Search

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by hyperphosphorylated tau (p‐tau) accumulation. The clinical features of CTE are heterogeneous and their association with CTE are unclear. We investigated the association of CTE p‐tau pathology density and location with cognitive and neuropsychiatric symptoms in brain donors with autopsy‐confirmed CTE. Method: 364 brain donors with autopsy confirmed CTE were evaluated to determine the density of p‐tau pathology in 10 cortical and subcortical regions using semi‐quantitative rating scales (score range: 0‐3). We summed ratings across 10 regions to form a global composite of p‐tau severity (score range:0‐30). Informants completed standardized scales of cognition (Cognitive Difficulties Scale, CDS; BRIEF‐A Metacognition Index, MI), activities of daily living (Functional Activities Questionnaire), neurobehavioral dysregulation (BRIEF‐A Behavioral Regulation Index, BRI; Barratt Impulsiveness Scale, BIS‐11), aggression (Brown‐Goodwin Aggression Scale), depression (Geriatric Depression Scale‐15, GDS‐15), and apathy (Apathy Evaluation Scale, AES). Multivariable linear regression analyses examined the association between global p‐tau severity and p‐tau severity in each region with each of the clinical scales, controlling for age at death, racial identity, education level, hypertension history, obstructive sleep apnea history, and substance use treatment history. Result: The sample predominantly consisted of football players (333; 91.2%) and 140 (38.5%) had low CTE and 224 (61.5%) had high CTE (Table 1). Figures 1‐2 are Forrest plots of the estimated effects between regional p‐tau and clinical scales. Global p‐tau severity was associated with cognitive and functional scales: MI (beta = 0.46, 95% CI = 0.11‐0.81), CDS (beta = 1.08, 95% CI = 0.31‐1.85), and FAQ (beta = 0.32, 95% CI = 0.16‐0.49). After false‐discovery rate (FDR) correction, p‐tau in the frontal, inferior parietal, superior temporal cortex, and the amygdala was significantly associated with the CDS and FAQ; frontal and inferior parietal cortex and amygdala p‐tau also was significantly associated with MI. Frontal cortex p‐tau was significantly associated with the BRI. There were no significant associations with the other neuropsychiatric scales after FDR correction. Entorhinal cortex, hippocampus, and locus coeruleus showed no significant associations. Conclusion: Accumulation of p‐tau aggregates, especially in the frontal cortex, are a driver of cognitive, function, and certain neurobehavioral symptoms in CTE. [ABSTRACT FROM AUTHOR]

Background: The Mobile Toolbox (MTB), an app‐based assessment platform, enables completely remote, self‐administered assessment using participants' own smartphones. We present psychometric evidence for eight MTB cognitive measures assessing language, working memory, episodic memory, executive function, and processing speed. Method: Three samples were used to evaluate convergent validity, age‐related change, internal consistency and test‐retest reliability. Sample I consisted of 94 adults ages 18‐85 who were administered "gold standard" cognitive measures followed by self‐administered MTB. Sample II, recruited for norming, included 1,020 participants ages 18‐90 who completed MTB measures remotely. Sample III was a convenience sample of 800 participants who completed MTB remotely with retest after 7, 14, or 21 days. Pearson correlation coefficients between MTB and external measures were used to evaluate convergent validity. Internal consistency was evaluated using measure‐appropriate tests: split‐half reliability, Cronbach's alpha or IRT‐based indices. For measures with timing‐dependent scores, separate analyses were performed for iOS and Android devices. Spearman correlation coefficients were calculated to evaluate relationships between age and test scores. Result: Convergent validity data from Sample I (64% female, 52% white, 99% non‐Hispanic, age = 48+/‐18) revealed moderate to strong correlations between MTB test scores and performance on external measures of similar constructs (Table 1). Table 2 shows results derived from Sample II (44% female, 13% Hispanic, 74% white, age = 45+/‐22). Internal consistency estimates ranged from 0.69 to 0.98. On timed tests, Shape‐Color Sorting and Arrow Matching showed significant score differences between Android and iOS devices when controlling for age. However, internal consistency was equivalent between the two, as indicated by overlapping confidence thresholds (Table 3). Performance on executive function, processing speed, and some memory tasks negatively correlated with age. Word Meaning scores improved with age while Spelling remained stable. Test‐retest reliability, using preliminary Sample III data, ranged from 0.47 (memory tests) to 0.86. Conclusion: Initial studies, using three diverse samples, support the validity and reliability of the first eight MTB cognitive measures. MTB tests showed satisfactory internal consistency and convergent validity and most measures correlated with age in the expected directions. Our results support the use of MTB in cognitive research. [ABSTRACT FROM AUTHOR]

