Murray, Anne M.

AbstractINTRODUCTIONIdentifying individuals with dementia is crucial for prevalence estimation and service planning, but reliable, scalable methods are lacking. We developed novel set algorithms using both structured and unstructured electronic health record (EHR) data, applying Diagnostic and Statistical Manual of Mental Disorders criteria for dementia case identification.METHODSOur cohort (n = 1082) included individuals aged ≥ 60 with dementia identified through specialist clinics and a comparison group without dementia. Clinicians from Australia and the United States informed predictor selection. We developed algorithms through a biostatistics stream for structured data and a natural language processing (NLP) stream for text, synthesizing results via logistic regression.RESULTSThe final structured model retained 16 variables (area under the receiver operating characteristic curve [AUC] 0.853, specificity 72.2%, sensitivity 80.6%). NLP classifiers (logistic regression, support vector machine, and random forest models) performed comparably. The final, combined model outperformed all others (AUC = 0.951, P < 0.001 for comparison to structured model).DISCUSSIONEmbedding text‐derived insights within algorithms trained on structured medical data significantly enhances dementia identification capacity.Highlights Algorithmic tools for detection of individuals with dementia are available; however, previous work has used heterogeneous case definitions which are not clinically meaningful, and has relied on proxies such as diagnostic codes or medications for case ascertainment. We used a novel, dual‐stream algorithmic development approach, simultaneously and separately modeling a clinically meaningful outcome (diagnosis of dementia according to specialized clinical impression) using structured and unstructured electronic health record datasets. Our clinically grounded case definition supported the inclusion of key structured variables (such as dementia International Classification of Disease codes and medications) as modeling predictors rather than outcomes. Our algorithms, published in detail to support validation and replication, represent a major step forward in the use of routinely collected data for detection of diagnosed dementia.

AbstractBackgroundThe higher prevalence and incidence of later life dementia among older Black Americans compared to older White Americans is incompletely understood and understudied. HATS is designed as a companion to the Mayo Clinic Study of Aging (MCSA) with a focus on identification of modifiable cardiovascular contributions to brain health among Black older adults living in urban areas in the upper Midwest.MethodHATS is enrolling 300 U.S. Black Minnesotans from the Twin Cities area aged 55 to 90 years without advanced dementia. Enrollment started 4/2023 and is expected to be complete by the end of 2025. Recruitment is primarily community‐based, led by two community engagement partners, the Linc and the Hue‐MAN Partnership. Electronic health record‐based recruitment will begin in 2024. Data collection includes medical comorbidities, structural and social determinants of health, cardiovascular health, functional status, physical performance, specific and non‐specific blood‐based biomarkers of Alzheimer’s disease, and comprehensive assessment of cognitive and neuropsychiatric status. Brain MRIs will be obtained on a subset of participants. A core component of HATS is distribution of meaningful health information back to participants and their community, guided by input from the HATS community engagement partners. The HATS cohort will serve as an initial effort to develop age and education adjusted normative cognitive test data for urban Black older adults in the upper Midwest.ResultAs of January 22 2024, HATS has enrolled 40 participants with a mean age of 70 years (range 51‐90) and mean education of 15 years. Mean informant‐reported Everyday Cognition scale‐12 score is 1.1 (range 1‐1.7), mean Short Test of Mental Status (STMS) score is 31 (range 24‐37), and CDR sum of boxes scores range from 0‐4 consistent with enrollment of participants with normal and mildly impaired cognition.ConclusionHATS is a novel longitudinal cohort study that is well‐positioned to advance understanding of risk factors for dementia among Black Americans living in urban areas in the upper Midwest. Recruitment is ongoing with a focus on enrolling older adults with a wide range of cognitive function. Ongoing community engagement is a central feature of HATS.

Abstract Using vaccine data combined with electronic health records, we report that mRNA boosters provide greater protection than a 2-dose regimen against SARS-CoV-2 infection and related hospitalizations. The benefit of a booster was more evident in the elderly and those with comorbidities.

Objective: Robust disease and syndromic surveillance tools are underdeveloped in the United States, as evidenced by limitations and heterogeneity in sociodemographic data collection throughout the COVID-19 pandemic. To monitor the COVID-19 pandemic in Minnesota, we developed a federated data network in March 2020 using electronic health record (EHR) data from 8 multispecialty health systems. Materials and Methods: In this serial cross-sectional study, we examined patients of all ages who received a COVID-19 polymerase chain reaction test, had symptoms of a viral illness, or received an influenza test from January 3, 2016, through November 7, 2020. We evaluated COVID-19 testing rates among patients with symptoms of viral illness and percentage positivity among all patients tested, in aggregate and by zip code. We stratified results by patient and area-level characteristics. Results: Cumulative COVID-19 positivity rates were similar for people aged 12-64 years (range, 15.1%-17.6%) but lower for adults aged ≥65 years (range, 9.3%-10.7%). We found notable racial and ethnic disparities in positivity rates early in the pandemic, whereas COVID-19 positivity was similarly elevated across most racial and ethnic groups by the end of 2020. Positivity rates remained substantially higher among Hispanic patients compared with other racial and ethnic groups throughout the study period. We found similar trends across area-level income and rurality, with disparities early in the pandemic converging over time. Practice Implications: We rapidly developed a distributed data network across Minnesota to monitor the COVID-19 pandemic. Our findings highlight the utility of using EHR data to monitor the current pandemic as well as future public health priorities. Building partnerships with public health agencies can help ensure data streams are flexible and tailored to meet the changing needs of decision makers.

