Frontotemporal dementia. Results from "Frontotemporal Demential and Pick's Disease Conference"

At the Frontotemporal Dementia and Pick's Disease Conference, recent data concerning the epidemiology, diagnosis, and therapy of frontotemporal dementia were presented. Topics included clinical manifestations, differential diagnosis, pathologic and genetic bases of the disease, therapy, and specific problems facing patients and care givers. A consensus in the terminology of this condition was sought.     

A polymorphism of the brain-derived neurotrophic factor (BDNF) is associated with Alzheimer's disease in patients lacking the Apolipoprotein E epsilon4 allele

Because of its implication in neuroprotection, formation of long lasting memories and a disturbed function in Alzheimer's disease (AD), brain-derived neurotrophic factor (BDNF) may represent an appropriate candidate gene conferring risk to AD. Recently, a single nucleotide polymorphism (C-270T) within the BDNF gene has been associated with late onset AD in a Japanese population giving an odds ratio (OR) of 3.8. Because of the importance of this finding we analysed the BDNF polymorphism in a German sample consisting of 210 patients with AD and 188 cognitively healthy controls. The T-allele frequency was higher in patients with AD (11.9%) compared to controls (6.9%) (P = 0.035; OR = 2.26; 95% CI: 1.04-4.48). The risk conferred by the T-allele was stronger in patients who lack the ApoE epsilon4 allele giving an OR of 2.61 (1.21-5.64) P = 0.015, particularly in patients with early onset of the disease; OR 3.13 (1.32-7.43); P= 0.01. Due to the small number of patients showing both, lack of the ApoE epsilon4 allele and the BDNF T allele (n = 18), the result needs to be confirmed in a larger sample. The results suggest that the BDNF C-270T polymorphism is a relevant risk factor for AD particularly in patients lacking the ApoE epsilon4 allele in this German sample.     

The economic impact of dementia in Belgium: results of the National Dementia Economic Study (NADES)

OBJECTIVES: To estimate costs associated with dementia and its severity and to identify main cost determinants. DESIGN: One-year prospective cohort study. SETTING: 231 general practitioners (GPs) and 15 specialist clinics throughout Belgium. SUBJECTS: 605 patients aged > or = 65 years (219 referent patients, 218 demented patients at home and 168 demented patients in institution). OUTCOME MEASURES: Medical costs (visits to GPs/specialists, physiotherapy, hospitalisation, nursing, incontinence, medication) and non-medical costs (special equipment, services, professional help and caregiving). RESULTS: Total monthly costs amounted to 368.50 Euro dollar for referent patients, 445.56 Euro dollar for demented patients at home and 2301.7 Euro dollar for demented patients in institutions. Highest costs were measured in patients with severe dementia (556.88 Euro dollar at home, 2465.28 Euro dollar in institutions). In demented patients at home, 60% of costs were accounted for by the health system, with hospitalisation and medication being the main cost components (36% and 20%). In demented patients in institution, 46% of the costs were accounted for by the health system, with residential costs and nursing being the main cost components (42% and 32%). In multivariate covariance analysis, the main determinants of costs for demented patients at home were physical dependence and co-morbidity (neoplasm, cardiovascular disease). The adjusted difference between demented and referent patients was 25 Euro dollar per month. CONCLUSIONS: A large fraction of the costs observed in dementia is explained by the association of dementia with physical dependence, co-morbidity and need for caregiving. From an economic point of view, the results support the caring for patients at home.     

Partial loss of dopaminergic neurons in the substantia nigra,ventrotegmental area and the retrorubral area -- model of the early beginning of Parkinson's symptomatology?

