Normative data for the Digit Symbol Substitution for diverse Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

INTRODUCTION: Executive functioning and processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we aimed to provide normative data for the Digit Symbol Substitution (DSS) test. METHODS: The target population for the Study of Latinos-Investigation of Neurocognitive Aging included six heritage backgrounds (n = 6177). Average age was 63.4 ± 8.3 years, 54.5% were female, and mean education was 11.0 ± 4.7 years. Participants were administered the DSS as part of a larger battery. Heritage-adjusted DSS scores, and percentile cut-points were created using survey-adjusted regression and quantile regression models. RESULTS: Age, education, sex, heritage, and language preference were associated with DSS scores. DISCUSSION: Significant correlates of DSS performance should be considered when evaluating cognitive performance. Representative DSS norms for Hispanics/Latinos will advance assessment and accuracy of neurocognitive disorder diagnosis in clinical practice. To facilitate interpretation, we provide norms to reduce test biases and developed an online dashboard. Highlights: Normative data for the Digit Symbol Substitution (DSS) for diverse Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) This study is the first to develop norms for the DSS test across four regions of the United States.Factors such as age, education, sex, and Hispanic/Latino heritage and language preference are associated with differences in executive functioning and information processing speed.We created norms and an online dashboard (https://solincalab.shinyapps.io/dsst_shiny/) providing an easily accessible tool to evaluate processing speed and executive functioning in Hispanic/Latino adults.

Neutrophil-to-Lymphocyte Ratio Amplifies the Effects of Aging on Decrements in Grip Strength and Its Functional Neural Underpinnings.

The neutrophil-to-lymphocyte ratio (NLR) is a trans-prognostic biomarker of physiologic stress and inflammation linked to muscle weakness in older adults. Generation of grip force coincides with sustained activity in the primary sensorimotor cortex (SM1). The current study investigates whether whole-brain functional connectivity, that is, degree centrality (CD) of SM1 relates to grip strength and whether both functional measures are predicted by advancing age as a function of the NLR. A structural regression model investigated the main and interactive effects of age and NLR on grip strength and CD of SM1 in 589 adults aged 21-85 years (M = 45.87, SD = 18.06). The model including the entire sample had a good fit (χ 2(4) = 1.63, p = .804). In individuals aged 50 years and older, age predicted lower grip strength and SM1 CD as a function of increasing NLR. In a model stratified by sex, the effect of age, NLR, and their interaction on grip strength are significant for older men but not older women. Analyses support CD of SM1 at rest as a neural biomarker of grip strength. Grip and its neural underpinnings decrease with advancing age and increasing NLR in mid to late life. Age-related decrements in grip strength and functional connectivity of brain regions involved in the generation of dynamic grip appear to be accelerated as a function of systemic physiological stress and inflammation, particularly in older men.

Serum Cystatin-C is linked to increased prevalence of diabetes and higher risk of mortality in diverse middle-aged and older adults.

OBJECTIVE: Type 2 Diabetes Mellitus (henceforth diabetes) affects roughly 35 million individuals in the US and is a major risk factor for cardiovascular and kidney disease. Serum Cystatin-C is used to monitor renal function and detect kidney damage. Recent research has focused on linking Cystatin-C to cardiovascular risk and disease, but most findings focus on small sample sizes and generalize poorly to diverse populations, thus limiting epidemiological inferences. The aim of this manuscript is to study the association between Cystatin-C, diabetes, and mortality and test for possible sex or racial/ethnic background modifications in these relationships. METHODS: We analyzed 8-years of biennial panel data from Health and Retirement Study participants 50-years and older who self-identified as White (unweighted N (uN) = 5,595), Black (uN = 867), or Latino (uN = 565) for a total of uN = 7,027 individuals. We modeled diabetes and death over 8-years as function of baseline Cystatin-C (log transformed) adjusting for covariates and tested modifications in associations by race/ethnic background and sex. RESULTS: Mean log Cystatin-C at visit 1 was 0.03±0.32 standard deviation. A 10% increase in Cystatin-C levels was associated with 13% increased relative risk of diabetes at baseline (11% and 9% by years 4 and 8). A 10% increase in Cystatin-C was highly associated with increased relative risk of death (28% and 31% by years 4 and 8). These associations were present even after adjusting for possible confounders and were not modified by sex or racial/ethnic background. CONCLUSION: Despite differential risks for diabetes and mortality by racial/ethnic groups, Cystatin-C was equally predictive of these outcomes across groups. Cystatin-C dysregulations could be used as a risk indicator for diabetes and as a warning sign for accelerated risk of mortality.

