Changes In Cognitive Test Scores Research Articles

History of preoperative COVID‐19 infection and postoperative cognitive change among older adults undergoing major elective surgeries

AbstractBackgroundEmerging evidence suggests that recovery from COVID‐19 infection may be associated with cognitive decline and possibly, incident dementia. Older adults undergoing major surgeries are at heightened risk for postoperative delirium and delayed cognitive recovery; however, it is unknown whether preoperative COVID‐19 infection is associated with worse perioperative cognitive outcomes. Therefore, the objective of this study was to investigate relationships between history of preoperative COVID‐19 infection and cognitive change following major elective surgery.MethodThe study population consisted of cognitively normal adults, ≥ 65years, enrolled in the Cognitive Recovery After Elective Surgery (CREATES) study, an ongoing investigation of BBB function and perioperative cognition. Participants who completed preoperative baseline and 2‐month postoperative assessments were included in the analyses. Cognitive performance (global function (MoCA) and age‐ and education‐adjusted letter fluency, category fluency, learning, memory) at baseline was compared with 2‐month postoperative test results in the entire sample and among those with/without preoperative COVID‐19. Between‐group differences were analyzed using independent samples t‐tests, chi‐square analyses, and repeated measures ANOVAs.ResultA total of 34 participants (mean age, 75 [SD] 4.9 years; 83% White; 54% orthopedic surgery) were included. Of these, 10 reported a preoperative, non‐hospitalized COVID‐19 infection and 24 did not have preoperative COVID‐19. No cases of postoperative delirium were observed. In the full sample, there was evidence of cognitive improvement in letter fluency (F = 5.53, p = 0.03, η2 = 0.18) and memory (F = 4.42, p = 0.04, η2 = 0.12), relative to preoperative baseline. On the MoCA, a global cognitive measure, 86% scored within normal range (MoCA ≥ 26) 2 months after surgery. COVID sub‐groups did not differ on baseline demographics, family history, medical, or cognitive variables (all p’s<0.5). There was no effect of time on change in cognitive test scores (all p’s<0.05) at the 2‐month postoperative assessment.ConclusionIn this modest sample of older surgical patients, history of preoperative COVID‐19 infection was not associated with cognitive decline after surgery; however, postoperative improvement on some cognitive tests was observed in the full sample. Future research in larger populations including biomarkers of neuroinflammation is needed to determine whether older adults with history of COVID‐19 infection are at additional risk of cognitive decline following surgery.

Association between anaesthesia-related factors and postoperative neurocognitive disorder: a post-hoc analysis

BackgroundPostoperative neurocognitive disorder (pNCD) is common after surgery. Exposure to anaesthetic drugs has been implicated as a potential cause of pNCD. Although several studies have investigated risk factors for the development of cognitive impairment in the early postoperative phase, risk factors for pNCD at 3 months have been less well studied. The aim of this study was to identify potential anaesthesia-related risk factors for pNCD at 3 months after surgery.MethodsWe analysed data obtained for a prospective observational study in patients aged ≥ 65 years who underwent surgery for excision of a solid tumour. Cognitive function was assessed preoperatively and at 3 months postoperatively using 5 neuropsychological tests. Postoperative NCD was defined as a postoperative decline of ≥ 25% relative to baseline in ≥ 2 tests. The association between anaesthesia-related factors (type of anaesthesia, duration of anaesthesia, agents used for induction and maintenance of anaesthesia and analgesia, the use of additional vasoactive medication, depth of anaesthesia [bispectral index] and mean arterial pressure) and pNCD was analysed using logistic regression analyses. Furthermore, the relation between anaesthesia-related factors and change in cognitive test scores expressed as a continuous variable was analysed using a z-score.ResultsOf the 196 included patients, 23 (12%) fulfilled the criteria for pNCD at 3 months postoperatively. A low preoperative score on Mini-Mental State Examination (OR, 8.9 [95% CI, (2.8–27.9)], p < 0.001) and a longer duration of anaesthesia (OR, 1.003 [95% CI, (1.001–1.005)], p = 0.013) were identified as risk factors for pNCD. On average, patients scored higher on postoperative tests (mean z-score 2.35[± 3.13]).ConclusionIn this cohort, duration of anaesthesia, which is probably an expression of the complexity of the surgery, was the only anaesthesia-related predictor of pNCD. On average, patients’ scores on cognitive tests improved postoperatively.

Antiplatelet therapy and incident cognitive impairment or dementia-a systematic review and meta-analysis of randomised clinical trials.

