[Associations between dementia and head circumference as a measure of brain reserve--results from the Bavarian School sisters study].

Objective: The aim of the study was to examine the relationship of head circumference as a marker of maximal attained brain size to late-life cognitive impairment and dementia.

Methods: Cognitive performance was assessed and the presence of dementia was diagnosed in a cross-sectional study of 442 Catholic sisters aged 65 years and over.

Results: A head circumference below average was significantly associated with the presence of dementia even after adjustment for age, body mass index and presence of one or two apolipoprotein E epsilon4 alleles (OR = 2.

Decline of cerebral glucose metabolism in frontotemporal dementia: a longitudinal 18F-FDG-PET-study.

Objective: To identify the pattern of progression of decline of cerebral glucose metabolism in frontotemporal dementia (FTD, frontal variant).

Methods: 22 patients with mild FTD underwent 18F-FDG-positron emission tomography at baseline and at follow-up in average 19.5 months later.

In situ analysis of integrin and growth factor receptor signaling pathways in human glioblastomas suggests overlapping relationships with focal adhesion kinase activation.

Deregulated integrin signaling is common in cancers, including glioblastoma. Integrin binding and growth factor receptor signaling activate focal adhesion kinase (FAK) and subsequently up-regulate extracellular regulated kinases (ERK-1/2), leading to cell-cycle progression and cell migration. Most studies of this pathway have used in vitro systems or tumor lysate-based approaches.

Prediction of individual clinical outcome in MCI by means of genetic assessment and (18)F-FDG PET.

Unlabelled: Patients with mild cognitive impairment (MCI) represent a risk population for progressing to dementia of the Alzheimer type (DAT). However, clinical criteria do not ensure reliable individual prognosis in these patients. The objective of this longitudinal, prospective study was to examine the value of (18)F-FDG PET of cerebral glucose metabolism and of genetic susceptibility, as defined by an APOEepsilon4-positive genotype, with regard to the early diagnosis of DAT in patients with MCI.

Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials.

Purpose: Most cases of non-small-cell lung cancer (NSCLC) with dramatic responses to gefitinib have specific activating mutations in the epidermal growth factor receptor (EGFR), but the predictive value of these mutations has not been defined in large clinical trials. The goal of this study was to determine the contribution of molecular alterations in EGFR to response and survival within the phase II (IDEAL) and phase III (INTACT) trials of gefitinib.

Patients And Methods: We analyzed the frequency of EGFR mutations in lung cancer specimens from both the IDEAL and INTACT trials and compared it with EGFR gene amplification, another genetic abnormality in NSCLC.

Potential biological markers for cerebrovascular disease.

Cerebrovascular diseases can causes cognitive impairment and dementia by loss of neurons and synaptic connections, destruction of axons, and demyelinization. Biological markers including genetic tests, brain imaging techniques, and biochemical assays in the CSF are valuable for the identification and quantification of cerebrovascular diseases. Genetic tests may be used to detect mutations that cause hereditary cerebral amyloid angiopathies or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL).

COMT Val108/158Met genotype affects the mu-opioid receptor system in the human brain: evidence from ligand-binding, G-protein activation and preproenkephalin mRNA expression.

Recent data from [(11)C]carfentanil ligand-PET indicate that in the human brain, the availability of mu-opioid (MOP) receptor binding sites is affected by the Val(108/158)Met polymorphism of the catechol-O-methyltransferase (COMT) gene. This prompted us to validate the impact of COMT Val(108/158)Met on MOP receptors in human post-mortem brain. [(3)H]DAMGO receptor autoradiography was performed in frontal cortex, basal ganglia, thalamus and cerebellum (8 Met/Met, 6 Met/Val, 3 Val/Val).

Association study between the D10S1423 microsatellite marker and Alzheimer's disease.

Several studies have reported conflicting results concerning the genetic association between Alzheimer's disease (AD) and the microsatellite marker D10S1423 on chromosome 10p12-14. In an ethnically homogeneous German population of 422 patients with AD and 254 cognitively healthy controls, the 238-bp allele of the D10S1423 marker showed a weak, but after correction for multiple testing no longer significant association with AD (p = 0.015, uncorrected; p = 0.

TNF polymorphisms in Alzheimer disease and functional implications on CSF beta-amyloid levels.

Alzheimer disease (AD), vascular dementia, and stroke are all associated with inflammation though their respective initiating factors differ. Recently a polymorphism in the proinflammatory cytokine tumor necrosis factor (TNF), in association with apolipoprotein E (APOE), was reported to increase AD risk. Two SNPs, rs1799724 (-850C>T; NT_007592.

O-(2-[18F]fluoroethyl)-L-tyrosine PET combined with MRI improves the diagnostic assessment of cerebral gliomas.

MRI is commonly used to determine the location and extent of cerebral gliomas. We investigated whether the diagnostic accuracy of MRI could be improved by the additional use of PET with the amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (FET). In a prospective study, PET with FET and MRI was performed in 31 patients with suspected cerebral gliomas.

Cerebral glucose metabolism in patients with AD and different APOE genotypes.

Objective: To examine the influence of the APOE epsilon4 allele on cerebral glucose metabolism in a large series of patients with Alzheimer disease (AD).

Methods: Eighty-three patients (41 APOE epsilon4 positive and 42 epsilon4 negative) were selected from a pre-existing databank of patients with AD (n > 1,000). The patients were carefully matched for age, age at onset, approximate disease duration, educational level, and overall degree of cognitive impairment.

The role of alpha-synuclein gene multiplications in early-onset Parkinson's disease and dementia with Lewy bodies.

