Biomedical subjects

Laurel A Beckett

Publications and source records attributed to Laurel A Beckett.

At least 19 recordsLinked to original sources

PubMed2007

On the analysis of count data of birth-and-death process type: with application to molecularly targeted cancer therapy.

For molecularly targeted cancer therapy, potency of a novel monoclonal antibody is typically studied in vitro in order to observe directly the effect of the antibody on a malignant tumour cell population. Numbers of viable cells of the population are counted over time to evaluate how the antibody may change the population growth pattern. Usually, such count data is analysed by a log-linear model to estimate the average antibody effects, but it is based on a Poisson-like process and is not appropriate for modelling the growth pattern of the tumour cells. In this paper, we propose to analyse the count data from the point of view of a birth-and-death process, which is a more natural description of the biological process in these experiments. Assuming a simple birth-and-death process and a naïve regression model for the birth rate and death rate, we show that the log-linear relationship still holds for the average count and the covariates, although the linear predictor needs to satisfy a specific functional form. The estimation can be based on the quasi-likelihood method. The variance is not a simple function of the mean, but can be adequately approximated by a function of mean of either quadratic form or linear form, available in most standard statistical packages. We perform a simulation study to show that the proposed method provides consistent and robust estimations. The utility of the method is demonstrated by the analysis of a data set for experiment for anti-lymphoma monoclonal antibodies.

Antibodies, Monoclonal↗

PubMed2006

Size bias of fragile X premutation alleles in late-onset movement disorders.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome (FXTAS), caused by premutation expansions (55-200 CGG repeats) of the FMR1 gene, shares clinical features with other movement disorders, particularly in the domains of gait ataxia, intention tremor and parkinsonism. However, the prevalence of FXTAS within other diagnostic categories is not well defined. METHODS: A meta-analysis was conducted of all published (n = 14) genetic screens for expanded FMR1 alleles to assess the prevalence and CGG-repeat size bias of FMR1 premutation alleles in those populations. RESULTS: In men with late-onset cerebellar ataxia, the prevalence of premutation alleles (1.5%; 16/1049) was 13 times greater than expected based on its prevalence in the general population (2%; 16/818 for age of onset >50 years; odds ratio 12.4; 95% confidence interval 1.6 to 93.5). Meta-analysis of CGG-repeat data for screened patients with premutation alleles shows a shift to larger repeat size than in the general population (p<0.001). 86% (19/22) of premutation alleles were larger than 70 repeats in the patients screened, whereas only approximately 22% of premutation alleles are larger than 70 repeats in the general population. CONCLUSIONS: Expanded FMR1 alleles contribute to cases of late-onset sporadic cerebellar ataxia, suggesting that FMR1 genetic testing should be carried out in such cases. The biased distribution of FMR1 allele sizes has substantial implications for genetic counselling of carriers with smaller alleles who are at a low risk of developing FXTAS, and suggests that the estimated prevalence of FXTAS among men >50 years of age in the general population may be two to threefold lower than the initial figure of 1 in 3000.

Adult↗

PubMed2006

Characterization of MUC1 glycoprotein on prostate cancer for selection of targeting molecules.

MUC1 glycoprotein that is overexpressed in aberrant forms in epithelial cancers has been used for diagnosis, staging and therapy. As normal prostate and prostate cancer tissues express MUC1, it represents a potential target, but MUC1 epitopes specific to prostate cancer have not been well characterized. In order to assess MUC1 epitopes in prostate cancer, and their correlation with Gleason grades, binding of 7 well-characterized anti-MUC1 monoclonal antibodies (MAbs) (BrE-3, SM3, BC2, EMA, B27.29, HMFG-1 and NCL MUC1 core), were studied on a prostate tissue microarray. This microarray contained 197 prostate tissue cores representing: i) normal/benign prostate; ii) prostatic intraepithelial neoplasia and Gleason grades 1 and 2; and iii) Gleason grades 3-5. These MAbs bind the MUC1 extracellular domain, but have variable sensitivity to MUC1 glycosylation. To further characterize the effect of glycosylation on their binding, MAb reactivities with unglycosylated MUC1 core peptide and breast and prostate cancer cell lysates were compared. These studies demonstrated strong binding of BrE-3, BC2 and EMA to the peptide core and recognition by BrE-3, SM3, BC2 and EMA of hypoglycosylated MUC1. The results for the microarray indicated that higher Gleason grades were associated with markedly increased cellular staining by MAbs that preferentially recognize less glycosylated MUC1 (BrE-3, p<0.001; SM3, p<0.004; EMA, p=0.009; and BC2, p<0.001). Staining by MAbs that bind preferentially to hyperglycosylated MUC1 (B27.29, p=0.33; HMFG-1, p=0.89; and NCL MUC1 core, p=0.96) did not correlate with Gleason grade. These results demonstrated that hypoglycosylated MUC1 expression increased with Gleason grade, thus supporting the targeting of hypoglycosylated MUC1 epitopes in prostate cancer for more specific imaging and therapy applications.

