Leukotriene receptor antagonist use and cognitive decline in normal cognition, mild cognitive impairment, and Alzheimer’s dementia

Abstract Background Leukotriene receptor antagonists (LTRAs) alleviate Alzheimer’s disease (AD) pathology and improve cognition in animal models; however, clinical evidence is limited. This study aimed to explore the associations between the use of LTRAs (montelukast or zafirlukast) and cognitive performance in people with normal cognition, mild cognitive impairment (MCI), or AD dementia. We hypothesized that LTRA use would be associated with better cognitive performance over time. Methods This longitudinal observational study used data from the National Alzheimer’s Coordinating Center. Within groups of participants with normal cognition, MCI, or AD dementia, LTRA users were matched 1:3 to non-users using propensity score matching. Cognitive domains including immediate and delayed memory (Wechsler Memory Scale Revised-Logical Memory IA and IIA), psychomotor processing speed (Digit Symbol Substitution Test), and language (animal naming, vegetable naming, and Boston Naming Test) were compared between users and non-users in mixed-effects linear or Poisson regression models. Results In AD dementia, LTRA use was associated with a slower decline in psychomotor processing speed, as measured by the Digit Symbol Substitution Test (Β = 1.466 [0.253, 2.678] symbols/year, n = 442), and language, as measured by animal naming (Β = 0.541 [0.215, 0.866] animals/year, n = 566), vegetable naming (B = 0.309 [0.056, 0.561] vegetables/year, n = 565), and the Boston Naming Test (B = 0.529 [0.005, 1.053] items/year, n = 561). Effect sizes were small but persisted after controlling for a 10% false discovery rate. LTRA use was not associated with changes in memory performance in AD, nor was it associated with changes in cognitive performance in people with normal cognition or MCI. In a post hoc analysis, LTRA use was associated with a slower decline in clinical progression in MCI (B = −0.200 [−0.380, −0.019] points/year, n = 800) and AD dementia (B = −0.321 [−0.597, −0.046] points/year, n = 604) as measured by CDR Sum of Boxes. Conclusions The use of LTRAs was associated with preserved function in non-amnestic cognitive domains in AD dementia. The role of leukotrienes and their receptors in cognitive decline warrants further investigation and the leukotriene pathway may represent a target for AD treatment.

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Perioperative pentoxifylline therapy attenuates early postoperative neuro-cognitive decline in patients undergoing coronary artery bypass grafting surgery using cardiopulmonary bypass

Journal of Neuroanaesthesiology and Critical Care ◽

10.4103/2348-0548.148389 ◽

2015 ◽

Vol 02 (01) ◽

pp. 044-050 ◽

Cited By ~ 1

Author(s):

Sambhunath Das ◽

Suparna Kailash ◽

Manu Mehta ◽

Akshya Bisoi

Keyword(s):