Background: Repetitive head impacts (RHI) from American style football (ASF) and other contact sports are a known risk factor for the neurodegenerative disease chronic traumatic encephalopathy (CTE). RHI can also lead to mixed neuropathologies that uniquely contribute to clinical symptoms. Here, we compared various types of vascular and white matter pathologies between brain donors with and without exposure to RHI from different types of contact and collision sports (CCS). Methods: The sample included 79 deceased male ASF players (RHI‐ASF) and 49 deceased male non‐ASF CCS athletes (RHI‐CCS) from the UNITE brain bank. Each RHI group had a comparison group that included similar aged (+/‐ 5 years) male brain donors without RHI from the Boston University Alzheimer's Disease Research Center and Framingham Heart Study brain banks. The modified Ischemic Injury Scale (mIIS) served as a global indicator of vascular and white matter pathologies and is a sum of hippocampal sclerosis, infarct/lacune, microinfarct, microbleeds, laminar necrosis, arteriolosclerosis, atherosclerosis of Circle of Willis, cerebral amyloid angiopathy, and white matter rarefaction. Dementia diagnoses were made during consensus conferences. Linear or logistic regression compared the RHI vs non‐RHI groups on the mIIS and its subcomponents. Logistic regression models examined the association between mIIS and dementia. Models were adjusted for age. Results: Table 1 shows sample characteristics. The RHI‐CCS group was comprised of boxers, amateur wrestlers, and ice hockey, soccer, rugby, and lacrosse players. 94 decedents had CTE, all of whom were in an RHI exposed group. Of the mIIS components, arteriolosclerosis was the most common across all groups. White matter rarefaction was also the most frequent mIIS component for both RHI groups, but not for non‐RHI groups. Compared to their respective controls, RHI‐ASF and RHI‐CCS were associated with higher mIIS scores (Table 2). Higher mIIS scores corresponded to increased odds for having dementia in both the RHI‐ASF and RHI‐CCS groups (Table 2). White matter rarefaction best discriminated both RHI groups from non‐RHI; atherosclerosis also discriminated RHI‐CCS group (Table 3). Conclusion: These results support vascular and white matter pathologies, specifically white matter rarefaction, as prominent and clinically relevant sequelae of RHI from CCS. [ABSTRACT FROM AUTHOR]