The benefit of antiplatelet therapy in preventing cognitive impairment or dementia is uncertain. We investigated the association between antiplatelet therapy and incident cognitive impairment or dementia in randomised clinical trials. We searched PubMed, EMBASE and CENTRAL for randomised clinical trials published from database inception through 1 February 2023. Trials that evaluated the association of antiplatelet therapy with incident cognitive impairment or dementia were included. For single-agent antiplatelet, the control group was placebo. For dual agent antiplatelet therapy, the control group was single-agent monotherapy. A random-effects meta-analysis model was used to report pooled treatment effects and 95% confidence intervals (CIs). The primary outcome was incident cognitive impairment or dementia. Secondary outcomes included change in cognitive test scores. A total of 11 randomised clinical trials were included (109,860 participants). All reported the incidence of cognitive impairment or dementia on follow-up. The mean (SD) age of trial participants was 66.2 (7.9) years. Antiplatelet therapy was not significantly associated with a reduced risk of cognitive impairment or dementia (11 trials; 109,860 participants) (3.49% versus 4.18% of patients over a mean trial follow-up of 5.8years; odds ratio [OR], 0.94 [95% CI, 0.88-1.00]; absolute risk reduction, 0.2% [95% CI, -0.4% to 0.009%]; I2 = 0.0%). Antiplatelet therapy was not significantly associated with mean change in cognitive test scores. In this meta-analysis, antiplatelet therapy was not significantly associated with a lower risk of incident cognitive impairment or dementia, but the CIs around this outcome do not exclude a modest preventative effect.

105 Antiplatelet therapy and incident cognitive impairment or dementia—a systematic review and Meta-analysis of randomised clinical trials.

Abstract Background The benefit of antiplatelet therapy in the prevention of cognitive impairment or dementia is uncertain. We investigated the association between antiplatelet therapy with incident cognitive impairment or dementia in randomised clinical trials. Methods We searched PubMed, EMBASE, and CENTRAL for randomised clinical trials published from database inception through Feb 1st, 2023. Trials that evaluated the association of antiplatelet therapy with incident cognitive impairment or dementia were included. For single agent antiplatelet, the control group was placebo and for dual agent antiplatelet therapy, the control group was single agent monotherapy. Two authors screened and independently extracted all data, and a random-effects meta-analysis model was used to report pooled treatment effects and 95% Confidence Intervals. The primary outcome was incident cognitive impairment or dementia. Secondary outcomes included change in cognitive test scores. Results Eleven randomised clinical trials were eligible for inclusion (109,860 participants), all of which reported the incidence of cognitive impairment or dementia on follow-up. The mean (SD) age of trial participants was 66.2 (7.9) years and 46,150 (42%) were women. The mean duration of follow-up was 70 months. Antiplatelet therapy, compared to control, was not significantly associated with a reduced risk of cognitive impairment or dementia (11 trials; 109,860 participants) (3.49% vs 4.18% of patients over a mean trial follow-up of 5.8 years; odds ratio [OR], 0.94 [95% CI, 0.88–1.00]; absolute risk reduction, 0.2% [95% CI, −0.4% to 0.009%]; I2 = 0.0%). Antiplatelet therapy was not significantly associated with mean change in cognitive test scores. Conclusion In this meta-analysis of randomised clinical trials, antiplatelet therapy was not significantly associated with a lower risk of incident cognitive impairment or dementia. The confidence intervals around this outcome do not exclude a modest preventative effect, and at a population level this could have a substantial benefit. Further large trials with longer term follow up are needed.

Association of Proton Pump Inhibitor Use With Incident Dementia and Cognitive Decline in Older Adults: A Prospective Cohort Study

Prior studies have suggested that proton pump inhibitor (PPI) use is associated with increased risk of dementia; however, these have been limited by incomplete assessment of medication use and failure to account for confounders. Furthermore, prior studies have relied on claims-based diagnoses for dementia, which can lead to misclassification. We investigated the associations of PPI and histamine-2 receptor antagonist (H2RA) use with dementia and cognitive decline. We conducted a post hoc analysis of ASPirin in Reducing Events in the Elderly (ASPREE), a randomized trial of aspirin in the United States and Australia, including 18,934 community-based adults ≥65 years of all races/ethnicities. Baseline and recent PPI and H2RA use were determined according to review of medications during annual in-person study visits. Incident dementia was defined according to Diagnostic and Statistical Manual for Mental Disorders, Fourth Edition, criteria. Secondary endpoints include cognitive impairment, no dementia (CIND) and changes in cognition. Associations of medication use with dementia and CIND outcomes were examined using Cox proportional hazards models. Changes in cognitive test scores were examined using linear mixed-effects models. Baseline PPI use vs nonuse was not associated with incident dementia (multivariable hazard ratio, 0.88; 95% confidence interval, 0.72-1.08), CIND (multivariable hazard ratio, 1.00; 95% confidence interval, 0.92-1.09), or with changes in overall cognitive test scores over time (multivariable B,-0.002; standard error, 0.01; P= .85). Similarly, no associations were observed between H2RA use and all cognitive endpoints. In adults ≥65 years of age, PPI and H2RA use were not associated with incident dementia, CIND, or decline in cognition over time. These data provide reassurance about the safety of long-term use of PPIs among older adults.

