Long non-coding RNAs H19 and NKILA are associated with the risk of death and lacunar stroke in the elderly population.

INTRODUCTION: Differential expression of long non-coding RNAs (lncRNAs) is a hallmark of cardiovascular aging, cerebrovascular diseases, and neurodegenerative disorders. This research article investigates the association between a panel of lncRNAs and the risk of death and ischemic stroke in a cohort of non-institutionalized elderly subjects. METHOD: A total of 361 healthy individuals aged 75 years old, prospectively recruited in the Vienna Transdanube Aging (VITA) cohort, were included. Expression of lncRNAs at baseline was assessed using quantitative polymerase chain reaction PCR with pre-amplification reaction, using 18S for normalization. The primary endpoint was all-cause mortality; the secondary endpoint was the incidence of new ischemic brain lesions. Death was assessed over a 14-year follow-up, and ischemic brain lesions were evaluated by magnetic resonance imaging (MRI) over a 90-month follow-up. Ischemic brain lesions were divided into large brain infarcts (Ø≥ 1.5 cm) or lacunes (Ø< 1.5 cm) RESULTS: The primary endpoint occurred in 53.5 % of the study population. The incidence of the secondary endpoint was 16 %, with a 3.3 % being large brain infarcts, and a 12.7 % lacunes. After adjustment for potential confounders, the lncRNA H19 predicted the incidence of the primary endpoint (HR 1.194, 95 % C.I. 1.012-1.409, p = 0.036), whereas the lncRNA NKILA was associated with lacunar stroke (HR 0.571, 95 % C.I. 0.375-0.868, p = 0.006). CONCLUSION: In a prospective cohort of non-institutionalized elderly subjects, high levels of lncRNA H19 are associated with a higher risk of death, while low levels of lncRNA NKILA predict an increased risk of lacunar stroke.

Prediction of Autopsy Verified Neuropathological Change of Alzheimer's Disease Using Machine Learning and MRI.

Background: Alzheimer's disease (AD) is the most common form of dementia. While neuropathological changes pathognomonic for AD have been defined, early detection of AD prior to cognitive impairment in the clinical setting is still lacking. Pioneer studies applying machine learning to magnetic-resonance imaging (MRI) data to predict mild cognitive impairment (MCI) or AD have yielded high accuracies, however, an algorithm predicting neuropathological change is still lacking. The objective of this study was to compute a prediction model supporting a more distinct diagnostic criterium for AD compared to clinical presentation, allowing identification of hallmark changes even before symptoms occur. Methods: Autopsy verified neuropathological changes attributed to AD, as described by a combined score for Aß-peptides, neurofibrillary tangles and neuritic plaques issued by the National Institute on Aging - Alzheimer's Association (NIAA), the ABC score for AD, were predicted from structural MRI data with RandomForest (RF). MRI scans were performed at least 2 years prior to death. All subjects derive from the prospective Vienna Trans-Danube Aging (VITA) study that targeted all 1750 inhabitants of the age of 75 in the starting year of 2000 in two districts of Vienna and included irregular follow-ups until death, irrespective of clinical symptoms or diagnoses. For 68 subjects MRI as well as neuropathological data were available and 49 subjects (mean age at death: 82.8 ± 2.9, 29 female) with sufficient MRI data quality were enrolled for further statistical analysis using nested cross-validation (CV). The decoding data of the inner loop was used for variable selection and parameter optimization with a fivefold CV design, the new data of the outer loop was used for model validation with optimal settings in a fivefold CV design. The whole procedure was performed ten times and average accuracies with standard deviations were reported. Results: The most informative ROIs included caudal and rostral anterior cingulate gyrus, entorhinal, fusiform and insular cortex and the subcortical ROIs anterior corpus callosum and the left vessel, a ROI comprising lacunar alterations in inferior putamen and pallidum. The resulting prediction models achieved an average accuracy for a three leveled NIAA AD score of 0.62 within the decoding sets and of 0.61 for validation sets. Higher accuracies of 0.77 for both sets, respectively, were achieved when predicting presence or absence of neuropathological change. Conclusion: Computer-aided prediction of neuropathological change according to the categorical NIAA score in AD, that currently can only be assessed post-mortem, may facilitate a more distinct and definite categorization of AD dementia. Reliable detection of neuropathological hallmarks of AD would enable risk stratification at an earlier level than prediction of MCI or clinical AD symptoms and advance precision medicine in neuropsychiatry.