Cardiopulmonary Bypass ◽

Coronary Artery ◽

Artery Bypass ◽

Treated Group ◽

Control Group ◽

Digit Symbol Substitution Test ◽

Bypass Grafting ◽

Digit Symbol ◽

Symbol Substitution ◽

Naming Test

Abstract Background: Postoperative cognitive decline (POCD) after coronary artery bypass grafting (CABG) is a common problem. Studies show that pentoxifylline administration reduces inflammation induced by cardiopulmonary bypass and brain injury after ischaemia. Hence the perioperative use of pentoxifylline in attenuating POCD was evaluated in the study. Materials and Methods: Eighty patients were divided randomly into two groups from 106 patients scheduled for CABG surgery. The study group was administered pentoxifylline 400 mg twice daily orally from day of admission to 7th day after surgery, whereas the control group patients received placebo. Neurocognitive assessment was assessed by an independent clinical psychologist one day after admission to hospital and again on 7th postoperative day. The data was analyzed and a P < 0.05 was considered significant results. Results: Pentoxifylline-treated group showed no statistically significant difference in animal naming test scores (10.3 ± 2.2 versus 9.4 ± 2.5, P = 0.07), digit symbol substitution test (26.1 ± 7.47 vs 22.2 ± 6.07, P = 0.09) and 8 subtests of Post Graduate Institute-memory scale. The control group had significant POCD as detected by animal naming test (10.5 ± 3.7 versus 8.6 ± 3.9, P = 0.008), digit symbol substitution test (20.2 ± 8.2 versus 14.7 ± 8.9, P = 0.008) and five subtests of memory scale (P = 0.01, 0.04, 0.003, 0.005 and 0.02). The incidence of POCD was 50% in placebo-treated group compared to 22.5% in pentoxifylline group. Conclusions: The perioperative use of pentoxifylline attenuates the early postoperative neurocognitive decline after CABG using cardiopulmonary bypass.

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A new computerised cognitive test for the detection of information processing speed impairment in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458513480251 ◽

2013 ◽

Vol 19 (12) ◽

pp. 1665-1672 ◽

Cited By ~ 40

Author(s):

Aurélie Ruet ◽

Mathilde SA Deloire ◽

Julie Charré-Morin ◽

Delphine Hamel ◽

Bruno Brochet

Keyword(s):

Multiple Sclerosis ◽

Information Processing ◽

Processing Speed ◽

Cognitive Test ◽

Digit Symbol Substitution Test ◽

Digit Symbol ◽

Information Processing Speed ◽

Good Reliability ◽

Digit Symbol Substitution ◽

Symbol Substitution

Background: Cognitive impairment in multiple sclerosis (MS) primarily applies to information processing speed (IPS). Objective: To evaluate psychometric properties of a new digit/symbol substitution test in healthy subjects and patients with MS, and assess its ability to detect IPS impairment in patients with MS. Methods: A sample of MS patients, 60 relapsing–remitting (RRMS) and 41 primary progressive MS (PPMS), and 415 healthy controls (HCs) underwent an IPS battery, including assessment of reaction times of subtests of the Test of Attentional Performance battery and a newly developed in-house digit/symbol substitution task, the Computerised Speed Cognitive Test (CSCT). The CSCT was additionally evaluated in a second cohort of 31 RRMS and 12 progressive MS patients, for comparison with the Symbol Digit Modalities Test (SDMT). Results: The CSCT had good reliability in both HCs and patients with MS. It showed a weak practice effect at the 6-month time point. This test had good ecological validity in MS patients. There was a strong correlation between the CSCT with the SDMT and with other IPS tests in patients with MS. The CSCT had the best sensitivity for predicting IPS impairment and was one of the most accurate tests among the IPS battery. Conclusion: The CSCT appeared as a good candidate for detecting IPS impairment in MS patients.

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Association Between Diet And Cognitive Performance In Adults Aged 60 And Over: NHANES, 2011–2014

Innovation in Aging ◽

10.1093/geroni/igab046.2636 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 710-710

Author(s):

Md Towfiqul Alam ◽

Elizabeth Vasquez ◽

Sandra Echeverria

Keyword(s):