Choline Intake and Cognitive Function Among U.S. Older Adults

Choline is an essential nutrient affects brain development in early life. However, evidence is lacking regarding its potential neuroprotective effects in later life from community-based cohorts. This study assessed the relationship between choline intake and cognitive functioning in a sample of older adults 60 years + from the National Health and Nutrition Examination Survey 2011–2012 and 2013–2014 waves (n = 2,796). Choline intake was assessed using two nonconsecutive 24-hour dietary recalls. Cognitive assessments included immediate and delayed word recalls, Animal Fluency, and Digit Symbol Substitution Test. The average daily dietary choline intake was 307.5 mg, and the total intake (including intake from dietary supplements) was 330.9 mg, both below the Adequate Intake level. Neither dietary OR = 0.94, 95% CI (0.75, 1.17) nor total choline intake OR = 0.87, 95% CI (0.70, 1.09) was associated with changes in cognitive test scores. Further investigation adopting longitudinal or experimental designs may shed light on the issue.

Augmentation therapy with tandospirone citrate in vascular depression patients with mild cognitive impairment: A prospective randomized clinical trial

Cognitive impairment is a prominent clinical manifestation of vascular depression (VaDep). The current study aimed to assess the efficacy of tandospirone citrate in VaDep cases with mild cognitive impairment (VaDep-MCI) as well as the role of plasma monoamine neurotransmitters during the treatment. In this single-blind, randomized controlled study, 116 participants were randomly assigned to the tandospirone (tandospirone citrate-escitalopram) and control (escitalopram) groups. The primary endpoints were changes in cognitive test scores from baseline to Week 8, including the Rey Auditory Verbal Learning Test (RAVLT), Semantic Verbal Fluency (SVF) test, Trail Making Test (TMT), Digital Span Test (DST) and Clock Drawing Test (CDT) scores. Generalized estimating equation models were used to examine repeated measures. The results showed that compared with the changes in the control group from baseline to Week 8, the tandospirone group showed more significant changes in SVF score at Weeks 4 (p < 0.05) and 8 (p < 0.001), and TMT (B-A) score at Week 8 (p < 0.05). RAVLT, DST and DCT scores were relatively stable in both groups during the study period. Moreover, mediation analysis showed that these results were not mediated by the alleviation of depression symptoms. Partial Spearman correlation analysis showed that only plasma 5-hydroxytryptamine (5-HT) was positively correlated with Hamilton Depression Rating Scale score after Bonferroni correction (r = 0.347, p < 0.001). Augmentation therapy with tandospirone citrate improved the executive and language functions of VaDep-MCI patients. Additionally, plasma 5-HT levels may serve as a potential biomarker of VaDep severity. These findings may provide clinical insights into the treatment of vascular depression.

The Association between Multimorbidity and Cognitive Decline: A Systematic Review

AbstractBackgroundThe worldwide population ageing is a major driver for the increasing prevalence of multimorbidity, which is the co‐occurrence/ coexistence of multiple chronic conditions in the same individual. Simultaneously, cognitive decline has become a worldwide burden. Previous research has shown that there might be an association between multimorbidity as a risk for cognitive decline but no systematic review has evaluated this association.ObjectiveTo quantify the association between multimorbidity and cognitive decline through a systematic review, defining cognitive decline as a change in neuropsychological test scores or clinical diagnosis of mild cognitive impairment or dementia.MethodWe followed the PRISMA guidelines. We searched Medline/Pubmed, EMBASE, PsychINFO, CINAHL, LILACS, Scopus and ProQuest for studies published between January 1996 and May 2021. We evaluated study references for additional studies. We selected studies with a clear definition of multimorbidity, and cognitive decline, defined as cognitive impairment, dementia, or change in cognitive test scores. With one exception, all data were from high‐income countries and largely Caucasian populations. We employed the critical appraisal tools from the Joanna Briggs Institute to assess the risk of bias. We present a narrative data synthesis from each study in conjunction with key design information. PROSPERO register (CRD42020167253).ResultWe initially identified 1433 references, of which 16 studies fulfilled inclusion criteria, and were included; we found three additional studies through studies references. These studies encompassed a total of 90606 participants. Thirteen studies were cohorts, four cross‐sectional and two case‐control designs. Ten studies were population registers, five memory clinics cohorts, two population‐based surveys and one from administrative data. We found a high degree of heterogeneity among studies, driven by the use of multiple definitions of multimorbidity and cognitive decline that precluded a meta‐analysis. In general, all studies noticed an increased risk of cognitive decline or diminishing test scores with increasing accumulation of chronic disease. Future research will need to address a standardized definition of multimorbidity and cognitive decline/scores as well as obtain and evaluate data from low‐ and middle‐income countries.ConclusionWe found an association between suffering multimorbidity and increasing risk of cognitive decline measured as cognitive test scores or diagnosis of MCI or dementia.