Reduction in serum aquaporin-4 antibody titers during development of a tumor-like brain lesion in a patient with neuromyelitis optica: a serum antibody-consuming effect?

Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the CNS with severe involvement of the optic nerve and spinal cord. Highly specific serum IgG autoantibodies (NMO-IgG) that react with aquaporin-4 (AQP4), the most abundant CNS water channel protein, are found in patients with NMO. However, in vivo evidence combining the results of AQP4 antibody serum levels and brain pathology is lacking. We report a patient with NMO whose AQP4 antibody levels decreased simultaneously with clinical deterioration caused by the development of a tumor-like brain lesion. In the seminecrotic biopsied brain lesion, there was activated complement complex, whereas only very scattered immunoreactivity to AQP4 protein was detectable. The decrease in serum AQP4 antibody levels and the loss of AQP4 in the tumor-like lesion could represent a "serum antibody-consuming effect" during lesion formation.

MRI features of Binswanger's disease predict prognosis and associated pathology.

OBJECTIVE: To identify the prevalence of MRI features of Binswanger's disease (BD), specifically MRI with diffuse white matter lesions and scattered multiple lacunes (BD-MRI), and to describe neurological features and pathological outcomes of a community-based cohort study. METHODS: Of 697 participants (all 75 years old), 503 completed neurological examinations at baseline and were followed-up every 30 months thereafter with MRIs, the mini-mental state examination (MMSE) and the Unified Parkinson Disease Rating Scale-Motor Section (UPDRSM). Data from participants with BD-MRI were compared with those from participants with predominant white matter lesions (WML-MRI), scattered multiple lacunes (ML-MRI), or normal MRIs. RESULTS: Fourteen BD-MRI patients (2.8%) were detected at baseline. The mean MMSE scores in the BD-MRI, WML-MRI, ML-MRI, and normal MRIs groups were 26.4, 28.2, 28.4, and 28.5, respectively, and the mean UPDRSM scores were 9.1, 1.3, 3.1, and 1.7, respectively. At the 30-month follow-up, mortality rates in the normal MRIs, WML-MRI and ML-MRI were 4%, 9.1%, and 22.2%, respectively, and follow-up MRIs were available for 80%, 82%, and 61% of the participants, respectively. In the BD-MRI, however, five patients were deceased, and only five follow-up individual MRIs were available (33.3%). Autopsies were performed on six of eight BD-MRI brains, and these brains fulfilled the pathological criteria for BD independent of Alzheimer disease pathology. All these six individuals also showed systemic atherosclerosis and renal arterio-arteriolosclerosis. INTERPRETATION: The BD-MRI participants had poor prognoses and showed pure BD pathology with advanced systemic vascular disease. BD-MRI appears to be a predictor of vascular neurocognitive impairment.

Disproportionate subarachnoid space hydrocephalus-outcome and perivascular space.

