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James D Bowen

Publications and source records attributed to James D Bowen.

At least 19 recordsLinked to original sources
PubMed2025

Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.

BACKGROUND: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. RESULTS: We identify 13 loci with cross-population associations including known loci at/near CR1, BIN1, TREM2, CD2AP, PTK2B, CLU, SHARPIN, MS4A6A, PICALM, ABCA7, APOE, and two novel loci not previously reported at 11p12 (LRRC4C) and 12q24.13 (LHX5-AS1). We additionally identify three population-specific loci with genome-wide significance at/near PTPRK and GRB14 in HIS and KIAA0825 in NHW. Pathway analysis implicates multiple amyloid regulation pathways and the classical complement pathway. Genes at/near our novel loci have known roles in neuronal development (LRRC4C, LHX5-AS1, and PTPRK) and insulin receptor activity regulation (GRB14). CONCLUSIONS: Using cross-population GWAS meta-analyses, we identify novel LOAD susceptibility loci in/near LRRC4C and LHX5-AS1, both with known roles in neuronal development, as well as several novel population-unique loci. Reflecting the power of diverse ancestry in GWAS, we detect the SHARPIN locus with only 13.7% of the sample size of the NHW GWAS study (n = 409,589) in which this locus was first observed. Continued expansion into larger multi-ancestry studies will provide even more power for further elucidating the genomics of late-onset Alzheimer's disease.

Humans↗
PubMed2011

Common variants at MS4A4/MS4A6E, CD2AP, CD33 and EPHA1 are associated with late-onset Alzheimer's disease.

The Alzheimer Disease Genetics Consortium (ADGC) performed a genome-wide association study of late-onset Alzheimer disease using a three-stage design consisting of a discovery stage (stage 1) and two replication stages (stages 2 and 3). Both joint analysis and meta-analysis approaches were used. We obtained genome-wide significant results at MS4A4A (rs4938933; stages 1 and 2, meta-analysis P (P(M)) = 1.7 × 10(-9), joint analysis P (P(J)) = 1.7 × 10(-9); stages 1, 2 and 3, P(M) = 8.2 × 10(-12)), CD2AP (rs9349407; stages 1, 2 and 3, P(M) = 8.6 × 10(-9)), EPHA1 (rs11767557; stages 1, 2 and 3, P(M) = 6.0 × 10(-10)) and CD33 (rs3865444; stages 1, 2 and 3, P(M) = 1.6 × 10(-9)). We also replicated previous associations at CR1 (rs6701713; P(M) = 4.6 × 10(-10), P(J) = 5.2 × 10(-11)), CLU (rs1532278; P(M) = 8.3 × 10(-8), P(J) = 1.9 × 10(-8)), BIN1 (rs7561528; P(M) = 4.0 × 10(-14), P(J) = 5.2 × 10(-14)) and PICALM (rs561655; P(M) = 7.0 × 10(-11), P(J) = 1.0 × 10(-10)), but not at EXOC3L2, to late-onset Alzheimer's disease susceptibility.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Performance-based physical function and future dementia in older people.

BACKGROUND: The association of physical function with progression to dementia has not been well investigated. We aimed to determine whether physical function is associated with incident dementia and Alzheimer disease (AD). METHODS: We performed a prospective cohort study of 2288 persons 65 years and older without dementia. Patients were enrolled from 1994 to 1996 and followed up through October 2003. Main outcome measures included incident dementia and AD. RESULTS: During follow-up 319 participants developed dementia (221 had AD). The age-specific incidence rate of dementia was 53.1 per 1000 person-years for participants who scored lower on a performance-based physical function test at baseline (< or = 10 points) compared with 17.4 per 1000 person-years for those who scored higher (> 10 points). A 1-point lower performance-based physical function score was associated with an increased risk of dementia (hazard ratio, 1.08; 95% confidence interval, 1.03-1.13; P < .001), an increased risk of AD (hazard ratio, 1.06; 95% confidence interval, 1.01-1.12; P = .01), and an increased rate of decline in the Cognitive Ability Screening Instrument scores (0.11 point per year; 95% confidence interval, 0.08-0.14; P < .001) after adjusting for age, sex, years of education, baseline cognitive function, APOE epsilon4 allele, family history of AD, depression, coronary heart disease, and cerebrovascular disease. CONCLUSIONS: Lower levels of physical performance were associated with an increased risk of dementia and AD. The study suggests that poor physical function may precede the onset of dementia and AD and higher levels of physical function may be associated with a delayed onset.