Visual Impairment, Eye Disease, and 3-Year Cognitive Decline: The Canadian Longitudinal Study on Aging

ABSTRACT Purpose To examine the longitudinal association between vision-related variables and the 3-year change in cognitive test scores in a community-dwelling sample of adults and to explore whether sex, education, or hearing loss act as effect modifiers. Methods Data came from two waves of a 3-year population-based prospective cohort study (Canadian Longitudinal Study on Aging), which consisted of 30,097 randomly selected people aged 45–85 years from 7 Canadian provinces. Visual impairment (VI) was defined as binocular presenting visual acuity worse than 20/40. Participants were asked if they had ever had a diagnosis of age-related macular degeneration (AMD), glaucoma, or cataract. Cognitive change over 3 years was examined by calculating the difference between baseline and follow-up scores for the Rey Auditory Verbal Learning Test (RAVLT) and the RAVLT delayed test (memory tests), the Controlled Oral Word Association Test (COWAT) and the Animal Naming Test (ANT) (verbal fluency tests), and the Mental Alternation Test (MAT) (processing speed test). Multiple linear regression was used. Results VI, AMD, and cataract were not associated with 3-year changes on any of the 5 cognitive tests after adjusting for age, sex, ethnicity, education, income, smoking, diabetes, stroke, heart disease, and province. A report of glaucoma was associated with greater declines in MAT scores (β = -0.60, 95% CI -1.03, -0.18). No effect modification was detected. Conclusions Glaucoma was associated with worsening processing speed. Further research to confirm this finding and to understand the possible reason is necessary.

Predicting progression and cognitive decline in amyloid-positive patients with Alzheimer\u2019s disease

BackgroundIn Alzheimer’s disease, amyloid- β (A β) peptides aggregate in the lowering CSF amyloid levels - a key pathological hallmark of the disease. However, lowered CSF amyloid levels may also be present in cognitively unimpaired elderly individuals. Therefore, it is of great value to explain the variance in disease progression among patients with A β pathology.MethodsA cohort of n=2293 participants, of whom n=749 were A β positive, was selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to study heterogeneity in disease progression for individuals with A β pathology. The analysis used baseline clinical variables including demographics, genetic markers, and neuropsychological data to predict how the cognitive ability and AD diagnosis of subjects progressed using statistical models and machine learning. Due to the relatively low prevalence of A β pathology, models fit only to A β-positive subjects were compared to models fit to an extended cohort including subjects without established A β pathology, adjusting for covariate differences between the cohorts.ResultsA β pathology status was determined based on the A β42/A β40 ratio. The best predictive model of change in cognitive test scores for A β-positive subjects at the 2-year follow-up achieved an R2 score of 0.388 while the best model predicting adverse changes in diagnosis achieved a weighted F1 score of 0.791. A β-positive subjects declined faster on average than those without A β pathology, but the specific level of CSF A β was not predictive of progression rate. When predicting cognitive score change 4 years after baseline, the best model achieved an R2 score of 0.325 and it was found that fitting models to the extended cohort improved performance. Moreover, using all clinical variables outperformed the best model based only on a suite of cognitive test scores which achieved an R2 score of 0.228.ConclusionOur analysis shows that CSF levels of A β are not strong predictors of the rate of cognitive decline in A β-positive subjects when adjusting for other variables. Baseline assessments of cognitive function accounts for the majority of variance explained in the prediction of 2-year decline but is insufficient for achieving optimal results in longer-term predictions. Predicting changes both in cognitive test scores and in diagnosis provides multiple perspectives of the progression of potential AD subjects.

