Prescription Medications and Co-Morbidities in Late Middle-Age are Associated with Greater Cognitive Declines: Results from WRAP

The present study investigated: 1) sex differences in polypharmacy, comorbidities, self-rated current health (SRH), and cognitive performance, 2) associations between comorbidities, polypharmacy, SRH, and objective measures of health, and 3) associations of these factors with longitudinal cognitive performance. Analyses included 1039 eligible Wisconsin Registry for Alzheimer’s Prevention (WRAP) participants who were cognitively unimpaired at baseline and had ≥2 visits with cognitive composites, self-reported health history, and concurrent medication records. Repeated measures correlation (rmcorr) examined the associations between medications, co-morbidities, SRH, and objective measures of health (including LIfestyle for BRAin Health Index (LIBRA), and depression). Linear mixed-effect models examined associations between medications, co-morbidities, and cognitive change over time using a preclinical Alzheimer’s cognitive composite (PACC3) and cognitive domain z-scores (executive function, working memory, immediate learning, and delayed recall). In secondary analyses, we also examined whether the number of medications interacted with co-morbidities and whether they modified age-related cognitive trajectories. The number of prescribed medications was associated with worse SRH and a higher number of self-reported co-morbidities. More prescribed medications were associated with a faster decline in executive function, and more comorbidities were associated with faster PACC3 decline. Those with a non-elevated number of co-morbidities and medications performed an average of 0.26 SD higher (better) in executive function and an average of 0.18 SD higher on PACC3 than those elevated on both. Associations between medications, co-morbidities, and executive function, and PACC3 suggest that persons with more co-morbidities and medications may be at increased risk of reaching clinical levels of impairment earlier than healthier, less medicated peers.

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Gamma-Glutamyltransferase (GGT) as a biomarker of cognitive decline at the end of life: contrasting age and time to death trajectories

International Psychogeriatrics ◽

10.1017/s1041610217002393 ◽

2017 ◽

Vol 30 (7) ◽

pp. 981-990 ◽

Cited By ~ 6

Author(s):

Marcus Praetorius Björk ◽

Boo Johansson

Keyword(s):

Longitudinal Study ◽

Cognitive Decline ◽

Cognitive Performance ◽

Late Life ◽

Cognitive Change ◽

Gamma Glutamyltransferase ◽

Time To Death ◽

Age Related ◽

Increased Risk ◽

Underlying Mechanisms

ABSTRACTBackground:A recently published study suggests that Gamma-Glutamyltransferase (GGT) in midlife is related to an increased risk of dementia. In the present longitudinal study, we explore the effects of serum GGT on cognitive decline and dementia also in more advanced ages.Methods:We analyzed GGT in a sample of 452 individuals, aged 80 years and older at baseline, with the purpose to explore subsequent effects on cognitive performance. We specifically modeled GGT to cognitive change, time to death, and dementia.Results:Our main finding is that a higher level of GGT is associated with cognitive decline prior to death and vascular dementia in late life. These findings were evident across cognitive domains.Conclusions:This is the first longitudinal study to report on significant associations in late life between GGT, cognitive performance and dementia. Further research is needed to examine the underlying mechanisms of GGT as a marker of age-related cognitive decline.

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PHYSICAL FRAILTY AND ITS ASSOCIATION WITH COGNITION: THE PREDICTIVE VALUE OF A SYNDROME BEYOND ITS COMPONENT PARTS

Innovation in Aging ◽

10.1093/geroni/igz038.377 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S100-S101

Author(s):

Nadia M Chu ◽

Karen Bandeen-Roche ◽

A Richey Sharrett ◽

Michelle C Carlson ◽

Qianli Xue ◽

...