Older Adults ◽

Cognitive Performance ◽

Word List ◽

Healthy Eating Index ◽

Future Research ◽

Digit Symbol Substitution Test ◽

Digit Symbol ◽

Dietary Recommendations ◽

Digit Symbol Substitution ◽

Symbol Substitution

Abstract There is limited evidence examining associations between diet and cognitive performance (CP) in older adults. We used the 2011-2014 National Health and Nutrition Examination Survey to determine if meeting dietary recommendations was associated with CP in adults 60+ years of age. Diet was based on the healthy eating index (HEI) 2015 and categorized into quintiles (higher quintiles indicating healthier diet). CP was based on word list learning, animal naming, and digit symbol substitution test, with scores above 25th percentile indicating adequate performance. Multivariate logistic regression modeling was conducted and adjusted for potential cofounders. A total of 3,068 participants completed the CP tests. A slightly higher percentage of participants were female (54.0%), predominantly White (80.5%) and the largest percentage (54.7%) was 60 to 69 years of age. The mean HEI-2015 score (0-100) was 54.89 (SE = 0.56). High CP scores increased with healthier dietary quintiles. However, results were only significant (p for trend <0.05) for digit symbol substitution test when comparing those in the highest quintile (82.53%) to those in the lowest (70.23%). Compared with participants in the lowest quintile of HEI-2015, participants in the highest quintile had a two-fold increased odds of better digit symbol substitution test scores, after adjusting for confounders (Odds Ratio [OR]: 1.96, 95% Confidence Interval [CI]: 1.28-3.01). Results showed that meeting healthy diet recommendations is associated with improved digit symbol substitution test, a marker of attention, processing speed and executive function. Future research should consider the role of diet in older adults to improve cognitive performance.

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Discriminant Validity of the WAIS-R Digit Symbol Substitution Test in Subjective Cognitive Decline, Mild Cognitive Impairment (Amnestic Subtype) and Alzheimer’s Disease Dementia (ADD) in Greece

Brain Sciences ◽

10.3390/brainsci11070881 ◽

2021 ◽

Vol 11 (7) ◽

pp. 881

Author(s):

Marianna Tsatali ◽

Eleni Poptsi ◽

Despina Moraitou ◽

Christina Agogiatou ◽

Evaggelia Bakoglidou ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Subjective Cognitive Decline ◽

Digit Symbol Substitution Test ◽

Digit Symbol ◽

Digit Symbol Substitution ◽

Symbol Substitution ◽

Alzheimer’S Disease Dementia

Objective: The aim of the current study was to estimate the discriminant potential and validity of the Digit Symbol Substitution Test (DSST) of the WAIS-R in the Greek elderly population meeting criteria for subjective cognitive decline (SCD), mild cognitive impairment (aMCI; amnestic subtype), or Alzheimer’s disease dementia (ADD). Method: Four hundred eighty-eight community-dwelling older adults, visitors of the Day Center of Alzheimer Hellas, participated in the study. Two hundred forty-three of them met the criteria for ADD, one hundred eighty-two for aMCI and sixty-three for SCD. Results: Path analysis indicated that the DSST score is affected by age group, educational level, and diagnostic category, but is not affected by gender. The ROC curve analysis showed that the DSST sum score could perfectly differentiate SCD from ADD patients, whereas test’s discriminant potential between aMCI and dementia ADD’s subtype was satisfactory. However, DSST was unable to separate the SCD from the aMCI group. Conclusion: It appears that the DSST is unable to separate the SCD from aMCI population. Therefore, the test in question may be insensitive to incipient cognitive decline. On the contrary, the discriminant potential of the DSST as regards SCD and ADD is excellent, while discrimination between aMCI and ADD is good.

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The pharmacokinetic-pharmacodynamic (Digit Symbol Substitution Test) relationship of flumazenil in a midazolam steady-state model in healthy volunteers

Clinical Pharmacology & Therapeutics ◽

10.1038/clpt.1994.174 ◽

1994 ◽

Vol 56 (5) ◽

pp. 530-536 ◽

Cited By ~ 11

Author(s):

Jianguo Zhi ◽

Joseph W Massarella ◽

Angela T Melia ◽

Stuart B Teller ◽

Janet Schmitt-Muskus ◽

...