Aged↗
PubMed2006

Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older.

BACKGROUND: Alzheimer disease and other dementing disorders are major sources of morbidity and mortality in aging societies. Proven strategies to delay onset or reduce risk for dementing disorders would be greatly beneficial. OBJECTIVE: To determine whether regular exercise is associated with a reduced risk for dementia and Alzheimer disease. DESIGN: Prospective cohort study. SETTING: Group Health Cooperative, Seattle, Washington. PARTICIPANTS: 1740 persons older than age 65 years without cognitive impairment who scored above the 25th percentile on the Cognitive Ability Screening Instrument (CASI) in the Adult Changes in Thought study and who were followed biennially to identify incident dementia. MEASUREMENTS: Baseline measurements, including exercise frequency, cognitive function, physical function, depression, health conditions, lifestyle characteristics, and other potential risk factors for dementia (for example, apolipoprotein E epsilon4); biennial assessment for dementia. RESULTS: During a mean follow-up of 6.2 years (SD, 2.0), 158 participants developed dementia (107 developed Alzheimer disease). The incidence rate of dementia was 13.0 per 1000 person-years for participants who exercised 3 or more times per week compared with 19.7 per 1000 person-years for those who exercised fewer than 3 times per week. The age- and sex-adjusted hazard ratio of dementia was 0.62 (95% CI, 0.44 to 0.86; P = 0.004). The interaction between exercise and performance-based physical function was statistically significant (P = 0.013). The risk reduction associated with exercise was greater in those with lower performance levels. Similar results were observed in analyses restricted to participants with incident Alzheimer disease. LIMITATIONS: Exercise was measured by self-reported frequency. The study population had a relatively high proportion of regular exercisers at baseline. CONCLUSION: These results suggest that regular exercise is associated with a delay in onset of dementia and Alzheimer disease, further supporting its value for elderly persons.

Age of Onset↗
PubMed2006

Suicidal ideation in multiple sclerosis.

OBJECTIVE: To examine risk factors for suicidal ideation among people with multiple sclerosis (MS). DESIGN: Cohort study linking computerized medical records with a mailed self-report survey. SETTING: Veteran's Health Administration (VHA) region covering the northwestern United States. PARTICIPANTS: VHA patients with MS (N=445) who returned mailed surveys. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Suicidal ideation is assessed by the Patient Health Questionnaire (PHQ) suicide item with suicidal ideation more than half the days considered persistent. RESULTS: One hundred thirty-one (29.4%) of 445 respondents (95% confidence interval [CI], 25.4%-33.9%) endorsed suicidal ideation, and 35 (7.9%; 95% CI, 5.7%-10.8%) endorsed persistent suicidal ideation over the last 2 weeks. In bivariate analyses, suicidal ideation was associated with younger age, earlier disease course, progressive disease subtype, lower income, not being married, lower social support, not driving, higher levels of physical disability (mobility, bowel, bladder), and depression. Analyses on persistent suicidal ideation yielded similar results. In fully adjusted multivariate logistic regression, only depression severity and bowel disability were independently associated with suicidal ideation. Only depression severity was independently associated with persistent suicidal ideation. By using the 2-question depression screen (U.S. Preventive Services Task Force) consisting of the depression and anhedonia items from the PHQ-9, sensitivity and specificity were marginal for suicidal ideation (65.6% and 79.9%) but acceptable for persistent suicidal ideation (88.6% and 71.2%). CONCLUSIONS: Suicidal ideation is common among VHA patients with MS, and depression severity is the best risk marker. Brief screening for depression in MS should include the assessment of suicidal ideation.