Correlations between retinal nerve fiber layer thickness and cognitive progression in Parkinson's disease: A longitudinal study

BackgroundRetinal abnormalities measured by optical coherence tomography (OCT) have been detected in both Parkinson's disease (PD) and Alzheimer's disease (AD). Cognitive impairment is not only found in AD, but 75–90% of PD patients will also develop dementia in the late stage of disease. We assessed whether baseline retinal nerve fiber layer (RNFL) thickness predicted worsening of cognitive status over time and the correlation between RNFL thickness and the detailed impaired cognitive domains in PD. MethodsRNFL thickness was measured using high-definition OCT in 78 non-dementia PD patients. Clinical and cognitive assessments were performed at baseline and at 3.61 ± 0.65 years follow-up. Linear mixed-effects models were used to examine associations between RNFL thickness and the changes in cognitive test scores, after adjusting for age, sex, disease duration and education. ResultsAnalysis of outcomes according to baseline RNFL tertiles showed worse performance in global cognitive tests, delayed memory, and executive functions in patients with a thin RNFL. During follow-up, greater cognitive deterioration was found in thin RNFL tertile patients. Lower baseline average RNFL thickness was associated with greater annualized decline in Mini-Mental State Examination and Montreal Cognitive Assessment. ConclusionThe correlation between RNFL thickness and cognitive dysfunction suggests that OCT may be useful for predicting cognitive dysfunction in PD patients.

Neuroimaging and Neuropsychological Outcomes Following Clinician-Delivered Cognitive Training for Six Patients With Mild Brain Injury: A Multiple Case Study.

Nearly half of all mild brain injury sufferers experience long-term cognitive impairment, so an important goal in rehabilitation is to address their multiple cognitive deficits to help them return to prior levels of functioning. Cognitive training, or the use of repeated mental exercises to enhance cognition, is one remediation method for brain injury. The primary purpose of this hypothesis-generating pilot study was to explore the statistical and clinical significance of cognitive changes and transfer of training to real-life functioning following 60 h of Brain Booster, a clinician-delivered cognitive training program, for six patients with mild traumatic brain injury (TBI) or non-traumatic acquired brain injury (ABI). The secondary purpose was to explore changes in functional connectivity and neural correlates of cognitive test gains following the training. We used a multiple case study design to document significant changes in cognitive test scores, overall IQ score, and symptom ratings; and we used magnetic resonance imaging (MRI) to explore trends in functional network connectivity and neural correlates of cognitive change. All cognitive test scores showed improvement with statistically significant changes on five of the seven measures (long-term memory, processing speed, reasoning, auditory processing, and overall IQ score). The mean change in IQ score was 20 points, from a mean of 108 to a mean of 128. Five themes emerged from the qualitative data analysis including improvements in cognition, mood, social identity, performance, and Instrumental Activities of Daily Living (IADLs). With MRI, we documented significant region-to-region changes in connectivity following cognitive training including those involving the cerebellum and cerebellar networks. We also found significant correlations between changes in IQ score and change in white matter integrity of bilateral corticospinal tracts (CST) and the left uncinate fasciculus. This study adds to the growing body of literature examining the effects of cognitive training for mild TBI and ABI, and to the collection of research on the benefits of cognitive training in general.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02918994.

Association of Blood Pressure Lowering With Incident Dementia or Cognitive Impairment

The benefit of blood pressure lowering for the prevention of dementia or cognitive impairment is unclear. To determine the association of blood pressure lowering with dementia or cognitive impairment. Search of PubMed, EMBASE, and CENTRAL for randomized clinical trials published from database inception through December 31, 2019, that evaluated the association of blood pressure lowering on cognitive outcomes. The control groups consisted of either placebo, alternative antihypertensive agents, or higher blood pressure targets. Data were screened and extracted independently by 2 authors. Random-effects meta-analysis models were used to report pooled treatment effects and CIs. The primary outcome was dementia or cognitive impairment. The secondary outcomes were cognitive decline and changes in cognitive test scores. Fourteen randomized clinical trials were eligible for inclusion (96 158 participants), of which 12 reported the incidence of dementia (or composite of dementia and cognitive impairment [3 trials]) on follow-up and were included in the primary meta-analysis, 8 reported cognitive decline, and 8 reported changes in cognitive test scores. The mean (SD) age of trial participants was 69 (5.4) years and 40 617 (42.2%) were women. The mean systolic baseline blood pressure was 154 (14.9) mm Hg and the mean diastolic blood pressure was 83.3 (9.9) mm Hg. The mean duration of follow-up was 49.2 months. Blood pressure lowering with antihypertensive agents compared with control was significantly associated with a reduced risk of dementia or cognitive impairment (12 trials; 92 135 participants) (7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years; odds ratio [OR], 0.93 [95% CI, 0.88-0.98]; absolute risk reduction, 0.39% [95% CI, 0.09%-0.68%]; I2 = 0.0%) and cognitive decline (8 trials) (20.2% vs 21.1% of participants over a mean trial follow-up of 4.1 years; OR, 0.93 [95% CI, 0.88-0.99]; absolute risk reduction, 0.71% [95% CI, 0.19%-1.2%]; I2 = 36.1%). Blood pressure lowering was not significantly associated with a change in cognitive test scores. In this meta-analysis of randomized clinical trials, blood pressure lowering with antihypertensive agents compared with control was significantly associated with a lower risk of incident dementia or cognitive impairment.

