Cerebrospinal Fluid Tau Protein Levels and F-18-Fluorodeoxyglucose Positron Emission Tomography in the Differential Diagnosis of Alzheimer's Disease

Aims: In this study, we aimed to compare cerebrospinal fluid (CSF) levels of total tau (t-tau), phosphorylated tau (p-tau(181)) and positron emission tomography with F-18-fluorodeoxyglucose (FDG-PET) in the differential diagnosis of Alzheimer's disease (AD) under clinical conditions. Method: In a cross-sectional, blinded, single-center study, we examined a sample of 75 unselected memory clinic patients with clinical diagnoses of dementia of Alzheimer type (DAT; n = 24), amnestic mild cognitive impairment (MCI; n = 16), other dementias (n = 13) and nondemented controls (n = 22). Discriminative accuracy, sensitivity and specificity were calculated and compared using ROC analyses. Results: p-tau(181) and FDG-PET were comparable in separating DAT from controls (sensitivity: 67 vs. 79%; specificity: 91% for both) and patients with other dementias (sensitivity: 71 vs. 79%; specificity: 100% for both). The sensitivity of p-tau 181 in differentiating MCI patients from controls was significantly (p < 0.05) superior to that of FDG-PET (75 vs. 44%) at a comparably high specificity (82 vs. 91%); t-tau measures were less accurate in all analyses. Conclusions: FDG-PET and CSF p-tau(181) levels are able to discriminate DAT in heterogeneous and unselected samples with a high accuracy. CSF p-tau(181) might be somewhat superior for a sensitive detection of patients with MCI. Copyright (C) 2010 S. Karger AG, Base

Cognitive reserve impacts on inter-individual variability in resting-state cerebral metabolism in normal aging

peer reviewedThere is a great deal of heterogeneity in the impact of aging on cognition and cerebral functioning. One potential factor contributing to individual differences among the elders is the cognitive reserve, which designates the partial protection from the deleterious effects of aging that lifetime experience provides. Neuroimaging studies examining task-related activation in elderly people suggested that cognitive reserve takes the form of more efficient use of brain networks and/or greater ability to recruit alternative networks to compensate for age-related cerebral changes. In this multi-centre study, we examined the relationships between cognitive reserve, as measured by education and verbal intelligence, and cerebral metabolism at rest (FDG-PET) in a sample of 74 healthy older participants. Higher degree of education and verbal intelligence was associated with less metabolic activity in the right posterior temporoparietal cortex and the left anterior intraparietal sulcus. Functional connectivity analyses of resting-state fMRI images in a subset of 41 participants indicated that these regions belong to the default mode network and the dorsal attention network respectively. Lower metabolism in the temporoparietal cortex was also associated with better memory abilities. The findings provide evidence for an inverse relationship between cognitive reserve and resting-state activity in key regions of two functional networks respectively involved in internal mentation and goal-directed attention

The effects of achievement motivation and coping with stress on the cognitive performance of alcohol dependent patients : An experimental investigation