Keyword(s):

Executive Function ◽

Cognitive Performance ◽

Predictive Value ◽

Cognitive Vulnerability ◽

Strong Predictor ◽

Word List ◽

Cognitive Change ◽

Community Dwelling ◽

Cohen’S D ◽

Cohen's D

Abstract The extent to which frailty (PFP) affects cognitive performance and change beyond that expected from its component parts is uncertain. Leveraging NHATS, a nationally-representative cohort of U.S. Medicare beneficiaries, we quantified associations between each PFP criterion and global and domain-specific cognitive level and change (memory: immediate/delayed word-list test, executive function: clock drawing test (CDT), orientation: date, time, president-vice-resident naming), using adjusted mixed effects models with random slopes (time) and intercepts (person). We tested whether presence of frailty was associated with excess cognitive vulnerability (synergistic/excess effects, Cohen’s d) above and beyond those found for its criteria by adding an interaction term between each PFP criterion and frailty. Among 7,439 community-dwelling older adults (mean age=75.2 years) followed for a weighted mean of 3.2 years (SE= 0.03), 14.1% were frail. The most prevalent PFP criteria were low activity (30.5%) and exhaustion (29.8%). Associations were strongest for executive function, where frailty added predictive value beyond its criteria (excess effects of cognitive vulnerability ranging from -0.38SD (SE-0.05) for slowness to -0.47SD (SE=0.06) for shrinking). Slowness was a strong predictor of cognitive change in both frail and non-frail participants, especially for executive function (frail: Cohen’s d per year=-0.16, SE= 0.02; non-frail: Cohen’s d per year=-0.15, SE= 0.02). PFP is an important measure of frailty that adds predictive value beyond its criteria, especially for cognitive levels. Additionally, gait speed remains an important predictor of change in executive function. These results suggest that frailty’s contribution to cognitive performance amounts to more than the sum of its component parts.

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Associations Between Midlife (but Not Late-Life) Elevated Coronary Heart Disease Risk and Lower Cognitive Performance: Results From the Framingham Offspring Study

American Journal of Epidemiology ◽

10.1093/aje/kwz210 ◽

2019 ◽

Vol 188 (12) ◽

pp. 2175-2187 ◽

Cited By ~ 2

Author(s):

Nicole M Armstrong ◽

Katherine J Bangen ◽

Rhoda Au ◽

Alden L Gross

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Executive Function ◽

Cognitive Performance ◽

Late Life ◽

Later Life ◽

Cognitive Change ◽

Carrier Status ◽

Allele Carrier ◽

Chd Risk

Abstract It is unclear how coronary heart disease (CHD) risk across the adult life span affects late-life cognition. We estimated associations of midlife and late-life elevated CHD risk with cognitive trajectories (general cognitive performance, processing speed/executive function, memory) in later life (after age 55 years or age 70 years) among 2,892 Framingham Offspring Study participants who had completed CHD risk assessments approximately every 4 years since 1971 and had undergone neuropsychological testing between 1999 and 2014. We stratified analyses by apolipoprotein E gene (APOE) Ɛ4 allele carrier status. Using linear mixed-effects models, elevated CHD risk in midlife (age 55 years) was associated with lower levels of general cognitive performance (β = −0.560 standard deviation (SD) units, 95% confidence interval (CI): −0.874, −0.246), executive function (β = −0.624 SD units, 95% CI: −0.916, −0.332), and memory (β = −0.560 SD units, 95% CI: −0.907, −0.213) at age 70 years but not with rates of cognitive change. Late-life (age 70 years) elevated CHD risk, however, was associated with somewhat better levels of general cognitive performance and memory. There were associations between duration of elevated CHD risk during midlife and levels (but not trajectories) of later-life cognitive outcomes. Associations were not modified by APOE-ɛ4 status. These findings suggest that midlife elevated CHD risk is associated with lower cognition, independently of APOE-ɛ4 status, suggesting that risk of vascular disease may not contribute a “second hit” to AD risk.