Interactive Associations of Neuropsychiatry Inventory-Questionnaire Assessed Sleep Disturbance and Vascular Risk on Alzheimer's Disease Stage Progression in Clinically Normal Older Adults.

Background: To determine whether sleep disturbance (SD) and vascular-risk interact to promote Alzheimer's disease (AD) stage-progression in normal, community-dwelling older adults and evaluate their combined risk beyond that of established AD biomarkers. Methods: Longitudinal data from the National Alzheimer's Coordinating Center Uniform-Dataset. SD data (i.e., SD+ vs. SD-), as characterized by the Neuropsychiatric Inventory-Questionnaire, were derived from 10,600 participants at baseline, with at-least one follow-up visit. A subset (n = 361) had baseline cerebrospinal fluid (CSF) biomarkers and MRI data. The Framingham heart study general cardiovascular disease (FHS-CVD) risk-score was used to quantify vascular risk. Amnestic mild cognitive impairment (aMCI) diagnosis during follow-up characterized AD stage-progression. Logistic mixed-effects models with random intercept and slope examined the interaction of SD and vascular risk on prospective aMCI diagnosis. Results: Of the 10,600 participants, 1,017 (9.6%) reported SD and 6,572 (62%) were female. The overall mean (SD) age was 70.5 (6.5), and follow-up time was 5.1 (2.7) years. SD and the FHS-CVD risk-score were each associated with incident aMCI (aOR: 1.42 and aOR: 2.11, p < 0.01 for both). The interaction of SD and FHS-CVD risk-score with time was significant (aOR: 2.87, p < 0.01), suggesting a synergistic effect. SD and FHS-CVD risk-score estimates remained significantly associated with incident aMCI even after adjusting for CSF (Aß, T-tau, P-tau) and hippocampal volume (n = 361) (aOR: 2.55, p < 0.01), and approximated risk-estimates of each biomarker in the sample where data was available. Conclusions: Clinical measures of sleep and vascular risk may complement current AD biomarkers in assessing risk of cognitive decline in older adults.

Modifying pathways by age and sex for the association between combined sleep disordered breathing and long sleep duration with neurocognitive decline in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).

INTRODUCTION: We aimed to determine whether obesity or metabolic syndrome (MetS) modify associations between sleep-disordered breathing (SDB), self-reported sleep duration (SD), and phenotypes of combined SDB/SD with 7-year neurocognitive decline (ND) in a community based-cohort of U.S. Hispanic/Latinos (N = 5500) in different age and sex groups. METHODS: The exposures were baseline SDB (respiratory event index ≥ 15), sleepiness (Epworth Sleepiness Scale ≥ 10), SD (< 6 hours, 6-9 hours, ≥ 9 hours). The outcome was 7-year ND. RESULTS: Mean age was 56.0 years, 54.8% were females. Obesity modified the association between SDB/SD and ND in memory (F = 21.49, P < 0.001) and global cognition (F = 9.14, P < 0.001) in the oldest age group. Women without MetS with combined long sleep/SDB exhibited most pronounced decline in global cognition (F = 3.07, P = 0.010). DISCUSSION: The association between combined SDB/long sleep and declines in memory and global cognition was most pronounced in obese older adults. Among women, MetS status modified the association between long sleep/SDB and decline in global cognition.

Association of Dementia and Vascular Risk Scores With Cortical Thickness and Cognition in Low-risk Middle-aged Adults.