Chi-Square Distribution↗
PubMed2005

Predictors of prescriptions for management of fatigue among veterans with multiple sclerosis.

OBJECTIVE: To determine predictors of fatigue-modifying medication use. DESIGN: Cross-sectional cohort. SETTING: Veterans Health Administration (VHA) facilities. PARTICIPANTS: Veterans with multiple sclerosis (MS) in the VHA in the northwestern United States from 1995 to 2000. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: A self-administered survey distributed by mail sought information from veterans with MS about demographics, symptoms, barriers to care, and disease characteristics. The variables were compared with prescriptions for fatigue-modifying medications during the study period. RESULTS: Of 1032 patients, 451 (44%) completed the survey, and 306 (68%) reported moderate or high fatigue levels. Only 40% of the 306 were prescribed fatigue-modifying medications. Those using specialized fatigue services or who received care at tertiary centers were more likely to receive fatigue treatments. Patient-perceived barriers to accessing care and other patient characteristics were not associated with prescription rates. CONCLUSIONS: Fatigue is undertreated among veterans with MS. However, there is considerable variability in the provision of fatigue care. Interventions to improve the quality and uniformity of fatigue care are warranted.

Adult↗
PubMed2005

Fatigue and psychiatric illness in a large community sample of persons with multiple sclerosis.

BACKGROUND: Fatigue and depression are among the most common and disabling symptoms in multiple sclerosis (MS), but the nature and extent of the relationships between fatigue and psychiatric disorders in MS patients remain poorly understood. METHODS: A mail survey was completed by 739 members of the King County (WA) MS Association. Fatigue was evaluated by questions from the Modified Fatigue Impact Scale (MFIS), depressive symptoms by the Center for Epidemiologic Studies Depression Scale (CES-D), substance-use disorders from the PRIME-MD. Information on demographics, employment and characteristics of MS was also collected. Logistic regression was used to identify covariates significantly associated with disabling fatigue. Receiver operating characteristic (ROC) curve analysis evaluated the sensitivity and specificity of fatigue for depression. RESULTS: Twenty-five percent of this community-dwelling sample reported that their activities were often or almost always limited by fatigue. Seventy-six percent of subjects with disabling fatigue had significant depressive symptoms (CES-D >16), compared with 31% of those without disabling fatigue. Depression was strongly associated with fatigue, after controlling for age, gender, marital status, and severity, course and duration of illness. In logistic regression analysis, subjects with clinically significant depressive symptoms (CES-D >16) were much more likely to report disabling fatigue: OR = 6.24 (4.16, 9.35). Anxiety and substance-use disorders did not have the same strong associations with fatigue. Fatigue was highly sensitive and specific for clinically significant depressive symptoms. CONCLUSIONS: Disabling fatigue is strongly associated with clinically significant depressive symptoms. Patients who report disabling fatigue should be screened for depression.

Adult↗
PubMed2005

Developmental and vascular risk factors for Alzheimer's disease.

To investigate developmental and vascular risk factors for Alzheimer's disease (AD), we examined 90 incident cases of probable AD in a cohort of 1859 individuals followed prospectively for six years. The presence of the APOE-epsilon4 allele was the strongest risk factor, and with increasing survival age, the effect of epsilon4 diminished. Among epsilon4 positives, developmental risk factors such as smaller head circumference (< or =54.4 cm) and having more than four children in the household at age 2-3 were independently associated with incident AD (hazard ratio (HR)=2.6 (95% CI 1.04-6.3) and 3.3 (1.2-9.2), respectively). Among epsilon4 negatives, vascular risk factors were related to AD risk (self-reported diagnoses of transient ischemic attack and diabetes (HR=5.1, 95% CI 1.7-15.5; HR 3.3, 95% CI 1.4-8.1)). These findings indicate that clinical AD is a result of early life as well as later life risk factors, and that genetic predisposition to the disease may modify the constellation of predictors.