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Examining cognitive training and executive function in older adults

University of Ottawa Science Undergraduate Research Journal ◽

10.18192/osurj.v1i1.3777 ◽

2018 ◽

Vol 1 ◽

Author(s):

Meggan Porteous ◽

Sheida Rabipour ◽

Patrick Davidson

Keyword(s):

Older Adults ◽

Executive Function ◽

Cognitive Training ◽

Repeated Measures ◽

Flanker Task ◽

Age Related ◽

Before And After ◽

Hit Rates ◽

Age Related Cognitive Decline ◽

Back Task

Studies have shown that cognitive functions decline with increasing age. As the population of older adults (OA) has grown, interest in cognitive training programs (CTP) has steadily expanded. The present study investigated whether CTP can lead to improvements in the performance of OA on cognitive tasks. Thirty-five adults (OA; 60-87 years) were recruited to complete 25 sessions of a CTP over five weeks, with assessments completed before and after the program. Thirty-two young adults (YA; 17-27 years) were also recruited to complete one assessment for baseline comparison with OA. During assessments, participants were evaluated using tasks of executive function, including the N-back task of working memory and Flanker task of inhibition. The response time (RT) and hit rates of YA and OA on these tasks were examined at baseline, as well as changes in OA pre- and post-training. Repeated measures analysis of variance indicated a reduction of pre- and post-training RT for the Flanker task. There was no post-training change in RT on the N-back task. While OA hit rates did not change significantly pre- and post-assessment on the Flanker task, they showed increased hit rates post-training in the N-back task. In both tasks, OA and YA hit rates and RT were significantly different, with YA demonstrating lower RT and hit rate compared to OA. Follow-up studies will determine whether other factors can also lead to improvement. Determining whether CTP can improve cognitive performance in OA can help determine the potential of such approaches to prevent or rehabilitate age-related cognitive decline.

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Self-reported sleep disturbances are associated with poorer cognitive performance in older adults with hypertension: a multi-parameter risk factor investigation

International Psychogeriatrics ◽

10.1017/s1041610219001492 ◽

2019 ◽

Vol 32 (7) ◽

pp. 815-825 ◽

Cited By ~ 2

Author(s):

Jordan N. Kohn ◽

Emily Troyer ◽

Robert N. Guay-Ross ◽

Kathleen Wilson ◽

Amanda Walker ◽

...

Keyword(s):

Risk Factors ◽

Older Adults ◽

Logistic Regression ◽

Cognitive Impairment ◽

Cognitive Performance ◽

Sleep Disturbances ◽

Depressive Symptomatology ◽

Cognitive Outcomes ◽

Cognitive Domain ◽

Increased Risk

ABSTRACTObjectives:Given the evidence of multi-parameter risk factors in shaping cognitive outcomes in aging, including sleep, inflammation, cardiometabolism, and mood disorders, multidimensional investigations of their impact on cognition are warranted. We sought to determine the extent to which self-reported sleep disturbances, metabolic syndrome (MetS) factors, cellular inflammation, depressive symptomatology, and diminished physical mobility were associated with cognitive impairment and poorer cognitive performance.Design:This is a cross-sectional study.Setting:Participants with elevated, well-controlled blood pressure were recruited from the local community for a Tai Chi and healthy-aging intervention study.Participants:One hundred forty-five older adults (72.7 ± 7.9 years old; 66% female), 54 (37%) with evidence of cognitive impairment (CI) based on Montreal Cognitive Assessment (MoCA) score ≤24, underwent medical, psychological, and mood assessments.Measurements:CI and cognitive domain performance were assessed using the MoCA. Univariate correlations were computed to determine relationships between risk factors and cognitive outcomes. Bootstrapped logistic regression was used to determine significant predictors of CI risk and linear regression to explore cognitive domains affected by risk factors.Results:The CI group were slower on the mobility task, satisfied more MetS criteria, and reported poorer sleep than normocognitive individuals (all p < 0.05). Multivariate logistic regression indicated that sleep disturbances, but no other risk factors, predicted increased risk of evidence of CI (OR = 2.00, 95% CI: 1.26–4.87, 99% CI: 1.08–7.48). Further examination of MoCA cognitive subdomains revealed that sleep disturbances predicted poorer executive function (β = –0.26, 95% CI: –0.51 to –0.06, 99% CI: –0.61 to –0.02), with lesser effects on visuospatial performance (β = –0.20, 95% CI: –0.35 to –0.02, 99% CI: –0.39 to 0.03), and memory (β = –0.29, 95% CI: –0.66 to –0.01, 99% CI: –0.76 to 0.08).Conclusions:Our results indicate that the deleterious impact of self-reported sleep disturbances on cognitive performance was prominent over other risk factors and illustrate the importance of clinician evaluation of sleep in patients with or at risk of diminished cognitive performance. Future, longitudinal studies implementing a comprehensive neuropsychological battery and objective sleep measurement are warranted to further explore these associations.

