Alzheimer's Coordinating Center Uniform Research Articles

Motor signs and incident dementia with Lewy bodies in older adults with mild cognitive impairment.

Motor signs may herald incident dementia and allow the earlier detection of high-risk individuals and the timely implementation of preventive interventions. The current study was performed to investigate the prognostic properties of motor signs with respect to incident dementia with Lewy bodies (DLB) in older adults with mild cognitive impairment (MCI). Emphasis was placed on sex differences. The specificity of these associations was explored. We analyzed data from the National Alzheimer's Coordinating Center Uniform Data Set. Participants 55 + years old with a diagnosis of MCI were included in the analysis. Those with Parkinson's disease (PD) or other parkinsonian disorders at baseline and those with PD dementia at follow-up were excluded. UPDRS III was used to assess the presence or absence of motor signs in nine domains: hypophonia; masked facies; resting tremor; action/postural tremor; rigidity; bradykinesia; impaired chair rise; impaired posture/gait; postural instability. Αdjusted Cox proportional hazards models featuring sex by motor sign interactions were estimated. Throughout the average follow-up of 3.7 ± 3.1 years, among 4623 individuals with MCI, 2211 progressed to dementia (66 of whom converted to DLB). Masked facies [HR = 4.21 (1.74-10.18)], resting tremor [HR = 4.71 (1.44-15.40)], and bradykinesia [HR = 3.43 (1.82-6.45)] exclusively increased the risk of DLB. The HR of DLB was approximately 15 times greater in women compared to men with masked facies. Impaired posture-gait (approximately 10 times) and resting tremor (approximately 8.5 times) exhibited a similar trend (prominent risk-conferring properties in women compared to men) but failed to achieve statistical significance. Rigidity and hypophonia elevated the risk of other dementia entities, as well. The remaining motor features were not related to incident dementia of any type. Specific motor signs may herald DLB among individuals with MCI. Different associations may exist between masked facies, impaired posture-gait, resting tremor, and incident DLB in men versus women.

Referral Sources Across Racial and Ethnic Groups at Alzheimer's Disease Research Centers.

Despite the need to increase engagement of underrepresented groups (URG) in Alzheimer's disease and related dementias (ADRD) studies, enrollment remains low. Compare referral sources across racial and ethnic groups among participants enrolled in ADRC studies. Data for this cross-sectional secondary analysis were extracted from the National Alzheimer's Coordinating Center Uniform Data Set. We performed mixed effects logistic regression models using generalized estimating equations for professional referral versus non-professional referral by racial and ethnic group, adjusted for age, gender, education, visit year, and Clinical Dementia Rating scale (CDR) with a random effect for study site. Included in the analysis were 48,330 participants across 46 ADRCs (mean [SD] age, 71.3 [10.5] years; 20,767 female [57%]; 4,138 Hispanic [8.6%]; 1,392 non-Hispanic Asian [2.9%]; 6,766 non-Hispanic Black [14%] individuals; and 676 individuals [1.4%] of other races. Non-Hispanic Black and Asian participants had lower odds of being referred by a professional contact compared to non-Hispanic White participants (Black: adjusted OR = 0.61, 95% CI = 0.44-0.86, p = 0.005; Asian: adjusted OR = 0.65, 95% CI, p = 0.004). In participants who had completed an MRI, there was no significant difference in referral source across ethnic and racial groups. Further studies are needed to better understand the systemic and structural factors that contribute to differences in referral sources and disparities in recruitment of URG into ADRD studies.

Co-Occurring Mental and Physical Health Conditions Among Older Adults With and Without Post-traumatic Stress Disorder: A Case Control Study.