BACKGROUND: Increased risk for the future development of Alzheimer disease begins as early as midlife. Algorithm-based scores, such as the Cardiovascular Risk Factors, Aging and Incidence of Dementia (CAIDE) dementia risk score, and the Framingham general cardiovascular disease (CVD) risk score, have been used to determine future risk for the development of cognitive decline and dementia. We evaluated the association between neuroimaging and cognitive measures with the 2 risk scores in middle-aged, cognitively intact adults (49±6 y). METHODS: In a cohort of 132 participants collected in 2014, magnetic resonance imaging was used to determine measures of cortical thickness in a priori regions of interest and a neuropsychological battery to assess memory and executive function. RESULTS: The CAIDE dementia risk score was significantly and inversely associated with the cortical thickness of the parahippocampal (r=-0.266; P=0.002) and superior frontal gyrus (r=-0.261; P=0.002) despite a considerable percentage of individuals (99.3%) at low risk for CVD. There was a significant negative association between CAIDE and memory (r=-0.251; P=0.003). Framingham general CVD score was not associated with brain structure or cognitive function. CONCLUSIONS: These results indicate that the CAIDE dementia risk score is associated with cortical thickness and cognitive function at midlife in a low-risk population. These data provide insight into subclinical structural and functional changes occurring during midlife associated with future risk for the development of dementia.

Vascular function, cerebral cortical thickness, and cognitive performance in middle-aged Hispanic and non-Hispanic Caucasian adults.

Hispanics are at increased risk for acquiring cardiovascular risk factors that contribute to cognitive dysfunction. To compare indices of vascular health with measures of cerebral gray matter integrity, 60 middle-aged Hispanic and non-Hispanic Caucasian participants were matched across age, sex, years of education, and mental status. Arterial stiffness was characterized by ß-stiffness index and carotid-femoral pulse wave velocity, and magnetic resonance imaging estimated cortical thickness in a priori regions of interest known to be susceptible to vascular risk factors. Measures of arterial stiffness were significantly higher in Hispanics than in non-Hispanic Caucasians. Hispanics exhibited thinner left inferior frontal gyrus (LIFG) cortical thickness (P=.04) with concurrently lower language (P=.02), memory (P=.03), and attention-executive functioning (P=.02). These results suggest that compromised vascular health may occur simultaneously with cortical thinning of the LIFG as an early neuropathological alteration in Hispanics.

Inflammation as a mediator of the relationship between cortical thickness and metabolic syndrome.

Metabolic Syndrome (MetS), the clustering of obesity, high blood pressure, and disordered glucose and lipid/lipoprotein metabolism within a single individual, is associated with poorer cognitive function. It has been hypothesized that cognitive impairment in MetS occurs primarily within the context of inflammation. MetS risk factors are also associated with thinning of the cerebral cortex. However, the mechanisms by which MetS and inflammation affect the brain are poorly understood. The present study used statistical mediation to examine the relationship between MetS risk factors, cortical thickness in a priori regions of interest (ROIs) and inflammation. ROIs were chosen from the previous literature. Forty-three adults between the ages of 40 and 60 years underwent a health screen, neuropsychological testing and structural magnetic resonance imaging. Serum levels of pro-inflammatory markers (interleukin 1, interleukin 2, interleukin 6 and C-Reactive Protein) were measured using enzyme-linked immunosorbent assays. A higher number of MetS risk factors were associated with thinning in the inferior frontal ROI (ß = -0.35, p = 0.019) as well as higher levels of serum interleukin 2 (ß = 0.31, p = 0.04). A higher level of serum interleukin 2 was also associated with reduced thickness in the inferior frontal gyrus (ß = -0.41, p = 0.013). After accounting for the effects of interleukin 2, the number of MetS risk factors was no longer associated with cortical thickness in the inferior frontal gyrus indicating successful statistical mediation. The results indicate a potentially important role for inflammation in linking MetS to cortical thinning and cognitive vulnerability.