Publications (11) View all
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Article: Progression of Alzheimer's disease as measured by Clinical Dementia Rating Sum of Boxes scores.
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ABSTRACT: BACKGROUND: This study examined rates of dementia progression as ascertained by the Clinical Dementia Rating Sum of Boxes (CDR-SB) for symptomatic Alzheimer's disease (sAD), and assessed participant characteristics as predictors of CDR-SB progression. METHODS: Participants (n = 792) were enrolled in longitudinal studies at an Alzheimer's Disease Research Center, received a diagnosis of sAD with a global CDR of 0.5 (n = 466) or 1 (n = 326), and had at least one follow-up assessment. Progression in CDR-SB over time as a function of baseline global CDR was examined. RESULTS: A longitudinal increase (P < .0001) in CDR-SB was observed. The annual rate of change in CDR-SB scores was 1.43 (standard error [SE] = 0.05) in the CDR 0.5 sample and 1.91 (SE = 0.07) in the CDR 1 sample. For participants followed from the beginning of the CDR stage, time to progression to a higher global CDR was longer for individuals who were CDR 0.5 (3.75 years; 95% confidence interval [CI]: 3.18-4.33) than those who were CDR 1 at baseline (2.98 years; 95% CI: 2.75-3.22). In the total CDR 0.5 sample, the significant predictors of progression to the next global CDR stage (P < .01) were age at first sAD diagnosis and apolipoprotein E4 genotype. CONCLUSIONS: The study findings are relevant to sAD clinical trial design and accurate, reliable ascertainment of the effect of disease-modifying treatments.Alzheimer's & dementia: the journal of the Alzheimer's Association 08/2012; · 5.90 Impact Factor -
Article: Improving CSF biomarker accuracy in predicting prevalent and incident Alzheimer disease.
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ABSTRACT: To investigate factors, including cognitive and brain reserve, which may independently predict prevalent and incident dementia of the Alzheimer type (DAT) and to determine whether inclusion of identified factors increases the predictive accuracy of the CSF biomarkers Aβ(42), tau, ptau(181), tau/Aβ(42), and ptau(181)/Aβ(42). Logistic regression identified variables that predicted prevalent DAT when considered together with each CSF biomarker in a cross-sectional sample of 201 participants with normal cognition and 46 with DAT. The area under the receiver operating characteristic curve (AUC) from the resulting model was compared with the AUC generated using the biomarker alone. In a second sample with normal cognition at baseline and longitudinal data available (n = 213), Cox proportional hazards models identified variables that predicted incident DAT together with each biomarker, and the models' concordance probability estimate (CPE), which was compared to the CPE generated using the biomarker alone. APOE genotype including an ε4 allele, male gender, and smaller normalized whole brain volumes (nWBV) were cross-sectionally associated with DAT when considered together with every biomarker. In the longitudinal sample (mean follow-up = 3.2 years), 14 participants (6.6%) developed DAT. Older age predicted a faster time to DAT in every model, and greater education predicted a slower time in 4 of 5 models. Inclusion of ancillary variables resulted in better cross-sectional prediction of DAT for all biomarkers (p < 0.0021), and better longitudinal prediction for 4 of 5 biomarkers (p < 0.0022). The predictive accuracy of CSF biomarkers is improved by including age, education, and nWBV in analyses.Neurology 02/2011; 76(6):501-10. · 8.31 Impact Factor -
Article: Alzheimer disease identification using amyloid imaging and reserve variables: proof of concept.
