Effect of Metabolic Syndrome Risk Factors on Processing Speed and Executive Function in Three Racialized Groups.

BACKGROUND: Metabolic syndrome (MetS) has been associated with increased risk for Alzheimer's disease and related dementias (ADRD). Understanding the association of MetS risk factors to processing speed and executive function in the pre-clinical stages of ADRD in under-represented groups would offer insight on potential mechanisms through which MetS associates with ADRD risk. OBJECTIVE: Examine association of MetS features and processing speed and executive function across three racial groups. METHODS: Cognitively unimpaired adults from the Wisconsin Alzheimer's Disease Research Center and the Wisconsin Registry for Alzheimer's Disease Prevention completed blood-draws and neuropsychological testing. Six cognitive outcomes were assessed in association to MetS risk factors: Trailmaking Tests A and B, Animal Fluency, Digit Symbol, and composite scores for Processing Speed and Executive Function. Linear mixed effect models were used to assess the relationship between MetS risk factor count and longitudinal cognitive performance across three racialized groups. RESULTS: Participant sample sizes varied by outcome analyzed (N = 714-1,088). African American and Native American groups exhibited higher rates of MetS than non-Hispanic Whites. MetS was associated with processing speed and executive function across all racialized groups. Three-way interaction by racialized group was limited to one cognitive outcome: Trailmaking Test A. CONCLUSION: Metabolic dysfunction incrementally affects cognitive trajectory, with generally similar associations across racial groups. Since racialized groups exhibit higher levels of both MetS and ADRD, MetS may represent a driving factor for increased ADRD risk experience by racialized group and an important and modifiable target through which to reduce risk of ADRD.

Wisconsin Healthcare Utilization Cost Among American Indians/Alaska Natives with and without Alzheimer's Disease and Related Dementias.

Individuals with Alzheimer's disease and related dementias (ADRD) accrue higher healthcare utilization costs than peers without ADRD, but incremental costs of ADRD among American Indians/Alaska Natives (AI/AN) is unknown. State-wide paid electronic health record data were retrospectively analyzed using percentile-based bootstrapped 95% confidence intervals of the weighted mean difference of total 5-year billed costs to compare total accrued for non-Tribal and Indian Health Service utilization costs among Medicaid and state program eligible AI/AN, ≥40 years, based on the presence/absence of ADRD (matching by demographic and medical factors). AI/AN individuals with ADRD accrued double the costs compared to those without ADRD, costing an additional $880.45 million to $1.91 billion/year.

Measurement batch differences and between-batch conversion of Alzheimer's disease cerebrospinal fluid biomarker values.

INTRODUCTION: Batch differences in cerebrospinal fluid (CSF) biomarker measurement can introduce bias into analyses for Alzheimer's disease studies. We evaluated and adjusted for batch differences using statistical methods. METHODS: A total of 792 CSF samples from 528 participants were assayed in three batches for 12 biomarkers and 3 biomarker ratios. Batch differences were assessed using Bland-Altman plot, paired t test, Pitman-Morgan test, and linear regression. Generalized linear models were applied to convert CSF values between batches. RESULTS: We found statistically significant batch differences for all biomarkers and ratios, except that neurofilament light was comparable between batches 1 and 2. The conversion models generally had high R 2 except for converting P-tau between batches 1 and 3. DISCUSSION: Between-batch conversion allows harmonized CSF values to be used in the same analysis. Such method may be applied to adjust for other sources of variability in measuring CSF or other types of biomarkers.

Cigarette Smoking Status, Cigarette Exposure, and Duration of Abstinence Predicting Incident Dementia and Death: A Multistate Model Approach.

