-50 years of age,450 ng/L in the group 51-70 years of age, and500 ng/L in the group 71-93 years of age. CSF-Abeta42 did not correlate with age (r = -0.045), and the reference value was set to500 ng/L. No correlation was found between blood-brain barrier function and CSF-tau or CSF-Abeta42.These reference values can be applied when using CSF-tau and CSF-Abeta42 in clinical practice.

The aims of this study were to describe the prevalence of mental disorders among elderly patients in primary care and to compare diagnoses from psychiatric interview with diagnoses in medical records.Patients aged 70 years and above attending a primary care centre (N = 350) were studied using a psychiatric and medical record examination.The prevalence of mental disorder according to the psychiatric interview was 33% (16% dementia, 17% other mental disorders). Only 49% of these had any psychiatric diagnosis in case records and 17-38% received specific treatments. The frequency of psychiatric symptoms among those with no mental disorder was between 1% and 66%. Patients with mental disorders were more often females, had more visits to a doctor, more diagnoses in medical records, and were prescribed more drugs.Mental disorders and symptoms are common among the elderly in primary care. More effort should be made to increase the recognition rate.

The binding of [3H]tiagabine ((RS-1-(4,4-(3-methyl-2-thienyl)-3-butenyl)-3-piperidine carboxylic acid) to homogenates of frozen post-mortem human brain has been characterized. Inhibition experiments with gamma-aminobutyric acid (GABA), GABA uptake inhibitors, ligands active at postsynaptic GABA receptors and receptors for other neurotransmitters, suggest that [3H]tiagabine binds with high affinity to GABA uptake sites. Inhibition and kinetic experiments suggests that 70%-80% of the binding is to a high affinity site. Saturation experiments showed that the binding was saturable. Bmax was 3.4 pmol/mg protein and Kd 16 nM in frontal cortex. The dissociation constants (Kd) measured in kinetic and equilibrium experiments were in the same range (16-56 nM). The regional distribution was studied in nine brain regions and the binding was heterogenous, with the highest binding in frontal cortex and parietal cortex and the lowest binding in nucleus caudatus and putamen. This is, to our knowledge, the first study on [3H]tiagabine binding in human tissue. It is concluded that [3H]tiagabine binding can be used as a specific marker for the GABA transporter GAT-1 in homogenates of human brain.

Alzheimer's disease (AD) and vascular dementia (VaD) share several features such as overactivation of microglial cells, damage induced by free radicals, glutamate and calcium overload. Propentofylline (HWA 285) has shown beneficial effects on all of these common elements, thus favouring its use in both subtypes of dementia. In a multinational, randomized, 12-month, double-blind, parallel-group study 260 out-patients with mild to moderate AD or VaD received 300 mg propentofylline (n = 129) or placebo (n = 131) three times daily 1 h before meals. The efficacy was tested at four independent rater levels (physician, psychologist, relative and patient) with assessments covering three major domains of dementia (global function, cognitive function and activities of daily living). After 12 months, the total patient population showed statistically significant treatment differences in favour of propentofylline for the global measures of dementia (Gottfries-Bråne-Steen scale, GBS, p = 0.001; Clinical Global Impressions, CGI, item I: p = 0.004, item II: p = 0.072) as well as for the cognitive measures (Syndrome Short Test, SKT, p = 0.002) and Mini-Mental State Examination (p = 0.001). The activities of daily living also showed a significant treatment difference in favour of propentofylline (p = 0.002). No significant treatment differences were found for rating scales performed by the patients. At month 12, VaD patients showed treatment differences in favour of propentofylline for the GBS total score (p = 0.006), CGI item I (p = 0.004), GGI item II (p = 0.044) and SKT (p = 0.028). Treatment differences for AD patients were all in favour of propentofylline and reached statistical significance for the SKT (p = 0.018). Propentofylline showed a good safety profile with respect to adverse events, vital signs, ECG and laboratory changes.

The binding of [3H]paroxetine and [3H]citalopram to the human brain serotonin (5-HT) uptake site has been characterized and compared. Our results reveal that the binding exclusively involved with the 5-HT uptake site is identical for both [3H]ligands. The selective 5-HT uptake inhibitor citalopram displays the highest affinity for this uptake site, as compared with the affinities obtained for desipramine and norzimeldine, which is in accordance with their respective blockage of 5-HT uptake. Similar Bmax values were obtained for both radioligands in the brain regions studied, indicating their binding to the same presynaptic membrane protein. Together these findings suggest that both [3H]paroxetine and [3H]citalopram are good markers of the 5-HT transporter as both bind selectively and with high affinity to the serotonin uptake sites. However, the higher affinity of [3H]paroxetine confirms that this compound is the best radioligand for the 5-HT uptake site available today.

The effect of age on serotonin uptake sites labeled with [3H]paroxetine was studied in two sets of brains. The first set included 28 subjects (19 males and 9 females) between the ages 0 and 100 years. The cortex of cingulate gyrus and the amygdala were studied. No age-related changes in binding capacity (Bmax) or binding affinity (Kd) were noted. In the second set, the frontal cortex and hypothalamus from 22 subjects (18 males and 4 females) between 16 and 75 years were studied. No age-related changes in the binding were observed. The interval between death and freezing of the tissue did not influence the binding. Regarding the [3H]paroxetine binding as an indirect marker for 5-HT terminals, the data suggest a stability of 5-HT terminals with increasing age in the human brain.

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