Neuropsychometric Tests Research Articles

Su1697 Restless Leg Syndrome (RLS) Is Associated With Hepatic Encephalopathy (HE) in Decompensated Cirrhosis. a Clinical Pilot Study

Introduction RLS affects 10% of the general population, affecting the quality of life (QOL). Exact aetiology is still unknown. Iron deficiency, small intestinal bacterial overgrowth (SIBO) and inflammatory bowel disease (IBD) have clear association with RLS. Decompensated cirrhosis with portal hypertension has multi-organ involvement causing minimal and overt encephalopathy with sleep: dysnomia, parasomnia, and stupor which has clear association with Sub acute bacterial Peritonitis (SBP ) which has precipitating clinical state with SIBO, This clinical study evaluates the association of RLS in HE amongst decompensated cirrhotics. Methods One hundred eight (n = 108) patients were recruited. Group A (n = 36) decompensated cirrhotic (mean MELD 16, OHE 20/36(55%), MHE 16/36(44%), esophageal varices grade II 24/36(67%). Group B (n = 36) chronic liver disease- Alcohol 9/36(25%) NASH 12/36(33%) HCV 12/36(33%) HBV 1/36(3%) AIH 2/36(6%) with mean MELD 6).without cirrhosis Group C (n = 36) healthy controls. Initially all received Xifaxan 550mg orally twice daily for 10 days to eradicate co-existing SIBO. All underwent Methane breath test for SIBO. Baseline labs: Serum levels for renal function, ferritin, iron studies, haemoglobin/hematocrit, ammonia, celiac, and IBD serology, stool lactoferrin & calprotectin and urine for toxicology screening. Groups A and B underwent neuro-psychometric and flicker testing for MHE and OHE and sleep testing for RLS (with Mayo RLS questionnaire). Exclusion: Chronic iron deficiency, Celiac, IBD, major depression, IBS, benzodiazepines, narcotics, alcohol, anti-psychotics and illicit drugs. Results Group A 24/36(67%) had RLS: [OHE 16/20 (80%), MHE 8/16 (50%), esophageal varices 8/10(80%), alcoholic cirrhotic 10/14(71%), CHC 3/6(50%), NASH 3/6 (50%) and SIBO 14/36 (39%)]. Group B 1/36(3%) RLS and SIBO 7/36(19%). Group C 2/36(6%) RLS and SIBO 3/36(8%). All confirmed by sleep study and RLS questionnaire. Serum ammonia has no impact on RLS. Conclusion This clinical trial postulates decompensated cirrhotics have high evidence of RLS with portal hypertension. Larger trials will validate. Disclosure of Interest None Declared.

Clinical impact of neurocognitive deficits after cardiac surgery

Postoperative neurocognitive deficits (POCDs) have been found to occur frequently after cardiac surgery. Although POCDs have received significant attention in the medical literature and public media, the true clinical impact of these deficits on patient outcomes and quality of life (QOL) is not well defined. Neuropsychometric testing was performed on 696 patients undergoing coronary artery bypass surgery using a battery of tests divided into 4 domains; memory, attention, speed, and psychomotor function. These were performed preoperatively, at hospital discharge, and at 3 months postoperatively. POCDs were defined as a drop in scores by 1 standard deviation in 1 domain or more. QOL was assessed using Short Form 36 and clinical outcomes were recorded. POCDs were identified in 265 (38%) patients at discharge and in 132 (19%) at 3 months. There was no observed difference in mortality or major morbidity in patients with or without POCDs. Predictors of POCDs at discharge were elevated preoperative creatinine (P=.04), increased cardiopulmonary bypass time (P=.005), and diabetes (P=.003). At 3 months, patients had improvements in both physical and mental components of QOL, independent of the occurrence of POCDs (P>.5). Independent predictors of improved QOL included younger age, severe preoperative anginal symptoms, normal left ventricular function, absence of postoperative wound infection, but not POCDs. Neurocognitive deficits can be frequently detected on comprehensive neuropsychometric testing after cardiac surgery. However, they are not associated with any clinically important differences in patient outcome or in QOL after surgery.

