Intraindividual Cognitive Variability and Magnetic Resonance Imaging in Aging American Indians: Data from the Strong Heart Study.

BACKGROUND: American Indians have high prevalence of risk factors for Alzheimer's disease and related dementias (ADRD) compared to the general population, yet dementia onset and frequency in this population are understudied. Intraindividual cognitive variability (IICV), a measure of variability in neuropsychological test performance within a person at a single timepoint, may be a novel, noninvasive biomarker of neurodegeneration and early dementia. OBJECTIVE: To characterize the cross-sectional associations between IICV and hippocampal, total brain volume, and white matter disease measured by magnetic resonance imaging (MRI) among older American Indians. METHODS: IICV measures for memory, executive function, and processing speed, and multidomain cognition were calculated for 746 American Indians (aged 64-95) who underwent MRI. Regression models were used to examine the associations of IICV score with hippocampal volume, total brain volume, and graded white matter disease, adjusting for age, sex, education, body mass index, intracranial volume, diabetes, stroke, hypertension, hypercholesterolemia, alcohol use, and smoking. RESULTS: Higher memory IICV measure was associated with lower hippocampal volume (Beta = -0.076; 95% CI -0.499, -0.023; p = 0.031). After adjustment for Bonferroni or IICV mean scores in the same tests, the associations were no longer significant. No IICV measures were associated with white matter disease or total brain volume. CONCLUSION: These findings suggest that the IICV measures used in this research cannot be robustly associated with cross-sectional neuroimaging features; nonetheless, the results encourage future studies investigating the associations between IICV and other brain regions, as well as its utility in the prediction of neurodegeneration and dementia in American Indians.

Using Optical Coherence Tomography to Screen for Cognitive Impairment and Dementia.

BACKGROUND: Screening for Alzheimer's disease and related disorders (ADRD) and mild cognitive impairment (MCI) could increase case identification, enhance clinical trial enrollment, and enable early intervention. MCI and ADRD screening would be most beneficial if detection measures reflect neurodegenerative changes. Optical coherence tomography (OCT) could be a marker of neurodegeneration (part of the amyloid-tau-neurodegeneration (ATN) framework). OBJECTIVE: To determine whether OCT measurements can be used as a screening measure to detect individuals with MCI and ADRD. METHODS: A retrospective cross-sectional study was performed on 136 participants with comprehensive clinical, cognitive, functional, and behavioral evaluations including OCT with a subset (n = 76) completing volumetric MRI. Pearson correlation coefficients tested strength of association between OCT and outcome measures. Receiver operator characteristic curves assessed the ability of OCT, patient-reported outcomes, and cognitive performance measures to discriminate between individuals with and without cognitive impairment. RESULTS: After controlling for age, of the 6 OCT measurements collected, granular cell layer-inner plexiform layer (GCL + IPL) thickness best correlated with memory, global cognitive performance, Clinical Dementia Rating, and hippocampal atrophy. GCL + IPL thickness provided good discrimination in cognitive status with a cut-off score of 75µm. Combining GCL + IPL thickness as a proxy marker for hippocampal atrophy with a brief patient-reported outcome and performance measure correctly classified 87%of MCI and ADRD participants. CONCLUSION: Multimodal approaches may improve recognition of MCI and ADRD. OCT has the potential to be a practical, non-invasive biomarker for ADRD providing a screening platform to quickly identify at-risk individuals for further clinical evaluation or research enrollment.

A Modified CAIDE Risk Score as a Screening Tool for Cognitive Impairment in Older Adults.

BACKGROUND: Although an efficacious dementia-risk score system, Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) was derived using midlife risk factors in a population with low educational attainment that does not reflect today's US population, and requires laboratory biomarkers, which are not always available. OBJECTIVE: Develop and validate a modified CAIDE (mCAIDE) system and test its ability to predict presence, severity, and etiology of cognitive impairment in older adults. METHODS: Population consisted of 449 participants in dementia research (N = 230; community sample; 67.9±10.0 years old, 29.6%male, 13.7±4.1 years education) or receiving dementia clinical services (N = 219; clinical sample; 74.3±9.8 years old, 50.2%male, 15.5±2.6 years education). The mCAIDE, which includes self-reported and performance-based rather than blood-derived measures, was developed in the community sample and tested in the independent clinical sample. Validity against Framingham, Hachinski, and CAIDE risk scores was assessed. RESULTS: Higher mCAIDE quartiles were associated with lower performance on global and domain-specific cognitive tests. Each one-point increase in mCAIDE increased the odds of mild cognitive impairment (MCI) by up to 65%, those of AD by 69%, and those for non-AD dementia by > 85%, with highest scores in cases with vascular etiologies. Being in the highest mCAIDE risk group improved ability to discriminate dementia from MCI and controls and MCI from controls, with a cut-off of ≥7 points offering the highest sensitivity, specificity, and positive and negative predictive values. CONCLUSION: mCAIDE is a robust indicator of cognitive impairment in community-dwelling seniors, which can discriminate well between dementia severity including MCI versus controls. The mCAIDE may be a valuable tool for case ascertainment in research studies, helping flag primary care patients for cognitive testing, and identify those in need of lifestyle interventions for symptomatic control.