Rates of post-traumatic stress disorder (PTSD) among older adults range from 0.4%-4.5%. Research examining PTSD in adults has demonstrated numerous associations between physical and mental health conditions; however, these are less well characterized in older adults. The current study aimed to identify base rates of such conditions among older adults with and without a history of PTSD. In a case control design using the National Alzheimer's Coordinating Center Uniform Data Set, adults 65 years or older from the United States who endorsed either the presence or absence of PTSD were matched by age to assess between-group differences (N = 472; 236 pairs). We examined differences across self-reported sociodemographics and physical health, mental health, and substance use histories. More participants with a history of PTSD identified as Hispanic, non-white, non-married, and functionally independent. Compared to individuals without a history of PTSD, significantly more individuals with a history of PTSD had histories of depression, anxiety, substance abuse, Parkinson's disease, seizures, insomnia, and TBI. Among participants without PTSD history, only 14.7% reported a history of TBI, compared to 41.1% of individuals with PTSD history. Findings showed expected trends toward worse physical and mental health among older adults with self-reported PTSD. There was a striking difference in the frequency of TBI history between participants with and without PTSD. These findings underscore a need to assess for PTSD among older adults, particularly those reporting a history of TBI.

Coping patterns associations with cognitive function in older adults.

Cognitive function may contribute to variability in older adults' ability to cope with chronic stress; however, limited research has evaluated this relationship. This study investigated the relationship between theoretically derived coping domains and cognitive function in 165 middle-to-older adults during the Omicron stage of COVID-19. Participants completed a clinical interview and self-report measures of health. The National Alzheimer's Coordinating Center Uniform Data Set neuropsychological battery was used to evaluate memory, language, executive function/speed, and working memory. Structural equation modeling evaluated the underlying factor structure of the Brief COPE adapted for COVID-19. The data supported the proposed second-order Approach factor comprised of Problem-Solving and Emotion Regulation (ER) strategies and a first-order Avoidance factor. Higher Avoidance was associated with greater depression symptoms, lower income and worse memory, executive function, working memory, and verbal fluency performance. Higher Problem-Solving was associated with better verbal fluency performance. ER strategies were not significantly associated with cognitive function. The use of Problem-Solving was not associated with less Avoidance. Greater use of Problem-Solving, ER, and Avoidance were all associated with higher levels of stress. Post-hoc analyses found that higher Acceptance was the only coping strategy associated with less stress. These findings demonstrate that older adults with worse cognitive function were more likely to use Avoidance during the pandemic, which could result in prolonged stress and adverse health consequences. Future research is warranted to investigate whether acceptance-based interventions reduce the avoidance and impact of stress on health in vulnerable older adults.

Neuropsychiatric symptoms: Risk factor or disease marker? A study of structural imaging biomarkers of Alzheimer's disease and incident cognitive decline.

Neuropsychiatric symptoms (NPS) are risk factors for Alzheimer's disease (AD) but can also manifest secondary to AD pathology. Mild behavioral impairment (MBI) refers to later-life emergent and persistent NPS that may mark early-stage AD. To distinguish MBI from NPS that are transient or which represent psychiatric conditions (non-MBI NPS), we investigated the effect of applying MBI criteria on NPS associations with AD structural imaging biomarkers and incident cognitive decline. Data for participants (n = 1273) with normal cognition (NC) or mild cognitive impairment (MCI) in the National Alzheimer's Coordinating Center Uniform Data Set were analyzed. NPS status (MBI, non-MBI NPS) was derived from the Neuropsychiatric Inventory Questionnaire and psychiatric history. Normalized measures of bilateral hippocampal (HPC) and entorhinal cortex (EC) volume, and AD meta-region of interest (ROI) mean cortical thickness were acquired from T1-weighted magnetic resonance imaging scans. Multivariable linear and Cox regressions examined NPS associations with imaging biomarkers and incident cognitive decline, respectively. MBI was associated with lower volume and cortical thickness in all ROIs in both NC and MCI, except for EC volume in NC. Non-MBI NPS were only associated with lower HPC volume in NC. Although both of the NPS groups showed higher hazards for MCI/dementia than No NPS, MBI participants showed more rapid decline. Although both types of NPS were linked to HPC atrophy, only NPS that emerged and persisted in later-life, consistent with MBI criteria, were related to AD neurodegenerative patterns beyond the HPC. Moreover, MBI predicted faster progression to dementia than non-MBI NPS.

Racial and ethnic disparities in potentially inappropriate medication use in patients with dementia.