Antibodies, Monoclonal↗

PubMed2005

Evaluation of factors affecting awareness of and willingness to participate in cancer clinical trials.

PURPOSE: Annually, only 3% of patients participate in cancer clinical trials (CCTs). Barriers to accrual include lack of CCT awareness and uncertain third-party payer coverage. In January 2002, a California law (Senate Bill 37 [SB37]) required all third-party payers to reimburse patient care costs related to CCTs. We evaluated the level of awareness of patients and/or their family members/friends regarding CCTs and SB37. METHODS: We used both a written survey for patients and/or their family members and friends seen in oncology clinics, and a verbal telephone version for Cancer Information Service callers. We tested for correlations between CCT awareness and SB37 knowledge, and willingness to participate in CCTs. RESULTS: Of 1,188 respondents, 59% were aware of CCTs, 19% knew of SB37, and 36% were very likely to consider a CCT. There were significant positive correlations between CCT awareness and willingness to participate (P < .001, Spearman), and between SB37 knowledge and willingness to participate (P = .001, Pearson chi2). Reduced awareness was seen in respondents who were either black or African American (odds ratio [OR], 0.44; P = .004), Hispanic (OR, 0.56; P = .03), had an annual income less than 25,000 dollars (OR, 0.38; P < .001), or had less than a college degree (OR, 0.12 to 0.53; P < .001 to .013). Reduced willingness to participate in CCTs was seen in black or African American participants (OR, 0.38; P < .001), Asians (OR, 0.44; P < .006), or respondents aged 18 to 24 years (OR, 0.35; P = .002). CONCLUSION: These results support the hypothesis that improving CCT awareness and SB37 knowledge especially among lower income, less educated, and minority patients, may potentially overcome barriers to participation and subsequently increase accrual in California.

Adolescent↗

PubMed2005

Asian Americans and cancer clinical trials: a mixed-methods approach to understanding awareness and experience.

Cancer clinical trials have been based on low accrual rates. Barriers to recruitment of minority populations affect the generalizability and impact of trial findings for those populations. The authors undertook a mixed-methods approach to understanding levels of awareness and experiences with cancer clinical trials. A survey was administered to new cancer patients and their caretakers (family, close friends, or other social support) at outpatient oncology clinics. Field observations of the trial accrual process also were conducted by employing the grounded theory approach in qualitative methods. Comparison of survey results for Asian-American respondents and non-Asian respondents indicated that Asians were less likely to have heard the term "clinical trial" and were more likely to define a clinical trial as "an experiment" or "a test procedure in a clinic" than non-Asians. Asians were more likely to have employer-based insurance and to report understanding issues related to cost reimbursement. Asians were less likely to have been involved in or to know someone in a trial and reported less willingness than white respondents to consider trial participation. Qualitative observations suggested that Asians who presented for a potential trial were interested in the availability of a novel cancer therapy but were not eligible for available trials. Multiple strategies will be necessary to enhance awareness of and experience with accrual to cancer clinical trials for Asians, including richer understanding and increased involvement of Asians in cancer clinical trials and greater attention to the location and diversity of the Asian population in structuring study centers and evaluating trial results.

Adult↗

PubMed2005

Ospemifene inhibits the growth of dimethylbenzanthracene-induced mammary tumors in Sencar mice.