Introduction: The National Institutes of Health (NIH) Toolbox (NIHTB) provides computerized measures of cognition, emotion, sensation, and motor abilities across the lifespan. The ARMADA (Assessing Reliable Measurement in Alzheimer's Disease and Cognitive Aging) study validated the NIHTB in individuals across the cognitive aging spectrum. This article reports the characteristics of our sample of participants. Methods: Participants were recruited across nine sites and classified clinically as cognitively normal (NC), with mild cognitive impairment (MCI), or with dementia of the Alzheimer's type (DAT.) They completed the NIHTB at multiple time points and many had at least one Alzheimer's biomarker previously obtained. Results: Groups differed with respect to dementia severity levels, as anticipated, but were well‐matched across many demographic characteristics. Discussion: The ARMADA study demographics and baseline characteristics provide a suitable sample for validating the NIHTB across the cognitive aging spectrum. Other enriched samples (African American participants, Spanish NIHTB, 85+ years of age) will be reported elsewhere. Highlights: There is a need for assessments that can detect the early stages of cognitive decline in older adults.The ARMADA (Assessing Reliable Measurement in Alzheimer's Disease and Cognitive Aging) study will validate the National Institutes of Health (NIH) Toolbox across the aging spectrum, including mild cognitive impairment (MCI) and dementia of the Alzheimer's type (DAT).Here we report the characteristics of participants.Groups were well‐matched across most demographic characteristics, and clinical characteristics differed as expected.ARMADA study cohorts reflect their respective clinical syndromes for validating the NIH Toolbox. [ABSTRACT FROM AUTHOR]

Background: The pathognomonic lesion of chronic traumatic encephalopathy (CTE) is the perivascular deposition of neuronal phosphorylated tau (p‐tau). Patchy p‐tau deposits initially accumulate in frontotemporal cortices. Medial temporal lobes (MTL) become involved in late stage. Validated in vivo biomarkers for CTE p‐tau do not exist. 18F‐MK‐6240 is a second‐generation tau PET ligand with improved imaging properties compared with first‐generation ligands, but its utility in CTE is unknown. We report initial results from an ongoing proof‐of‐concept study investigating MK‐6240 in people at risk for CTE. Method: Ten older adult male symptomatic former National Football League (NFL) players completed tau (MK‐6240) and amyloid (florbetapir) PET imaging and neuropsychological testing. MK‐6240 data were acquired from 36 cognitively unimpaired males without traumatic brain injury history (but unknown contact sport history) from the Wisconsin Registry for Alzheimer's Prevention (mean age=66.3, SD=6.3; mean MMSE=29.6, SD=0.5). Using cerebellar gray matter reference, 70‐90 min MK‐6240 SUVR images were created. W‐score (age‐adjusted z‐scores) maps were generated using the control data and thresholded at w>1.65 to visualize high binding voxels. Images and scatter plots of uptake in NFL players and controls were qualitatively assessed due to the small sample size. Results: Sample characteristics are in Table 1 (age range:51‐72, 5/10 Black). All NFL players had a negative florbetapir PET. 9/10 were cognitively impaired, particularly in memory and executive functions (Table 2). One former NFL player (case 4) had MTL MK‐6240 uptake greater than all controls, along with focal low intensity uptake in the superior frontal cortex (Figure 1). Two NFL players (cases 6 and 9) had mildly elevated MTL MK‐6240 uptake, particularly in entorhinal cortex and parahippocampus, though similar binding was seen in some controls (Figure 2). There was minimal MTL uptake in the remaining NFL players. Cortical uptake was complicated by contamination from off‐target meningeal binding. Conclusions: Existing data suggests current radioligands (e.g., flortaucipir) developed for Alzheimer's disease might have restricted utility to late stage CTE. This might be true for MK‐6240 and off‐target meningeal binding complicates detection of cortical p‐tau. Data collection is ongoing and the larger data set will inform on MK‐6240 as a biomarker for CTE. [ABSTRACT FROM AUTHOR]

Introduction: Early detection of cognitive decline in older adults is a public health priority. Advancing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA), a multisite study, is validating cognition, emotion, motor, and sensory modules of the National Institutes of Health Toolbox for Assessment of Neurological and Behavioral Function (NIHTB) in the aging spectrum from cognitively normal to dementia of the Alzheimer's type (DAT). Methods: Participants 65 to 85 years old, in demographic groups racially proportional to the general US population, are recruited in one of three groups to validate the NIHTB: cognitively normal, amnestic mild cognitive impairment (aMCI), or mild DAT. Additional special emphasis cohorts include (1) Blacks in the three clinical groups; (2) Spanish‐speakers in the three clinical groups; (3) cognitively normal, population‐proportional, over age 85. Discussion: Longitudinal study will determine whether NIHTB can predict cognitive decline and is associated with Alzheimer's disease biomarkers. Here, we detail the methods for the ARMADA study. [ABSTRACT FROM AUTHOR]