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Feeling Older and Constrained: Synergistic Influences of Control Beliefs and Subjective Age on Cognition

Innovation in Aging ◽

10.1093/geroni/igaa057.1246 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 387-387

Author(s):

Eric Cerino ◽

Erica O’Brien ◽

David Almeida

Keyword(s):

Executive Function ◽

Episodic Memory ◽

Cognitive Performance ◽

The United States ◽

Cognitive Domain ◽

Control Beliefs ◽

Hierarchical Regression ◽

Subjective Age ◽

Using Data ◽

Perceived Constraints

Abstract Control beliefs are important correlates of cognitive health and aging. In addition, how old or young one feels is a self-perception of aging that may play a role in understanding control-cognition associations. We explored whether subjective age moderates associations among control beliefs and cognitive performance using data from the third wave of the national Midlife in the United States study. The analytic sample comprised of 2,621 adults aged 39–93 (Mage=64.06, SD=11.15; 55.51% female) that completed measures of control (mastery, perceived constraints), subjective age (how old you feel most of the time), and cognition (executive function, episodic memory) via telephone administration. Hierarchical regression analyses were conducted to examine whether mastery, perceived constraints, and subjective age were associated with cognitive performance, adjusting for chronological age, gender, education, marital status, and self-rated health. For executive function, there was a significant perceived constraints by subjective age interaction. Higher levels of perceived constraints were associated with worse executive function (Est.=-0.05, SE=0.01, p<.001), and this association was amplified among those with relatively older subjective ages (Est.-0.10, SE=0.02, p<.001). For episodic memory, higher levels of perceived constraints were associated with worse performance (Est.=-0.07, SE=0.03, p<.001), while reporting a more youthful subjective age was associated with better performance (Est.-0.10, SE=0.02, p<.001). Mastery was not associated with either cognitive domain (ps>.05). Results suggest that perceiving constraints in life may confer greatest risk to cognitive performance among adults who feel older than their actual age, whereas perceiving a more youthful subjective age may be more facilitative.

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Post-Operative Delirium and Cognitive Decline in Kidney Transplant Recipients

Innovation in Aging ◽

10.1093/geroni/igaa057.1677 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 520-520

Author(s):

Nadia Chu ◽

Xiaomeng Chen ◽

Dorry Segev ◽

Mara McAdams-DeMarco

Keyword(s):

Executive Function ◽

Cognitive Performance ◽

Repeated Measures ◽

Cognitive Vulnerability ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Fixed And Random Effects ◽

