Search

Background: There is no practical dementia risk score in the clinical setting. Objective: To derive and validate a score obtained by a rapid and simple assessment, which guides primary care providers in predicting the risk of dementia among older adults. Design: A total of 4178 participants from three longitudinal cohorts (mean age at baseline = 76.8 [SD = 7.6] years), without baseline dementia, followed annually for a median of 10 years (IQR: 5 to16 years, Reverse Kaplan-Meier). Participants: To derive the score, we used data from 1,780 participants from the Rush Memory and Aging Project (93% White). To validate the score, we used data from 1,299 participants from the Religious Order Study (92% White), and to assess generalizability, 679 participants from the Minority Aging Research Study (100% Black). Measurements: Clinician-based dementia diagnosis at any time after baseline and predictive variables associated with dementia risk that can be collected in a primary care setting: demographics, clinical indicators, medical history, memory complaints, cognitive and motor tests, and questions to assess functional disability, depressive symptoms, sleep, social isolation, and genetics (APOE e4 and AD polygenic risk score). Results: At baseline, age, memory complaint, the ability to handle finances, the recall of the month, recall of the room, and recall of three words, were associated with the cumulative incidence of dementia, in the derivation cohort. The discrimination of the RADaR (Rapid Risk Assessment of Dementia) was good for the derivation and external-validation cohorts (AUC3 years = 0.82–0.86), compared to the overall discrimination of age alone (AUC3 years = 0.73), a major risk factor for dementia. Adding genetic data did not increase discrimination. Limitations: Participants were volunteers, may not represent the general population. Conclusions: The RADaR, derived from community-dwelling older persons, is a brief and valid tool to predict dementia risk at 3 years in older White and Black persons. [ABSTRACT FROM AUTHOR]

Background: This study examines the effect of initiating medications with anticholinergic activity on the cognitive functions of older persons. Methods: Participants were 896 older community-dwelling, Catholic clergy without baseline dementia. Medication data was collected annually. The Anticholinergic Cognitive Burden Scale was utilized to identify use of a medication with probable or definite anticholinergic activity. Participants had at least two annual cognitive evaluations. Results: Over a mean follow-up of 10 years, the annual rate of global cognitive function decline for never users, prevalent users, and incident users was −0.062 (SE = 0.005), −0.081(SE = 0.011), and −0.096 (SE = 0.007) z-score units/year, respectively. Compared to never users, incident users had a more rapid decline (difference = −0.034 z-score units/year, SE = 0.008, p<0.001) while prevalent users did not have a significantly more rapid decline (p = 0.1). Conclusions: Older persons initiating a medication with anticholinergic activity have a steeper annual decline in cognitive functioning than those who are not taking these medications. [ABSTRACT FROM AUTHOR]

Introduction: The NIH All of Us Research Program will have the scale and scope to enable research for a wide range of diseases, including cancer. The program's focus on diversity and inclusion promises a better understanding of the unequal burden of cancer. Preliminary cancer ascertainment in the All of Us cohort from two data sources (self-reported versus electronic health records (EHR)) is considered. Materials and methods: This work was performed on data collected from the All of Us Research Program's 315,297 enrolled participants to date using the Researcher Workbench, where approved researchers can access and analyze All of Us data on cancer and other diseases. Cancer case ascertainment was performed using data from EHR and self-reported surveys across key factors. Distribution of cancer types and concordance of data sources by cancer site and demographics is analyzed. Results and discussion: Data collected from 315,297 participants resulted in 13,298 cancer cases detected in the survey (in 89,261 participants), 23,520 cancer cases detected in the EHR (in 203,813 participants), and 7,123 cancer cases detected across both sources (in 62,497 participants). Key differences in survey completion by race/ethnicity impacted the makeup of cohorts when compared to cancer in the EHR and national NCI SEER data. Conclusions: This study provides key insight into cancer detection in the All of Us Research Program and points to the existing strengths and limitations of All of Us as a platform for cancer research now and in the future. [ABSTRACT FROM AUTHOR]

To assess the value of exosomal miRNAs as biomarkers for Alzheimer disease (AD), the expression of microRNAs was measured in a plasma fraction enriched in exosomes by differential centrifugation, using Illumina deep sequencing. Samples from 35 persons with a clinical diagnosis of AD dementia were compared to 35 age and sex matched controls. Although these samples contained less than 0.1 microgram of total RNA, deep sequencing gave reliable and informative results. Twenty miRNAs showed significant differences in the AD group in initial screening (miR-23b-3p, miR-24-3p, miR-29b-3p, miR-125b-5p, miR-138-5p, miR-139-5p, miR-141-3p, miR-150-5p, miR-152-3p, miR-185-5p, miR-338-3p, miR-342-3p, miR-342-5p, miR-548at-5p, miR-659-5p, miR-3065-5p, miR-3613-3p, miR-3916, miR-4772-3p, miR-5001-3p), many of which satisfied additional biological and statistical criteria, and among which a panel of seven miRNAs were highly informative in a machine learning model for predicting AD status of individual samples with 83–89% accuracy. This performance is not due to over-fitting, because a) we used separate samples for training and testing, and b) similar performance was achieved when tested on technical replicate data. Perhaps the most interesting single miRNA was miR-342-3p, which was a) expressed in the AD group at about 60% of control levels, b) highly correlated with several of the other miRNAs that were significantly down-regulated in AD, and c) was also reported to be down-regulated in AD in two previous studies. The findings warrant replication and follow-up with a larger cohort of patients and controls who have been carefully characterized in terms of cognitive and imaging data, other biomarkers (e.g., CSF amyloid and tau levels) and risk factors (e.g., apoE4 status), and who are sampled repeatedly over time. Integrating miRNA expression data with other data is likely to provide informative and robust biomarkers in Alzheimer disease. [ABSTRACT FROM AUTHOR]

Objective: The objective was to evaluate the association of peripheral and central hearing abilities with cognitive function in older adults. Methods: Recruited from epidemiological studies of aging and cognition at the Rush Alzheimer’s Disease Center, participants were a community-dwelling cohort of older adults (range 63–98 years) without diagnosis of dementia. The cohort contained roughly equal numbers of Black (n=61) and White (n=63) subjects with groups similar in terms of age, gender, and years of education. Auditory abilities were measured with pure-tone audiometry, speech-in-noise perception, and discrimination thresholds for both static and dynamic spectral patterns. Cognitive performance was evaluated with a 12-test battery assessing episodic, semantic, and working memory, perceptual speed, and visuospatial abilities. Results: Among the auditory measures, only the static and dynamic spectral-pattern discrimination thresholds were associated with cognitive performance in a regression model that included the demographic covariates race, age, gender, and years of education. Subsequent analysis indicated substantial shared variance among the covariates race and both measures of spectral-pattern discrimination in accounting for cognitive performance. Among cognitive measures, working memory and visuospatial abilities showed the strongest interrelationship to spectral-pattern discrimination performance. Conclusions: For a cohort of older adults without diagnosis of dementia, neither hearing thresholds nor speech-in-noise ability showed significant association with a summary measure of global cognition. In contrast, the two auditory metrics of spectral-pattern discrimination ability significantly contributed to a regression model prediction of cognitive performance, demonstrating association of central auditory ability to cognitive status using auditory metrics that avoided the confounding effect of speech materials. [ABSTRACT FROM AUTHOR]