Racial and ethnic disparities in potentially inappropriate medication (PIM) use among older adults with dementia are unclear. Data were drawn from the baseline visits of participants who were ≥60 years old and diagnosed with dementia in the National Alzheimer's Coordinating Center Uniform Data Set (NACCUDS) recruited from National Institute on Aging (NIA)-funded Alzheimer's Disease Research Centers (ADCs) throughout the United States. PIM utilization was evaluated using the 2019 American Geriatrics Society Beers Criteria for PIM Use in Older Adults. We estimated the association between race and ethnicity and the following outcomes and estimation models: (1) any PIM use, any PIM in each drug class, and any PIM best avoided in dementia patients using logistic regression models, (2) total number of medications, total number of PIMs, and anticholinergic burden scale (ACBS) using Poisson or negative binomial regression models, and (3) proportion of total medications that were PIMs using generalized linear models (GLM). Compared to White participants, Black, Hispanic, and Asian participants reported taking fewer total medications (incidence rate ratio [IRR] ± standard error[SE] = 0.903 ± 0.017, 0.875 ± 0.021, and 0.912 ± 0.041, respectively, all p < 0.01). Asian participants were less likely to be exposed to any PIM (odds ratio [OR] ± SE = 0.619 ± 0.118, p < 0.05). Compared to White participants, Black participants were less likely to be exposed to benzodiazepine (OR ± SE = 0.609 ± 0.094, p < 0.01) and antidepressant (OR ± SE = 0.416 ± 0.103, p < 0.001) PIMs, but greater antipsychotic (OR ± SE = 1.496 ± 0.204, p < 0.01), cardiovascular (OR ± SE = 2.193 ± 0.255, p < 0.001), and skeletal muscle relaxant (OR ± SE = 2.977 ± 0.860, p < 0.001) PIMs. Hispanic participants were exposed to greater skeletal muscle relaxant PIMs and had lower anticholinergic burden. Asian participants were exposed to fewer benzodiazepine PIMs. Significant racial and ethnic disparities in exposure to PIMs and PIMs by medication category in dementia research participants who have access to dementia experts found in the study suggest that disparities may be wider in the larger community.

The Association of Gabapentin Initiation with Cognitive and Behavioral Changes in Older Adults with Cognitive Impairment: A Retrospective Cohort Study.

Although gabapentin has been increasingly prescribed to older adults, the relation between gabapentin initiation and longer-term neurocognitive changes is not well understood. Thus, this study aimed to examine the association of gabapentin initiation with cognitive and motor function decline in older adult participants with cognitive impairment. A retrospective cohort study was conducted using the National Alzheimer's Coordinating Center Uniform Data Set (2005-March 2023). Participants with cognitive impairment at the visit of gabapentin initiation (i.e., index visit) were included. Using the incidence density sampling method, up to nine non-users were randomly selected for each initiator. Cognitive decline over 1 year was defined as any increase in Clinical Dementia Rating global score (CDR®GLOB) or a 1-point increase in CDR® sum of boxes (CDR®SB). Functional status decline over 1 year was defined as at least a 3-point increase in the Functional Activities Questionnaire (FAQ) sum or a 0.3-point increase of mean of FAQ. Motoric decline over 1 year was defined as new clinician reports of gait disorder, falls, and slowness. To mitigate confounding and selection bias, joint stabilized inverse probability of treatment weights and censoring weights were used. Analyses compared index with index+1 and index+2 visits. For the study of cognitive and functional status decline, we included 505 initiators (mean age [SD] 78.8 [7.4]; male = 45%) and 4545 non-users (79.2 [7.6]; 50.1%). For the study of motor decline, we included 353 initiators (78.3 [7.2]; 42.8%) and 3177 non-users (78.5 [7.4]; 48.1%). Gabapentin initiation was not statistically associated with decline on CDR®GLOB, CDR®SB, FAQ sum, or mean FAQ at the index+1 or index+2 visits. However, gabapentin initiation was significantly associated with increased odds of new falls at the index+2 visit (odds ratio [95% confidence interval] 2.5 [1.3, 4.6]). Over 1 or 2 years of follow-up, gabapentin initiation was not associated with decline in cognitive or functional status but was associated with increased odds of falling among research participants with cognitive impairment.

