Identification of Heterogeneous Cognitive Subgroups in Community-Dwelling Older Adults: A Latent Class Analysis of the Einstein Aging Study.
ABSTRACT: OBJECTIVES:The aim of this study was to identify natural subgroups of older adults based on cognitive performance, and to establish each subgroup's characteristics based on demographic factors, physical function, psychosocial well-being, and comorbidity. METHODS:We applied latent class (LC) modeling to identify subgroups in baseline assessments of 1345 Einstein Aging Study (EAS) participants free of dementia. The EAS is a community-dwelling cohort study of 70+ year-old adults living in the Bronx, NY. We used 10 neurocognitive tests and 3 covariates (age, sex, education) to identify latent subgroups. We used goodness-of-fit statistics to identify the optimal class solution and assess model adequacy. We also validated our model using two-fold split-half cross-validation. RESULTS:The sample had a mean age of 78.0 (SD=5.4) and a mean of 13.6 years of education (SD=3.5). A 9-class solution based on cognitive performance at baseline was the best-fitting model. We characterized the 9 identified classes as (i) disadvantaged, (ii) poor language, (iii) poor episodic memory and fluency, (iv) poor processing speed and executive function, (v) low average, (vi) high average, (vii) average, (viii) poor executive and poor working memory, (ix) elite. The cross validation indicated stable class assignment with the exception of the average and high average classes. CONCLUSIONS:LC modeling in a community sample of older adults revealed 9 cognitive subgroups. Assignment of subgroups was reliable and associated with external validators. Future work will test the predictive validity of these groups for outcomes such as Alzheimer's disease, vascular dementia and death, as well as markers of biological pathways that contribute to cognitive decline. (JINS, 2018, 24, 511-523).
Project description:BACKGROUND:In a previous report, we used latent class analysis (LCA) to identify natural subgroups of older adults in the Einstein Aging Study (EAS) based on neuropsychological performance. These subgroups differed in demographics, genetic profile, and prognosis. Herein, we assess the generalizability of these findings to an independent sample, the Rush Memory and Aging Project (MAP), which used an overlapping, but distinct neuropsychological battery. OBJECTIVE:Our aim was to identify the association of natural subgroups based on neuropsychological performance in the MAP cohort with incident dementia and compare them with the associations identified in the EAS. METHODS:MAP is a community-dwelling cohort of older adults living in the northeastern Illinois, Chicago. Latent class models were applied to baseline scores of 10 neuropsychological measures across 1,662 dementia-free MAP participants. Results were compared to prior findings from the EAS. RESULTS:LCA resulted in a 5-class model: Mixed-Domain Impairment (n?=?71, 4.3%), Memory-specific-Impairment (n?=?274, 16.5%), Average (n?=?767, 46.1%), Frontal Impairment (n?=?222, 13.4%), and a class of Superior Cognition (n?=?328, 19.7%). Similar to the EAS, the Mixed-Domain Impairment, the Memory-Specific Impairment, and the Frontal Impairment classes had higher risk of incident Alzheimer's disease when compared to the Average class. By contrast, the Superior Cognition had a lower risk of Alzheimer's disease when compared to the Average class. CONCLUSIONS:Natural cognitive subgroups in MAP are similar to those identified in EAS. These similarities, despite study differences in geography, sampling strategy, and cognitive tests, suggest that LCA is capable of identifying classes that are not limited to a single sample or a set of cognitive tests.
Project description:To examine if incident and preexisting diabetes mellitus (DM) were associated with cognitive decline among African Americans (AAs) and European Americans (EAs).Based on a prospective study of 7,740 older adults (mean age 72.3 years, 64% AA, 63% female), DM was ascertained by hypoglycemic medication use and Medicare claims during physician or hospital visits, and cognition by performance on a brief battery for executive functioning, episodic memory, and Mini-Mental State Examination (MMSE). Decline in composite and individual tests among those with incident DM, with preexisting DM, and without DM was studied using a linear mixed effects model with and without change point.At baseline, 737 (15%) AAs and 269 (10%) EAs had preexisting DM. Another 721 (17%) AAs and 289 (12%) EAs had incident DM in old age. Following incident DM, cognitive decline increased by 36% among AAs and by 40% among EAs compared to those without DM. No significant difference was observed between AAs and EAs (p = 0.64). However, cognitive decline increased by 17% among AAs with preexisting DM compared to those without DM, but no increased decline was observed among EAs with preexisting DM. In secondary analyses, faster decline in executive functioning and episodic memory was observed following incident DM.In old age, faster cognitive decline was present among AAs and EAs following incident DM, compared to cognitive decline prior to DM, and among those without DM. This underscores the need for stronger prevention and control of DM in old age.