Background: Early identification of cognitive impairment (CI), including Alzheimer's disease and related dementias (ADRD), is a top public health priority. Yet in primary care settings that manage the health of most community‐dwelling older adults, less than half of patients with any CI are detected and/or diagnosed. Among community health centers that serve marginalized patients, rates of detection may be far lower. To address this, we sought to test a primary care‐based strategy ('MyCog') to improve CI detection as part of an NIH‐sponsored consortium (DetectCID). Method: The MyCog strategy includes a brief iPad‐based, self‐administered, electronic health record (EHR)‐linked cognitive assessment that leverages two well validated measures from the NIH Toolbox Cognition Battery and has easily interpretable results with 'turnkey' recommendations to enhance clinical decision making. Clinician and practice administrator feedback was sought via cognitive interviews and focus groups to ensure the assessment could properly function in typical workflows. Based on this feedback a self‐administered tool was built, with a simple interpretable result (yes or no, cognitive impairment detected). It was then validated in one academic geriatrics practice among 111 older adults. Result: The refined self‐administered tool was further validated in a geriatric clinical population, with interviewer and self‐administered MyCog versions strongly correlated (Spearman r = 0.75) and similar average response time per trial (0.914 sec. vs. 0.958 sec.). Use of the two tests demonstrated acceptable AUC values separately for detecting CI (0.84 and 0.79, respectively). But combined, these measures provide incremental diagnostic utility (AUC = 0.95). Conclusion: We will launch the MyCog Trial at 24 practices from a national network of primary care centers for older adults on Medicare that will be randomized to MyCog or usual care. Clinics receiving MyCog will utilize a protocol to implement the intervention during Medicare Annual Wellness Visits and whenever a cognitive concern is expressed. Findings from the DetectCID consortium and MyCog Trial will directly inform future standards in primary care settings, especially those that serve health disparate patient populations. [ABSTRACT FROM AUTHOR]

Introduction: Validity of the 2014 traumatic encephalopathy syndrome (TES) criteria, proposed to diagnose chronic traumatic encephalopathy (CTE) in life, has not been assessed. Methods: A total of 336 consecutive brain donors exposed to repetitive head impacts from contact sports, military service, and/or physical violence were included. Blinded to clinical information, neuropathologists applied National Institute on Neurological Disorders and Stroke/National Institute of Biomedical Imaging and Bioengineering CTE criteria. Blinded to neuropathological information, clinicians interviewed informants and reviewed medical records. An expert panel adjudicated TES diagnoses. Results: A total of 309 donors were diagnosed with TES; 244 donors had CTE pathology. TES criteria demonstrated sensitivity and specificity of 0.97 and 0.21, respectively. Cognitive (odds ratio [OR] = 3.6; 95% confidence interval [CI]: 1.2–5.1), but not mood/behavior or motor symptoms, were significantly associated with CTE pathology. Having Alzheimer's disease (AD) pathology was significantly associated with reduced TES accuracy (OR = 0.27; 95% CI: 0.12–0.59). Discussion: TES criteria provided good evidence to rule out, but limited evidence to rule in, CTE pathology. Requiring cognitive symptoms in revised criteria and using AD biomarkers may improve CTE pathology prediction. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disease predominantly found in former athletes and associated with repetitive brain injury (TBI). Despite the increased number of studies, several questions about prevalence and risk factors for CTE in the general population remain unknown. Method: to investigate the presence of CTE pathology in a population‐based clinicopathological cohort, we analyzed brain sections immunostained with tau antibody (AT8) of 1151 individuals over 30 years of age with previous neuropathological assessment. The presence of CTE pathology was evaluated according to the current neuropathological consensus criteria. Demographic and clinical data were collected through interviews with a next‐of‐kin. All cases are from the Biobank for Aging Studies of the University of São Paulo University. Internationally accepted criteria were used to diagnose and stage the brain tissue pathologies. Result: Only 7 cases (0.6%) met neuropathological criteria for CTE, contrasting with the high frequency of aging‐related tau astrocyte pathology (ARTAG) (50%) The mean age of death was 73.4 12.5 and only one individual were female. Presence of co‐pathologies was observed in all cases, being the most frequent comorbidity AD‐type pathology, followed by argyrophilic grain disease. Dementia was present in 43%, meanwhile 57% had some degree of neuropsychiatric symptoms (NPS). The most frequent NPS was depression, followed by anxiety. The history of sport practice was complete only for two cases. Both played soccer, however only one semi‐professionally. Conclusion: The low frequency of CTE pathology corroborate findings from other studies that CTE is not a frequent finding in population‐based samples. The overlapping between CTE and ARTAG may contribute with the misclassification of ARTAG as CTE. [ABSTRACT FROM AUTHOR]

