Monique M. Williams

Cancer linked to Alzheimer disease but not vascular dementia

Objective: To investigate whether cancer is associated with Alzheimer disease (AD) and vascular dementia (VaD). Methods: 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. Results: 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 ε4 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. Conclusions: 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.

Survival and mortality differences between dementia with Lewy bodies vs Alzheimer disease

Objective: To determine whether dementia with Lewy bodies (DLB) progresses more rapidly than Alzheimer disease (AD). Methods: We compared 315 participants (63 with DLB and 252 with AD) enrolled in a prospective longitudinal study of memory and aging with annual clinical and cognitive assessments and followed until death. The main outcome measure was dementia progression to institutionalization and death. Neuropathologic examinations were performed on all participants in this study. Subject classification (DLB vs AD) was based on neuropathology. Results: Patients with DLB had an increased risk of mortality vs patients with AD (hazard ratio [HR] 1.88, 95% CI: 1.4 to 2.5). The median survival time for DLB was 78.0 years and for AD was 84.6 years (χ2 = 19.9, p < 0.001) with significant modification effects due to gender (HR 1.51, 95% CI: 1.0 to 2.3) and the presence of at least 1 APOE ε4 allele (HR 1.50, 95% CI: 1.0 to 2.2). Survival after dementia onset was also different between DLB and AD (7.3 vs 8.5 years; χ2 = 5.4, p < 0.02). DLB cases had similar risks of institutionalization and survival in long-term care facilities to AD cases. Self-reports of depression and the presence of extrapyramidal signs were important covariates. The rate of cognitive decline as measured by psychometric performance and clinical staging methods did not differ between DLB and AD. Conclusions: Dementia with Lewy bodies (DLB) increases the risk of mortality compared with Alzheimer disease (AD), but the two groups did not differ in rate of cognitive decline. The greater risk for noncognitive disease progression for DLB compared with AD suggests clinically meaningful differences for the two disorders.

Alzheimer disease identification using amyloid imaging and reserve variables: Proof of concept

Objective: 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. Methods: 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. Results: 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. Conclusion: 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.

Progression of Alzheimer's disease as measured by Clinical Dementia Rating Sum of Boxes scores.

This study examined rates of dementia progression as ascertained by the Clinical Dementia Rating Sum of Boxes (CDR‐SB) for symptomatic Alzheimers disease (sAD), and assessed participant characteristics as predictors of CDR‐SB progression.

Stability of the Clinical Dementia Rating: 1979–2007

OBJECTIVE To examine dementia severity as determined by the Clinical Dementia Rating (CDR) over time. DESIGN Secondary analysis of data from longitudinal studies of aging and dementia. SETTING Alzheimers Disease Research Center, where a variety of clinicians contributed CDR ratings during the study. PARTICIPANTS Adults aged 63 to 83 years with no (CDR 0), very mild (CDR 0.5), or mild (CDR 1) dementia enrolled in the Alzheimers Disease Research Center at any time from August 13, 1979, through May 30, 2007. MAIN OUTCOME MEASURES Within each CDR group, changes in scores on standardized psychometric tests with time were examined using multiple linear regression analyses. These tests included the Mini-Mental State Examination, Short Blessed Test, Logical Memory IA-Immediate from the Wechsler Memory Scale-Revised, and Blessed Dementia Scale, and a psychometric composite score. RESULTS A total of 1768 participants met the inclusion criteria. With time, participants were older, more educated, and more likely to be nonwhite and less likely to be men. Statistically significant change in psychometric test performance with time occurred only within the CDR 1 group for Logical Memory and the psychometric composite, but the degree of change was minimal. CONCLUSION Despite changes in participant characteristics, the CDR demonstrates general stability for assessment of dementia for almost 3 decades.

Barriers and Facilitators of African American Participation in Alzheimer Disease Biomarker Research

African Americans experience a greater risk of Alzheimer disease (AD), but are underrepresented in AD research. Our study examined barriers and facilitators of AD research participation among African Americans. Investigators conducted 11 focus groups with African American participants (n=70) who discussed barriers and facilitators to AD research participation including lumbar puncture studies. The moderator and comoderator independently reviewed the transcripts, identified themes, and coded transcripts for analysis. Participants were predominately female (73%) with a mean age of 52 years (range 21 to 86 y). Concerns and attitudes were consistent across education, socioeconomic status, and sex. Mistrust was a fundamental reason for nonparticipation. Additional barriers included insufficient information dissemination in the African American community, inconvenience, and reputation of the researcher and research institution. Barriers to participation in AD biomarker studies were fear of the unknown and adverse effects. Altruism and relevance of research projects to the individual, family members, or the African American community facilitate participation. Increased participation results from relationships with the community that extend beyond immediate research interests, dissemination of research findings, and emphasis on relevance of proposed studies. Pervasive barriers impede African American participation in AD research but can be overcome through a sustained presence in the community.

An Interdisciplinary Outreach Model of African American Recruitment for Alzheimer’s Disease Research

PURPOSE The African American Outreach Satellite (Satellite) provides educational outreach to facilitate African American recruitment for longitudinal studies at the Washington University Alzheimers Disease Research Center (ADRC). This descriptive article characterizes the Satellites recruitment methods, plan for community engagement, results of recruitment efforts, and potential for replication. DESIGN AND METHODS 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. RESULTS 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. IMPLICATIONS 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.

Preclinical Alzheimer's disease and longitudinal driving decline

Links between preclinical Alzheimers disease (AD) and driving difficulty onset would support the use of driving performance as an outcome in primary and secondary prevention trials among older adults (OAs). We examined whether AD biomarkers predicted the onset of driving difficulties among OAs.

Driving Outcomes among Older Adults: A Systematic Review on Racial and Ethnic Differences over 20 Years

The population of older adults (aged 65 years and older) in the United States will become more racially and ethnically diverse in the next three decades. Additionally, the growth of the aging population will come with an expansion in the number of older drivers and an increased prevalence of chronic neurological conditions. A major gap in the aging literature is an almost exclusive focus on homogenous, non-Hispanic white samples of older adults. It is unclear if this extends to the driving literature. A systematic review of SCOPUS, PubMed, CINAHL Plus, and Web of Science examined articles on driving and racial/ethnic differences among older adults. Eighteen studies met inclusion criteria and their results indicate that racial and ethnic minorities face a greater risk for driving reduction, mobility restriction, and driving cessation. The majority of studies compared African Americans to non-Hispanic whites but only examined race as a covariate. Only four studies explicitly examined racial/ethnic differences. Future research in aging and driving research needs to be more inclusive and actively involve different racial/ethnic groups in study design and analysis.

Driving cessation over a 24-year period: Dementia severity and cerebrospinal fluid biomarkers

With 36 million older adult U.S. drivers, safety is a critical concern, particularly among those with dementia. It is unclear at what stage of Alzheimers disease (AD) older adults stop driving and whether preclinical AD affects driving cessation.