Efficacy of nicergoline treatment in Parkinson’s disease associated with dementia

Parkinson’s disease (PD) has a variable spectrum of cognitive impairment. However, there are no clear evident-based management guidelines for PD with dementia (PDD). Alternative treatments for PDD are therefore required. We conducted this longitudinal study to evaluate the efficacy of nicergoline in treating PDD by analyzing changes in regional cerebral blood flow (rCBF) and neuropsychological tests before and after nicergoline administration. A total of nine PDD patients who received nicergoline therapy (PDD + N) and 14 PD patients who did not receive nicergoline therapy (PDD − N) underwent single photon emission computed tomography (SPECT) and clinical assessments at baseline and 12-month follow-up visits. The PDD + N received nicergoline at 30 mg twice per day. Changes in rCBF were compared between the groups, and correlation analysis was performed to determine possible relationship between rCBF and clinical characteristics. There were no significant differences in rCBF between the two groups at baseline. Although changes in cognitive test scores and the motor severity scale were not significantly different between baseline and the 12-month follow-up within groups, rCBF was lower in both the temporal and inferior frontal restricted areas in the PDD − N group than the PDD + N at the 12-month follow-up visit. In conclusions, nicergoline appears to delay the speed of deterioration of cognitive function in patients with PDD based on our observation of decreased rCBF in the temporal regions and inferior frontal regions of PDD − N patients compared to PDD + N patients after 12-month of nicergoline therapy. Therefore, we cautiously suggest that nicergoline administration in PDD patients may slow progression of cognitive impairment in affected brain regions.

Learning effect and its prediction for cognitive tests used in studies on indoor environmental quality

This study aimed to identify the law of cognitive test scores with the number of repetitions, and to establish a prediction model that quantitatively describes the changes in cognitive test scores. The experiments were conducted in a chamber that simulated an office environment. Participants performed neurobehavioral, Tsai-Partington, typing and d2 tests at 26 ℃. The speed and accuracy were used to reflect the cognitive test scores. The results demonstrated that a significant learning effect occurred in these cognitive test scores. The speed and accuracy of completing cognitive tests increased as the number of repetitions increased. The majority of cognitive tests could achieve stability after five repetitions and, at most, eight repetitions. The learning effect had different effects on the speed and accuracy. The percentage improvement of the speed was higher compared with accuracy, but it took more attempts to reach stability. The regression model based on the logistic function could accurately quantify the tendency for the variation in cognitive test scores with the number of repetitions. Compared with the power, linear and logarithmic functions, the logistic function had a higher R2(> 0.99). A method for correcting the learning effect of these cognitive tests was proposed based on the prediction model.

Effects of Homocysteine on white matter diffusion parameters in Alzheimer\u2019s disease

BackgroundThe clinical features of Alzheimer’s disease (AD) are related to brain network degeneration, and hyperhomocysteinemia is related to greater white matter hyperintensities. We investigated the changes in four diffusion tensor imaging parameters in the white matter of patients with early stage AD, examined their associations with homocysteine level, and tested the clinical significance of the diffusion tensor imaging parameters and homocysteine level in correlation analysis with cognitive test scores.MethodsWe enrolled 132 patients with AD and analyzed white matter (WM) macrostructural changes using diffusion tensor neuroimaging parameters including fractional anisotropy (FA), mean diffusion (MD), axial diffusivity (axial-D) and radial diffusivity (RD). Two neuroimaging post-processing analyses were performed to provide complementary data. First, we calculated 11 major bundle microstructural integrities using a WM parcellation algorithm, and correlated them with serum homocysteine levels to explore whether the fiber bundles were affected by homocysteine. Second, we used tract-based spatial statistics to explore the anatomical regions associated with homocysteine levels. Changes in cognitive test scores caused by homocysteine served as the major outcome factor.ResultsThe results suggested that homocysteine levels did not have a direct impact on cross-sectional cognitive test scores, but that they were inversely correlated with renal function, B12 and folate levels. Topographies showing independent correlations with homocysteine in FA and MD were more diffusely located compared to the posterior brain regions in axial-D and RD. In the association bundle analysis, homocysteine levels were significantly correlated with the four diffusion parameters even after correcting for confounders, however no association between homocysteine and WM to predict cognitive outcomes was established.ConclusionsIn our patients with AD, homocysteine levels were associated with renal dysfunction and decreased levels of vitamin B12 and folate, all of which require clinical attention as they may have been associated with impaired WM microstructural integrity and modulated cognitive performance in cross-sectional observations.