Ospemifene is a new selective estrogen receptor modulator (SERM) that is being developed for the treatment of urogenital atrophy and osteoporosis. Similarly to other SERMs, ospemifene exhibits antiestrogenic effects in breast tissue, which led to the hypothesis that it may be a potential breast cancer chemopreventive agent. We first assessed the ability of ospemifene, compared to tamoxifen and raloxifene, to prevent dimethylbenzanthracene (DMBA)-induced mammary tumors in female Sencar mice. Ospemifene (N = 18), tamoxifen (N = 20) and raloxifene (N = 17), each dosed at 50 mg/kg, were administered daily by oral gavage, in combination with 20 microg DMBA for the first 6 weeks. Control mice (N = 21) received vehicle plus DMBA only for the first 6 weeks. Daily treatment then continued for 37 weeks. As hypothesized, ospemifene greatly reduced the incidence of mammary carcinomas compared to control mice (p = 0.003), similar to tamoxifen (p = 0.0004); however, in the raloxifene group, no significant effect was seen in mammary tumor prevention (p = 0.20). A follow-up study comparing ospemifene (N = 20) to tamoxifen (N = 20) in the same model was then performed to confirm the results of the first study. The results of the follow-up study, which extended the treatment to 52 weeks, confirmed the results of our previous study, with ospemifene (p = 0.01) and tamoxifen (p = 0.004) significantly decreasing mammary carcinomas compared to controls. The results of these two studies suggest that women taking ospemifene for osteoporosis and/or urogenital atrophy may further benefit from ospemifene's breast cancer chemopreventive effects.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2005

Residential proximity to naturally occurring asbestos and mesothelioma risk in California.

RATIONALE: Little is known about environmental exposure to low levels of naturally occurring asbestos (NOA) and malignant mesothelioma (MM) risk. OBJECTIVES: To conduct a cancer registry-based case control study of residential proximity to NOA with MM in California. METHODS: Incident MM cases (n = 2,908) aged 35 yr or more, diagnosed between 1988 and 1997, were selected from the California Cancer Registry and frequency matched to control subjects with pancreatic cancer (n = 2,908) by 5-yr age group and sex. Control subjects were selected by stratified random sampling from 28,123 incident pancreatic cancers in the same time period. We located 93.7% of subjects at the house or street level at initial diagnosis. Individual occupational exposure to asbestos was derived from the longest held occupation, available for 74% of MM cases and 63% of pancreatic cancers. Occupational exposure to asbestos was determined by a priori classification and confirmed by association with mesothelioma. MAIN RESULTS: The adjusted odds ratios and 95% confidence interval for low, medium, and high probabilities of occupational exposures to asbestos were 1.71 (1.32-2.21), 2.51 (1.91-3.30), and 14.94 (8.37-26.67), respectively. Logistic regression analysis from a subset of 1,133 mesothelioma cases and 890 control subjects with pancreatic cancer showed that the odds of mesothelioma decreased approximately 6.3% for every 10 km farther from the nearest asbestos source, an odds ratio of 0.937 (95% confidence interval = 0.895-0.982), adjusted for age, sex, and occupational exposure to asbestos. CONCLUSIONS: These data support the hypothesis that residential proximity to NOA is significantly associated with increased risk of MM in California.

Adult↗

PubMed2005

Seroprevalence of antibodies against Bartonella species and evaluation of risk factors and clinical signs associated with seropositivity in dogs.

OBJECTIVE: To determine the seroprevalence of antibodies against Bartonella spp in a population of sick dogs from northern California and identify potential risk factors and clinical signs associated with seropositivity. SAMPLE POPULATION: Sera from 3,417 dogs. PROCEDURE: Via an ELISA, sera were analyzed for antibodies against Bartonella vinsonii subsp berkhoffii, Bartonella clarridgeiae, and Bartonella henselae; test results were used to classify dogs as seropositive (mean optical density value > or = 0.350 for B henselae or > or = 0.300 for B clarridgeiae or B vinsonii subsp berkhoffi) or seronegative. Overall, 305 dogs (102 seropositive and 203 seronegative dogs) were included in a matched case-control study. RESULTS: 102 of 3,417 (2.99%) dogs were seropositive for > or = 1 species of Bartonella. Of these, 36 (35.3%) had antibodies against B henselae only, 34 (33.3%) had antibodies against B clarridgeiae only, 2 (2.0%) had antibodies against B vinsonii subsp berkhoffii only, and 30 (29.4%) had antibodies against a combination of those antigens. Compared with seronegative dogs, seropositive dogs were more likely to be herding dogs and to be female, whereas toy dogs were less likely to be seropositive. Seropositive dogs were also more likely to be lame or have arthritis-related lameness, nasal discharge or epistaxis, or splenomegaly. CONCLUSIONS AND CLINICAL RELEVANCE: Only a small percentage of dogs from which serum samples were obtained had antibodies against Bartonella spp. Breed appeared to be an important risk factor for seropositivity. Bartonella infection should be considered in dogs with clinical signs of lameness, arthritis-related lameness, nasal discharge or epistaxis, or splenomegaly.

Animals↗

PubMed2005

Acculturation and its association with health-risk behaviors in a rural Latina population.