Neuropsychometric correlates of efavirenz pharmacokinetics and pharmacogenetics following a single oral dose

To determine pharmacokinetic and pharmacogenomic correlates of efavirenz central nervous system (CNS) side effects following a single dose. Thirty-four healthy HIV-negative African Americans were administered a 600 mg dose of efavirenz. Blood samples for pharmacokinetics were drawn serially from 0 to 12 h post-dose. Neuropsychometric testing with drowsiness visual analogue scale, grooved pegboard and letter digit substitution tests was done the day prior to dosing and at 1, 2, 3, 4 and 6 h post-dose. Subjective CNS symptoms were assessed at 6 h post-dose. Composite CYP2B6 516/983 genotype was determined. Pharmacokinetic indices reflecting increased plasma efavirenz exposure were associated with slower non-dominant hand grooved pegboard task completion (Cmax , P1 h = 0.01, P2 h = 0.05, P3 h = 0.03, P4 h = 0.01; AUC, P1 h = 0.04; clearance P1 h = 0.05, P2 h = 0.02, P6 h = 0.01). In a repeated measures model analysis that adjusted timing of neuropsychometric testing for timing of peak drug concentration, clearance (P < 0.001), AUC(0.312 h) (P = 0.001) and Cmax (P = 0.008) were associated with non-dominant grooved pegboard test performance. CYP2B6 genotype trended to correlate with non-dominant hand grooved pegboard at 4 and 6 h (P = 0.07 and 0.06). Decreased drowsiness at 6 h was associated with higher Cmax (P = 0.02). Following a single dose of efavirenz, an association between pharmacokinetics and neuropsychometric performance was discernable. A weaker association between genotype and neurocognitive test performance is likely mediated by effect of genotype on plasma clearance. Strategies that lower Cmax during initial dosing may decrease CNS side effects.

Relationship between the Wada test and preoperative/postoperative memory in mesial temporal lobe epilepsy patients

Objectives: To study the correlation between Wada memory test and neuropsychometric tests which were applied preoperatively to mesial temporal lobe epilepsy patients associated with hippocampal sclerosis (MTLE-HS) who had undergone selective amygdalohippocampectomy and find out the effects of early onset epileptic seizures on atypical memory dominance. Methods: Drug-resistant 27 patients (16 left, 11 right MTLE-HS) had video EEG, cranial MRI and Wada test preoperatively. Weschler visual subtest and verbal memory processing tests were applied to all patients before surgery and the first year after the operation. Results: The number of left hemisphere memory dominant patients was 6 (22.2%) and the number of atypical memory dominant patients was 21 (77.8%) according to the Wada test. There was a significant difference between the two groups when compared for epileptic seizure onset age; (p=0.042), and also a significant diffference when compared for HS (right/left) side (p=0.002). When we analyzed the correlation between preoperative and postoperative verbal and nonverbal tests and left memory Wada dominance; in verbal memory processing tests ‘delayed recall’ scores between groups were significant (p=0.042), on the other hand in patients with atypical memory dominance ‘total learning’ scores between groups were significant (p<0.001). Conclusion: As a result, we found that the earlier the onset of seizures, the more atypical the memory dominance (right or bilateral). The Wada test was effective for assessing verbal memory; on the other hand, it was inadequate for assessing visual memory dominance. If the scores of ‘delayed recall’ in verbal memory were high in the patients with typical verbal dominance and ‘total learning’ scores in the patients with atypical verbal dominance, the scores also tended to rise after the operation.