Age Factors↗
PubMed2005

The biceps squeeze test for diagnosis of distal biceps tendon ruptures.

UNLABELLED: Using the Thompson test for Achilles tendon rupture as a model, we developed the biceps squeeze test to test the integrity of the distal biceps tendon. We wanted to determine if failure to elicit supination with the biceps squeeze test would indicate complete distal biceps rupture. We also wanted to determine if surgical reattachment of the tendon would reestablish the supination response of the biceps squeeze test, and if patients who did not have surgery would have the same response to the biceps squeeze test months after injury. Twenty-five consecutive patients with 26 presumptive distal biceps tendon ruptures were evaluated with the biceps squeeze test. The biceps squeeze test was positive in 24 patients. Twenty-two patients had surgical repair. Twenty-one of 22 patients had operative confirmation of a complete distal biceps tendon rupture. All patients who had surgery had return of supination with the biceps squeeze test immediately after reattachment and at 3 months followup. Two patients with a positive biceps squeeze test declined surgery and did not have a return of supination with the biceps squeeze test at 3 months followup. Sixty-five patients with no history of upper extremity trauma were evaluated with the biceps squeeze test as a control group. All 65 patients had supination of the forearm in response to the test. The biceps squeeze test is simple, reliable, cost-effective, and aids in the diagnosis of distal biceps tendon ruptures. LEVEL OF EVIDENCE: Diagnostic study, Level II-1 (development of diagnostic criteria on basis of consecutive patients-with universally applied reference "gold" standard). See the Guidelines for Authors for a complete description of levels of evidence.

Adult↗
PubMed2005

Interrater reliability and accuracy in identifying ischemic strokes using computed tomography scans in people with dementia.

OBJECTIVES: To assess the reliability and interobserver agreement of stroke identification on neuroimaging in patients presenting with dementia. DESIGN: Comparison study between neurologists, radiology reports, and autopsy. SETTING: Dementia registry within a health maintenance organization. PARTICIPANTS: Dementia patients with computed tomography (CT) scans obtained near the time of diagnosis and postmortem neuropathological examinations (N=99). MEASUREMENTS: Three neurologists independently read CT scans for the presence and locations of strokes. Radiology reports from these scans were reviewed. The results from neurologists, radiologists, and autopsies were compared. RESULTS: The positive predictive value for CT-observed strokes compared with their presence on autopsy was 0.44 to 0.49, regardless of the specialty of the observer. Strokes were present at autopsy in 46 of 99 cases. Agreement between neurologists on the presence of strokes was fair to moderate (kappa=0.27-0.56). Less agreement was found between neurologists and radiologists (kappa=0.00-0.11). Results improved slightly when each case was evaluated as any stroke present versus no stroke on imaging (kappa=0.34-0.75) or for the presence of multiple strokes (kappa=0.17-0.69). CONCLUSION: There is only fair to moderate agreement between observers regarding the identification of strokes on CT scans in patients presenting with dementia. Furthermore, strokes identified on imaging were present on pathology only half the time.

Aged↗
PubMed2004

Survival after initial diagnosis of Alzheimer disease.