Rationale, study design and implementation of the LUCINDA Trial: Leuprolide plus Cholinesterase Inhibition to reduce Neurologic Decline in Alzheimer's.

The LUCINDA Trial (Leuprolide plus Cholinesterase Inhibition to reduce Neurologic Decline in Alzheimer's) is a 52 week, randomized, placebo-controlled trial of leuprolide acetate (Eligard) in women with Alzheimer's disease (AD). Leuprolide acetate is a gonadotropin analogue commonly used for hormone-sensitive conditions such as prostate cancer and endometriosis. This repurposed drug demonstrated efficacy in a previous Phase II clinical trial in those women with AD who also received a stable dose of the acetylcholinesterase inhibitor donepezil (Bowen et al., 2015). Basic biological, epidemiological and clinical trial data suggest leuprolide acetate mediates improvement and stabilization of neuropathology and cognitive performance via the modulation of gonadotropin and/or gonadotropin-releasing hormone signaling. LUCINDA will enroll 150 women with mild-moderate AD who are receiving a stable dose of donepezil from three study sites in the United States. Cognition and function are the primary outcome measures as assessed by the Alzheimer's Disease Assessment Scale-Cognitive Subscale. Blood and MRI biomarkers are also measured to assess hormonal, inflammatory and AD biomarker changes. We present the protocol for LUCINDA and discuss trial innovations and challenges including changes necessitated by the covid-19 pandemic and study drug procurement issues.

Screening for Early-Stage Alzheimer's Disease Using Optimized Feature Sets and Machine Learning.

BACKGROUND: Detecting early-stage Alzheimer's disease in clinical practice is difficult due to a lack of efficient and easily administered cognitive assessments that are sensitive to very mild impairment, a likely contributor to the high rate of undetected dementia. OBJECTIVE: We aim to identify groups of cognitive assessment features optimized for detecting mild impairment that may be used to improve routine screening. We also compare the efficacy of classifying impairment using either a two-class (impaired versus non-impaired) or three-class using the Clinical Dementia Rating (CDR 0 versus CDR 0.5 versus CDR 1) approach. METHODS: Supervised feature selection methods generated groups of cognitive measurements targeting impairment defined at CDR 0.5 and above. Random forest classifiers then generated predictions of impairment for each group using highly stochastic cross-validation, with group outputs examined using general linear models. RESULTS: The strategy of combining impairment levels for two-class classification resulted in significantly higher sensitivities and negative predictive values, two metrics useful in clinical screening, compared to the three-class approach. Four features (delayed WAIS Logical Memory, trail-making, patient and informant memory questions), totaling about 15 minutes of testing time (∼30 minutes with delay), enabled classification sensitivity of 94.53% (88.43% positive predictive value, PPV). The addition of four more features significantly increased sensitivity to 95.18% (88.77% PPV) when added to the model as a second classifier. CONCLUSION: The high detection rate paired with the minimal assessment time of the four identified features may act as an effective starting point for developing screening protocols targeting cognitive impairment defined at CDR 0.5 and above.

HCMMCNVs: hierarchical clustering mixture model of copy number variants detection using whole exome sequencing technology.