Background: Chronic kidney disease (CKD), a growing public health issue in the elderly, is associated with increased risk of cognitive impairment. Objective: To investigate the mechanisms through which CKD impacts brain health using longitudinal imaging. Methods: We identified 97 participants (74 CKD and 23 non-CKD) from the BRINK (BRain IN Kidney Disease), a longitudinal study of CKD with two MRI scans (baseline and 3-year follow-up). We measured the associations between baseline and change in kidney disease biomarkers of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR), considered a measure of microvascular inflammation, and imaging outcomes of cortical thickness and ventricular volume from structural MRI, white matter hyperintensities (WMH) volume from FLAIR images, and fractional anisotropy of the corpus callosum (FACC). Results: There were white matter-specific changes as observed by increased WMH volume and decreased FACC in CKD participants, as well as ventricular volume increase in both CKD and non-CKD groups reflective of aging-related changes. Decline in eGFR was associated with decrease in the FACC, suggesting that subtle early white matter changes due to kidney disease can be captured using DTI. An increase in UACR was associated with increase in ventricular volume. Conclusion: Our results support the role of eGFR as a measure of kidney microvascular disease which is associated with concurrent white matter damage in CKD. Future work is needed to investigate the possible link between endothelial microvascular inflammation (as measured by an increased UACR) and ventricular volume increase.

AbstractBackgroundWe report the associations between change in renal biomarkers in CKD and non‐ CKD participants and change in structural MRI outcomes over 3 years in the BRain IN Kidney disease (BRINK) study MRI cohort. The imaging outcomes were cortical thickness in Alzheimer’s disease signature regions, white matter hyperintensities (WMH), and fractional anisotropy in the corpus callosum (FA CC), an early marker of cerebrovascular disease.MethodsParticipants were ≥ 45 years with CKD (estimated glomerular filtration rate (eGFR) in mL/min/1.73 m2< 60; non‐ dialysis) or non – CKD (eGFR ≥ 60) in Minneapolis/St. Paul. CKD severity was measured by the eGFR and urine albumin creatinine ratio (UACR‐albuminuria, a measure of microvascular disease). Brain images were obtained on a 1.5 T Phillips Ingenia machine at baseline and 3 years. Linear regression models measured the associations between 3 year change in eGFR and UACR, as predictors of change in MRI measures: AD cortical thickness, WMH, and FA CC over 3 years. Adjusted models included age, gender, AA race, education years, cerebrovascular disease risk factor score (CVD RF), smoker/alcohol use, and pulse pressure as covariates, and TIV for change in WMH models.ResultsAt baseline, mean age of the 97 participants was 67 years, and mean eGFR was 37 for the CKD group vs. 83.2 for non‐ CKD (Table 1). Mean change in eGFR and UACR in the CKD group were ‐3.6 and +212, respectively compared with ‐ 8.5 and +1.7 in the non‐ CKD group. Mean WMH volume increase (+5.8 cc) and mean FA CC decrease (‐0.012) were significant in CKD (p < 0.001) for both (Table 2). In adjusted models both a 1% decrease and a ≥ 3 unit/year decline in eGFR were associated with a decline in FA CC over 3 years in the CKD group (β (SE) =‐0.020 (0.007); p = 0.004) and ‐0.0097 (0.0042); p = 0.025, respectively). Cortical thickness models were not significant. Unexpectedly, change in UACR was not associated with change in any MRI outcomes.ConclusionsDecreased eGFR was associated with decreased FA CC in CKD, suggesting that CKD progression exerts its influence largely through cerebrovascular mechanisms.

Abstract White matter hyperintensities (WMHs) are frequently seen on brain magnetic resonance imaging scans of older people. Usually interpreted clinically as a surrogate for cerebral small vessel disease, WMHs are associated with increased likelihood of cognitive impairment and dementia (including Alzheimer's disease [AD]). WMHs are also seen in cognitively healthy people. In this collaboration of academic, clinical, and pharmaceutical industry perspectives, we identify outstanding questions about WMHs and their relation to cognition, dementia, and AD. What molecular and cellular changes underlie WMHs? What are the neuropathological correlates of WMHs? To what extent are demyelination and inflammation present? Is it helpful to subdivide into periventricular and subcortical WMHs? What do WMHs signify in people diagnosed with AD? What are the risk factors for developing WMHs? What preventive and therapeutic strategies target WMHs? Answering these questions will improve prevention and treatment of WMHs and dementia.