PURPOSE: To evaluate the performance of proxy measures of acculturation and to examine the association between acculturation and selected health-risk behaviors. METHODS: Participants were 1062 Latina pregnant women who received prenatal care at clinics in San Joaquin County, California between 1999 and 2001. We used the receiver-operating characteristic (ROC) curve to characterize the sensitivity and specificity of proxy measures and regression analysis to examine health-risk behaviors. RESULTS: Using the ARSMA-II short version scale as a reference, age at immigration had the highest percentage of correctly classified individuals. Acculturation was significantly associated with a lifetime history of substance use, risky sexual behavior, low fruit consumption, and high fast-food meal consumption. CONCLUSIONS: Acculturation is an important predictor of health-risk behavior among women. Further research is needed to better understand the phenomenon and to avert associated adverse health consequences.

Acculturation↗

PubMed2004

Pulmonary function and exercise-associated changes with chronic low-level paraquat exposure.

The present study was undertaken to test the hypothesis that chronic, low-level paraquat exposure causes restrictive lung function with gas transfer impairment. Three hundred thirty-eight Costa Rican farm workers from banana, coffee, and palm oil farms completed a questionnaire, spirometry, and a test of single-breath carbon monoxide diffusing capacity. Subjects 40 years of age or older, without other medical risk factors, completed maximal cardiopulmonary exercise tests. Most (66.6%) were paraquat handlers; 24.8% of handlers and 27.3% of nonhandlers reported current cigarette smoking. In linear regression models, cumulative paraquat exposure was not an independent predictor of VA, carbon monoxide diffusing capacity, peak oxygen uptake, FVC, or oxygen pulse peak. However, the ventilatory equivalent for CO(2), although within normal range, was significantly higher with increased cumulative paraquat exposure. Oxygen desaturation greater than 5% from rest to peak exercise had an odds ratio of 1.7 (95% confidence interval = 0.9-3.0) with the cumulative paraquat exposure index in models adjusted for age, weight, and smoking status. The association of paraquat exposure with ventilatory equivalent and oxygen desaturation suggests that paraquat may be associated with subclinical gas exchange abnormalities, but overall these findings are consistent with no clinically significant increases in interstitial thickening or restrictive lung disease among this population.

Adolescent↗

PubMed2004

Effects of a genistein-rich extract on PSA levels in men with a history of prostate cancer.

OBJECTIVES: To determine whether supplemental amounts of soy isoflavone (genistein-rich extract) would lower prostate-specific antigen (PSA) levels more than 50% in patients with prostate cancer (CaP). METHODS: A total of 62 men (mean age 73.6 years, range 61.4 to 89.3) with histologically proven CaP who had two consecutive elevated PSA readings were accrued during a 13-month period. An open-label pilot study was conducted for 6 months in which the patients took capsules containing the genistein-rich extract three times daily by mouth. The subjects were in one of five groups: after radical retropubic prostatectomy (n = 9), after radiotherapy (n = 17), after both radical retropubic prostatectomy and radiotherapy (n = 6), off-cycle during hormonal therapy (intermittent hormones; n = 14), or active surveillance (n = 16). The primary endpoint for the trial was a 50% reduction in the PSA level at 6 months compared with before treatment. RESULTS: Of the 62 men enrolled, 52 were available for evaluation at 6 months. Three patients discontinued because of adverse events (diarrhea) and seven because of personal choice. One of 52 patients had a more than 50% reduction in the PSA level (1.9% response, 95% confidence interval 0.1% to 10.3%). An additional 7 patients had PSA reductions that were less than 50%. All 8 patients with lower PSA levels at 6 months were in the active surveillance (watchful waiting) treatment subgroup. Repeated measure regression models allowing for correlation between initial levels and change also indicated a decline in PSA in this group compared with other groups: 0 of 52 had a complete response, 9 (17%) had a partial response, 8 (15%) had stable disease, and 35 (67%) had disease progression. In the 9 patients with a partial response, 6 had pathologic findings that were moderately differentiated, 2 had well-differentiated findings, and 1 had poorly differentiated findings. Therefore, the response in this group of patients did not appear to be driven by the Gleason score. The total testosterone level was lowered in one of the patients responding, but it was higher in five others. CONCLUSIONS: A genistein-rich extract as the sole treatment for CaP did not reduce PSA levels by 50% or more in 51 of 52 subjects. Thus, it does not appear to be an effective treatment for CaP when given alone. However, 8 of 13 evaluated patients in the active surveillance group had either no rise or a decline in PSA levels of less than 50%. More study is warranted for those choosing active surveillance.