SUMMARY: In this article, we introduce a hierarchical clustering and Gaussian mixture model with expectation-maximization (EM) algorithm for detecting copy number variants (CNVs) using whole exome sequencing (WES) data. The R shiny package 'HCMMCNVs' is also developed for processing user-provided bam files, running CNVs detection algorithm and conducting visualization. Through applying our approach to 325 cancer cell lines in 22 tumor types from Cancer Cell Line Encyclopedia (CCLE), we show that our algorithm is competitive with other existing methods and feasible in using multiple cancer cell lines for CNVs estimation. In addition, by applying our approach to WES data of 120 oral squamous cell carcinoma (OSCC) samples, our algorithm, using the tumor sample only, exhibits more power in detecting CNVs as compared with the methods using both tumors and matched normal counterparts. AVAILABILITY AND IMPLEMENTATION: HCMMCNVs R shiny software is freely available at github repository https://github.com/lunching/HCMM_CNVs.and Zenodo https://doi.org/10.5281/zenodo.4593371. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Fluid and Tissue Biomarkers of Lewy Body Dementia: Report of an LBDA Symposium.

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Europe and the United States and attracted over 200 scientists and physicians from academic centers, the National Institutes of Health, and the pharmaceutical industry. Methods for confirming and quantifying the presence of Lewy body and Alzheimer's pathology and novel biomarkers were discussed.

Discerning rural Appalachian stakeholder attitudes toward memory screening.

OBJECTIVE: The aim of this descriptive study was to examine Appalachian stakeholder attitudes toward routine memory screening, and to compare and contrast results from a similar study conducted in an ethnically diverse rural Florida cohort. Determining perceptions about memory screening is essential prior to developing culturally relevant programs for increasing early dementia detection and management among rural underserved older adults at risk of cognitive impairment. Benefits of early detection include ruling out other causes of illness and treating accordingly, delaying onset of dementia symptoms through behavior management and medications, and improving long-term care planning (Dubois, Padovani, Scheltens, Rossi, & Dell'Agnello, 2016). These interventions can potentially help to maintain independence, decrease dementia care costs, and reduce family burdens (Frisoni, et al., 2017). METHOD: Researchers applied a parallel mixed method design (Tashakkori & Newman, 2010) of semi-structured interviews, measurements of health literacy (REALM-SF) (Arozullah, et al., 2007), sociodemographics, and cognitive screening perceptions (PRISM-PC) (Boustani, et al., 2008), to examine beliefs and attitudes about memory screening among 22 FL and 21 WV rural stakeholders (residents, health providers, and administrators). RESULTS: Findings included that > 90% participants across both cohorts were highly supportive of earlier dementia detection through routine screening regardless of sample characteristics. However, half of those interviewed were doubtful that provider care or assistance would be adequate for this terminal illness. Despite previous concerns of stigma associated with an Alzheimer's disease diagnosis, rural providers are encouraged to educate patients and community members regarding Alzheimer's disease and offer routine cognitive screening and follow-through.

Detecting dementia among older, ethnically diverse residents of rural subsidized housing.

Rural, ethnically diverse residents face at least twice the risk of Alzheimer's disease than urban residents. Chronic diseases such as diabetes and hypertension which increase dementia risk are more prevalent in rural areas with less access to specialty providers. A home-based approach for increasing dementia detection and treatment rates was tested among rural residents of government-assisted independent living facilities (N = 139; 78% non-White, and 70% with health literacy below 5th grade). Of 28 residents identified at risk during cognitive screening, 25 agreed to further in-depth assessment by adult gerontological nurse practitioners (AGNP). Fifteen of 25 (60%) completing consequent primary provider referrals were diagnosed with dementia and receiving new care (statistically significant; [χ2(1) = 76.67, p < .001, Phi = 0.743]). Home-based dementia management through a community engagement approach can help to meet the Healthy People 2030 goals of earlier detection and treatment and reduce the length of costly institutionalizations.

The Effect of Sociodemographics, Physical Function, and Mood on Dementia Screening in a Multicultural Cohort.

PURPOSE: To assess age, sex, race and ethnicity disparities in cognitive function in community-dwelling older adults and identify factors that contribute to these disparities. PATIENTS AND METHODS: Cognitive performance (global and domain-specific) and self-reported cognitive function were compared among Black (N=57), Hispanic (N=139), and White (N=108) older adults. The impact of socioeconomic status (SES), physical functionality, and mood indicators was assessed with a combination of hierarchical general linear models and mediation analysis. RESULTS: Poorer cognitive performance and higher levels of impairment were found in older adults from racial and ethnic backgrounds. The contribution of lower SES to the observed racial and ethnic disparities in objective cognitive performance was 33% in Hispanics and about 20% in Blacks, while poorer physical functionality explained over half of the differences between Black and White participants. Higher self-reported cognitive impairment in minorities was explained by lower SES and higher depressive symptoms in Hispanics but not in Blacks. CONCLUSION: Performance on objective memory testing and self-reported cognition are greatly influenced by relevant biological, sociodemographic and medical variables. Dementia screening programs should be tailored to individual sociodemographic groups based on contributors that are specific to each group.

