Anticholinergic Drug Burden and Neurocognitive Performance in the Study of Latinos-Investigation of Neurocognitive Aging

Background: Studies of cumulative anticholinergic drug burden on cognitive function and impairment are emerging, yet few for Hispanics/Latinos. Objective: To examine associations between anticholinergic use and neurocognitive performance outcomes among diverse Hispanics/Latinos. Methods: This prospective cohort study included diverse Hispanic/Latino participants, enrolled in the Study of Latinos-Investigation of Neurocognitive, from New York, Chicago, Miami, and San Diego (n = 6,249). Survey linear regression examined associations between anticholinergic use (measured during baseline [Visit 1] and average 7-year follow up [Visit 2]) with global cognition, episodic learning, memory, phonemic fluency, processing speed, executive functioning, and average 7-year change. Results: Anticholinergic use was associated with lower cognitive global cognition (β= –0.21; 95% CI [–0.36; –0.05]), learning (β= –0.27; 95% CI [–0.47; –0.07]), memory (β= –0.22; 95% CI [–0.41; –0.03]), and executive functioning (β= –0.22; 95% CI [–0.40; –0.03]) scores, particularly among those who took anticholinergics at both visits. Anticholinergic use was associated with faster decline in global cognition, learning, and verbal fluency (β: –0.28 [95% CI: –0.55, –0.01]; β: –0.28 [95% CI: –0.55, –0.01]; β: –0.25, [95% CI –0.47, –0.04], respectively). Sex modified associations between anticholinergic use with global cognition, learning, and executive functioning (F 3 = 3.59, F 3 = 2.84, F 3 = 3.88, respectively). Conclusion: Anticholinergic use was associated with lower neurocognitive performance, especially among those who used anticholinergics at both visits, among a study population of diverse Hispanics/Latinos. Findings will support evidence-based decisions regarding anticholinergic prescriptions and efforts to minimize cognitive impact.

Bridging Patterns of Neurocognitive Aging Across the Older Adult Lifespan

Magnetic resonance imaging (MRI) studies of brain and neurocognitive aging rarely include oldest-old adults (ages 85+). But predictions of neurocognitive aging theories derived from MRI findings in younger-old adults (ages 65-85) may not generalize into advanced age, particularly given the increased prevalence of cognitive impairment/dementia in the oldest-old. Here, we reviewed the MRI literature in oldest-old adults and interpreted findings within the context of regional variation, compensation, brain maintenance, and reserve theories. Structural MRI studies revealed regional variation in brain aging as larger age effects on medial temporal and posterior regions for oldest-old than younger-old adults. They also revealed that brain maintenance explained preserved cognitive functioning into the tenth decade of life. Very few functional MRI studies support compensatory activity in oldest-old adults who perform as well as younger groups, although there was evidence that higher brain reserve in oldest-old adults may mediate effects of brain aging on cognition. Despite some continuity, different cognitive and neural profiles across the older adult lifespan should be addressed in modern neurocognitive aging theories.

Low-Resolution Neurocognitive Aging and Cognition: An Embodied Perspective

Consistent with embodied cognition, a growing evidence in young adults show that sensorimotor processing is at the core of cognition. Considering that this approach predicts direct interaction between sensorimotor processing and cognition, embodied cognition may thus be particularly relevant to study aging, since this population is characterized by concomitant changes in sensorimotor and cognitive processing. The present perspective aims at showing the value and interest to explore normal aging throughout embodiment by focusing on the neurophysiological and cognitive changes occurring in aging. To this end, we report some of the neurophysiological substrates underpinning the perceptual and memory interactions in older adults, from the low and high perceptual processing to the conjunction in the medial temporal lobe. We then explore how these changes could explain more broadly the cognitive changes associated with aging in terms of losses and gains.

Blood metabolites predicting Mild Cognitive Impairment in the Study of Latinos-Investigation of Neurocognitive Aging (HCHS/SOL)

INTRODUCTION: Blood metabolomics-based biomarkers may be useful to predict measures of neurocognitive aging. METHODS: We tested the association between 707 blood metabolites measured in 1,451 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), with MCI and global cognitive change assessed seven years later. We further used Lasso penalized regression to construct a metabolomics risk score (MRS) that predicts MCI, potentially identifying a different set of metabolites than those discovered in individual-metabolite analysis. RESULTS: We identified 20 metabolites associated with MCI and/or global cognitive change. Six of them were novel and 14 were previously reported as associated with neurocognitive aging outcomes. The MCI MRS comprised 61 metabolites and improved prediction accuracy from 84% (minimally adjusted model) to 89% in the entire dataset and from 75% to 87% among APOE-ε4 carriers. Conclusions: Blood metabolites may serve as biomarkers identifying individuals at risk for MCI among U.S. Hispanics/Latinos.

Central Obesity, Cardiometabolic Risk, and Cognitive Change in the Study of Latinos: Investigation of Neurocognitive Aging

Background: The relationships between obesity and cognitive decline in aging are mixed and understudied among Hispanics/Latinos. Objective: To understand associations between central obesity, cognitive aging, and the role of concomitant cardiometabolic abnormalities among Hispanics/Latinos. Methods: Participants included 6,377 diverse Hispanics/Latinos enrolled in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL-Investigation for Neurocognitive Aging (SOL-INCA). Participants were 45 years and older at the first cognitive testing session (Visit 1). Cognitive outcomes (z-score units) included global composite and domain specific (learning, memory, executive functioning, processing speed) measures at a second visit (SOL-INCA, on average, 7 years later), and 7-year change. We used survey linear regression to examine associations between central obesity (waist circumference≥88 cm and≥102 cm for women and men, respectively) and cognition. We also tested whether the relationships between obesity and cognition differed by cardiometabolic status (indication of/treatment for 2 + of the following: high triglycerides, hypertension, hyperglycemia, low high-density lipoprotein cholesterol). Results: Central obesity was largely unassociated with cognitive outcomes, adjusting for covariates. However, among individuals with central obesity, cardiometabolic abnormality was linked to poorer cognitive function at SOL-INCA (ΔGlobalCognition =–0.165, p < 0.001) and to more pronounced cognitive declines over the average 7 years (ΔGlobalCognition = –0.109, p < 0.05); this was consistent across cognitive domains. Conclusion: Central obesity alone was not associated with cognitive function. However, presence of both central obesity and cardiometabolic abnormalities was robustly predictive of cognition and 7-year cognitive declines, suggesting that in combination these factors may alter the cognitive trajectories of middle-aged and older Hispanics/Latinos.