Project description:BACKGROUND:The association of the APOE?4 allele with incident Alzheimer's dementia is higher among European Americans (EAs) than African Americans (AAs), but similar for the rate of cognitive decline. OBJECTIVE:To examine the racial differences in the association of the APOE?4 allele with incident Alzheimer's dementia and cognitive decline. METHODS:Using a population-based sample of 5,117 older adults (66% AAs and 63% females), we identified cognitive trajectory groups from a latent class mixed model and examined the association of the APOE?4 allele with these groups. RESULTS:The frequency of the APOE?4 allele was higher among AAs than EAs (37% versus 26%). Four cognitive trajectories were identified: slow, mild, moderate, and rapid. Overall, AAs had a lower baseline global cognition than EAs, and a higher proportion had rapid (7% versus 5%) and moderate (20% versus 15%) decline, but similar mild (44% versus 46%), and lesser slow (29% versus 34%) decline compared to EAs. Additionally, 25% of AAs (13% of EAs) with mild and 5% (<1% of EAs) with slow decline were diagnosed with incident Alzheimer's dementia. The APOE?4 allele was associated with higher odds of rapid and moderate decline compared to slow decline among AAs and EAs, but not with mild decline. CONCLUSIONS:AAs had lower cognitive levels and were more likely to meet the cognitive threshold for Alzheimer's dementia among mild and slow decliners, explaining the attenuated association of the ?4 allele with incident Alzheimer's dementia among AAs.
Project description:Cognitive changes during the preclinical phase of Alzheimer's disease (AD) dementia have been characterized among European Americans (EAs), but studies of preclinical changes among African Americans (AAs) are notably absent.Preclinical changes in cognition before the development of AD dementia and mild cognitive impairment over a period of 18 years were examined using change points in a biracial sample of 2,125 older adults.Of 2,125 participants, 442 (21%) developed AD dementia and 661 (31%) developed mild cognitive impairment. A cognitive change point occurred between 4 and 5 years before the clinical diagnosis of AD dementia. Differences between AAs and EAs were observed: EAs had a higher starting level of composite cognitive function, and a change point occurred 4.3 years before AD dementia among AAs and 4.7 years among EAs. The slope of cognitive decline after the change point among those developing clinical AD dementia was significantly greater among EAs (0.233 units/y) than among AAs (0.171 units/y; p < .001). This difference in slope of cognitive decline persisted after diagnosis of AD dementia so that at the conclusion of observation the difference in average cognitive level was reversed. AAs without cognitive impairment had a lower average baseline of cognition than EAs, but the slopes of cognitive decline were similar.A prominent change to a steeper slope of cognitive decline occurs between 4 and 5 years prior to the diagnosis of AD dementia. The slope of cognitive decline after the change point is steeper among EAs than AAs.
Project description:OBJECTIVE:Use latent class analysis (LCA) to identify patterns of cognitive functioning in a sample of older adults with clinical depression and without dementia and assess demographic, psychiatric, and neurobiological predictors of class membership. METHOD:Neuropsychological assessment data from 121 participants in the Alzheimer's Disease Neuroimaging Initiative-Depression project (ADNI-D) were analyzed, including measures of executive functioning, verbal and visual memory, visuospatial and language functioning, and processing speed. These data were analyzed using LCA, with predictors of class membership such as depression severity, depression and treatment history, amyloid burden, and APOE e4 allele also assessed. RESULTS:A two-class model of cognitive functioning best fit the data, with the Lower Cognitive Class (46.1% of the sample) performing approximately one standard deviation below the Higher Cognitive Class (53.9%) on most tests. When predictors of class membership were assessed, carrying an APOE e4 allele was significantly associated with membership in the Lower Cognitive Class. Demographic characteristics, age of depression onset, depression severity, history of psychopharmacological treatment for depression, and amyloid positivity did not predict class membership. CONCLUSION:LCA allows for identification of subgroups of cognitive functioning in a mostly cognitively intact late life depression (LLD) population. One subgroup, the Lower Cognitive Class, more likely to carry an APOE e4 allele, may be at a greater risk for subsequent cognitive decline, even though current performance on neuropsychological testing is within normal limits. These findings have implications for early identification of those at greatest risk, risk factors, and avenues for preventive intervention.
