Biomedical subjects

L Launer

Publications and source records attributed to L Launer.

8 recordsLinked to original sources

PubMed2006

Automation of sample mounting for macromolecular crystallography.

A standard sample holder and vial for cryocooled macromolecular crystals has been defined for use with robotic sample changers. This SPINE standard sample holder is a modified version, with added features and specifications, of sample holders in common use. In particular, the SPINE standard meets the precision required for automatic sample exchange and includes a cap that is identified by a two-dimensional datamatrix code as well as an optional vial. At the ESRF, the sample holder standard is in use with the EMBL/ESRF/BM14 robotic sample changer (SC3) which is installed on eight beamlines. The SC3 can hold up to 50 crystals stored in five baskets. A datamatrix reader in the SC3 ensures safe management of the sample flow and facilitates fully automatic screening and characterization of samples. Tools for handling and transporting 50 samples in a dry shipping dewar have been developed. In addition to the SC3, the SPINE sample holder is currently compatible with a number of other robotic sample changers.

Automation↗

PubMed2006

High-throughput sample handling and data collection at synchrotrons: embedding the ESRF into the high-throughput gene-to-structure pipeline.

An automatic data-collection system has been implemented and installed on seven insertion-device beamlines and a bending-magnet beamline at the ESRF (European Synchrotron Radiation Facility) as part of the SPINE (Structural Proteomics In Europe) development of an automated structure-determination pipeline. The system allows remote interaction with beamline-control systems and automatic sample mounting, alignment, characterization, data collection and processing. Reports of all actions taken are available for inspection via database modules and web services.

Data Collection↗

PubMed2006

Measuring longitudinal white matter changes: comparison of a visual rating scale with a volumetric measurement.

BACKGROUND AND PURPOSE: Detection of longitudinal changes in white matter hyperintensities (WMH) by using visual rating scales is problematic. We compared a widely used visual rating scale with a volumetric method to study longitudinal white matter changes. METHODS: WMH were assessed with the visual Scheltens scale and a volumetric method in 100 elderly subjects aged 70-81 years for whom repetitive MR images were available with an interval of 33 (SD, 1.4) months. Reliability was determined by intraclass correlation coefficients. To examine the sensitivity of both the visual and volumetric method, we calculated Spearman rank correlations of WMH ratings and volume measurements with age. RESULTS: Reliability of the visual rating scale was good, whereas reliability of the volumetric measurement was excellent. For baseline measurements of WMH, we found weaker associations between WMH and age when assessed with the visual scale (r = 0.20, P = .045) than with the volumetric method (r = 0.31, P = .002). Longitudinal evaluation of WMH assessments showed regression in 26% of the subjects when analyzed with the visual rating scale against 12% of the subjects when using volumetric measurements. Compared with the visual rating, the correlation between progression in WMH and age was twice as high when using the volumetric measurement (r = 0.19, P = .062 and r = 0.39, P < .001, respectively). CONCLUSION: Volumetric measurements of WMH offer a more reliable, sensitive, and objective alternative to visual rating scales in studying longitudinal white matter changes.

Aged↗

PubMed2003

Inflammatory markers and cognition in well-functioning African-American and white elders.

BACKGROUND: Several lines of evidence suggest that inflammatory mechanisms contribute to AD. OBJECTIVE: To examine whether several markers of inflammation are associated with cognitive decline in African-American and white well-functioning elders. METHODS: The authors studied 3,031 African-American and white men and women (mean age 74 years) enrolled in the Health, Aging, and Body Composition Study. Serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) and plasma levels of tumor necrosis factor-alpha (TNFalpha) were measured at baseline; cognition was assessed with the Modified Mini-Mental State Examination (3MS) at baseline and at follow-up. Cognitive decline was defined as a decline of >5 points. RESULTS: In age-adjusted analyses, participants in the highest tertile of IL-6 or CRP performed nearly 2 points lower (worse) on baseline and follow-up 3MS (p < 0.001 for all) and declined by almost 1 point over the >2 years (p = 0.01 for IL-6 and p = 0.04 for CRP) compared with those in the lowest tertile. After multivariate adjustment, 3MS scores among participants in the highest tertile of IL-6 and CRP were similar at baseline but remained significantly lower at follow-up (p < or = 0.05 for both). Those in the highest inflammatory marker tertile were also more likely to have cognitive decline compared with the lowest tertile for IL-6 (26 vs 20%; age-adjusted odds ratio [OR] = 1.34; 95% CI 1.06 to 1.69) and for CRP (24 vs 19%; OR = 1.41; 95% CI 1.10 to 1.79) but not for TNFalpha (23 vs 21%; OR = 1.12; 95% CI 0.88 to 1.43). There was no significant interaction between race and inflammatory marker or between nonsteroidal anti-inflammatory drug use and inflammatory marker on cognition. CONCLUSIONS: Serum markers of inflammation, especially IL-6 and CRP, are prospectively associated with cognitive decline in well-functioning elders. These findings support the hypothesis that inflammation contributes to cognitive decline in the elderly.

Black or African American↗

PubMed2003

The role of APOE-epsilon4 in longitudinal cognitive decline: MacArthur Studies of Successful Aging.