BACKGROUND: Alzheimer disease is an increasingly common condition in older people. Knowledge of life expectancy after the diagnosis of Alzheimer disease and of associations of patient characteristics with survival may help planning for future care. OBJECTIVE: To investigate the course of Alzheimer disease after initial diagnosis and examine associations hypothesized to correlate with survival among community-dwelling patients with Alzheimer disease. DESIGN: Prospective observational study. SETTING: An Alzheimer disease patient registry from a base population of 23 000 persons age 60 years and older in the Group Health Cooperative, Seattle, Washington. PATIENTS: 521 newly recognized persons with Alzheimer disease enrolled from 1987 to 1996 in an Alzheimer disease patient registry. MEASUREMENTS: Baseline measurements included patient demographic features, Mini-Mental State Examination score, Blessed Dementia Rating Scale score, duration since reported onset of symptoms, associated symptoms, comorbid conditions, and selected signs. Survival was the outcome of interest. RESULTS: The median survival from initial diagnosis was 4.2 years for men and 5.7 years for women with Alzheimer disease. Men had poorer survival across all age groups compared with females. Survival was decreased in all age groups compared with the life expectancy of the U.S. population. Predictors of mortality based on proportional hazards models included a baseline Mini-Mental State Examination score of 17 or less, baseline Blessed Dementia Rating Scale score of 5.0 or greater, presence of frontal lobe release signs, presence of extrapyramidal signs, gait disturbance, history of falls, congestive heart failure, ischemic heart disease, and diabetes at baseline. LIMITATIONS: The base population, although typical of the surrounding Seattle community, may not be representative of other, more diverse populations. CONCLUSIONS: In this sample of community-dwelling elderly persons who received a diagnosis of Alzheimer disease, survival duration was shorter than predicted on the basis of U.S. population data, especially for persons with onset at relatively younger ages. Features significantly associated with reduced survival at diagnosis were increased severity of cognitive impairment, decreased functional level, history of falls, physical examination findings of frontal release signs, and abnormal gait. The variables most strongly associated with survival were measures of disease severity at the time of diagnosis. These results should be useful to patients and families experiencing Alzheimer disease, other caregivers, clinicians, and policymakers when planning for future care needs.

Aged↗
PubMed2004

Effect of vascular lesions on cognition in Alzheimer's disease: a community-based study.

OBJECTIVES: To investigate whether clinical and neuropathological differences exist between Alzheimer's disease (AD) cases with and without vascular lesions neuropathologically diagnosed using Consortium to Establish a Registry for Alzheimer's Disease (CERAD) criteria. DESIGN: Descriptive observational study. SETTING: A community-based registry that identified incident dementia cases. PARTICIPANTS: Of the 124 subjects with available clinical and neuropathological assessments, 30 had AD lesions alone, and 18 had AD with vascular lesions. Patients with other neuropathological findings were excluded. MEASUREMENTS: Dependent measures included demographic, clinical, and neuropathological characteristics. Neuropathological diagnoses were made using the CERAD criteria and Braak and Braak staging. RESULTS: Of the 124 autopsied cases, 85 cases were diagnosed with neuropathological AD. Of these, 30 had pathology consistent with "pure" AD, whereas 18 had AD pathology with significant vascular lesions (AD/V). There were no differences in age, sex, or education between groups. AD/V cases had higher baseline and final Mini-Mental State Examination (MMSE) scores than pure AD cases, but after adjusting for education, differences in MMSE scores were not statistically significant. The AD/V group had significantly lower Braak staging than the pure AD group, after adjusting for education and final MMSE scores. CONCLUSION: In this comparison study of AD cases with and without vascular lesions, AD/V cases had less severe AD pathology than those with AD alone, indicating that cerebrovascular disease likely contributes to the severity of cognitive impairment in those with AD. Controlling for vascular risk factors in patients with AD may have a significant effect on severity of dementia.

Activities of Daily Living↗
PubMed2004

Subjective memory deterioration and future dementia in people aged 65 and older.