Project description:Fall prevention is important for maintaining mobility and independence into old age. Approaches for reducing falls include exercise, tai chi, and home modifications; however, causes of falling are multifactorial and include not just physical but cognitive factors. Cognitive decline occurs with age, but older adults with the greatest declines in executive function experience more falls. The purpose of this study was twofold: to demonstrate the feasibility of a community-based cognitive training program for cognitively intact Black older adults and to analyze its impact on gait and balance in this population.This pilot study used a pretest/posttest randomized trial design with assignment to an intervention or control group. Participants assigned to the intervention completed a computer-based cognitive training class that met 2 days a week for 60 min over 10 weeks. Classes were held at senior/community centers. Primary outcomes included balance as measured by the Berg Balance Scale (BBS), 10-meter gait speed, and 10-meter gait speed under visuospatial dual-task condition. All measures were assessed at baseline and immediately post-intervention.Participants were community-dwelling Black adults with a mean age of 72.5 and history of falls (N = 45). Compared to controls, intervention participants experienced statistically significant improvements in BBS and gait speed. Mean performance on distracted gait speed also improved more for intervention participants compared to controls.Findings from this pilot randomized trial demonstrate the feasibility of a community-based cognitive training intervention. They provide initial evidence that cognitive training may be an efficacious approach toward improving balance and gait in older adults known to have a history of falls.
Project description:To examine associations between specific inflammatory biomarkers and cognitive function in African Americans (AAs) and European Americans (EAs) with prevalent vascular risk factors.Cross-sectional analysis using generalized estimating equations to account for familial clustering; standardized ?-coefficients, adjusted for age, sex, and education are reported.Community cohort study in Jackson, Mississippi, and Rochester, Minnesota.Genetic Epidemiology Network of Arteriopathy (GENOA)-Genetics of Microangiopathic Brain Injury (GMBI) Study participants.Associations between inflammation (high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, soluble tumor necrosis factor (TNF) receptor 1 and 2 (sTNFR1, sTNFR2)) and cognitive function (global, processing speed, language, memory, and executive function) were examined in AAs and EAs (N = 1,965; aged 26-95, 64% women, 52% AA, 75% with hypertension).In AAs, higher sTNFR2 was associated with poorer cognition in all domains (global: -0.11, P = .009; processing speed: -0.11, P < .001; language: -0.08, P = .002; memory: -0.09, P = .008; executive function: -0.07, P = .03); sTNFR1 was associated with slower processing speed (-0.08, P < .001) and poorer executive function (-0.08, P = .008); higher CRP was associated with slower processing speed (-0.04, P = .024), and higher IL6 was associated with poorer executive function (-0.07, P = .02). In EA, only higher sTNFR1 was associated with slower processing speed (-0.05, P = .007). Associations were not found between cognition and sTNFR2, CRP, or IL6 in EA.In a population with high vascular risk, adverse associations between inflammation and cognitive function were especially apparent in AAs, primarily involving markers of TNF? activity.
Project description:Cognitive flexibility is a critical component of executive function and is strongly influenced by genetic factors. We conducted a genome-wide association study of cognitive flexibility (as measured by perseverative errors on the Wisconsin Card Sorting Test) in two sets of African American (AA) and European American (EA) subjects (Yale-Penn-1: 1,411 AAs/949 EAs; Yale-Penn-2: 1,178 AAs/1,335 EAs). We examined the association of cognitive flexibility with genotyped or imputed SNPs across the genome. In AAs, two correlated common single nucleotide polymorphisms (SNPs) (rs7165213/rs35633795) in the downstream region of the noncoding gene LOC101927286 on chromosome 15 showed genome-wide significant (GWS) associations with cognitive flexibility (Yale-Penn-1: p?=?6.0 × 10-9 /1.3 × 10-8 ; Yale-Penn-2: p?=?.029/.010; meta-analysis: p?=?4.2 × 10-7 /1.0 × 10-7 ) in the same effect direction. In EAs, no GWS associations were observed. Enriched gene sets identified by Data-driven Expression-Prioritized Integration for Complex Traits (DEPICT) analysis of the top SNPs (pmeta-analysis ?<?10-5 ) included the signalosome and ubiquitin-specific peptidase 9, X-linked (USP9X) subnetwork in AAs, and abnormal frontal and occipital bone morphology in EAs. We also performed polygenic risk score (PRS) analysis to examine the genetic correlation of cognition-proxy phenotypes (general cognitive function, education attainment, childhood intelligence, and infant head circumference) and cognitive flexibility in EAs. The PRS derived from general cognitive function-associated SNPs was significantly associated with cognitive flexibility. Nongenetic factors (age, education, sex, and tobacco recency) also exerted significant effects on cognitive flexibility. Our study demonstrates that both genetic and nongenetic factors impact cognitive flexibility, and variants in genes involved in protein degradation and brain development may contribute to population variation in cognitive function.