Reduce Risk ◽

Preventative Interventions ◽

Function Time

Abstract Post-operative delirium may be a marker for cognitive reserve, or a greater cognitive vulnerability to stressors. As a result, those with post-operative delirium may experience steeper decline in cognitive performance following stressors of surgery post-KT. We leveraged a single-center cohort study of 912 adult KT recipients with delirium assessments abstracted from medical records. Global cognitive function (3MS) and executive function (time to complete TMT-B minus TMT-A) were measured at time of KT, 1-month, 3-months, 6-months, 1-year, and annually thereafter post-KT. We used mixed effects models with fixed and random effects for person and time to describe repeated measures of cognitive performance and compared trajectories by post-operative delirium. Among 912 KT recipients, 44 (4.8%) had post-operative delirium. Post-operative delirium was associated with higher levels of cognitive impairment at KT (18.2% vs 8.0%), and was associated with lower 3MS component scores including in memory, identification/association, and orientation. After adjustment, those with delirium had 3MS scores that were on average 3.6 points lower than those without delirium (95%CI: -6.9, 0.3) at time of KT; delirium was not associated with differing global cognitive trajectories post-KT (difference=0.04 points/month, 95%CI:-0.1, 0.2). However, delirium was associated with lower executive function at KT (difference=44.0s, 95%CI: 17.4, 70.6) and steeper decline in executive function post-KT (difference=-1.1s/month, 95%CI:-2.1,-0.05). KT recipients with delirium experience greater decline in executive function, indicating greater cognitive vulnerability with potential vascular etiologies. Transplant centers should be aware of the cognitive risks associated with post-KT delirium and implement available preventative interventions to reduce risk of delirium.

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Brain Exercising Games With Consumer-Grade Single-Channel Electroencephalogram Neurofeedback: Pre-Post Intervention Study (Preprint)

10.2196/preprints.26872 ◽

2020 ◽

Author(s):

Pasin Israsena ◽

Suwicha Jirayucharoensak ◽

Solaphat Hemrungrojn ◽

Setha Pan-Ngum

Keyword(s):

Cognitive Performance ◽

Cognitive Assessment ◽

Visual Memory ◽

Elderly Population ◽

Single Channel ◽

Spatial Working Memory ◽

Physiological State ◽

The Elderly ◽

Cognitive Domain ◽

Age Related

BACKGROUND The aging population is one of the major challenges affecting societies worldwide. As the proportion of older people grows dramatically, so does the number of age-related illnesses such as dementia-related illnesses. Preventive care should be emphasized as an effective tool to combat and manage this situation. OBJECTIVE The aim of this pilot project was to study the benefits of using neurofeedback-based brain training games for enhancing cognitive performance in the elderly population. In particular, aiming for practicality, the training games were designed to operate with a low-cost consumer-grade single-channel electroencephalogram (EEG) headset that should make the service scalable and more accessible for wider adoption such as for home use. METHODS Our training system, which consisted of five brain exercise games using neurofeedback, was serviced at 5 hospitals in Thailand. Participants were screened for cognitive levels using the Thai Mental State Examination and Montreal Cognitive Assessment. Those who passed the criteria were further assessed with the Cambridge Neuropsychological Test Automated Battery (CANTAB) computerized cognitive assessment battery. The physiological state of the brain was also assessed using 16-channel EEG. After 20 sessions of training, cognitive performance and EEG were assessed again to compare pretraining and posttraining results. RESULTS Thirty-five participants completed the training. CANTAB results showed positive and significant effects in the visual memory (delayed matching to sample [percent correct] P=.04), attention (median latency P=.009), and visual recognition (spatial working memory [between errors] P=.03) domains. EEG also showed improvement in upper alpha activity in a resting state (open-eyed) measured from the occipital area (P=.04), which similarly indicated improvement in the cognitive domain (attention). CONCLUSIONS Outcomes of this study show the potential use of practical neurofeedback-based training games for brain exercise to enhance cognitive performance in the elderly population.

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Threat-Modulation of Executive Functions—A Novel Biomarker of Depression?