OBJECTIVE: We sought to identify the prevalence of MRI features of disproportionately enlarged subarachnoid space hydrocephalus in possible idiopathic normal pressure hydrocephalus (DESH-iNPH) and to describe the clinico-radiological features and outcomes of a community-based investigation (The Vienna Trans-Danube Aging study). METHODS: Of the 697 inhabitants (all 75 years old), 503 completed extensive neurological examinations at baseline and were followed up every 30 months thereafter with MRIs, mini-mental state examination (MMSE), and the Unified Parkinson Disease Rating Scale-Motor Section (UPDRSM). The DESH-iNPH participant data were compared with the data from participants with Evans index ratios >0.3 (ex vacuo hydrocephalus), cerebral small-vessel diseases, and normal MRIs. The widening of perivascular space was also evaluated by MRI in these groups. RESULTS: Eight participants with DESH-iNPH (1.6%) and 76 with ex vacuo hydrocephalus (16.1%) at baseline were identified. The mean MMSE in DESH-iNPH, ex vacuo hydrocephalus, and normal MRIs was 26.4, 27.9, and 28.3, respectively, and the mean UPDRSM was 9.75, 2.96, and 1.87, respectively. After a 90-month follow-up, the mortality rates for DESH-iNPH, ex vacuo hydrocephalus, and normal MRIs were 25.0%, 21.3%, and 10.9%, respectively. The perivascular-space widening scores were significantly smaller in the DESH-iNPH cases, particularly at the centrum semiovale, compared to cerebral small-vessel disease and ex vacuo hydrocephalus cases. INTERPRETATION: The prevalence of DESH-iNPH was 1.6% for participants aged 75 years and revealed significantly lower MMSE and higher UPDRSM scores compared to the ex vacuo hydrocephalus and controls. Moreover, it is suggested that perivascular-space narrowing is a morphological and pathophysiological marker of DESH-iNPH.

The relationship between cerebral white matter hyperintensities and lower urinary tract function in a population based, geriatric cohort.

INTRODUCTION: White matter hyperintensities (WHM) in cerebral MRI-scan have been suspected to be involved in the pathogenesis for geriatric LUTS. Aim of this study was to investigate this association in a geriatric cohort. MATERIALS AND METHODS: The VITA-study is a prospective, population-based study initiated 2000/2001. All inhabitants of a well-defined area in Vienna aged 75 years were recruited and underwent detailed regular visits including cerebral MRI-scans. Subcortical and periventricular WMHs were classified according to the Fazekas-classification. In 2010, all subjects alive were contacted to complete the Bristol LUTS questionnaire. RESULTS: Two hundred seventeen participants (75 men, 142 women), all 85 years old, entered this analysis. Urgency, frequency, and nocturia was present in 39 (50.7%), 53 (52%), and 55 (73.3%) men and 79 (55.6%), 81 (78.2%), and 68 (47.9%) women, respectively. OAB symptoms were seen in 55% of women and 50% of men. At baseline, WMH were present in 68.2% and this percentage increased to 85.7% at the most recent follow-up. Several symptoms were more prevalent in participants without WMH as compared to those with WMH, (urgency: 71% vs. 53%, P=0.06, nocturia: 77% vs. 53%, P=0.01: OAB-symptoms: 71% vs. 51%, P=0.05. Only frequency was more prevalent in participants with WMH (77% vs. 68%, P=0.27). In general, sub-categorization into periventricular and subcortical WMH confirmed these data. Furthermore the amount of WMH-burden did not correlate to LUT dysfunction. CONCLUSION: This study failed to demonstrate a clear association between several aspects of LUTS and WMH in a rather healthy, population-based 85-year-old cohort.

Non-Alzheimer neurodegenerative pathologies and their combinations are more frequent than commonly believed in the elderly brain: a community-based autopsy series.

