Nonlinear Relationship of Non-High-Density Lipoprotein Cholesterol and Cognitive Function in American Elders: A Cross-Sectional NHANES Study (2011–2014)

Background: Serum non-high-density lipoprotein-cholesterol (non-HDL-C) levels may be associated with cognitive function. Objective: The objective of this study was to evaluate the association between non-HDL-C and cognitive function among American elders. Methods: We used data from the 2011 to 2014 U.S. National Health and Nutrition Examination Survey (NHANES). A total of 3,001 participants aged over 60 years were enrolled in our analysis. The cognitive function was evaluated with the word learning subtest from the Consortium to Establish a Registry for Alzheimer’s disease (CERAD W-L), the Animal Fluency Test (AFT), and the digit symbol substitution test (DSST). We also created a composite cognitive z-score to represent a global cognition. We applied multivariate linear regression analyses to estimate the associations between non-HDL-C levels and all domains of cognitive function. Further, the generalized additive model and the smooth curve were conducted to investigate the dose-response relationship between non-HDL-C and global cognition. Results: Serum non-HDL-C was positively associated with global cognition (β= 0.20, 95% CI: 0.11, 0.28), AFT score (β= 0.54, 95% CI: 0.33, 0.76), and DSST score (β= 1.13, 95% CI: 0.56, 1.69) after fully adjusted. While non-HDL-C was not related to CERAD W-L score. In addition, an inverted U-shape curve was observed in the dose-response relationship between non-HDL-C and global cognition (p for non-linearity < 0.001). Conclusion: Serum non-HDL-C is positively and nonlinearly associated with cognitive function among American older adults. Maintaining serum cholesterol levels at an appropriate range may be helpful to the cognitive health of the elderly.

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.

Investigating Potential Dose–Response Relationships between Vitamin D Status and Cognitive Performance: A Cross-Sectional Analysis in Middle- to Older-Aged Adults in the Busselton Healthy Ageing Study

Low vitamin D status has been linked to adverse cognitive outcomes in older adults. However, relationships at higher levels remain uncertain. We aimed to clarify patterns of association between vitamin D status and cognitive performance, using flexible regression methods, in 4872 middle- to older-aged adults (2678 females) from the Busselton Healthy Ageing Study. Cross-sectional associations of serum levels of 25-hydroxyvitamin D (25OHD) and performance in cognitive domains were modelled using linear regression and restricted cubic splines, controlling for demographic, lifestyle, and health factors. Mean ± SD serum 25OHD levels were 78 ± 24 nM/L for women and 85 ± 25 nM/L for men. Increasing levels in women were associated with better global cognition (linear trend, p = 0.023) and attention accuracy (continuity of attention), with improvement in the latter plateauing around levels of 80 nM/L (nonlinear trend, p = 0.035). In men, increasing levels of serum 25OHD were associated with better attention accuracy (linear trend, p = 0.022), but poorer semantic verbal fluency (linear trend, p = 0.025) and global cognition (nonlinear trend, p = 0.015). We identified patterns of association between serum 25OHD levels and cognitive performance that may reflect early dose–response relationships, particularly in women. Longitudinal analyses extending through to older ages may help to clarify the nature, strength, and temporality of these relationships.

Effects of Virtual Reality-Based Intervention on Cognition, Motor Function, Mood, and Activities of Daily Living in Patients With Chronic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: The efficacy of virtual reality (VR)-based intervention for improving cognition in patients with the chronic stage of stroke is controversial. The aims of this meta-analysis were to evaluate the effect of VR-based training combined with traditional rehabilitation on cognition, motor function, mood, and activities of daily living (ADL) after chronic stroke.Methods: The search was performed in the Cochrane Library (CENTRAL), EBSCO, EMBASE, Medline (OVID), Web of Science databases, PubMed, CINAHL Ovid, and Scopus from inception to May 31, 2021. All included studies were randomized controlled trials (RCTs) examining VR-based intervention combined with traditional rehabilitation for chronic stroke. The main outcomes of this study were cognition, including overall cognition (combined with all cognitive measurement results), global cognition (measured by the Montreal Cognitive Assessment, MoCA, and/or Mini-Mental State Examination, MMSE), and attention/execution. The additional outcomes were motor function, mood, and ADL. Subgroup analyses were conducted to verify the potential factors for heterogeneity.Results: Six RCTs including 209 participants were included for systematic review, and five studies of 177 participants were included in meta-analyses. Main outcome analyses showed large and significant effect size (ES) of VR-based training on overall cognition (g = 0.642; 95% CI = 0.134–1.149; and P = 0.013) and attention/execution (g = 0.695; 95% CI = 0.052–1.339; and P = 0.034). Non-significant result was found for VR-based intervention on global cognition (g = 0.553; 95% CI = −0.273–1.379; and P = 0.189). Additional outcome analyses showed no superiority of VR-based intervention over traditional rehabilitation on motor function and ADL. The ES of VR-based intervention on mood (g = 1.421; 95% CI = 0.448–2.393; and P = 0.004) was large and significant. In the subgroup analysis, large effects for higher daily intensity, higher weekly frequency, or greater dose of VR intervention were found.Conclusion: Our findings indicate that VR-based intervention combined with traditional rehabilitation showed better outcomes for overall cognition, attention/execution, and depressive mood in individuals with chronic stroke. However, VR-based training combined with traditional rehabilitation showed a non-significant effect for global cognition, motor function, and ADL in individuals with chronic stroke.