508 Clinical Impact of Neurocognitive Deficits Following Cardiac Surgery

Neurocognitive deficits (NCDs) have been found to occur frequently following cardiac surgery. Although NCDs have received significant attention in the medical literature and public media, the true clinical impact of these deficits on patient outcomes and quality of life is not well defined. Neuropsychometric testing was performed on 696 patients undergoing coronary artery bypass surgery using a battery of 14 tests divided into 4 domains assessing memory, attention, speed, and psychomotor function. Neurocognitive assessments were performed preoperatively (100% complete), at hospital discharge (99% complete), and at 3 months postoperatively (94% complete). Neurocognitive deficits were defined as a drop in scores by 1 standard deviation in ≥ 1 domain. Quality of life was assessed using Short Form 36 and clinical outcomes were recorded. Mean age was 65 ± 8 years and 88% were male. There was an in-hospital mortality rate of 1.6% (11 patients) while 98.4% (685 patients) survived at 3 months. NCDs were identified in 265 (38%) patients at discharge and in 132 (19%) at 3 months. Predictors of NCD at discharge were elevated preoperative creatinine (p = 0.04), increased cardiopulmonary bypass time (p = 0.005), and diabetes (p = 0.003) while predictors of NCD at 3 months was prolonged ICU stay (p = 0.01). Intensive care unit stay (1.8 ± 2.9 vs. 1.3 ± 1.3 days, p = 0.03) and hospital stay (6.8 ± 5.3 vs. 6.4 ± 3.0 days, p = 0.11) were slightly longer in NCD patients. At 3 months, patients experienced improvements in both physical (34 ± 2% increase vs. baseline) and mental (10 ± 1% increase vs. baseline) components of quality of life, independent of the occurrence of NCDs (p > 0.5). Independent predictors of quality of life improvement included younger age, severe preoperative symptoms, normal left ventricular function, and absence of post-operative wound infection, but not NCDs (Table 1).Tabled 1 Neurocognitive deficits can be frequently detected on comprehensive neuropsychometric testing following cardiac surgery. However, they are not associated with any clinically important differences in patient outcome or in quality of life after surgery.

An Open-Label Exploratory Study with Memantine: Correlation between Proton Magnetic Resonance Spectroscopy and Cognition in Patients with Mild to Moderate Alzheimer's Disease (P04.198)

Objective: To characterize Alzheimer9s disease (AD) progression using proton magnetic resonance spectroscopy ( 1 H MRS) and cognitive measures in mild-moderate AD patients treated with open-label memantine in addition to cholinesterase inhibitor (ChEI). Background While cross-sectional studies have shown reduced N-acetylaspartate (NAA) and elevated myo-inositol (mI) in AD patients, the feasibility of 1 H MRS as a longitudinal biomarker for clinical trials remains to be elucidated. Design/Methods: 11 subjects with mild-moderate AD (baseline MMSE 21.9 ± 3.0) were on stable dose ChEI for at least 3 months prior to study entry. Neuropsychometric testing and single-voxel 1 H MRS from the precuneus and posterior cingulate region were performed at baseline, after 24 weeks of ongoing ChEI monotherapy, and after another 24 weeks of open-label memantine in addition to ChEI. Baseline 1 H MRS metabolite [NAA, mI, choline (Cho), and creatine (Cr)] ratios in AD subjects were compared to 29 age-matched, cognitively normal controls (MMSE 28.3 ± 1.6). Results: Compared to controls, AD subjects had significantly higher mI/Cr (p=0.0155) and lower NAA/Cr (p=0.0487), NAA/Cho (p=0.0222) and NAA/mI (p=0.0105). In AD subjects, baseline Alzheimer9s Disease Cooperative Study Activities of Daily Living (ADCS-ADL) scores significantly correlated with NAA/Cr (Spearman r = 0.80, p=0.0032), mI/Cr (Spearman r = -0.73, p=0.0115), and NAA/mI (Spearman r = 0.83, p=0.0014). Baseline cognitive measures did not correlate with metabolite ratios. There was no significant change in neuropsychometric test performance on combination therapy as compared with ChEI monotherapy. There was a decrease in NAA/mI on combination therapy as compared with ChEI monotherapy, but this was not significant after correction for multiple comparisons. Conclusions: We found significant differences in 1 H MRS metabolite ratios between mild-moderate AD and control subjects. Baseline 1 H MRS metabolite ratios correlated with function (ADCS-ADL). There was no significant change in neuropsychometric performance or 1 H MRS metabolite ratios when open-label memantine was added to stable dose ChEI. Supported by: Forest Research Institute. Disclosure: Dr. Gordon has received personal compensation for activities with Accera Inc. and Eli Lilly & Company as a consultant. Dr. Gordon has received research support from Forest Laboratories and Eli Lilly & Company. Dr. Kingsley has nothing to disclose. Dr. Goldberg has received personal compensation for activities with Merck & Co., Inc. as a consultant. Dr. Koppel holds stock and/or stock options in Eli Lilly & Company. Dr. Christen has nothing to disclose. Dr. Keehlisen has nothing to disclose. Dr. Kohn has nothing to disclose. Dr. Davies has has received (royalty or license fee or contractual rights) payments from Eli Lilly.Dr. Davies has received research support from Eli Lilly.