What older adults do with the results of dementia screening programs.

INTRODUCTION: Alzheimer's disease and related dementias (ADRD) and mild cognitive impairment (MCI) are often under-recognized in the community. MCI/ADRD screening could offer benefits such as early treatment, research participation, lifestyle modification, and advanced care planning. To date, there are no clear guidelines regarding the benefits vs. harms of dementia screening or whether a dementia screening program could be successful. METHODS: A community-based study was conducted to evaluate an MCI/ADRD screening program and determine what older adults would do with the information. Measures of cognition, physical health, functionality, and mood were collected. Participants met with a health professional, were given screening results with recommendations, and then contacted 60 days later to determine what was done with the results. Logistic regression models were used to build predictive models. RESULTS: Participants (n = 288) had a mean age of 71.5±8.3y, mean education of 13.3±4.8y, and were 70% female, 67% White, 26% African American, and 48% Hispanic. After 60 days, 75% of participants were re-contacted; 54% shared results with family, 33% shared results with health care providers (HCPs), and 52% initiated behavioral change. Among participants sharing results with HCPs, 51% reported HCPs did not follow-up on the results, and 18% that HCPs did not show any interest in the screening visit or its results. Predictors of sharing results with HCPs were elevated hemoglobin A1C (OR = 1.85;95%CI:1.19-2.88), uncontrolled hypertension (OR = 2.73;95%CI:1.09-6.83), and mobility issues (OR = 2.43;95%CI: 1.93-5.54). Participant behavioral changes included lifestyle modification (58%), social engagement (10%), cognitive stimulation (5%), and advanced care planning (4%). The most significant predictors of sharing with family were better overall mental health (OR = 0.19; 95%CI: 0.06-0.59) and better physical function (OR = 0.38; 95%CI: 0.17-0.81). DISCUSSION: MCI/ADRD screening was well-received by a diverse community sample. Participants showed interest in sharing the results with their family and HCPs and many attempted behavioral change. While HCPs did not always act on screening results, 25% ordered further testing and evaluation. Efforts need to be directed toward (1) increasing self-efficacy of older adults to discuss screening results with their HCPs, and (2) educating HCPs on the value of early detection of MCI/ADRD. Community dementia screening programs can increase MCI/ADRD detection and improve patient-centered outcomes and medical decision-making.

Intention to Screen for Alzheimer's Disease by Residential Locale.

A random digit dialing sample from Missouri (USA) was used to compare associations between psychosocial factors and Alzheimer's disease (AD) screening intention based on residential locale. Linear regression associations between demographics and five psychosocial constructs (dementia knowledge, perceived screening benefits, preventive health behaviors, perceived susceptibility, and self-efficacy) and screening intention were compared by residential locale. Participants (n = 932) had a mean age of 62 years (urban: n = 375; suburban: n = 319, rural: n = 238). African Americans more often lived in urban than suburban/rural neighborhoods, and more urban than suburban/rural residents reported insufficient income. Preventative health behaviors (e.g., dentist visits) were higher in urban and suburban versus rural participants. AD screening intention did not differ by residential locale. Among urban participants, self-efficacy to get screened was associated with screening intention. Among rural participants, dementia knowledge was associated with screening intention. Perceived screening benefits and perceived susceptibility to AD were associated with screening intention regardless of locale. Unlike urban participants, rural participants demonstrated greater screening intention with greater dementia knowledge. Our findings suggest that psychosocial factors associated with AD screening intention differ depending on residential locale. Strategies to increase dementia screening may need to account for regional variations to be maximally effective.

Protocol for an embedded pragmatic clinical trial to test the effectiveness of Aliviado Dementia Care in improving quality of life for persons living with dementia and their informal caregivers.