Background: Given the growing population of aging adults, and subsequently individuals with dementia, there is a need for instruments that can detect cognitive impairment in early stages. The NIH Toolbox® for Assessment of Neurological and Behavioral Function (NIHTB) is a computerized battery of assessments measuring multiple domains cognition, emotion, sensation, and motor abilities. The goal of the ARMADA study is to validate the NIHTB in individuals with mild cognitive impairment (MCI) and dementia of the Alzheimer type (DAT). Here, we describe the demographic and clinical characteristics of participants ages 65 to 85 from the general population sample. Method: Normal control (NC), MCI, and DAT groups racially proportional to the US population were recruited from existing cohorts across nine Alzheimer's Disease Research Centers and sites with cognitive aging studies. Diagnoses were based on the Uniform Data Set methodology, and included multiple clinical and cognitive assessments. Participants completed the NIH Toolbox at baseline, 12‐, and 24‐month visits. Result: Groups were matched with respect to multiple demographic characteristics. There were some differences in age and sex, such that the NC group had more female participants and was the youngest. Dementia severity levels differed as expected, with the DAT group demonstrating greater cognitive and functional impairment compared to the MCI group, and the NC group demonstrating minimal cognitive or functional symptoms. Additionally, the DAT group reported more neuropsychiatric symptoms compared to the NC and MCI groups. There was no difference in reported family history of cognitive impairment across groups. Many participants across groups had at least one Alzheimer biomarker collected. Conclusion: The study cohorts included in the ARMADA study accurately reflect their respective clinical syndromes for validating the NIHTB across the cognitive aging spectrum. The goals for the ARMADA study include comparing performance on all four modules of the NIHTB across groups, evaluating the relationship between Alzheimer biomarkers and NIHTB measures, and measuring changes in performance longitudinally. Special emphasis groups, including individuals over age 85, African American participants, and Spanish‐Speaking participants, were also recruited and are reported elsewhere. [ABSTRACT FROM AUTHOR]