Die Studie untersuchte den Einfluss der Leistungsmotivation und Stressverarbeitung auf die kognitive Leistung alkoholabhängiger Patienten. Die Patienten zeigten vor der Untersuchung erhöhte emotionale Labilität und Ängstlichkeit. Die Patienten konnten im Experiment zum Einfluss der Motivation durch die Vorgabe einer Zielsetzungsinstruktion (Goal-Setting Theorie), im nächsten Durchgang 20% mehr einfache Additionen zu lösen, ihre Leistung signifikant steigern (Anzahl der richtig gelösten Aufgaben, bearbeitete Aufgaben, Reaktionszeit). Die Kontrollpersonen unter der Zielsetzungsinstruktion erreichten nur eine Tendenz für eine Steigerung. Der Leistungszuwachs der Patienten war jedoch nicht signifikant größer als der bei den Kontrollpersonen. Demnach zeigten die Patienten intakte motivationale Ressourcen, es ergaben sich jedoch keine Hinweise für motivational bedingte kognitive Defizite. Sechs Untertests der Testbatterie zur Aufmerksamkeitsprüfung wurden unter Standardbedingungen und unter drei verschiedenen Stressbedingungen durchgeführt: wiederholte fiktive negative Rückmeldung, wiederholte fiktive positive Rückmeldung und unter Lärm (90 dB (A)). In der Bedingung negative Rückmeldung zeigten die Patienten in 'Visuelles Scanning' und in 'Reaktionswechsel' eine schlechtere Reaktionszeit als die Kontrollpersonen unter negativer Rückmeldung. Parallel zur Leistungsminderung zeigten die Patienten unter negativer Rückmeldung ansteigendes Stresserleben. Es zeigten sich keine Effekte durch die stressinduzierende Lärmbeschallung. Die Patienten erlebten im Gegensatz zu den Kontrollpersonen durch die negative Rückmeldung leistungsmindernde Testängstlichkeit. Für die Gruppe der Patienten ergab sich im Zuge der Untersuchung, hypothetisch durch das Ausbleiben gravierender Defizite, eine signifikante Angstreduktion. Für die Patienten mit der fiktiven negativen Rückmeldung blieb diese Beruhigung infolge der Untersuchung (Angstminderung) aus.The study aimed at determining the influence of achievement motivation and stress coping on the cognitive performance of alcohol dependent patients. Prior to examination the patients reported increased emotional instability and anxiety. Concerning the influence of motivation, patients with goal setting instructions (to increase performance in the next run by 20%) demonstrated significant increase in solving simple mathematical problems (increase in amount of correct responses, total amount of tasks, decrease in reaction time). For control subjects with goal setting instructions there was only a trend for higher performance. However, the increase in test-performance through goal setting for the patients was not significantly larger than that for the control subjects. Therefore, our results demonstrated motivational resources but no systematic influence of motivation on the testing results of alcohol dependent patients. Concerning the influence of stress coping, six subtests of the Test for Attentional Performance have been used. The stress inducing conditions were fictitious negative feedback concerning the results repeatedly during examination and exposure to noise. Following negative feedback, patients demonstrated slower reaction times in the subsequent subtests 'visual scanning' and 'flexibility' relative to control subjects with negative feedback. Additionally, patients with negative feedback demonstrated elevated levels of stress experiences. There were no effects under exposure to noise. Therefore, patients with negative feedback contrary to control subjects experienced debilitating test anxiety. There was significant decrease in anxiety for the group of patients posterior to examination hypothetically due to nonappearance of major cognitive deficits. But, contrary to the other alcohol dependent patients, there was no decrease of anxiety posterior to the neuropsychological investigation for patients with negative feedback

Contact between doctors and the pharmaceutical industry, their perceptions, and the effects on prescribing habits.

BACKGROUND: The prescribing behaviour of doctors is influenced by the pharmaceutical industry. This study investigated the extent to which contacts with pharmaceutical sales representatives (PSR) and the perception of these contacts influence prescribing habits. METHOD: An online questionnaire regarding contact with PSRs and perceptions of this contact was sent to 1,388 doctors, 11.5% (n = 160) of whom completed the survey. Individual prescribing data over a year (number of prescriptions, expenditure, and daily doses) for all on-patent branded, off-patent branded, and generic drugs were obtained from the Bavarian Association of Statutory Health Insurance Physicians. RESULTS: 84% of the doctors saw PSR at least once a week, and 14% daily. 69% accepted drug samples, 39% accepted stationery and 37% took part in sponsored continuing medical education (CME) frequently. 5 physicians (3%) accepted no benefits at all. 43% of doctors believed that they received adequate and accurate information from PSRs frequently or always and 42% believed that their prescribing habits were influenced by PSR visits occasionally or frequently. Practices that saw PSRs frequently had significantly higher total prescriptions and total daily doses (but not expenditure) than practices that were less frequently visited. Doctors who believed that they received accurate information from PSRs showed higher expenditures on off-patent branded drugs (thus available as generics) and a lower proportion of generics. The eschewal of sponsored CME was associated with a lower proportion of on patent-branded drug prescriptions, lower expenditure on off-patent branded drug prescriptions and a higher proportion of generics. Acceptance of office stationery was associated with higher daily doses. CONCLUSIONS: Avoidance of industry-sponsored CME is associated with more rational prescribing habits. Furthermore, gift acceptance and the belief that one is receiving adequate information from a PSR are associated with changed prescribing habits. Further studies with larger sample sizes are needed

Influence of the frequency at which the doctors accepted gifts on the number of prescriptions, the daily doses (defined daily dose, DDD) and expenditure per patient (means +/− SD).

<p>The p-values result from two-sided tests comparing the means reported above and below. Differences nominally significant at a level of p≤0.005 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0110130#s2" target="_blank">methods</a>) are reported with a bold font p-value.</p><p>Influence of the frequency at which the doctors accepted gifts on the number of prescriptions, the daily doses (defined daily dose, DDD) and expenditure per patient (means +/− SD).</p

Connectivity within the default mode network is related to working memory performance in young but not elderly healthy adults

peer reviewe

Association of Structural Global Brain Network Properties with Intelligence in Normal Aging

<div><p>Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60–85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R) and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient) were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience.</p></div

Comparison of network measures.

<p>Mean values ± standard deviation. Younger elderly: subjects aged 60 to 74. Advanced elderly: Subjects aged 75 to 85. P-value: t-test for independent samples. Significant group differences after Holm-Bonferroni correction: * alpha = 0.05/3 = 0.017,** alpha = 0.05/2 = 0.025.</p