Project description:PURPOSE: Cognitive functions in community-dwelling adults at high risk of obstructive sleep apnea have not been described and nor are associations between cognitive functions and obstructive sleep apnea severity fully understood. The study aimed to describe verbal memory and executive function in community-dwelling adults identified by the Berlin Questionnaire and to investigate associations between these cognitive domains and different obstructive sleep apnea severity indicators. METHODS: Among 29,258 age- and gender-stratified persons 30-65 years who received the Berlin Questionnaire by mail, 16,302 (55.7%) responded. From 654 randomly drawn respondents with BQ high risk who were approached for study participation, 290 participants (55.9% males, mean age 48.2 years) were included. Verbal memory was assessed by Rey Auditory Verbal Learning Test and executive function by Stroop test. Obstructive sleep apnea severity indicators were assessed by polysomnography. RESULTS: Mean (standard deviation) verbal learning score was 42.0 (8.9), mean interference time was 31.1 (12.7), median (25th percentile, 75th percentile) apnea-hypopnea index was 7.7 (2.4-22.2), and mean average oxygen saturation was 94.3 (2.0). Verbal learning score was independently associated with average oxygen saturation (? = 0.721, p = 0.025) in multivariate linear regression models adjusted for putative confounders. Interference time was only related to OSA severity indicators in bivariate analyses. CONCLUSIONS: Verbal memory and executive function impairments were mild in community-dwelling adults at high risk of obstructive sleep apnea. Average oxygen saturation was the indicator of obstructive sleep apnea severity most strongly associated with cognitive function.
Project description:BACKGROUND:Advanced chronic kidney disease (CKD) is associated with altered cerebral structure and function. Relationships between mild-to-moderate CKD and brain morphology and cognitive performance were evaluated in European Americans (EAs). METHODS:A total of 478 EAs with estimated glomerular filtration rate (eGFR) >45 mL/min/1.73 m(2) and urine albumin:creatinine ratio (UACR) < 300 mg/g, most with type 2 diabetes (T2D), were included. Measures of total intracranial volume (TICV), cerebrospinal fluid volume, total white matter volume (TWMV), total gray matter volume (TGMV), total white matter lesion volume (TWMLV), hippocampal white matter volume (HWMV) and hippocampal gray matter volume (HGMV) were obtained with magnetic resonance imaging. Cognitive testing included memory (Rey Auditory Visual Learning Test), global cognition (Modified Mini-Mental State Examination) and executive function (Stroop Task, Semantic Fluency, Digit Symbol Substitution Test). Associations with CKD were assessed using log-transformed eGFR and UACR, adjusted for age, sex, body mass index, smoking, hemoglobin A1c, blood pressure, diabetes duration, cardiovascular disease and education. RESULTS:Participants were 55.2% female, 78.2% had T2D; mean ± SD age 67.6 ± 9.0 years, T2D duration 16.4 ± 6.5 years, eGFR 92.0 ± 22.3 mL/min/1.73 m(2) and UACR 23.8 ± 39.6 mg/g. In adjusted models, eGFR was negatively associated with TICV only in participants with T2D [parameter estimate (?): -72.2, P = 0.002]. In non-diabetic participants, inverse relationships were observed between eGFR and HGMV (?: -1.0, P = 0.03) and UACR and normalized TWMLV (?: -0.2, P = 0.03). Kidney function and albuminuria did not correlate with cognitive testing. CONCLUSIONS:In EAs with mild CKD enriched for T2D, brain structure and cognitive performance were generally not impacted. Longitudinal studies are necessary to determine when cerebral structural changes and cognitive dysfunction develop with progressive CKD in EAs.