Cognitive Impacts of Ambient Air Pollution in the National Social Health and Aging Project (NSHAP) Cohort

Introduction: Despite a growing body of research, our understanding of the impact of air pollution exposures on cognition remains poor. To address this knowledge gap we estimated the association between exposure to ambient air pollution and cognitive outcomes among older adults who were part of the National Social Life, Health, and Aging Project (NSHAP). Methods: We linked participant data to fine particle (PM2.5), ozone (O3), and nitrogen dioxide (NO2) exposures. Cognitive function was assessed in 2010-2011 using the Chicago Cognitive Function Measure (CCFM) that measures 8 cognitive domains on a 20 point scale. PM2.5 exposures were estimated using spatio-temporal models, while O3 (April-September only) and NO2 concentrations were obtained from the nearest EPA monitors. Associations between cognitive function and air pollution levels were examined with linear regression models controlling for race, gender, education, age, season, smoking, geographic region, and median household income of census tract. Results: IQR increases in 1 to 7 year moving average PM2.5 exposures were significantly associated with decreased CCFM scores, with a -0.22 (95% CI -0.44, -0.01) point change in CCFM score for a 1 year moving average. Likewise, 1 to 7 year moving averages of NO2 exposures were associated with similar decreases (-0.13 (95% CI -0.34, 0.08) and -0.27 (95% CI -0.48, -0.07), respectively). In contrast, exposures to O3 associated with small but significant increases in scores (0.17, 95% CI 0.02, 0.31 for 2 yr moving average exposure). Conclusions: We found that increases in PM2.5 and NO2 exposures are significantly associated with changes in cognitive test scores. Our study is unique in its use of spatio-temporal models for estimating PM2.5 exposures, and use of the CCFM, a reliable measure of cognitive function. These results suggest that limiting exposure to PM2.5 and NO2 may prevent deterioration in cognitive function that affects an increasing number of older adults.

Peri-Operative Inflammatory Cytokines in Plasma of the Elderly Correlate in Prospective Study with Postoperative Changes in Cognitive Test Scores.

Increasingly, postoperative cognitive dysfunction (POCD) is recognized as a complication after surgery in the elderly; but it's etiology remains unclear. Here we examine changes in cytokine levels during both the pre-operative and postoperative period, comparing them with long term variation in cognitive test scores. Forty-one patients aged 65 and older undergoing major surgery with general anesthesia were recruited after written consent in this IRB approved study. Thirty went on to complete this prospective, non-interven-tional and non-randomized study. Plasma levels of cytokines Il-6, Il-8, Il-10, and TNF were determined using ELISA with MILLIPLEX Multi-Analyte Profiling (Billerica, MA). All subjects had neurocognitive tests pre-operatively and 6 months post-surgery, including Paragraph Recall Immediate and Delayed, Digit Span Forward (DSF) and Backward (DSB), and Trail Making A and B. Spearman's Rho and repeated measure rank analysis were used to examine the dependence of z score changes in cognitive tests (baseline versus 6 months) as a function of 3 cytokine time points (presurgical, post anesthesia care unit (PACU), and post-operative day one (POD1)). A greater increase in PACU inflammatory burden correlated with a greater decline in performance on the DSB (IL6, IL8; r>-0.560; p<= 0.008). DSF changes correlated slightly better with pre-surgical cytokines, declining more with higher cytokines (IL6, r= -0.551, p=0.002; IL8, -0.468, 0.009). TNF, examining all 3 values, changed only slightly postoperatively, but still correlated with a decline in DSB (p=0.014). Thus, cognitive performance, over 6 months post surgery, declines with elevated perioperative inflammation. Specific cytokines at specific perioperative times may impact specific cognitive functions, serving as diagnostics as well as contributing causation.

Cognitive Decline in a Colombian Kindred With Autosomal Dominant Alzheimer Disease: A Retrospective Cohort Study.