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.670974 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jari Peräkylä ◽

Kaija Järventausta ◽

Piia Haapaniemi ◽

Joan A. Camprodon ◽

Kaisa M. Hartikainen

Keyword(s):

Working Memory ◽

Emotion Regulation ◽

Executive Function ◽

Executive Functions ◽

Cognitive Performance ◽

Performance Measures ◽

Cognitive Outcome ◽

Objective Measures ◽

Depression Severity ◽

The Impact

Background: Alterations in executive functions, emotion regulation, and their interaction are common concomitants of depression. Executive dysfunction frequently lingers after treatment, has adverse effects on daily life, and predisposes to recurrence of depression. Yet, sensitive measures of executive function for reliable assessment of cognitive outcomes are still lacking in clinical practice. To better understand the impact of depression and its most effective treatment, electroconvulsive therapy (ECT), on cognition, we assessed executive functions pre- and post-ECT and whether objective measures reflecting alterations in emotion–executive function interaction correlate with depression severity or with cognitive outcome.Methods: Executive functions were assessed in 21 patients with major depressive disorder (MDD) before and after ECT using subjective measures from the Behavior Rating Inventory of Executive Function—Adult version (BRIEF-A) and objective cognitive performance measures derived from computer-based test of executive function, Executive Reaction Time (RT) Test. In addition, we created novel indices reflecting emotional modulation of cognitive performance by subtracting different performance measures in the context of neutral distractors from those in the context of threat-related distractors. We correlated these indices with Beck Depression Inventory (BDI) and BRIEF-A scores.Results: Depression was significantly alleviated, and executive functions improved post-ECT, as seen in reduced BDI scores, BRIEF-A scores, and number of errors in Executive RT Test. Pre-ECT BDI scores correlated with threat modulation of RT (tmRT) and threat modulation of working memory (tmWM). Post-ECT tmRT correlated with several Behavioral Regulation scales and tmWM with several Metacognition scales of BRIEF-A.Conclusion: While caution is warranted, results from both subjective and objective measures suggest that ECT significantly improves executive functions and emotion regulation along with alleviation of depression. Novel indices derived from threat modulation of executive function and working memory show promise as objective biomarkers of depression severity pre-ECT and cognitive outcome post-ECT with potential for guiding depression treatments.

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Temporal emergence of age-associated changes in cognitive and physical function in vervets (Chlorocebus aethiops sabaeus)

10.1101/2020.09.28.313460 ◽

2020 ◽

Author(s):

Brett M. Frye ◽

Payton M. Valure ◽

Suzanne Craft ◽

Mark G. Baxter ◽

Christie Scott ◽

...

Keyword(s):

Working Memory ◽

Executive Function ◽

Cognitive Performance ◽

Gait Speed ◽

Integrative Approach ◽

Delayed Response ◽

Vervet Monkeys ◽

Chlorocebus Aethiops ◽

Increased Risk ◽

Response Task

ABSTRACTDual declines in gait speed and cognitive performance are associated with increased risk of developing dementia. Characterizing the patterns of such impairments therefore is paramount to distinguishing healthy from pathological aging. Nonhuman primates such as vervet/African green monkeys (Chlorocebus aethiops sabaeus) are important models of human neurocognitive aging, yet the trajectory of dual decline has not been characterized. We therefore 1) assessed whether cognitive and physical performance (i.e., gait speed) are lower in older aged animals; 2) explored the relationship between performance in a novel task of executive function (Wake Forest Maze Task – WFMT) and a well-established assessment of working memory (Delayed Response Task – DR Task); and 3) examined the association between baseline gait speed with executive function and working memory at one-year follow-up. We found 1) physical and cognitive declines with age; 2) strong agreement between performance in the novel WFMT and DR task; and 3) that slow gait predicted poor cognitive performance in both domains. Our results suggest that older-aged vervets exhibit a coordinated suite of traits consistent with human aging and that slow gait may be a risk factor for cognitive decline. This integrative approach provides evidence that gait speed and cognitive function differ across the lifespan in female vervet monkeys, which advances them as a model that could be used to evaluate the trajectory of dual decline over time.

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