Neurodegenerative diseases are characterised by neuronal loss and cerebral deposition of proteins with altered physicochemical properties. The major proteins are amyloid-ß (Aß), tau, α-synuclein, and TDP-43. Although neuropathological studies on elderly individuals have emphasised the importance of mixed pathologies, there have been few observations on the full spectrum of proteinopathies in the ageing brain. During a community-based study we performed comprehensive mapping of neurodegeneration-related proteins and vascular pathology in the brains of 233 individuals (age at death 77-87; 73 examined clinically in detail). While all brains (from individuals with and without dementia) showed some degree of neurofibrillary degeneration, Aß deposits were observed only in 160 (68.7 %). Further pathologies included α-synucleinopathies (24.9 %), non-Alzheimer tauopathies (23.2 %; including novel forms), TDP-43 proteinopathy (13.3 %), vascular lesions (48.9 %), and others (15.1 %; inflammation, metabolic encephalopathy, and tumours). TDP-43 proteinopathy correlated with hippocampal sclerosis (p < 0.001) and Alzheimer-related pathology (CERAD score and Braak and Braak stages, p = 0.001). The presence of one specific variable (cerebral amyloid angiopathy, Aß parenchymal deposits, TDP-43 proteinopathy, α-synucleinopathy, vascular lesions, non-Alzheimer type tauopathy) did not increase the probability of the co-occurrence of others (p = 0.24). The number of observed pathologies correlated with AD-neuropathologic change (p < 0.0001). In addition to AD-neuropathologic change, tauopathies associated well with dementia, while TDP-43 pathology and α-synucleinopathy showed strong effects but lost significance when evaluated together with AD-neuropathologic change. Non-AD neurodegenerative pathologies and their combinations have been underestimated, but are frequent in reality as demonstrated here. This should be considered in diagnostic evaluation of biomarkers, and for better clinical stratification of patients.

Long-term survivorship of rotator cuff repairs using ultrasound and magnetic resonance imaging analysis.

BACKGROUND: Important differences in clinical outcomes likely exist between patients with healed and nonhealed rotator cuff repairs. The survival probability of rotator cuff repairs has not been published in a time-dependent manner up to now. HYPOTHESES: Recurrent tears occur more frequently in the early postoperative period. Early failures of the repair are a prognostic factor for the long-term outcome. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A series of 107 consecutive patients undergoing arthroscopically assisted mini-open repair of the rotator cuff between 1998 and 2002 were evaluated in a prospective study. Of these, 95 patients finished the study after a maximum follow-up of 11 years. The evaluation included 1 postoperative magnetic resonance imaging scan as well as multiple ultrasonographies and determinations of the American Shoulder and Elbow Surgeons (ASES) and Constant scores at 3 months, 6 months, 1 year, and then yearly with a median follow-up of 96 months. RESULTS: The overall failure rate was 33% (35 of 107). The survivorship analysis revealed that 74% of all failures occurred atraumatically in the first 3 months and 11% occurred between the third and the sixth month after the repair. The remaining reruptures (14%) happened 2 to 5 years postoperatively and were related to sports activities or direct trauma. The overall clinical results did not deteriorate over time. The parameters healed tendon, rerupture of less than 2 cm(2), and rerupture of more than 2 cm(2) at 6 months were predictors of the gender- and age-adjusted (normalized) Constant score at 84 months (P < .0001). CONCLUSION: The majority of recurrent tears occurred in the first 3 months after surgical repair. The parameters "recurrent tear" as well as "healed tendon" evaluated at 6 months postoperatively appear to be predictors for the clinical outcomes at 7 years. Efforts to improve healing during the initial 3 months have long-term implications for maintenance of cuff integrity and clinical outcomes.

Is testicular germ cell cancer associated with increased muscle mass or adiposity?

INTRODUCTION: The correlation between an increased body mass index and testicular germ cell cancer has been a topical subject matter of literature. The thesis examines whether for patients with germ cell cancer of the testis the relation between the body cross section and the muscle mass at a particular spot at the abdomen is dislocated toward muscle hypertrophy. PATIENTS, MATERIALS, AND METHODS: CT examinations of 120 patients with testicular tumor have been compared to CTs of 60 trauma surgery patients. MEASUREMENTS: In thickness of the layer at the lowest point of the umbilicus the area of the total body cross section and the Mm. psoas majores were determined and their quotient was calculated. Furthermore, the thickness of the M. rectus abdominis and the Mm. obliquii abdominis have been determined at the broadest spot. RESULTS: The reproducibility of the measured data has been extremely high (kappa >0.9). There has been no significant difference in any of the examined parameters between the comparison group and the total patient group. DISCUSSION: According to the literature, patients with germ cell cancer of the testis on average show a higher body-mass-index (BMI) compared to a comparable group of equivalent age. The height of the umbilicus is a body region, where for adipose humans the amplitude increases markedly, hence for reference measurement appropriate. On the basis of the outcome of this thesis, the most probable explanation for the BMI rise is weight gain at other body parts.