Keyword(s):

Steady State ◽

Healthy Volunteers ◽

State Model ◽

Digit Symbol Substitution Test ◽

Digit Symbol ◽

Digit Symbol Substitution ◽

Steady State Model ◽

Symbol Substitution ◽

Relationship Of

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An automated version of the digit symbol substitution test (DSST)

Behavior Research Methods ◽

10.3758/bf03203313 ◽

1982 ◽

Vol 14 (5) ◽

pp. 463-466 ◽

Cited By ~ 241

Author(s):

Daniel R. McLeod ◽

Roland R. Griffiths ◽

George E. Bigelow ◽

John Yingling

Keyword(s):

Digit Symbol Substitution Test ◽

Digit Symbol ◽

Digit Symbol Substitution ◽

Symbol Substitution

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Digit Symbol Substitution Test Performance: Sex Differences in a Hebrew-Readers' Health Population

Perceptual and Motor Skills ◽

10.2466/pms.103.1.121-130 ◽

2006 ◽

Vol 103 (1) ◽

pp. 121-130 ◽

Cited By ~ 3

Author(s):

Semion Kertzman ◽

Zeev Ben-Nahum ◽

Iosef Gotzlav ◽

Haim Grinspan ◽

Moshe Birger ◽

...

Keyword(s):

Sex Differences ◽

Test Performance ◽

Digit Symbol Substitution Test ◽

Digit Symbol ◽

Digit Symbol Substitution ◽

Symbol Substitution

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Peripheral Insulin Resistance in Cognitively Normal Older Adults Relates to Poorer Performance on a Test for Speed of Processing

Current Developments in Nutrition ◽

10.1093/cdn/nzaa040_076 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 76-76

Author(s):

Aaron Smith ◽

Matthew Taylor ◽

Jim Backes ◽

Juleah Littrell ◽

Caitlin Boeckman ◽

...

Keyword(s):

Insulin Resistance ◽

Older Adults ◽

Digit Symbol Substitution Test ◽

Digit Symbol ◽

Speed Of Processing ◽

Cognitively Normal ◽

Peripheral Insulin Resistance ◽

Digit Symbol Substitution ◽

Symbol Substitution ◽

The Relationship

Abstract Objectives Peripheral insulin resistance (IR) and impaired glucose metabolism increases the risk for cognitive decline. However, data looking at peripheral IR's relationship with cognition in cognitively normal adults is limited. This study aimed to assess the relationship between peripheral IR and tests of speed of processing (SOP) in cognitively normal older adults using a novel IR measure. Methods Baseline data from 56 cognitively normal older adults participating in a nutrition intervention study (Nutrition Interventions for Cognitive Enhancement study; NICE study) were analyzed. Fasting blood draws were attained, and peripheral IR was measured using Quest Diagnostics’ Cardio IQ Insulin Resistance Panel (Test Code: 36,509). A cognitive battery was conducted by a trained psychometrician. Z-Scores of the Digit Symbol Substitution Test, Stroop Color, Stroop Word, Stroop Interference, and Stroop Letter Number Sequencing and Crossing-Off tests were combined to give a global SOP score. We constructed ordinary least squares regression models to assess IR's relationships with individual SOP tests and global SOP, including age and education as covariates. Statistical analyses were performed using R (v. 3.6.2; R Foundation, Vienna, Austria). Statistical significance was set at P < 0.05. Results Participants were 77% female and had a mean age of 72.1 ± 4.9 years. Higher IR scores were related to poorer performance on the Digit Symbol Substitution Test (β = −0.26, P = 0.04). IR scores were not related to other individual cognitive tests: Stroop Color (β = −0.17, P = 0.20), Stroop Word (β = −0.19, P = 0.11), Stroop Interference (β = −0.14, P = 0.28), Stroop Letter Number Sequencing (β = 0.03, P = 0.83), Crossing-Off (β = −0.18, P = 0.15), or Global SOP (β = −0.20, P = 0.11). Conclusions There was a relationship between higher IR scores and poorer performance on the Digit Symbol Substitution Test. Although other SOP tests were not significantly correlated with IR scores, directionality of the relationships indicated trend for higher IR being related to lower SOP. Consequently, maintaining insulin sensitivity with healthy lifestyle choices may be important for healthy aging. Future analyses with a larger sample size will be more informative for understanding the relationship between IR and SOP. Funding Sources National Institute on Aging.

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