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ABSTRACT: Several factors may influence the relationship between Alzheimer disease (AD) lesions and the expression of dementia, including those related to brain and cognitive reserve. Other factors may confound the association between AD pathology and dementia. We tested whether factors thought to influence the association of AD pathology and dementia help to accurately identify dementia of the Alzheimer type (DAT) when considered together with amyloid imaging. Participants with normal cognition (n = 180) and with DAT (n = 25), aged 50 years or older, took part in clinical, neurologic, and psychometric assessments. PET with the Pittsburgh compound B (PiB) tracer was used to measure brain amyloid, yielding a mean cortical binding potential (MCBP) reflecting PiB uptake. Logistic regression was used to generate receiver operating characteristic curves, and the areas under those curves (AUC), to compare the predictive accuracy of using MCBP alone vs MCBP together with other variables selected using a stepwise selection procedure to identify participants with DAT vs normal cognition. The AUC resulting from MCBP alone was 0.84 (95% confidence interval [CI] = 0.73-0.94; cross-validated AUC = 0.80, 95% CI = 0.68-0.92). The AUC for the predictive equation generated by a stepwise model including education, normalized whole brain volume, physical health rating, gender, and use of medications that may interfere with cognition was 0.94 (95% CI = 0.90-0.98; cross-validated AUC = 0.91, 95% CI = 0.85-0.96), an improvement (p = 0.025) over that yielded using MCBP alone. Results suggest that factors reported to influence associations between AD pathology and dementia can improve the predictive accuracy of amyloid imaging for the identification of symptomatic AD.Neurology 07/2010; 75(1):42-8. · 8.31 Impact Factor -
Article: Cancer linked to Alzheimer disease but not vascular dementia.
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ABSTRACT: To investigate whether cancer is associated with Alzheimer disease (AD) and vascular dementia (VaD). Cox proportional hazards models were used to test associations between prevalent dementia and risk of future cancer hospitalization, and associations between prevalent cancer and risk of subsequent dementia. Participants in the Cardiovascular Health Study-Cognition Substudy, a prospective cohort study, aged 65 years or older (n = 3,020) were followed a mean of 5.4 years for dementia and 8.3 years for cancer. The presence of any AD (pure AD + mixed AD/VaD; hazard ratio [HR] = 0.41, 95% confidence interval [CI] = 0.20-0.84) and pure AD (HR = 0.31, 95% CI = 0.12-0.86) was associated with a reduced risk of future cancer hospitalization, adjusted for demographic factors, smoking, obesity, and physical activity. No significant associations were found between dementia at baseline and rate of cancer hospitalizations for participants with diagnoses of VaD. Prevalent cancer was associated with reduced risk of any AD (HR = 0.72; 95% CI = 0.52-0.997) and pure AD (HR = 0.57; 95% CI = 0.36-0.90) among white subjects after adjustment for demographics, number of APOE epsilon4 alleles, hypertension, diabetes, and coronary heart disease; the opposite association was found among minorities, but the sample size was too small to provide stable estimates. No significant association was found between cancer and subsequent development of VaD. In white older adults, prevalent Alzheimer disease (AD) was longitudinally associated with a reduced risk of cancer, and a history of cancer was associated with a reduced risk of AD. Together with other work showing associations between cancer and Parkinson disease, these findings suggest the possibility that cancer is linked to neurodegeneration.Neurology 01/2010; 74(2):106-12. · 8.31 Impact Factor -
Article: An interdisciplinary outreach model of African American recruitment for Alzheimer's disease research.
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ABSTRACT: The African American Outreach Satellite (Satellite) provides educational outreach to facilitate African American recruitment for longitudinal studies at the Washington University Alzheimer's Disease Research Center (ADRC). This descriptive article characterizes the Satellite's recruitment methods, plan for community engagement, results of recruitment efforts, and potential for replication. The Satellite developed a comprehensive outreach and recruitment plan that identifies and addresses barriers to research participation. The Satellite conducts community outreach and recruitment programs and training for health care providers. Enrollment of cognitively healthy and mildly demented African Americans for participation in all ADRC studies increased following implementation of the recruitment plan. Current African American participation rates for ADRC studies include 39% for lumbar puncture, 43% for positron emission tomography with Pittsburgh Compound-B, 52% for magnetic resonance imaging, 95% for apolipoprotein E genotype testing, and 100% for clinical and cognitive assessment. The Satellite reduces barriers to research participation, encourages retention through sustained interactions with participants and their families, and develops lasting partnerships with community organizations and health professionals who care for African American elders.The Gerontologist 12/2010; 51 Suppl 1:S134-41. · 2.48 Impact Factor