Plasma amyloid beta-42 independently predicts both late-onset depression and Alzheimer disease.

OBJECTIVES: Depression in the elderly might represent a prodromal phase of Alzheimer disease (AD). High levels of plasma amyloid beta-42 (Aß42) were found in prestages of AD and also in depressed patients in cross-sectional studies. This study examined the association of emerging late-onset depression (LOD) and AD with plasma Aß42 in a sample of never depressed and not demented persons at baseline. DESIGN: Prospective 5-year longitudinal study. PARTICIPANTS: A community dwelling of older adults (N = 331) from the Vienna Transdanube Aging study. MEASUREMENTS: Laboratory measurements, cognitive functioning, and depressive symptoms were assessed at baseline, 2.5, and 5 years follow-ups. RESULTS: After exclusion of converters to AD, regression analysis revealed that higher plasma Aß42 at baseline was a positive predictor for conversion to first episode of LOD. Independent of whether persons with mild cognitive impairment (MCI) at 2.5 years were included or excluded into regressions, higher plasma Aß42 at baseline was a significant predictor for the development of probable or possible AD at 5 years. Higher conversion to AD was also associated with male gender but not with either higher scores on the Geriatric Depression Scale (GDS), with stroke or cerebral infarction nor apolipoprotein E ε4 allele. No association was found for an interaction between plasma Aß42 levels and GDS. CONCLUSIONS: Higher plasma Aß42 at baseline predicted the development of first episode of LOD and conversion to probable or possible AD. Emerging depression as measured by scores on GDS at the 2.5-year follow-up, either alone or as an interaction factor with plasma Aß42, failed to predict the conversion to AD at 5 years.

Spinal cord lesions in patients with neuromyelitis optica: a retrospective long-term MRI follow-up study.

Neuromyelitis optica (NMO) is characterised by a particular pattern of the optic nerves and the spinal cord. Long-term MRI follow-up studies of spinal NMO lesions are rare, or limited by short observation periods. In nine patients with definite NMO or recurrent longitudinally extensive transverse myelitis (LETM) with NMO-IgG serum antibodies, repeated MRI examinations of the spine were carried out over a period of up to 11 years and evaluated regarding the changes over time in this retrospective study. In eight patients spinal cord lesions were located centrally, involving the grey and white matter. In the first examination after clinical onset changes resembled a stroke of the anterior spinal artery in two patients. Symmetrical signal alterations within the grey matter were observed. In one patient this pattern was transient, but it remained in the other. During the chronic stage, either a variable degree of spinal cord atrophy and high signal alterations, or almost complete remission of the lesions, was observed. Spinal MRI of patients with NMO myelitis can resemble a stroke. MRI of acute NMO stages did not allow a prediction of the clinical outcome. To a variable degree, NMO left behind typical defects which correlated with the clinical outcome.

Changes on magnetic resonance tomography in the knee joints of marathon runners: a 10-year longitudinal study.

OBJECTIVE: The aim of the study was to evaluate long-term damage in the internal structures of the knee joints of recreational long-distance runners. MATERIALS AND METHODS: Ten years after their participation in a baseline study concerning their knee joints, seven long-distance runners and one who had given up long-distance running were invited to participate in a repeat magnetic resonance imaging (MRI) investigation. The same evaluation criteria and the same technical equipment were used, and the results of the two investigations were compared. RESULT: No adverse long-term consequences were observed in six of the seven active runners, regardless of pre-existing damage at the baseline investigation. In one case the arthrotic changes were progressive in nature. The person who had given up running presented with severe deterioration of the internal structures of the knee joint. CONCLUSION: Non-physiological maximal loads secondary to the marathon race do not cause any permanent damage in the internal structures of the knee joint in individuals without significant pre-existing damage. A disposition for premature arthrosis was not registered in the population investigated. A protective value of long distance running on the internal structures of the knee joint is discussed.