Adenocarcinoma↗

PubMed2004

Do behavioral disturbances in persons with Alzheimer's disease predict caregiver depression over time?

Random effects models were used to examine the association between behavioral disturbances in persons with Alzheimer's disease (N = 90) and caregiver depressive symptoms at 2-month intervals over an 18-month period. There was substantial variability in trajectories of change in caregiver depressive symptoms over time but no systematic increase in distress despite increased severity of dementia symptoms. Total behavioral disturbances were associated with higher levels of caregiver depressive symptoms: this effect was primarily attributable to aggressive behaviors. No consistent departure from linearity was evident in the relationship between behavior and depression over time.

Adult↗

PubMed2004

Temporal patterns of negative and positive behavior among nursing home residents with Alzheimer's disease.

Although clinical observations suggest a late-day peak in disruptive behavior in persons with dementia, results from studies of temporal patterns of behavior are equivocal. This study used direct observation methods and systematic time sampling to examine temporal patterns of negative and positive behavior in 177 residents of 2 long-term care facilities with clinically diagnosed Alzheimer's disease (AD). The authors found small statistically significant diurnal variation in both negative and positive behavior, characterized by a curvilinear pattern with a single peak. This pattern was unaffected by seasonal differences in length of day, severity of cognitive impairment, level of behavior, or sleep disturbances. Time when behavior peaked differed by type of behavior and by facility, and there was substantial heterogeneity in behavior patterns.

Affect↗

PubMed2004

A longitudinal study of parkinsonism and disability in a community population of older people.

BACKGROUND: Parkinsonian signs in patients without Parkinson's disease are often undetected but occur frequently in older people, and are often considered benign. We measured the association between parkinsonism and subsequent disability. METHODS: We conducted a prospective, longitudinal, community-based population study in East Boston, Massachusetts, using a stratified random sample of 455 community residents, aged 65 years and older. Four categories of parkinsonian signs were measured at baseline: bradykinesia, gait disturbance, rigidity, and tremor. Parkinsonism was defined as the presence of two or more categories of parkinsonian signs, and cases of Parkinson's disease were excluded from analyses. Disability was assessed annually over a mean of 4.7 years using the Katz, Rosow-Breslau, and Nagi disability measures. RESULTS: Parkinsonism at baseline strongly predicted subsequent disability as assessed with the three disability measures (on the Katz measure, beta = -1.30, p < .001). On average, a person with parkinsonism had a disability level at follow-up equal to that of a comparable person approximately 16.7 years for men and 8 years for women. The rate of developing disability for persons with parkinsonism increased each year; on the Katz measure, participants with parkinsonism declined on average 16.4% faster than those without. Gait impairment and bradykinesia strongly predicted subsequent disability; tremor and rigidity did not. The effect of parkinsonism was attenuated but still persistent in persons with coexistent moderate-to-severe cognitive impairment or stroke. CONCLUSIONS: Parkinsonism strongly predicts progressive disability in the older community population and has a marked aging effect on disability level.

Aged↗

PubMed2004

A modified yeast assay used on archival samples of localized prostate cancer tissue improves the detection of p53 abnormalities and increases their predictive value.

OBJECTIVE: To determine the frequency and predictive value of p53 mutations in localized prostate cancer, comparing the accuracy of detection using immunohistochemistry (IHC) with a modified yeast assay, on archival tissue samples. MATERIALS AND METHODS: Prostate cancer tissue was obtained from 98 patients who had >/= 2 years of clinical follow-up after radical prostatectomy. DNA sequencing was used to verify the presence of p53 mutations in samples that were immunopositive or that gave evidence for p53 alterations using the yeast assay. The IHC and yeast findings were compared with patient outcome to determine the predictive value of these two test types. RESULTS: Fifty-five tumours (57%) were immunopositive, and 58 (59%) were positive using the yeast assay. Sequence-confirmed p53 mutations occurred in 44 (45%) cases. The IHC protocol generated 49% (27/55) false-positive and 36% (15/42) false-negative results, and was 65% sensitive and 50% specific, with an overall accuracy of 57%. The yeast assay resulted in 24% (14/58) false-positive results with a specificity of 74% and an accuracy of 86%. When the p53 status of these patients was correlated with their clinical outcome, patients who had sequence-confirmed p53 mutations had a 2.6-fold greater failure rate (P = 0.026) and a 2.5-fold greater risk of dying from prostate cancer (P = 0.05). Notably, mutations in exon 6 predicted a six-fold increase in treatment failure (P = 0.043) and a 5.3-fold increase in the chance of dying from prostate cancer (P = 0.009). Abnormal yeast-assay findings gave similar predictive results to those obtained for DNA sequencing, while immunopositivity did not correspond to patient outcome. CONCLUSIONS: Mutations of p53 occurred in 45% of localized prostate cancers. These alterations have important prognostic implications. The yeast assay was more accurate for detecting p53 mutations than the IHC protocol used and, unlike IHC, the results of the yeast assay were predictive of patient outcome.