INTRODUCTION: Persons living with Alzheimer's disease and related dementias (ADRD) frequently experience pain and behavioral and psychological symptoms of dementia (BPSD) which decrease quality of life (QOL) and influence caregiver burden. Home healthcare professionals however may underrecognize or lack the ability to manage BPSD. INTERVENTION: This protocol describes an ADRD palliative quality assurance performance improvement program for home healthcare, Aliviado Dementia Care-Home Health Edition. It includes training, mentoring, and a toolbox containing intervention strategies. METHODS: This embedded pragmatic clinical trial will utilize a multi-site, cluster randomized control design. Recruitment will occur from three home healthcare agencies located in New Jersey, Utah, and Florida. At each agency, care teams will be randomized as clusters and assigned to either the Aliviado Dementia Care program or usual care. We plan to enroll 345 persons living with ADRD and their informal caregiver dyads. The primary outcome will be to measure QOL in both the person living with ADRD and their informal caregiver, and emergency department visits and hospital admissions. Secondary outcomes in the person living with ADRD will include the examination of pain, BPSD, antipsychotic and analgesic use. Secondary outcomes in caregivers include burden, depressive symptoms, functional health and wellbeing, and healthcare utilization. CONCLUSION: This study will be the first large-scale embedded pragmatic clinical trial in home healthcare focused on care quality and outcomes in addressing QOL in ADRD. If proven successful, the intervention can then be disseminated to agencies throughout the country to improve the quality of care for this vulnerable, underserved population. TRIAL REGISTRATION: Clinical Trials.gov: NCT03255967.

Rural stakeholder perceptions about cognitive screening.

Objectives: The study aims were to explore stakeholder perceptions about cognitive screening in a rural, ethnically diverse, underserved setting, and to examine whether perceptions varied by years lived in a rural area, career, health literacy, willingness to be screened, ethnicity, education, or age. Methods: Twenty-one rural, ethnically diverse stakeholders completed an open-ended interview of five questions and a measure regarding perceptions about cognitive screening (PRISM-PC, Boustani, et al., 2008 ). Open coding using the in vivo process (Saldaña, 2015 ) to "derive codes from the actual participant language" (p. 77) was used to analyze the qualitative data. We used Pearson correlation to examine relationships between the PRISM-PC and sociodemographics including age, years of education, health literacy, years lived in rural areas, and willingness to participate in cognitive screening. Results: Eight codes and two themes were identified from the in vivo analysis. The eight codes were "a sentence being pronounced over the lives", "keep everybody at home", "Education is big", the trust issues is everything here", "identify support systems", "access to care", and "there is a cost to do that". The two themes were "Trust is the essential component of connecting with Community", and (2) "The Community recognizes the importance of knowledge in improving care. PRISM-PC results added new information in that persons were concerned about the emotional and financial burden on their families. Overall, regardless of age, careers, care involvement, health literacy, or education, 81% of stakeholders indicated they would seek annual cognitive screening. Discussion: It is important for rural health professionals to consider that contrary to previous stigma concerns, stakeholders may support earlier dementia detection.

Improving data collection, documentation, and workflow in a dementia screening study.

BACKGROUND: A clinical study team performing three multicultural dementia screening studies identified the need to improve data management practices and facilitate data sharing. A collaboration was initiated with librarians as part of the National Library of Medicine (NLM) informationist supplement program. The librarians identified areas for improvement in the studies' data collection, entry, and processing workflows. CASE PRESENTATION: The librarians' role in this project was to meet needs expressed by the study team around improving data collection and processing workflows to increase study efficiency and ensure data quality. The librarians addressed the data collection, entry, and processing weaknesses through standardizing and renaming variables, creating an electronic data capture system using REDCap, and developing well-documented, reproducible data processing workflows. CONCLUSIONS: NLM informationist supplements provide librarians with valuable experience in collaborating with study teams to address their data needs. For this project, the librarians gained skills in project management, REDCap, and understanding of the challenges and specifics of a clinical research study. However, the time and effort required to provide targeted and intensive support for one study team was not scalable to the library's broader user community.

Comparison of 2 informant questionnaire screening tools for dementia and mild cognitive impairment: AD8 and IQCODE.