Neuropsychiatric Symptom Profile in Alzheimer's Disease and Their Relationship With Functional Decline

ObjectiveUnderstanding the course of individual neuropsychiatric symptoms (NPS) and their relationship with function is important for planning targeted interventions for preventing and delaying functional decline. This study aims to disentangle relative contributions of individual NPS on functional decline. MethodsLongitudinal study of 9,358 well-characterized participants with baseline diagnoses of Mild Cognitive Impairment or AD in the National Alzheimer's Coordinating Center Uniform Data Set. Function was measured using the Functional Assessment Questionnaire (FAQ). Clinician judgment of seven common behavioral symptoms were examined simultaneously: apathy-withdrawal, depressed mood, visual or auditory hallucinations, delusions, disinhibition, irritability, and agitation. ResultsApathy was the most common NPS at baseline (33.7%) and throughout follow-up, endorsed by clinicians in 63.7% of visits. Apathy was the most persistent with 36.7% of participants having clinician-endorsed apathy in ≥50% of their visits. Apathy strongly correlated with faster rate of functional decline. Compared to those who never had apathy, baseline FAQ was worse in those with intermittent or persistent/always apathy (intermittent: estimated coefficient ±SE=1.228±0.210, 95% CI=[0.817, 1.639]; persistent/always: 2.354±0.244 (95% CI=[1.876, 2.832], both p <0.001). Over time, rate of functional decline was faster in those with intermittent and persistent/always apathy (intermittent: 0.454±0.091, 95% CI=[0.276, 0.632]; persistent/always: 0.635±0.102, 95% CI=[0.436, 0.835], both p <0.001). Worse agitation, delusions, and hallucinations also correlated with functional decline, but magnitudes of the estimates were smaller. ConclusionIndividual NPS may be sensitive targets for tracking longitudinal change in function. The study raises awareness of the need for more comprehensive assessment of functional decline in AD patients with noncognitive symptoms.

Neuropsychiatric symptoms and white matter hyperintensities in older adults without dementia.

We aimed to examine associations between neuropsychiatric symptoms (NPS) and white matter hyperintensities (WMH) status in older adults without dementia under the hypothesis that WMH increased the odds of having NPS. Longitudinal analysis of data acquired from the National Alzheimer's Coordinating Center Uniform Data Set. Data were derived from 46 National Institute on Aging - funded Alzheimer's Disease Research Centers. NACC participants aged ≥50 years with available data on WMH severity with a diagnosis of mild cognitive impairment (MCI) or who were cognitively unimpaired (CU) were studied. Among 4617 CU participants, 376 had moderate and 54 extensive WMH. Among 3170 participants with MCI, 471 had moderate and 88 had extensive WMH. Using Cardiovascular Health Study (CHS) scores, WMH were coded as no to mild (CHS score: 0-4), moderate (score: 5-6) or extensive (score: 7-8). NPS were quantified on the Neuropsychiatric Inventory Questionnaire. Binary logistic regression models estimated the odds of reporting each of 12 NPS by WMH status separately for individuals with MCI or who were CU. Compared to CU individuals with no to mild WMH, the odds of having elation [9.87, (2.63-37.10)], disinhibition [4.42, (1.28-15.32)], agitation [3.51, (1.29-9.54)] or anxiety [2.74, (1.28-5.88)] were higher for the extensive WMH group, whereas the odds of having disinhibition were higher for the moderate WMH group [1.94, (1.05-3.61)]. In the MCI group, he odds of NPS did not vary by WMH status. Extensive WMH were associated with higher odds of NPS in CU older adults but not in those with MCI.

The Montreal Cognitive Assessment: Norms and Reliable Change Indices for Standard and MoCA-22 Administrations.

The Montreal Cognitive Assessment (MoCA) is among the most frequently administered cognitive screening tests, yet demographically diverse normative data are needed for repeated administrations. Data were obtained from 18,410 participants using the National Alzheimer's Coordinating Center Uniform Data Set. We developed regression-based norms using Tobit regression to account for ceiling effects, explored test-retest reliability of total scores and by domain stratified by age and diagnosis with Cronbach's alpha, and reported the cumulative change frequencies for individuals with serial MoCA administrations to gage expected change. Strong ceiling effects and negative skew were observed at the total score, domain, and item levels for the cognitively normal group, and performances became more normally distributed as the degree of cognitive impairment increased. In regression models, years of education was associated with higher MoCA scores, whereas older age, male sex, Black and American Indian or Alaska Native race, and Hispanic ethnicity were associated with lower predicted scores. Temporal stability was adequate and good at the total score level for the cognitively normal and cognitive disorders groups, respectively, but fell short of reliability standards at the domain level. MoCA total scores are adequately reproducible among those with cognitive diagnoses, but domain scores are unstable. Robust regression-based norms should be used to adjust for demographic performance differences, and the limited reliability, along with the ceiling effects and negative skew, should be considered when interpreting MoCA scores.