Association Between Dual-Task Gait and Cognitive Function in Older Adults

Community mobility involves walking with physical and cognitive challenges. In older adults (N=116; results here from initial analyses: N=29, Age=75±5 years, 51% females), we assessed gait speed and smoothness (harmonic-ratio) while walking on even and uneven surfaces, with or without an alternate alphabeting dual-task (ABC). ANOVA assessed surface and dual-task effects; Pearson correlations compared gait with global cognition and executive function composite z-scores. The four conditions (even, uneven, even-ABC and uneven-ABC) affected speed(m/s) (0.97±0.14 vs 0.90±0.15 vs 0.83±0.17 vs 0.79±0.16). Smoothness (2.19±0.48 vs 1.89±0.38 vs 1.92±0.53 vs 1.7±0.43) was affected by only surface (controlled for speed). Greater speed was associated with better global cognition(ρ=0.47 to 0.49, p&lt;0.05) for all conditions and with better executive function for even-ABC(ρ=0.39, p=0.04) and uneven-ABC(ρ=0.40, p=0.03). Executive function was associated with smoothness during even(ρp=-0.42, p=0.03) and uneven(ρp=-0.39, p=0.04) walking. Type of walking challenge differentially affects gait quality and associations with cognitive function.

Polyvictimization and Cognitive Function in an Ethnic Minority Aging Population

Globally, around 1 in 6 older adults experienced some form of elder mistreatment in community settings. However, little is known about the prevalence of polyvictimization, or experience of multiple forms of abuse, which may exacerbate negative outcomes over that of any one form of victimization in isolation. Data were drawn from the PINE study. Polyvictimization was defined as exposure to multiple forms of victimization, including psychological, physical, and sexual mistreatment, financial exploitation, and caregiver neglect. Cognitive function was evaluated by global cognition, episodic memory, executive function, working memory, and MMSE. Regression analyses were performed. Among 3153 participants, 128 experienced two forms of abuse while 12 experienced three or more forms of abuse. Polyvictimization was associated with lower global cognition (b=-0.05, SE=0.02, p&lt;.05), episodic memory (b=-0.06, SE=0.03, p&lt;.05), working memory (b=-0.14, SE=0.07, p&lt;.05), and processing speed (b=-0.68, SE=0.33, p&lt;.05). Interventions could target older adults with polyvictimization and protect their cognitive function.

Arterial Stiffness and Age Moderate the Association Between Physical Activity and Cognition in Older Adults

Background Evidence supports that time spent on physical activity has beneficial effects on cognition in older adults. Nevertheless, this beneficial effect is likely to change in function of individual modifying factors like age and level of arterial stiffness. This study aims to reveal whether arterial stiffness and age modulate the positive impact of physical activity on cognition by developing a double moderation model. Methods 110 healthy older adults aged 60 to 75 years old were examined for arterial stiffness (carotid-femoral Pulse Wave Velocity [cf-PWV]), global cognition (composite score of Montreal Cognitive Assessment, and Mini-Mental State Examination), and self-reported physical activity (PACED diary). Using PROCESS macro for SPSS, we evaluated if cf-PWV (moderator 1), and age (moderator 2) moderate the relationship between physical activity (X) and global cognition (Y). The threshold for high stiffness was set at 8.5 m/s based on previous studies that reported this cut-off more appropriate for classifying cerebrovascular risk groups. Results The interaction of arterial stiffness x age moderated the effect of physical activity on global cognition (β=-.89, SE=.42, p=.037) (Model: R2=.15, p=.018). Physical activity had a positive effect on cognition in younger-older adults (aged 60 to 68.5 years) with cf-PWV&gt;8.5 m/s (β=.57, SE=.222, p=.011, 95% CI.133 to 1.014) and on older-older adults (aged 68.6 to 75 years) with cf-PWV&lt;8.5 m/s (β=.49, SE=.190, p=.010, 95% CI=.116 to .869). Conclusions Identifying the right age groups and arterial stiffness levels at which physical activity can have beneficial effects on cognition is a key step in providing tailored behavioral interventions.