OBJECTIVES: To study whether subjective memory deterioration is associated with future dementia in older people. DESIGN: A population-based prospective cohort study begun in 1994 with biennial follow-up interviews. SETTING: Community-based members of Group Health Cooperative, a large health maintenance organization in the Seattle area. PARTICIPANTS: A sample of 1,883 subjects, dementia free, aged 65 and older, who scored 91 or higher on the 100-point Cognitive Ability Screening Instrument (CASI) at study entry. MEASUREMENTS: Subjective memory was assessed by asking whether memory had changed on 5-point Likert scales (e.g., 1=definitely improved, 3=no change, 5=definitely deteriorated) with regard to five items: remembering names, faces, friends, and appointments and judging the time. The items were summed for a possible total score ranging from 5 to 25. Subjective memory deterioration was defined as present if the total score was 20 or above. Cognitive performance was measured using the CASI. Incident dementia cases were identified using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. RESULTS: Of 1,883 subjects, 126 developed dementia during 5 years of follow-up. Subjective memory deterioration was associated with cognitive decline and incident dementia. Age modified the association between subjective memory deterioration and future dementia. For persons reporting subjective memory deterioration at the ages of 70, 75, and 80, the hazard ratios of developing dementia were 6.0 (95% confidence interval (CI)=2.1-18), 3.2 (95% CI=1.6-6.2) and 1.6 (95% CI=0.86-3.1), respectively. CONCLUSION: Subjective memory deterioration was found to precede the development of dementia in older people with normal cognitive screening results. These findings suggest that a high level of subjective memory deterioration in persons with normal objective cognitive function may identify a subset of individuals at greater risk for developing dementia.

Aged↗
PubMed2004

Alcohol, gender, and cognitive performance: a longitudinal study comparing older Japanese and non-Hispanic white Americans.

BACKGROUND: Recent data demonstrate that moderate consumption of alcohol may be beneficial to cognition. DESIGN: Longitudinal growth curve analyses controlling for variables related to cognition were used to examine the relationship between alcohol consumption, ethnic differences, gender, and cognition over a 4-year-follow-up period. SAMPLE: The sample included 1,836 Japanese American and 2,581 Non-Hispanic White American community-dwelling adults age 65 and older who were cognitively intact at baseline and participated in at least one follow-up examination. MEASUREMENT: Cognitive performance was measured using the Cognitive Abilities Screening Instrument (CASI) and reaction time. RESULTS: Current drinkers scored significantly higher on CASI over time than past drinkers or abstainers. The same association between alcohol and CASI was observed in both genders and both ethnic groups. CONCLUSION: This study provides support regarding the potential beneficial outcomes associated with alcohol consumption and cognition and that these benefits were not modified by gender or ethnicity.

Acculturation↗
PubMed2003

High-dose immunosuppressive therapy and autologous peripheral blood stem cell transplantation for severe multiple sclerosis.

There were 26 patients enrolled in a pilot study of high-dose immunosuppressive therapy (HDIT) for severe multiple sclerosis (MS). Median baseline expanded disability status scale (EDSS) was 7.0 (range, 5.0-8.0). HDIT consisted of total body irradiation, cyclophosphamide, and antithymocyte globulin (ATG) and was followed by transplantation of autologous, granulocyte colony-stimulating factor (G-CSF)-mobilized CD34-selected stem cells. Regimen-related toxicities were mild. Because of bladder dysfunction, there were 8 infectious events of the lower urinary tract. One patient died from Epstein-Barr virus (EBV)-related posttransplantation lymphoproliferative disorder (PTLD) associated with a change from horse-derived to rabbit-derived ATG in the HDIT regimen. An engraftment syndrome characterized by noninfectious fever with or without rash developed in 13 of the first 18 patients and was associated in some cases with transient worsening of neurologic symptoms. There were 2 significant adverse neurologic events that occurred, including a flare of MS during mobilization and an episode of irreversible neurologic deterioration after HDIT associated with fever. With a median follow-up of 24 (range, 3-36) months, the Kaplan-Meier estimate of progression (>/= 1.0 point EDSS) at 3 years was 27%. Of 12 patients who had oligoclonal bands in the cerebrospinal fluid at baseline, 9 had persistence after HDIT. After HDIT, 4 patients developed new enhancing lesions on magnetic resonance imaging of the brain. The estimate of survival at 3 years was 91%. Important clinical issues in the use of HDIT and stem cell transplantation for MS were identified; however, modifications of the initial approaches appear to reduce treatment risks. This was a heterogeneous high-risk group, and a phase 3 study is planned to fully assess efficacy.