Depression, Vascular Burden, and Dementia Prevalence in Late Middle-Aged and Older Black Adults.

Late-life depression and white matter hyperintensities (WMH) have been linked to increased dementia risk. However, there is a dearth of literature examining these relationships in Black adults. We investigated whether depression or WMH volume are associated with a higher likelihood of dementia diagnosis in a sample of late middle-aged to older Black adults, and whether dementia prevalence is highest in individuals with both depression and higher WMH volume. Secondary data analysis involved 443 Black participants aged 55+ with brain imaging within 1 year of baseline visit in the National Alzheimer's Coordinating Center Uniform Data Set. Chi-square analyses and logistic regression models controlling for demographic variables examined whether active depression in the past 2 years, WMH volume, or their combination were associated with higher odds of all-cause dementia. Depression and higher WMH volume were associated with a higher prevalence of dementia. These associations remained after controlling for demographic factors, as well as vascular disease burden. Dementia risk was highest in the depression/high WMH volume group compared to the depression-only group, high WMH volume-only group, and the no depression/low WMH volume group. Post hoc analyses comparing the Black sample to a demographically matched non-Hispanic White sample showed associations of depression and the combination of depression and higher WMH burden with dementia were greater in Black compared to non-Hispanic White individuals. Results suggest late-life depression and WMH have independent and joint relationships with dementia and that Black individuals may be particularly at risk due to these factors.

Association between clinical dementia rating and clinical outcomes in Alzheimer's disease.

We examined associations between the Clinical Dementia Rating Scale (CDR) and function (Functional Assessment Scale [FAS]), neuropsychiatric symptoms (Neuropsychiatric Inventory Questionnaire [NPI-Q]), and cognitive impairment in Alzheimer's disease (AD). We used data from the National Alzheimer's Coordinating Center Uniform Data Set and defined cognitively unimpaired and AD stages using CDR-global. Functional and neuropsychiatric symptoms occur as early as the mild cognitive impairment (MCI) phase. The adjusted lest square mean FAS (95% confidence interval [CI]) was lowest in cognitively unimpaired (3.88 [3.66, 4.11] to 5.01 [4.76, 5.26]) and higher with more advanced AD (MCI: 8.17 [6.92, 9.43] to 20.87 [19.53, 22.20]; mild: 18.54 [17.57, 19.50] to 28.13 [27.14, 29.12]; moderate: 26.01 [25.31, 26.70] to 29.42 [28.73, 30.10]). FAS and NPI-Q scores increased steeply with MCI (NPI-Q: 5.55 [4.89, 6.20] to 7.11 [6.43, 7.78]) and mild AD dementia (NPI-Q: 6.66 [5.72, 7.60] to 8.32 [7.32, 9.33]). CDR-global staged AD by capturing differences in relevant outcomes along AD progression. There were strong associations among CDR and the various outcomes relevant to healthcare providers, patients, and their care givers, such as activities of daily living.Overall, activities of daily living, neuropsychiatric symptoms, and cognitive function outcomes deteriorated over time and can be observed in early stages of AD (MCI or mild dementia).Our findings directly inform the current understanding of AD progression and can aid in care planning and benefit assessments of early AD interventions to delay the progression of AD to more advanced stages.

Retention of American Indian and Alaska Native participants in the National Alzheimer's Coordinating Center Uniform Data Set.