BACKGROUND: To fully characterize the risk for dementia associated with cigarette smoking, studies must consider competing risks that hinder the observation of dementia or modify the chance that dementia occurs (i.e., death). Extant research examining the competing risks fails to account for the occurrence of death following dementia, limiting our understanding of the relation between smoking and dementia. OBJECTIVE: Examine the impact of smoking status, lifetime smoking exposure, and duration of abstinence on incident dementia, death following dementia, and death without dementia. METHODS: Multi-state models estimated hazard ratios (HR) for 95% confidence interval (CI) of 10,681 cognitively healthy adults for transition from baseline to dementia, baseline to death, and dementia to death based on smoking status, lifetime cigarette exposure, and abstinence duration. RESULTS: Compared to never smokers, current smokers had increased risk of dementia (HR = 1.66; 95% CI 1.18- 2.32; p = 0.004), and death from baseline (HR = 2.98; 95% CI 2.24- 3.98; p < 0.001) and incident dementia (HR = 1.88; 95% CI 1.08- 3.27; p = 0.03). Pack years increased risk of death from baseline (HR = 1.01; 95% CI 1.00- 1.01; p < 0.001), but not dementia risk (HR = 1.00; 95% CI 1.00- 1.00; p = 0.78) or death following dementia (HR = 1.01; 95% CI 1.00- 1.01; p = 0.05). Recent quitters (quit < 10 years), compared to never smokers, had increased risk of death after baseline (HR = 2.31; 95% CI 1.55- 3.43; p < 0.001), but not dementia (HR = 1.17; 95% CI 0.73- 1.88; p = 0.52) or death following dementia (HR = 1.01; 95% CI 0.42- 2.41; p = 0.99). CONCLUSION: Current smoking increases the risk for dementia and death, but dementia is better attributed to smoking recency than lifetime exposure. Smoking cessation at any age might reduce these risks for cognitively healthy individuals.

BrainAGE and regional volumetric analysis of a Buddhist monk: a longitudinal MRI case study.

Yongey Mingyur Rinpoche (YMR) is a Tibetan Buddhist monk, and renowned meditation practitioner and teacher who has spent an extraordinary number of hours of his life meditating. The brain-aging profile of this expert meditator in comparison to a control population was examined using a machine learning framework, which estimates "brain-age" from brain imaging. YMR's brain-aging rate appeared slower than that of controls suggesting early maturation and delayed aging. At 41 years, his brain resembled that of a 33-year-old. Specific regional changes did not differentiate YMR from controls, suggesting that the brain-aging differences may arise from coordinated changes spread throughout the gray matter.

Characterizing the Effects of Sex, APOE ɛ4, and Literacy on Mid-life Cognitive Trajectories: Application of Information-Theoretic Model Averaging and Multi-model Inference Techniques to the Wisconsin Registry for Alzheimer's Prevention Study.

OBJECTIVES: Prior research has identified numerous genetic (including sex), education, health, and lifestyle factors that predict cognitive decline. Traditional model selection approaches (e.g., backward or stepwise selection) attempt to find one model that best fits the observed data, risking interpretations that only the selected predictors are important. In reality, several predictor combinations may fit similarly well but result in different conclusions (e.g., about size and significance of parameter estimates). In this study, we describe an alternative method, Information-Theoretic (IT) model averaging, and apply it to characterize a set of complex interactions in a longitudinal study on cognitive decline. METHODS: Here, we used longitudinal cognitive data from 1256 late-middle aged adults from the Wisconsin Registry for Alzheimer's Prevention study to examine the effects of sex, apolipoprotein E (APOE) ɛ4 allele (non-modifiable factors), and literacy achievement (modifiable) on cognitive decline. For each outcome, we applied IT model averaging to a set of models with different combinations of interactions among sex, APOE, literacy, and age. RESULTS: For a list-learning test, model-averaged results showed better performance for women versus men, with faster decline among men; increased literacy was associated with better performance, particularly among men. APOE had less of an association with cognitive performance in this age range (∼40-70 years). CONCLUSIONS: These results illustrate the utility of the IT approach and point to literacy as a potential modifier of cognitive decline. Whether the protective effect of literacy is due to educational attainment or intrinsic verbal intellectual ability is the topic of ongoing work. (JINS, 2019, 25, 119-133).