Background: Differentiating normal from pathological cognitive change in adults is essential for both preventing and treating abnormal cognitive decline. The Mobile Toolbox (MTB) is an app‐based research platform and expandable test library enabling remote assessment of cognition using participants' own smartphones (iOS and Android). MTB facilitates conduct of diverse types of cognitive research with a broad range of participants, including those who may be hard to reach. However, evidence for MTB test validity, including demonstration of expected age‐related changes in adulthood, is needed to support MTB use. We present findings on associations between age and MTB performance. Method: 1,120 English‐speaking participants, ages 18–90, were recruited by a market research company as part of a larger study. Participants completed MTB remote measures of executive function, episodic and working memory, processing speed, and language on their smartphones. Measure order was fixed ((Vocabulary, Memory for Sequences, Spelling, Picture Sequence Memory (PSM), Flanker, Face Name (FNAME) Learning, Dimensional Change Card Sort (DCCS), Number Match, Face Name Memory)); individual tests could be taken anytime within a 14‐day period. Spearman correlation coefficients were calculated to evaluate relationships between age and test scores. Result: Our participant sample was 57% female, 13% Hispanic, 72% white; mean age = 45 (sd = 21). Education distribution was: < high school (2%); high school (34%); some college (34%), college (20%), graduate degree (11%). Measures of executive function (DCCS and Flanker: r = ‐0.50; ‐0.57) and processing speed (r = ‐0.56) showed decreased performance with age (all p < 0.001). Episodic memory scores also decreased with age, but correlations were weaker (PSM and FNAME: ‐0.2, ‐0.35; p.<.001). Performance on language tests did not significantly decrease with age. Conclusion: Most MTB measures correlated with age in the expected directions. Fluid cognition (e.g., executive function and processing speed) and memory typically decrease with age, and this decrease was reflected in MTB test performance. In contrast, crystallized abilities (e.g., spelling and vocabulary), which are typically preserved as we age, did not decrease in our sample. Initial results suggest MTB can be used to identify abnormal cognitive decline and support its use in cognitive aging research. [ABSTRACT FROM AUTHOR]

Background: Changes in emotional health are common both as part of typical aging and for individuals with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Thus, there is a critical need to identify differences in emotional functioning between adults with and without cognitive impairment. In the current study, we explore whether the NIH‐Toolbox Emotional Battery (NIHTB‐EB), a set of validated, reliable, and efficient measures of emotional functioning, can be used to potentially detect differences in emotional functioning across older adults with varying levels of cognitive impairment. Method: Data were drawn from a longitudinal, multi‐site study ‐ the Advancing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA). Participants were recruited from 11 existing cohorts nationwide, and included 1) cognitively normal (NC) adults (N=276), 2) individuals with MCI (N=103), and 3) individuals with AD (N=69); Mage= 78 (SD = 8.25); 53.2% were female. Baseline emotional health was assessed from 2019 to 2020 using NIHTB‐EB. Univariate and ANCOVA analyses tested differences in a variety of emotion dimensions across three groups, adjusting for important covariates, and post‐hoc Tukey pairwise comparisons were performed. Result: Controlling for age, gender, marital status, and education, a significant main effect of clinical group was found on measures of sadness, fear‐affect, anger‐physical aggression, loneliness, self‐efficacy, and the negative affect composite score [all ps<0.05; see Figure 1]. Tukey post‐hoc pairwise comparison showed MCI and NC differed in negative affect (diff=4.18), sadness (diff=3.08), and anger‐physical aggression (diff=3.08); and AD and NC differed in negative affect (diff=3.65), anger‐physical aggression (diff=4.60), loneliness (diff=3.95), sadness (diff=4.60), and self‐efficacy (diff=‐3.18) [all ps < 0.05; Figure 1]. Conclusion: Individuals with MCI and AD reported higher levels of negative emotions and a lower level of self‐efficacy than normal controls. Based on a comprehensive set of emotional functioning measures, these findings extended our understanding of how older adults with and without cognitive impairment differ on aspects emotional functioning essential to quality of life. Importantly, we found that the NIHTB‐EB is a useful tool to assess and differentiate emotional health outcomes among cognitively normal adults as well as those with MCI and AD diagnoses. [ABSTRACT FROM AUTHOR]