The number of American Indian and Alaska Native (AI/AN) elders is expected to double by 2060. Thus it is imperative to retain AI/AN participants in longitudinal research studies to identify novel risk factors and potential targets for intervention for Alzheimer's disease and related dementias in these communities. The National Alzheimer's Coordinating Center houses uniformly collected longitudinal data from the network of National Institute on Aging (NIA)-funded Alzheimer's Disease Research Centers (ADRCs). We used logistic regression to quantify participant retention at 43 ADRCs, comparing self-identified AI/AN participants to non-Hispanic White (NHW) participants, adjusting for potential confounding factors including baseline diagnosis, age, sex, education, and smoking. The odds of AI/AN participant retention at the first follow-up visit were significantly lower than those for NHW participants (adjusted odds ratio [aOR]: 0.599; 95%: 0.46-0.78; p<0.001). These results suggest the need for improved strategies to retain AI/AN participants, perhaps including improved researcher-community relationships and community engagement and education. American Indian and Alaska Native (AI/AN) research participants were retained to the first follow-up appointment at lower rates than non-Hispanic White (NHW) participants. AI/AN participants are retained at lower rates than NHW participants for long-term follow-up. The majority of AI/AN participants were not retained to the second follow-up visit.

Clinical Manifestations.

Mild behavioral impairment (MBI) identifies a high-risk group for Alzheimer's disease and related dementias (ADRD), leveraging the risk associated with later-life emergent and persistent neuropsychiatric symptoms (NPS). MBI may act as a complementary behavioral analog to later-life emergent cognitive symptoms (mild cognitive impairment, MCI). These constructs are not mutually exclusive and can co-occur. We characterized the relationship between MBI, grey matter volume in the hippocampus and entorhinal cortex, and incident cognitive decline in older adults with normal cognition (NC) and MCI. Seven-hundred-forty-two participants were included from the National Alzheimer's Coordinating Center Uniform Dataset. The Normative Morphometry Image Statistics tool was used to generate estimates of grey matter volume for the bilateral hippocampi and entorhinal cortices, normalized by age, sex, total intracranial volume, and image quality. NPS were evaluated using the informant-rated Neuropsychiatric Inventory Questionnaire, from which MBI scores were derived based on a published algorithm. Associations between MBI status and the regions-of-interest were modelled separately in NC and MCI using multivariable linear regressions, adjusting for education and clinical-MRI visit interval time. Associations between MBI status and incident cognitive decline were modelled using Cox proportional hazards regressions. Participant characteristics are summarized in Table 1. As per Figures 1 and 2, NC participants with MBI had lower grey matter volume in the bilateral hippocampi (B = -0.40, 95%CI:[-0.66, -0.15], p = .004), and a greater hazard of incident MCI or dementia, than those without MBI (HR = 3.34, 95%CI:[2.04, 5.48), p<.001). NC MBI+ participants also had lower grey matter volume in the bilateral entorhinal cortices compared to NC MBI- participants, although not statistically significant (B = -0.13, 95%CI:[-0.35, -0.08], p = .22). In MCI, participants with MBI had lower grey matter volume bilaterally in both the hippocampus (B = -0.46, 95%CI:[-0.80, -0.12], p = .01) and entorhinal cortex (B = -0.42, 95%CI:[-0.76, -0.12], p = .009), and had greater progression-rates to dementia (HR = 4.13, 95%CI:[2.45, 6.94), p<.001), than those without MBI. Our findings suggest that evaluating dementia-free older adults for MBI status in conjunction with cognitive status identifies a group further along the ADRD continuum than those without MBI, who have greater baseline atrophy in key ADRD regions and greater progression rates to later cognitive stages.

Reliability of remote National Alzheimer's Coordinating Center Uniform Data Set data.

The National Alzheimer's Coordinating Center (NACC) Uniform Data Set (UDS) neuropsychological battery is being used to track cognition in participants across the country, but it is unknown if scores obtained through remote administration can be combined with data obtained in person. The remote UDS battery includes the blind version of the Montreal Cognitive Assessment (MoCA), Number Span, Semantic and Phonemic Fluency, and Craft Story. For these tests, we assessed intraclass correlation coefficients (ICCs) between in-person and remote scores in 3838 participants with both in-person and remote UDS assessments, and we compared annual score changes between modalities in a subset that had two remote assessments. All tests exhibited moderate to good reliability between modalities (ICCs=0.590-0.787). Annual score changes were also comparable between modalities except for Craft Story Immediate Recall, Semantic Fluency, and Phonemic Fluency. Our findings generally support combining remote and in-person scores for the majority of UDS tests.