BACKGROUND: Dementia and mild cognitive impairment (MCI) are underrecognized in community settings. This may be due in part to the lack of brief dementia screening tools available to clinicians. We compared 2 brief, informant-based screening tests: the AD8 and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) in a community-based neurology practice in the midwestern United States. METHODS: We examined 186 consecutive patients (44 controls, 13 with MCI, and 129 with dementia). Receiver operator characteristic curves were used to examine the ability of AD8 and IQCODE to discriminate between controls and MCI or dementia. Sensitivity, specificity, predictive values, and likelihood ratios were reported. RESULTS: AD8 differentiated healthy controls from MCI (P<0.001) or dementia (P<0.001), and MCI from dementia (P=0.008). The IQCODE differentiated controls and MCI from dementia (both P<0.001), and between controls and MCI (P=0.002). Both AD8 (AUC=0.953; 95% confidence interval, 0.92-0.99) and IQCODE (AUC=0.930, 95% confidence interval, 0.88-0.97) provided discrimination between controls and patients with dementia; however, the AD8 had superior sensitivity detecting dementia (99.2%) and MCI (100%) compared with the IQCODE (79.1% for dementia, 46.1% for MCI) with nonoverlapping confidence intervals. Using published cut-offs (AD8≥2, IQCODE≥3.4), only 1 case of dementia was missed with the AD8, whereas the IQCODE failed to detect dementia in 27 individuals. The AD8 detected MCI in all 13 individuals, whereas the IQCODE misclassified 7 individuals. CONCLUSIONS: Both the AD8 and IQCODE were able to detect dementia in a community setting. The AD8, however, was more successful than IQCODE in detecting MCI. If simple and efficient screening for early cognitive impairment is the goal, particularly in the early stages (e.g., for prevention trials or public screening), the combination of an informant interview (the AD8) and a brief performance measure could be considered as they meet the basic requirements of the Personalized Prevention Plan for Medicare beneficiaries.

Practical guidelines for the recognition and diagnosis of dementia.

To date, user-friendly, practical guidelines for dementia have not been available for busy family physicians. However, the growing number of patients with dementia means that primary care physicians will have an increasingly important role in the diagnosis and subsequent management of dementia. This article provides practical guidance for the recognition and diagnosis of dementia and is aimed at family physicians, who are usually the first clinicians to whom patients present with dementia symptoms. Because Alzheimer disease (AD) is the most common form of dementia, this condition is the main focus of this article. We review the pathophysiology of AD and discuss recommended diagnostic protocols and the importance of early diagnosis. An AD diagnostic algorithm is provided, with clearly defined steps for screening and diagnosing AD and assessing daily functioning, behavioral symptoms, and caregiver status.

Four sensitive screening tools to detect cognitive dysfunction in geriatric emergency department patients: brief Alzheimer's Screen, Short Blessed Test, Ottawa 3DY, and the caregiver-completed AD8.

BACKGROUND: Cognitive dysfunction, including dementia and delirium, is prevalent in geriatric emergency department (ED) patients, but often remains undetected. One barrier to reliable identification of acutely or chronically impaired cognitive function is the lack of an acceptable screening tool. While multiple brief screening instruments have been derived, ED validation trials have not previously demonstrated tools that are appropriately sensitive for clinical use. OBJECTIVES: The primary objective was to evaluate and compare the Ottawa 3DY (O3DY), Brief Alzheimer's Screen (BAS), Short Blessed Test (SBT), and caregiver-completed AD8 (cAD8) diagnostic test performance for cognitive dysfunction in geriatric ED patients using the Mini Mental Status Exam (MMSE) as the criterion standard. A secondary objective was to assess the diagnostic accuracy for the cAD8 (which is an informant-based instrument) when used in combination with the other performance-based screening tools. METHODS: In an observational cross-sectional cohort study at one urban academic university-affiliated medical center, trained research assistants (RAs) collected patients' responses on the Confusion Assessment Method for the Intensive Care Unit, BAS, and SBT. When available, reliable caregivers completed the cAD8. The MMSE was then obtained. The O3DY was reconstructed from elements of the MMSE and the BAS. Consenting subjects were non-critically ill, English-speaking adults over age 65 years, who had not received potentially sedating medications prior to or during cognitive testing. Using an MMSE score of ≤23 as the criterion standard for cognitive dysfunction, the sensitivity, specificity, likelihood ratios, and receiver operating characteristic (ROC) area under the curve (AUC) were computed. Venn diagrams were constructed to quantitatively compare the degree of overlap among positive test results between the performance-based instruments. RESULTS: The prevalence of cognitive dysfunction for the 163 patients enrolled with complete data collection was 37%, including 5.5% with delirium. Dementia was self-reported in 3%. Caregivers were available to complete the cAD8 for 56% of patients. The SBT, BAS, and O3DY each demonstrated 95% sensitivity, compared with 83% sensitivity for the cAD8. The SBT had a superior specificity of 65%. No combination of instruments with the cAD8 significantly improved diagnostic accuracy. The SBT provided the optimal overlap with the MMSE. CONCLUSIONS: The SBT, BAS, and O3DY are three brief performance-based screening instruments to identify geriatric patients with cognitive dysfunction more rapidly than the MMSE. Among these three instruments, the SBT provides the best diagnostic test characteristics and overlap with MMSE results. The addition of the cAD8 to the other instruments does not enhance diagnostic accuracy.