Background: A triplication of the alpha-synuclein gene was found to cause autosomal dominant Lewy body disease in two distinct families.

Method: We searched for alterations of alpha-synuclein gene dosage and analysed the entire coding region for point mutations in 54 dementia with Lewy body disease (DLB) and in 103 young onset Parkinson's disease (PD) patients from Central Europe.

Results: We could not detect any quantitative alterations in the gene dosage of alpha-synuclein.

Can the apparent diffusion coefficient be used as a noninvasive parameter to distinguish tumor tissue from peritumoral tissue in cerebral gliomas?

Purpose: To determine whether the apparent diffusion coefficient (ADC) can be used to distinguish between tumor tissue and peritumoral brain tissue in cerebral gliomas.

Materials And Methods: Twenty-two patients with 44 biopsies were enrolled in this study. ADC maps calculated from a diffusion-weighted (DW) multislice EPI sequence were coregistered with conventional MR images.

Association analysis of genes involved in cholesterol metabolism located within the linkage region on chromosome 10 and Alzheimer's disease.

Epidemiological studies identified a higher risk of developing Alzheimer's disease (AD) among subjects with elevated cholesterol levels. This association may be caused by a modulation of the amyloid precursor protein (APP) processing in response to the cellular cholesterol content. High cholesterol levels may favor the amyloidogenic pathway by inhibition of the alpha-secretase probably leading to elevated beta-Amyloid (Abeta) production.

Prion protein codon 129 polymorphism and risk of Alzheimer disease.

The authors investigated the PRNP Met129Val polymorphism in 1,393 subjects including 482 patients with Alzheimer disease (AD) and two independent control groups. In patients, PRNP Met homozygosity conferred increasing risk with decreasing age at onset (onset: 61 to 70 years, n = 151, p = 0.02, odds ratio [OR] = 1.

Cerebral metabolic patterns at early stages of frontotemporal dementia and semantic dementia. A PET study.

Objective: To determine the patterns of cerebral glucose metabolism in frontotemporal dementia (FTD) and semantic dementia (SD).

Methods: 25 patients with mild FTD and 9 patients with mild SD as well as 15 healthy age-matched control subjects underwent 18F-FDG- positron emission tomography. Patient scans were compared with control scans using SPM-99.

Expression of oligodendrocyte lineage genes in oligodendroglial and astrocytic gliomas.

The oligodendrocyte lineage genes OLIG1 and OLIG2 have been reported as potential diagnostic markers for oligodendrogliomas [Lu et al. (2001) Proc Natl Acad Sci USA 98:10851-10856; Marie et al. (2001) Lancet 358:298-300].

[Mild cognitive disorder. Questions of definition, diagnosis, prognosis and therapy].

The syndrome of mild cognitive impairment (MCI) is heterogeneous in terms of aetiology, psychopathology, and prognosis. It is characterised by cognitive deterioration significantly exceeding the decline attributable to aging but not reaching the severity of dementia. The prevalence of MCI is estimated to be 17% in the population over 65 years old.

Lack of association between a single nucleotide polymorphism within the choline acetyltransferase gene and patients with Alzheimer's disease.

Alterations of the cholinergic system may account for typical clinical and pathophysiological disturbances of Alzheimer's disease (AD). In particular, a marked decline of choline acetyltransferase activity (CHAT) and as a consequence of acetylcholine during the course of the disease has been described. Due to the chromosomal localization of CHAT at 10q11.

Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: a PET follow-up study.

A high percentage of patients with mild cognitive impairment (MCI) develop clinical dementia of the Alzheimer type (AD) within 1 year. The aim of this longitudinal study was to identify characteristic patterns of cerebral metabolism at baseline in patients converting from MCI to AD, and to evaluate the changes in these patterns over time. Baseline and follow-up examinations after 1 year were performed in 22 MCI patients (12 males, 10 females, aged 69.

Lack of association of interleukin-10 promoter region polymorphisms with Alzheimer's disease.

There is increasing evidence that immune mechanisms are involved in the pathogenesis of Alzheimer's disease (AD). Recently, polymorphisms of the interleukin (IL)-1 and IL-6 genes were found to be associated with late-onset AD. The immunoregulatory IL-10 downregulates synthesis of pro-inflammatory cytokines such as IL-1.

Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias.

Early clinical symptoms of sporadic Creutzfeldt-Jakob disease (CJD) may overlap with other neurodegenerative diseases like Alzheimer's disease (AD) and frontotemporal degeneration (FTD). On entering an era in which pharmaceutical treatment of CJD occurs, reliable diagnostic markers like immunodetection of 14-3-3 proteins in the cerebrospinal fluid (CSF) are required. However, false negative results in autopsy-proven, sporadic CJD cases, as well as false positive results in several other disorders including AD and FTD showing high CSF tau protein levels, limit the potential of this marker.

Refined mapping of 1q32 amplicons in malignant gliomas confirms MDM4 as the main amplification target.

We previously reported on the amplification and overexpression of the mouse double minute 4 homolog gene (MDM4) from 1q32 in a subset of malignant gliomas (Riemenschneider et al., Cancer Res 1999;59:6091-6). More recently, amplification and overexpression of the neighboring contactin 2 gene (CNTN2) was reported in individual malignant gliomas without MDM4 amplification (Rickman et al.

The role of biological markers in the early and differential diagnosis of Alzheimer's disease.

Biological markers can be used to identify the neurodegenerative process of Alzheimer's disease (AD) and to differentiate it from other brain diseases which may cause similar symptoms. Structural imaging can detect atrophic changes which are largely non-specific and provide little diagnostic information in single patients. Increasing atrophy upon repeated measurement is much more specific to AD.