Demographically-adjusted normative data among Latinos for the version 3 of the Alzheimer's Disease Centers' Neuropsychological Test Battery in the Uniform Data Set.

We developed demographically-adjusted normative data for Spanish- and English-speaking Latinos on the Version 3.0 of the National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDS3-NB). Healthy Latino adults (N=437) age 50-94 (191 Spanish- and 246 English-speaking) enrolled in Alzheimer's Disease Research Centers completed the UDS3-NB in their preferred language. Normative data were developed via multiple linear regression models on UDS3-NB raw scores stratified by language group with terms for demographic characteristics (age, years of formal education, and sex). Younger age and more years of education were associated with better performance on most tests in both language groups, with education being particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and language groups. These normative data are a crucial step toward improving diagnostic accuracy of the UDS3-NB for neurocognitive disorders among Latinos in the United States and addressing disparities in Alzheimer's disease and related dementias. We developed normative data on the UDS3-NB for Latinos in the US ages 50-94. Younger age and more years of education were linked to better raw scores in several cognitive tests. Education was particularly influential on raw scores among Spanish-speakers. Sex effects varied across tests and between English- and Spanish-speaking Latinos. These normative data might improve diagnostic accuracy of the UDS3-NB among Latinos.

Quantile partially linear additive model for data with dropouts and an application to modeling cognitive decline.

The National Alzheimer's Coordinating Center Uniform Data Set includes test results from a battery of cognitive exams. Motivated by the need to model the cognitive ability of low-performing patients we create a composite score from ten tests and propose to model this score using a partially linear quantile regression model for longitudinal studies with non-ignorable dropouts. Quantile regression allows for modeling non-central tendencies. The partially linear model accommodates nonlinear relationships between some of the covariates and cognitive ability. The data set includes patients that leave the study prior to the conclusion. Ignoring such dropouts will result in biased estimates if the probability of dropout depends on the response. To handle this challenge, we propose a weighted quantile regression estimator where the weights are inversely proportional to the estimated probability a subject remains in the study. We prove that this weighted estimator is a consistent and efficient estimator of both linear and nonlinear effects.

Exploring the combined effects of sleep apnea and APOE-e4 on biomarkers of Alzheimer's disease.

We determined the interactive associations of apolipoprotein e4 (APOE-e4), and obstructive sleep apnea (OSA) on biomarkers of Alzheimer's disease and examined for racial/ethnic differences of this association. We used data from the National Alzheimer's Coordinating Center Uniform Dataset (NACC UDS). All participants undergo annual observations, including demographic survey, battery of neuropsychological tests, blood draw (with genotyping), and a clinical evaluation with medical and cognitive/dementia status assessment, while a subset of participants have cerebrospinal fluid (CSF) biomarkers and neuroimaging data. Biomarkers of AD were characterized as the presence of abnormally low amyloid in CSF, via validated Aβ42 cut off protocols, and total segmented hippocampal volume, and volume of white matter hyper intensities (WMH). While clinical markers (to preview cognitive relationships) were characterized via the Montreal Cognitive Assessment (MOCA). Biomarker and clinical marker data were derived from 1,387 participants at baseline (mean age = 69.73 ± 8.32; 58.6% female; 13.7% Black/African American), 18.4% of the sample had sleep apnea, and 37.9% were APOE-e4 carriers. Our results confirmed previous reports that OSA and APOE-e4 were independently associated with AD through abnormal levels of amyloid (F (1,306) = 4.27; p = 0.040; F (1,285) = 60.88; p < 0.000, respectively), WMH volume (F (1,306) = 4.27; p = 0.040; F (1,285) = 60.88; p < 0.000, respectively), and MOCA scores (F (1,306) = 4.27; p = 0.040; F (1,285) = 60.88; p < 0.000, respectively). No significant interaction between OSA and APOE-e4 relative to amyloid emerged, however, race stratified analyses indicated the interaction of OSA and APOE-e4 and was significantly associated with WMH and hippocampal volume in Black/African American, but not white participants. OSA and APOE-e4 are interactively associated with WHM in Black/African Americans. This interaction may partially explicate increased levels of risk in this population.