Adult↗

PubMed2003

Incidence of Alzheimer disease in a biracial urban community: relation to apolipoprotein E allele status.

CONTEXT: Few studies compare Alzheimer disease (AD) incidence among black and white subjects. OBJECTIVE: To estimate incidence and the effect of the apolipoprotein E (APOE) epsilon4 allele in these races. DESIGN: Population-based study of disease incidence using a random, stratified sample. SETTING: A geographically defined community of 3 adjacent neighborhoods in Chicago, Ill. PARTICIPANTS: A total of 6158 persons (78.7% overall; 80.5% of the black subjects and 74.6% of the white subjects) participated; 4.1 years later, persons initially free of AD were sampled for clinical evaluation for disease incidence (overall 842 persons [74.8%] participated; 67.6% of the black subjects and 81.9% of the white subjects). INTERVENTIONS: None. MAIN OUTCOME MEASURE: Incident, clinically diagnosed AD. RESULTS: The effect of the APOE epsilon4 allele on the risk of AD differed strongly for black and white subjects. Among white subjects, the presence of the APOE epsilon4 allele was associated with a 2.73-fold (95% confidence interval [CI], 1.40-5.32) increase in risk while among black subjects there was no increase in risk (odds ratio, 1.02; 95% confidence interval, 0.39-2.68). Black race was associated with a nonsignificantly increased risk of AD with an odds ratio of 1.84 (95% CI, 0.73-4.66) if APOE and its interaction with race are considered, and an odds ratio of 1.28 (95% CI, 0.54-2.98) if they are not. The incidence of AD was 1.45% (95% CI, 0.89%-2.01%) per year among persons 65 to 74 years old, 4.73% (95% CI, 3.83%-5.64%) among those 75 to 84 years old, and 9.11% (95% CI, 7.36%-10.9%) among those 85 years and older. CONCLUSION: Apolipoprotein E epsilon4 led to increased risk of AD among white subjects but not black subjects.

Aged↗

PubMed2003

Design of the Chicago Health and Aging Project (CHAP).

The design of the Chicago Health and Aging Project (CHAP) is described. CHAP is a longitudinal population study of common chronic health problems of older persons, especially of risk factors for incident Alzheimer's disease, in a biracial neighborhood of the south side of Chicago. Special attention is given to three unusual design features of the study. One feature is that clinical evaluation for Alzheimer's disease is confined to a stratified random sample of all participants. This feature results in substantial cost savings and substantially less bias than screening approaches but has the disadvantages of adding analytic complexity and requiring the use of indirect means to identify a disease-free cohort for the development of incident Alzheimer's disease. The second unusual feature is efficiently combining in analyses the successive independent multiple samples that are drawn, one from each data collection cycle. The third unusual feature is entering successive age cohorts of community residents into the study as they attain 65 years of age. This has the advantages of enhancing direct investigation of the effect of age on the action of risk factors for Alzheimer's disease and direct examination of cohort effects. The interaction of these features is described, especially as they pertain to a study in which data are collected in successive waves. The results from these waves must be combined for effective analysis of the relation among risk factors and incident disease.

Age Factors↗

PubMed2003

Multivariate modeling of two associated cognitive outcomes in a longitudinal study.

Longitudinal studies of Alzheimer's disease provide information about cognitive decline and predictors of this decline. However, overall cognitive function is comprised of many underlying processes, each of which may respond differently over time and may be affected by different predictors. In addition to studying how these processes decline independently, one might also be interested in how the processes decline together. Multivariate growth models, an extension and modification of random effects models, provide a means of dealing with these issues and enable assessing the association between the processes of interest. This technique allows for separate random effects and predictors for each process in the same model, thereby providing simultaneous estimates of the model parameters and variability for each process. We can then determine if factors associated with decline in one process are also associated with decline in another process and the extent to which the processes differ. We provide data that include information on two underlying processes of cognitive function, namely memory and executive function, to illustrate this methodology.

Aged↗