BACKGROUND: While a genetic risk factor for late-onset AD, the effects of the epsilon4 allele of the APOE gene on cognitive functioning more generally remain unclear. OBJECTIVE: To assess the role of the epsilon4 allele of the APOE gene in longitudinal cognitive decline. METHODS: Multiple measures of cognitive function were assessed longitudinally in the MacArthur Successful Aging Study, a population-based cohort free of frank impairment at baseline. Subjects were 965 Caucasian and African American men and women from Durham NC, East Boston, MA, and New Haven, CT, aged 70 to 79 years, recruited in 1988 through 1989, who completed two follow-up evaluations, one at 3 years and another at 7 years. RESULTS: At the first follow-up, modest but significant declines in naming and spatial ability were associated with the APOE-epsilon4 genotype. By the second follow-up, more pronounced and significant associations were noted between the APOE-epsilon4 genotype and cognitive decline from six of the eight cognitive outcomes. After 7 years, APOE-epsilon4 allele carriers were twice as likely to have declined on a global cognitive score (odds ratio = 2.0; 95% CI: 1.1, 3.6) as noncarriers. CONCLUSIONS: APOE-epsilon4 is associated with cognitive decline among a high-functioning elderly cohort, with effects most pronounced after 7 years of follow-up. Hence, the epsilon4 allele either may function as a risk factor for cognitive impairment in normal aging across a broad spectrum of domains or may exert detectable effects early in a long prodromal AD trajectory.

Aged↗

PubMed2001

Daytime sleepiness is associated with 3-year incident dementia and cognitive decline in older Japanese-American men.

OBJECTIVES: To assess the longitudinal association between sleep disturbances (insomnia and daytime sleepiness) and incidence of dementia and cognitive decline in older men. DESIGN: Community-based longitudinal cohort study. SETTING: The Honolulu-Asia Aging Study of dementia that is linked to the Honolulu Heart Program's fourth examination, conducted 1991-1993, and the 3-year follow-up fifth examination, conducted 1994-1996. PARTICIPANTS: Two thousand three hundred forty-six Japanese-American men age 71 to 93 years who screened negative for prevalent dementia at baseline and were screened again for dementia incidence in a 3-year follow-up examination. MEASUREMENTS: Baseline self-reports of trouble falling asleep or early morning awakening (insomnia) and being sleepy during the day (daytime sleepiness); Cognitive Abilities Screening Instrument (CASI) scores from baseline and followup; clinical diagnosis of incident dementia; and other baseline measures including age, years of education, body mass index, depressive symptoms, and history of hypertension, heart disease, diabetes mellitus, asthma, and use of benzodiazepines. RESULTS: After adjusting for age and other factors, persons reporting excessive daytime sleepiness at baseline (8%) were twice as likely to be diagnosed with incident dementia than were those not reporting daytime sleepiness (odds ratio (OR)=2.19, 95% confidence interval (CI)=1.37-3.50) and about 40% more likely to have >or=9 point drop in their CASI score between examinations (OR=1.44, 95% CI=1.01-2.08). In contrast, insomnia was not associated with cognitive decline or incidence of dementia. CONCLUSIONS: Daytime sleepiness in older adults may be an early indicator of decline in cognitive functioning and onset of dementia.

Aged↗

PubMed1999

Association between bone mineral density and cognitive decline in older women.

OBJECTIVE: To test the hypothesis that bone mineral density (BMD), a marker of cumulative estrogen exposure, is associated with cognitive function in nondemented older women. DESIGN: A prospective cohort study. SETTING: Clinical centers in Baltimore, Maryland, Minneapolis, Minnesota, the Monongahela Valley near Pittsburgh, Pennsylvania, and Portland, Oregon. PARTICIPANTS: We evaluated 8333 older community-dwelling women enrolled in the Study of Osteoporotic Fractures who were not taking estrogen replacement. MEASUREMENTS: Calcaneal and hip BMD were measured at baseline and at follow-up (4-6 years later); vertebral fractures were ascertained radiologically at year 6. Women were administered a modified Mini-Mental State Exam, Trails B, and Digit Symbol at baseline and at follow-up. RESULTS: Compared with women with higher bone mineral density, women with low baseline BMD had up to 8% worse baseline cognitive scores (P = .001) and up to 6% worse repeat cognitive scores (P = .001), even after multivariate adjustments. For 1 SD decrease in baseline hip BMD or calcaneal BMD, women had a 32% (95% CI, 19-47%) or a 33% (95% CI, 20-48%) greater odds of cognitive deterioration (worst 10th percentile of change). Women with vertebral fractures had lower cognitive test scores and a greater odds of cognitive deterioration than those without fractures (OR = 1.29; 95% CI, 1.03-1.60). CONCLUSIONS: Women with osteoporosis, whether measured by baseline BMD, reductions in BMD, or vertebral fractures, have poorer cognitive function and greater risk of cognitive deterioration. Our findings suggest a link between two of the most common conditions affecting older women. Further understanding of this association may be important for new treatment and prevention directions.

Absorptiometry, Photon↗

PubMed1998

A study of familial aggregation of depression, dementia and Parkinson's disease.

Depression is often accompanied by other disorders including Alzheimer's disease and Parkinson's disease. We studied the familial aggregation of these disorders in order to examine the possibility of a shared genetic origin. In a population-based study of 6596 subjects, we studied the association of self-reported depression, which required treatment by a psychiatrist, to family history of psychiatric disease, dementia, and Parkinson's disease. A family history of psychiatric disease was significantly associated with overall depression as well as with unipolar (n = 303 patients) and bipolar (n = 27 patients) depression. The risk of unipolar depression was associated with the presence of two or more demented individuals among their first degree relatives (e.g. parents, siblings and children). Since there was no evidence for familial aggregation in subjects with only one demented relative, our study suggests that unipolar depression may be associated specifically to a strongly familial, form of dementia. The risk of bipolar depression was increased for those with one or more relatives with dementia and, perhaps, for those with relatives with Parkinson's disease. The familial aggregation of depression with dementia and perhaps Parkinson's disease suggests that there may be shared susceptibility gene(s) underlying these diseases. Our study indicates further that there may be differences in the genetic etiology between unipolar and bipolar depression.

Aged↗