Risk factors for Alzheimer dementia in a community-based birth cohort at the age of 75 years.

BACKGROUND: Few prospective community-based cohort studies have so far concentrated specifically on the risk factors for Alzheimer dementia (AD) with onset after the age of 75 years. METHODS: We prospectively investigated a birth cohort of 585 nondemented inhabitants in the area on the East bank of the river Danube who were born between 1925 and 1926. They were investigated at the age of 75 years and followed up after 30 months. The follow-up was possible with 488 probands; 36 died, and 61 refused to participate. RESULTS: In multivariate analysis an elevated risk for late-onset AD could be found for (1) history of depressive episodes (OR = 2.09; 95% CI = 1.25-3.48); (2) the epsilon 4 allele of the APOE gene (OR = 1.86; 95% CI = 1.08-3.23); (3) lower serum level of folate (OR = 0.92; 95% CI = 0.87-0.98); (4) no chronic use of nonsteroidal anti-inflammatory drugs (OR = 0.40; 95% CI = 0.20-0.81), and (5) lower education (OR = 1.43; 95% CI = 1.03-2.00). CONCLUSIONS: Five risk factors for late-onset AD could be confirmed, which might be targets for preventive strategies.

Effects of medications on plasma amyloid beta (Abeta) 42: longitudinal data from the VITA cohort.

In the course of cognitive deterioration leading to Alzheimer's disease (AD) the increase of amyloid beta (Abeta42) in cerebrospinal fluid or plasma might be an initial event. We previously reported about the associations between concomitant medication and plasma Abeta42 levels in the non-demented population cohort of the Vienna transdanube aging study at baseline. In the present study, the longitudinal influence of insulin, gingko biloba, non-steroidal anti-inflammatory drugs (NSAIDs), oral anti-diabetics (sulfonylurea and biguanides), estrogens, fibrates, and statins on plasma Abeta42 are presented. Associated with medial temporal lobe atrophy (MTA), users of insulin showed significantly increased levels of Abeta42. Long-term users of gingko biloba, independent of their MTA, had significantly decreased plasma Abeta42 and the age-dependent increase of plasma Abeta42 was significantly smaller in long-term gingko biloba treated subjects. The use of fibrates also decreased plasma Abeta42 levels. In multiple testing considering interactions between medications, gender, APOE-epsilon4 presence and creatinine, insulin long-term users again showed significantly increased levels; fibrate and gingko biloba users showed a trend to rather decreased plasma Abeta42 levels compared to the non-users (p=0.05-0.08). Neither statins nor NSAIDs showed a significant effect on plasma Abeta42 in this model. Measuring the effect on cognition, no single medication studied was a significant predictor of conversion to AD or mild cognitive impairment (MCI). Whether the use of gingko biloba might prevent the conversion to MCI or AD needs to be proven in prospective, clinical trials.

Conversion from cognitive health to mild cognitive impairment and Alzheimer's disease: prediction by plasma amyloid beta 42, medial temporal lobe atrophy and homocysteine.