Data from an autosomal dominant Alzheimer disease (ADAD) kindred were used to track the longitudinal trajectory of cognitive decline associated with preclinical ADAD and explore factors that may modify the rate of cognitive decline. To evaluate the onset and rate of cognitive decline during preclinical ADAD and the effect of socioeconomic, vascular, and genetic factors on the cognitive decline. We performed a retrospective cohort study from January 1, 1995, through June 31, 2012, of individuals from Antioquia, Colombia, who tested positive for the ADAD-associated PSEN1 E280A mutation. Data analysis was performed from August 20, 2014, through November 30, 2015. A mixed-effects model was used to estimate annual rates of change in cognitive test scores and to mark the onset of cognitive decline. Memory, language, praxis, and total scores from the Consortium to Establish a Registry for Alzheimer Disease test battery. Chronologic age was used as a time scale in the models. We explore the effects of sex; educational level; socioeconomic status; residence area; occupation type; marital status; history of hypertension, diabetes mellitus, and dyslipidemia; tobacco and alcohol use; and APOE ε4 on the rates of cognitive decline. A total of 493 carriers met the inclusion criteria and were analyzed. A total of 256 carriers had 2 or more assessments. At the time of the initial assessment, participants had a mean (SD) age of 33.4 (11.7) years and a mean (SD) educational level of 7.2 (4.2) years. They were predominantly female (270 [54.8%]), married (293 [59.4%]), and of low socioeconomic status (322 [65.3%]). Word list recall scores provided the earliest indicator of preclinical cognitive decline at 32 years of age, 12 and 17 years before the kindred's respective median ages at mild cognitive impairment and dementia onset. After the change point, carriers had a statistically significant cognitive decline with a loss of 0.24 (95% CI, -0.26 to -0.22) points per year for the word list recall test and 2.13 (95% CI, -2.29 to -1.96) points per year for total scores. Carriers with high educational levels had an increase of approximately 36% in the rate of cognitive decline after the change point when compared with those with low educational levels (-2.89 vs -2.13 points per year, respectively). Onset of cognitive decline was delayed by 3 years in individuals with higher educational levels compared with those with lower educational levels. Those with higher educational level, middle/high socioeconomic status, history of diabetes and hypertension, and tobacco and alcohol use had a steeper cognitive decline after onset. Preclinical cognitive decline was evident in PSEN1 E280A mutation carriers 12 years before the onset of clinical impairment. Educational level may be a protective factor against the onset of cognitive impairment.

Treatment for Schistosoma japonicum, Reduction of Intestinal Parasite Load, and Cognitive Test Score Improvements in School-Aged Children

BackgroundTo determine whether treatment of intestinal parasitic infections improves cognitive function in school-aged children, we examined changes in cognitive testscores over 18 months in relation to: (i) treatment-related Schistosoma japonicum intensity decline, (ii) spontaneous reduction of single soil-transmitted helminth (STH) species, and (iii) ≥2 STH infections among 253 S. japonicum-infected children.MethodologyHelminth infections were assessed at baseline and quarterly by the Kato-Katz method. S. japonicum infection was treated at baseline using praziquantel. An intensity-based indicator of lower vs. no change/higher infection was defined separately for each helminth species and joint intensity declines of ≥2 STH species. In addition, S. japonicum infection-free duration was defined in four categories based on time of schistosome re-infection: >18 (i.e. cured), >12 to ≤18, 6 to ≤12 and ≤6 (persistently infected) months. There was no baseline treatment for STHs but their intensity varied possibly due to spontaneous infection clearance/acquisition. Four cognitive tests were administered at baseline, 6, 12, and 18 months following S. japonicum treatment: learning and memory domains of Wide Range Assessment of Memory and Learning (WRAML), verbal fluency (VF), and Philippine nonverbal intelligence test (PNIT). Linear regression models were used to relate changes in respective infections to test performance with adjustment for sociodemographic confounders and coincident helminth infections.Principal FindingsChildren cured (β = 5.8; P = 0.02) and those schistosome-free for >12 months (β = 1.5; P = 0.03) scored higher in WRAML memory and VF tests compared to persistently infected children independent of STH infections. A decline vs. no change/increase of any individual STH species (β:11.5–14.5; all P<0.01) and the joint decline of ≥2 STH (β = 13.1; P = 0.01) species were associated with higher scores in WRAML learning test independent of schistosome infection. Hookworm and Trichuris trichiura declines were independently associated with improvements in WRAML memory scores as was the joint decline in ≥2 STH species. Baseline coinfection by ≥2 STH species was associated with low PNIT scores (β = −1.9; P = 0.04).Conclusion/SignificanceChildren cured/S. japonicum-free for >12 months post-treatment and those who experienced declines of ≥2 STH species scored higher in three of four cognitive tests. Our result suggests that sustained deworming and simultaneous control for schistosome and STH infections could improve children's ability to take advantage of educational opportunities in helminth-endemic regions.