Application of AD8 questionnaire to screen very mild dementia in Taiwanese.

The AD8 questionnaire developed by Washington University in St Louis is a screening tool with 8 questions to reliably differentiate nondemented from demented individuals even at the very mild stage. We recruited 239 participants, including 114 cognitively normal, 73 very mild dementia, and 52 mild dementia to validate its application in Taiwanese. The cut-off value of AD8 was 2 in discriminating cognitively normal from demented individuals with the area under curve (AUC) = 0.961, sensitivity = 97.6%, specificity = 78.1%, positive likelihood ratio (PLR) = 4.5, and negative likelihood ratio (NLR) = 0.03. The cut-off value also was 2 in discriminating nondemented from very mild dementia with the AUC = 0.948, sensitivity = 95.9%, specificity = 78.1%, PLR = 4.4, and NLR = 0.05. The Chinese AD8 is effective in discriminating individuals with dementia, even at its mildest stages from those without dementia with properties identical to the original English version. The cAD8 is a quick dementia screening tool that can be applied across cultures.

Relationship of dementia screening tests with biomarkers of Alzheimer's disease.

Screening tests for Alzheimer's disease lack sensitivity and specificity. We developed the AD8, a brief dementia screening interview validated against clinical and cognitive evaluations, as an improvement over current screening methods. Because insufficient follow-up has occurred to validate the AD8 against the neuropathologic findings of Alzheimer's disease, we investigated whether AD8 scores correspond to impairment in episodic memory testing and changes in biomarkers of Alzheimer's disease (cerebrospinal fluid and amyloid imaging with Pittsburgh compound B) characteristic of symptomatic Alzheimer's disease. We also compared informant-based assessments with brief performance-based dementia screening measurements such as the Mini Mental State Exam. The sample (n = 257) had a mean age of 75.4 years with 15.1 years of education; 88.7% were Caucasian and 45.5% were male. The sample was divided into two groups based on their AD8 scores: those with a negative dementia screening test (AD8 score 0 or 1, n = 137) and those with a positive dementia screening test (AD8 score ≥2, n = 120). Individuals with positive AD8 scores had abnormal Pittsburgh compound B binding (P < 0.001) and cerebrospinal fluid biomarkers (P < 0.001) compared with individuals with negative AD8 scores. Individuals with positive AD8 tests and positive biomarkers scored in the impaired range on the Wechsler Logical Memory Story A (mean score 7.0 ± 4.5 for Pittsburgh compound B; mean score 7.6 ± 5.3 for cerebrospinal fluid amyloid beta protein 1-42). The AD8 area under the curve for Pittsburgh compound B was 0.737 (95% confidence interval: 0.64-0.83) and for cerebrospinal fluid amyloid beta protein 1-42 was 0.685 (95% confidence interval: 0.60-0.77) suggesting good discrimination. The AD8 had superior sensitivity in detecting early stages of dementia compared with the Mini Mental State Examination. The AD8 had a likelihood ratio of a positive test of 5.8 (95% confidence interval: 5.4-6.3) and likelihood ratio of a negative test of 0.04 (95% confidence interval: 0.03-0.06), increasing the pre-test probability of an individual having symptomatic Alzheimer's disease. Individuals with AD8 scores of ≥2 had a biomarker phenotype consistent with Alzheimer's disease and lower performance on episodic memory tests, supporting a diagnosis of Alzheimer's disease. Informant-based assessments may be superior to performance-based screening measures such as the Mini Mental State Examination in corresponding to underlying Alzheimer's disease pathology, particularly at the earliest stages of decline. The use of a brief test such as the AD8 may improve strategies for detecting dementia in community settings where biomarkers may not be readily available, and may enrich clinical trial recruitment by increasing the likelihood that participants have underlying biomarker abnormalities.