Background: Chronic traumatic encephalopathy (CTE) is a tauopathy associated with repeated brain injuries. The presence of co‐pathologies is not uncommon in individuals with CTE. Here, we described clinical and neuropathological findings of amateur soccer with a history of progressive parkinsonism and dementia. Method: 63‐years old male with no family history of neurodegenerative disease or alcohol abuse. He played amateur soccer as a goalkeeper for 42 years. Episode of concussion with loss of conciseness at age of 20, without symptoms afterward. He denied any non‐soccer related episodes of brain trauma. At the age of 65, he started with REM behavior disorder, followed by apathy. At age 67, he developed asymmetric bradykinesia, limb rigidity, and complete anosmia. At the age of 73, a neurological examination demonstrated asymmetric parkinsonism, worse in the left. He denied motor fluctuations or hallucinations. At age 75, cognitive impairment was observed and his MMSE score was 22/30 with temporal disorientation, executive and delayed recall impairments. The working diagnosis was Parkinson's disease dementia. He died at age of 81. Result: Neuropathological examination showed prominent frontal and temporal atrophy, hippocampal asymmetry and moderate depigmentation of substantia nigra, and locus coeruleus. Hematoxylin and eosin staining showed left hippocampal sclerosis and white matter arteriolosclerosis. Immunohistochemistry evaluation showed aggregates of hyperphosphorylated tau in neurons, astrocytes and cell processes in a patch distribution around vessels, with deep sulcal accentuation in several cortical regions fulfilling criteria for CTE stage III. Additionally, neurofibrillary pathology was found in subcortical and cortical areas (BRAAK stage V) and Aß plaques were distributed in cortical, limbic and diencephalon areas (Thal 4), altogether meeting criteria for an intermediated ADNC. Also, phosphorylated TDP‐43 immunoreactive dot‐like and neuronal cytoplasmatic inclusions were found in entorhinal cortex, amygdala and hippocampus (LATE stage 3). Moreover, diffuse Lewy pathology was observed (Braak 5 of Parkinson´s disease). Conclusion: Despite showing multiple co‐pathologies, former soccer players may develop CTE changes. This case adds to the increased number of former soccer players showing dementia due to multiple pathologies and CTE. If soccer‐related brain trauma triggers multiple neuropathological processes or if they develop independently remains an open question. [ABSTRACT FROM AUTHOR]

Background: The world population is rapidly aging, and the prevalence of dementia due to Alzheimer's disease (AD) and related disorders is correspondingly increasing. Thus, detecting cognitive decline in older individuals is an urgent public health concern. There is a need for brief, practical, standardized measures that are sensitive to cognitive decline and can be broadly deployed in diverse settings. Advancing Reliable Measurement in Alzheimer's Disease and Cognitive Aging (ARMADA) aims to meet this need by validating the NIH Toolbox for Assessment of Neurological and Behavioral Function® (NIHTB®) in individuals ages 65 to 85 who are cognitively healthy or diagnosed with either mild cognitive impairment (MCI) or dementia of the Alzheimer type (AD). A broad range of clinical and healthy samples have been recruited to date, including an African American sample and a Spanish‐speaking Hispanic sample to reflect the diversity of people affected by cognitive decline and to enable validation of the Spanish NIHTB. We will present baseline NIHTB results for each sample. Method: Individuals age 65 or older who are either cognitively normal or diagnosed with cognitive impairment (MCI or early AD) have been recruited from nine clinical centers with established research cohorts. Participants complete the NIHTB and gold standard neuropsychological assessment at baseline. AD biomarkers, including PET beta amyloid level, CSF tau, and APoE genotype, are also available. Result: As of January 2020, 656 participants have completed the baseline assessment. Early results indicate the NIHTB Cognition battery, as well as individual measures, successfully discriminates among MCI, AD and healthy controls in the general population sample (N=259). Baseline data collection for the African American and Hispanic samples will be largely complete by June 2020, and initial results will be presented. Conclusion: Initial baseline results from the ARMADA study provide evidence that the NIHTB discriminates among older individuals with normal cognition, MCI, and early AD. Two annual longitudinal follow‐ups will evaluate how well NIH Toolbox measures predict future cognitive decline, their sensitivity to change and their association with AD biomarkers. [ABSTRACT FROM AUTHOR]