The changes of plasma amyloid beta (Abeta42) protein, homocysteine and medial temporal lobe atrophy (MTA) were studied by the transition from cognitive health to mild cognitive impairment (MCI) and to Alzheimer's disease (AD) in a prospective cohort of individuals aged 75 years. MTA but not plasma Abeta42 measured at baseline predicted which persons remained cognitively healthy (CH) and who developed AD 2.5 years later. The increase of plasma Abeta42 over time significantly distinguished between persons who remained CH on the one hand and MCI converters and AD converters out of cognitive health on the other (CH-to-MCI and CH-to-AD converters). Although both groups showed similar increase of Abeta42 levels, CH-to-AD converters had a higher increase of homocysteine compared to CH-to-MCI converters or to persons remaining CH. In comparison to all cognitive subgroups, the AD converters from MCI at baseline showed the smallest increase of Abeta42 levels and rather no increase of homocysteine. In logistic regression analysis, the increase of plasma Abeta42 but not change of MTA significantly predicted the conversion from CH to MCI, and changes of MTA and homocysteine but not of plasma Abeta42 predicted the conversion from CH to AD. The increase of plasma Abeta42 correctly allocated CH-to-MCI and CH-to-AD converters with low (63%) specificity (for both) and low (60%) sensitivity (54% for AD group). These results indicate that (1) plasma Abeta42 alone is not suitable as a biomarker for AD, (2) in the course of cognitive deterioration of the AD-type the increase of plasma Abeta42 seems to be an initial event, (3) similar to cerebrospinal fluid, changes of plasma Abeta42 may reflect the transition from cognitive health to AD, and (4) whether persons with MCI develop AD may depend on an accumulation of further toxic metabolites such as homocysteine.

Fluorescent in situ hybridization and ex vivo 1H magnetic resonance spectroscopic examinations of meningioma tumor tissue: is it possible to identify a clinically-aggressive subset of benign meningiomas?

OBJECTIVE: Although histologically benign, Grade I meningiomas can sometimes behave aggressively. The clinically-aggressive subset of Grade I meningiomas is typically indistinguishable from clinically-benign Grade I meningiomas in vivo. We compared molecular genetic and biochemical findings to clinical, pathological, and immunohistochemical information in a series of clinically-aggressive Grade I meningiomas with a series of clinically-benign meningiomas to identify characteristics that may be used to distinguish between these two groups. METHODS: Tumor tissue samples from 30 patients with Grade I meningiomas were harvested. Half of the sample was embedded in paraffin to be used for fluorescent in situ hybridization to examine aberrations of chromosomes 1p, 14q, and 22q; the other half was snap frozen and examined with proton magnetic resonance spectroscopy to identify concentrations of key metabolites in the tissue ex vivo. Clinical and pathological parameters were retrospectively reviewed as part of routine clinical management. These data were evaluated for potential unique associations with diagnostic significance. RESULTS: Molecular genetic and biochemical findings correlated with clinical behavior of the two Grade I meningioma groups. Specific chromosomal abnormalities correlated with the aggressive phenotype: homogeneous loss of 1p, homogeneous loss of 14q, and the presence of any of the examined chromosomal aberrations (P < 0.05). The presence of aberrations also influenced meningioma regrowth after subtotal resection. The ratio of choline to glutamate correlated with histopathological subtype (P < 0.05). The ratio of glutamine to glutamate, and the ratio of glycine to total glutamine and glutamate, and creatine correlated with recurrence. Alanine was decreased in meningiomas with chromosomal aberrations in tumors that recurred. CONCLUSION: Distinct molecular genetic and biochemical alterations differentiated clinically-aggressive Grade I meningiomas from clinically-benign Grade I meningiomas.

Cumulative Exposure to General anesthesias and cognitive dysfunction at age 75 in the Vienna Transdanube Aging "VITA" study.

Some reports have described general anesthesias as a risk factor for dementia in the elderly. The authors investigated whether the number of general anesthesias during a lifetime was associated with cognitive functioning in the community-based age cohort of a geographical area of Vienna. Out of 606 seventy-five-year-old subjects, 43 reported not having undergone anesthesia and 113 reported five or more anesthesias. The number of general anesthesias was not associated with extensive psychometric data. Cognitive dysfunction at age 75 was significantly associated with level of education, a history of major head trauma, and having lived in a rural environment during childhood.