Concordance Between Logical Memory and Craft Story 21 in Community-Dwelling Older Adults: The Role of Demographic Factors And Cognitive Status.

Episodic memory loss, a hallmark symptom of Alzheimer's Disease, is frequently quantified by story memory performance. The National Alzheimer's Coordinating Center Uniform Data Set Neuropsychological Battery (UDSNB) replaced Logical Memory with Craft Story 21 in UDSNB Version 3. The concordance between these story memory tasks is poorly characterized in demographically diverse older adults, possibly jeopardizing the integrity of longitudinal data in aging cohorts. Einstein Aging Study participants (n = 298; Mage = 76.6; Meducation = 15; 66.4% women; 43.3% Non-Hispanic White) completed UDSNB measures, including Craft Story and Logical Memory. Classification as normal cognition (n = 206) or mild cognitive impairment (n = 90) was based on Jak/Bondi criteria. Analyses included correlations, linear regression, and equipercentile equating methods to characterize the relationship between Logical Memory and Craft Story. Multivariate linear mixed effects models explored the association of covariates and practice effects over follow-up, stratified by cognitive status and race/ethnicity. Immediate (r = 0.54) and delayed (r = 0.56) versions of Logical Memory and Craft Story were moderately correlated. Age, education, depression, and female sex were associated with Logical Memory, while age, education, cognitive status, and male sex were associated with Craft Story. Significant differential effects of sex on story memory were observed. We demonstrated that Logical Memory and Craft Story may be used largely interchangeably; however, memory may be enhanced for stories with a protagonist of the same sex as the participant. Craft Story was somewhat more associated with mild cognitive impairment in the overall sample, but especially in non-Hispanic Black participants. We discuss how results inform test selection considerations.

Educational and Clinical Associations With Longitudinal Cognitive Function and Brain Imaging in American Indians: The Strong Heart Study.

Little is known about incidence of vascular and Alzheimer dementias in American Indians. We conducted a large, heterogeneous, population-based, longitudinal cohort study of brain aging in community-dwelling American Indians aged 64-95 years from 11 tribes across 3 states, with neurologic examinations, 1.5T MRI, and extensive cognitive testing. Visit 1 in 2010-2013 (n = 817) and visit 2 in 2017-2019 (n = 403) included all willing, surviving participants. Standardized cognitive tests at both visits included Modified Mini-Mental Status Examination (MMSE), Wechsler Adult Intelligence Scale digit symbol coding (WAIS), Controlled Oral Word Association (COWA), and California Verbal Learning Test short form (CVLT). Test materials added at follow-up included Wide Range Achievement (reading) Test (WRAT) and National Alzheimer Coordinating Center Uniform Data Set cognitive battery (v3 form C2), including Montreal Cognitive Assessment (MoCA). MRI neuroradiologists coded infarcts, hemorrhages, white matter hyperintensities, sulcal atrophy, and ventricle enlargement. The mean time between examinations was 6.7 years (SD 1.1, range 3.8-9.1 years). Years of formal education had modest correlation with WRAT reading score (r = 0.45). Prevalence and incidence (respectively) of infarcts were 32% and 12.8/1,000 person-years (PYs) hemorrhages 6% and 4.4/1000 PY worsening sulci 74% and 19.0/1000 PY worsening ventricle 79% and 30.1/1000 PY worsening leukoaraiosis 44% and 26.1/1000 PY. Linear losses per year in cognitive scores were 0.6% MMSE, 1.2% WAIS, 0.6% COWA, and 2.2% CVLT. The mean MoCA scores were 18.9 (SD 4.3). These are the first data on longitudinal cognitive and imaging changes in American Indians and first reports of Alzheimer disease-related features. The mean scores in MoCA were similar or lower than standard cutoffs used to diagnose dementia in other racial/ethnic groups, suggesting that standardized cognitive tests may not perform well in this population. Test validation, adaptation, and score adjustment are warranted. Years of education were a poor proxy for premorbid function, suggesting novel methods for cognitive score contextualization is also needed in this population. Evaluation of selective survival suggests attrition from death, and frailty should be accounted for in causal analyses. Overall, these data represent a unique opportunity to examine neurology topics of critical importance to an understudied population.