Summary. To test substances which might have protective effects on the dopaminergic system it is necessary to use models with a pathological symptomatology of the early beginning, i.e. models in which the chance exists to arrest the otherwise progressive pathological processes (see Heim et al., 2001). 6-hydroxydopamine (6-OHDA) injected unilaterally into the ventrolateral striatum of rats (6 μg dissolved in 2 μl 0.2% ascorbic acid) leads to specific stereotyped movements after subcutaneous injection of apomor-phine both 3 and 13 weeks after surgery. Ten weeks after surgery decreased spontaneous motor activity could be observed. Twelve weeks after 6-hydroxydopamine injection, the animals had difficulties in performing a spatial navigation task when the submerged escape platform was moved to another position. The switching of motor programs was less pronounced. The application of tyrosine-hydroxylase-staining showed a loss of ipsilateral neurones of the substantia nigra compacta as well as of dendrites in the pars reticulata, neurones in the ventral tegmental area and in the retrorubral area ipsilaterally as well as a loss of dopaminergic fibres both ipsilaterally and contralaterally in the striatum which should belong to the contralateral acting substantia nigra afferents. The loss of the neurones and the afferents was induced by the retrograde denervation following the 6-OHDA injection within the ventrolateral striatum. The question arises whether the model used here with the partially loss of dopaminergic neurons and fibres reflects some of pathological symptoms of Parkinson's disease in the early states. Received December 21, 2001; accepted February 25, 2002     

A genetic variation of cathepsin D is a major risk factor for Alzheimer's disease

Cathepsin D (catD) is an intracellular acid protease possibly involved in Alzheimer's disease (AD)-related neurodegeneration through cleavage of amyloid precursor protein into amyloidogenic components. We studied whether an exonic polymorphism of the catD gene (C --> T [Ala --> Val] transition at position 224), which possibly influences pro-catD secretion and intracellular maturation of the enzyme, was associated with the risk for the development of AD in 127 demented patients and 184 controls. The catD*T allele was significantly overrepresented in demented patients (11.8%) compared with nondemented controls (4.9%). Carriers of the catD*T allele had a 3.1-fold increased risk for developing AD than noncarriers. Carriers of the apolipoprotein E (ApoE) epsilon4 allele (ApoE*4) had a 3.9-fold increased risk than non-carriers. The adjusted odds ratio for subjects with the ApoE*4 and the catD*T allele was 19.0 compared with subjects with neither of these two alleles. Our data confirm the results of a recently performed pilot study in an independent sample and suggest that the catD genotype is strongly associated with the risk for AD.     

Congenital central hypoventilation syndrome (Ondine's curse syndrome) in two siblings: Delayed diagnosis and successful noninvasive treatment

Congenital central hypoventilation syndrome (CCHS, Ondine's curse syndrome) is a rare respiratory disorder; less than 100 cases have been reported. Familiality of the disease has been discussed, but only few familial cases have been reported so far. In this report we describe the occurrence of CCHS in two male siblings. Diagnosis was established only at the age of 4 years in the first case, although the patient had disease related symptoms since early infancy. The second patient was one of dizygotic twins, he was diagnosed with CCHS at the age of 8 months. Up to that age only moderate desaturations had been observed. The other twin was unaffected by the disease. Both patients were successfully treated by nocturnal positive-pressure ventilation via a specially adapted face mask. They show satisfactory physical and neurologic development.     

The Graz SIDS Risk Questionnaire: I. Development and validation]

Based on the results from semistructured interviews with parents of fifty SIDS victims and of fifty matched controls we developed a SIDS risk questionnaire, the so-called SRFB Graz. In a retrospective study this questionnaire was applied to 65 SIDS victims and 195 comparable controls. By statistical analysis a cut point was computed, which discriminates SIDS cases from controls with a sensitivity of 86% and a specificity of 95%.     

Clinical assessment of fetal blood flow velocimetry.

A statistical procedure is presented to analyze the relation between Doppler indices (DIs) such as pulsatility index (PI), resistance index (RI), A/B and clinical data of pregnancy and fetal outcome of three groups: (1) uncomplicated pregnancy, eutrophic fetus (NF), (2) pregnancy-induced hypertension (PIH), and (3) pregnancy and delivery of a dystrophic fetus (IUGR), and the acidity classes according to Saling, respectively. Proceeding and mathematical requirements as well as the possibilities to validate the methodology are introduced, and an application to previously published data is presented. By multivariate analysis of the data a fair prognosis of NF, PIH and IUGR was possible. The variability inherent to the data sampling requires a mathematical postprocessing in the framework of an adequate model before any clinical conclusions can be derived from DIs.