Adult↗
PubMed2003

Epstein-Barr virus-associated posttransplantation lymphoproliferative disorder after high-dose immunosuppressive therapy and autologous CD34-selected hematopoietic stem cell transplantation for severe autoimmune diseases.

High-dose immunosuppressive therapy followed by autologous hematopoietic stem cell transplantation (HSCT) is currently being evaluated for the control of severe autoimmune diseases. The addition of antithymocyte globulin (ATG) to high-dose chemoradiotherapy in the high-dose immunosuppressive therapy regimen and CD34 selection of the autologous graft may induce a higher degree of immunosuppression compared with conventional autologous HSCT for malignant diseases. Patients may be at higher risk of transplant-related complications secondary to the immunosuppressed state, including Epstein-Barr virus (EBV)-associated posttransplantation lymphoproliferative disorder (PTLD), but this is an unusual complication after autologous HSCT. Fifty-six patients (median age, 42 years; range, 23-61 years) with either multiple sclerosis (n = 26) or systemic sclerosis (n = 30) have been treated. The median follow-up has been 24 months (range, 2-60 months). Two patients (multiple sclerosis, n = 1; systemic sclerosis, n = 1) had significant reactivations of herpesvirus infections early after HSCT and then developed aggressive EBV-PTLD and died on days +53 and +64. Multiorgan clonal B-cell infiltrates that were EBV positive by molecular studies or immunohistology were identified at both autopsies. Both patients had positive screening skin tests for equine ATG (Atgam) and had been converted to rabbit ATG (Thymoglobulin) from the first dose. Of the other 54 patients, 2 of whom had partial courses of rabbit ATG because of a reaction to the intravenous infusion of equine ATG, only 1 patient had a significant clinical reactivation of a herpesvirus infection (herpes simplex virus 2) early after HSCT, and none developed EBV-PTLD. The T-cell count in the peripheral blood on day 28 was 0/microL in all 4 patients who received rabbit ATG; this was significantly less than in patients who received equine ATG (median, 174/microL; P =.001; Mann-Whitney ranked sum test). Although the numbers are limited, the time course and similarity of the 2 cases of EBV-PTLD and the effect on day 28 T-cell counts support a relationship between the development of EBV-PTLD and the administration of rabbit ATG. The differences between equine and rabbit ATG are not yet clearly defined, and they should not be considered interchangeable in this regimen without further study.

Adult↗
PubMed2003

Alcohol, aging, and cognitive performance: a cross-cultural comparison.

This study investigated the relationship between alcohol consumption and cognitive performance in two culturally diverse community-based populations. METHODS. A cross-sectional analysis was used including Japanese Americans (n = 1,836) and Caucasians (n = 2,581) aged 65 and older. Cognitive performance was measured using the Cognitive Abilities Screening Instrument (CASI) (0 to 100 point scale) and reaction time. RESULTS. Multivariate analysis revealed significant cultural and gender differences with cognitive performance. Compared to abstainers, Caucasian drinkers scored higher than Japanese American drinkers on the CASI (adjusted means = 93.4 versus 91.6). In contrast, Japanese American drinkers scored faster than Caucasian drinkers on choice reaction time (adjusted means = 505 versus 579 milliseconds). DISCUSSION. Results showed that current drinking was associated with better cognition in both the Caucasian and Japanese American groups. Longitudinal studies are needed to support the possible protective effects of alcohol on cognition and explore whether culture may modify this apparent benefit.

Age Factors↗