Depressive Symptoms, Leisure Activity Engagement, and Global Cognition in Non-Hispanic White and Black Older Adults

Prior research has linked more depressive symptoms to worse global cognition in older adulthood through lower leisure activity engagement. Less is known regarding which types of activities drive these associations. Additionally, depressive symptoms disproportionately affect cognition in Non-Hispanic Blacks (NHB) versus Non-Hispanic Whites (NHW). This cross-sectional study used data from the Michigan Cognitive Aging Project (n=453, 52% NHB, Mage=63.60 years) to examine whether distinct leisure activities (solitary-cognitive, solitary-creative, community-social, physical, intergenerational-social, cognitive-games) mediated the association between depressive symptoms and global cognition and whether race moderated these associations. Lower engagement in solitary-cognitive activities partially mediated the negative association between depressive symptoms and global cognition. In multi-group models, this indirect effect was only evident in NHBs, who showed a stronger negative association between depressive symptoms and activity engagement than NHWs. While cross-sectional, findings indicate that depressive symptoms may negatively impact cognition by reducing engagement in activities that promote cognitive reserve.

Impact of Vision and Hearing Impairment on Cognition and Loneliness: Evidence From the Mexican Health and Aging Study

Poor vision and hearing have been associated with lower cognitive function and greater social isolation (i.e., loneliness) among older adults. However, this evidence is based largely on data from non-Hispanic populations. Therefore, we investigated whether self-reported vision and hearing was associated with cognitive function and loneliness in a nationally-representative study of Mexican adults aged 50 and older in Wave 3 of the Mexican Health and Aging Study. The final sample included 12,426 participants. The majority were female (58%), and the mean age was 67. Self-reported vision and hearing status were categorized as excellent-very good [ref], good, and fair-poor. Measures for global cognition, memory, and non-memory cognition were calculated using z-scores based on nine cognitive tests. Participants who reported frequently feeling a lack of companionship, left out, or isolated were categorized as feeling lonely. All analyses controlled for age, sex, and years of education. Participants with fair-poor vision had lower global (β= -0.06, p &lt;.01), memory (β= -0.07, p &lt;.01), and non-memory cognition (β= -0.06, p &lt;.01) than participants with excellent-very good vision. In addition, participants with fair-poor hearing had higher non-memory cognition (β= 0.03, p &lt;.05) but not global cognition (β=0.02) or memory (β=0.001). Fair-poor vision (OR=1.53, 95% CI=1.25-1.87) but not fair-poor hearing (OR=1.16, 95% CI=0.97-1.38) was associated with higher odds of being lonely. Poor vision may be a potentially modifiable risk factor for lower cognition and loneliness among Mexican adults. Future research should incorporate robust measures of sensory health and investigate the longitudinal association between vision, cognition, and loneliness.

Vitamin D, Insulin-Like Growth Factor, and Cognitive Performance: Age and Sex Variations

Vitamin D has been consistently linked to better cognitive function in observational studies. This impact may be due in part through its influence on neurotrophins. Whether the relationships between vitamin D, neurotrophins, and cognition vary based on biological factors such as age and sex is unclear. Using data from a sample of 400 community-dwelling older (mean age=75.3±9.4; 47% female) participants in a cross-sectional study of cognitive aging, we assessed relationships between plasma 25-hydroxy-Vitamin D and performance on a neuropsychological battery modeled after the UDSv3.0. Moderation by age and sex and the impact of vitamin D on the relationship between Insulin-like Growth Factor-1 and cognitive performance were assessed by linear regression stratified by sex and age (median split at 76y). We found vitamin D to be positively linked to global cognition (MoCA: β=0.095±0.025SE, p&lt;0.001), working memory (Number Span Forward: β=0.017±0.007SE, p=0.011; Number Span Backward: β=0.016±0.007SE, p=0.028), episodic memory (Immediate Recall : β=0.089±0.027SE, p=0.001; Delayed Recall: β=0.047±0.015SE, p=0.002), attention and processing speed (Trail Making A: β=-0.365±0.163SE, p=0.026), executive function (Trail Making B: β=-0.537±0.215SE, p=0.014; Number-Symbol Coding: β=0.139±0.057SE, p=0.016), and an overall measure of cognitive function (z score: β=0.049±0.018SE, p=0.007). Most of these relationships were observed in women and younger older individuals (&lt;76y). In addition, vitamin D increased the effect of IGF-1 on global cognition and memory by 13% and 8%, respectively. Our findings suggest that vitamin D-focused dementia prevention efforts would benefit if targeted to women and younger segments of the senior population and/or as an adjuvant to cognitive enhancement interventions.