APOE modifies the association between Aβ load and cognition in cognitively normal older adults

To determine the relationship between β-amyloid (Aβ) load as measured by [(11)C]-Pittsburgh compound B (PiB) PET and cognitive function in cognitively normal older adults. We studied 408 cognitively normal older adults who participated in the population-based Mayo Clinic Study of Aging (MCSA) from January 2009 through March 2011. The participants underwent PiB PET and neuropsychometric testing within 6 months. The association between PiB retention and cognitive function was measured by partial correlation and an interaction with APOE status was tested using linear regression after adjusting for age, sex, and education. Higher PiB retention was associated with cognitive performance (Spearman partial r = -0.18; p < 0.01), specifically the memory, language, attention/executive, and visual-spatial processing domains in the whole group of participants. The association between PiB retention and cognition was modified by the APOE status on linear regression analysis even after controlling for the differences in the distribution of PiB values among APOE ε4 carriers and noncarriers (p = 0.02). Cognitive performance was associated with the Aβ deposition in the frontal, temporal, and parietal lobe association cortices in APOE ε4 carriers on SPM analysis (p < 0.001). There is a modest association between PiB retention and cognitive function in cognitively normal older adults and this relationship between Aβ load and cognitive function is modified by APOE status. Whereas Aβ load is associated with greater cognitive impairment in APOE ε4 carriers, the cognitive function in APOE ε4 noncarriers is influenced less by the Aβ load, suggesting that APOE isoforms modulate the harmful effects of Aβ on cognitive function.

Focal brain atrophy in gastric bypass patients with cognitive complaints

Recently, we have identified a series of patients presenting with cognitive complaints after gastric bypass, without any identifiable etiology. We aimed to determine if focal brain atrophy could account for the complaints. A retrospective case series was performed to identify patients with cognitive complaints following gastric bypass who had a volumetric MRI. Voxel-based morphometry was used to assess patterns of grey matter loss in all 10 patients identified, compared to 10 age and gender-matched controls. All patients had undergone Roux-en-Y gastric bypass surgery at a median age of 54 (range: 46–64). Cognitive complaints developed at a median age of 57 (52–69). Formal neuropsychometric testing revealed only minor deficits. No nutritional abnormalities were identified. Voxel-based morphometry demonstrated focal thalamic atrophy in the gastric bypass patients when compared to controls. Patients with cognitive complaints after gastric bypass surgery may have focal thalamic brain atrophy that could result in cognitive impairment.

Non-amnestic mild cognitive impairment is a prominent aspect in Parkinson’s disease patients being considered for deep brain stimulation

Cognitive deficits increase with disease duration in Parkinson’s disease (PD). Patients referred for deep brain stimulation (DBS) usually have advanced disease, and some cognitive deficits are expected pre-operatively. Improved prediction of cognitive risk is one goal for DBS services. As a first step, the detailed cognitive profiles of patients referred for consideration of DBS should be described. This is the aim of this manuscript. We document comprehensively the pre-operative types and prevalence of neuropsychological deficits in advanced PD patients being considered for DBS. Routinely, pre-operatively, we performed neuropsychometric testing in 46 consecutive PD patients attending a DBS clinic to assess suitability for DBS. Five domains were assessed: intellectual, memory, language, perception and executive functions. Patient performance was compared with standard published normative data of the neuropsychological tests. Patients had mild intellectual decline relative to their premorbid IQ. The main impairment of verbal recall memory was on list-learning. Selective impairments on executive tests were found, most commonly (54%) being on the Brixton test, a test of inductive reasoning rarely reported in the PD literature. By contrast, verbal-fluency tasks were unimpaired in a small subgroup. Mild pre-operative neuropsychological impairments of executive and memory cognitive domains are common in a DBS clinic. The natural history of these deficits remains to be determined. The potential relevance to a DBS service is discussed.

Magnetic resonance spectroscopy, β-amyloid load, and cognition in a population-based sample of cognitively normal older adults

To determine the relationship between proton magnetic resonance spectroscopy ((1)H MRS) metabolites and β-amyloid (Aβ) load and the effects of Aβ load on the association between (1)H MRS metabolites and cognitive function in cognitively normal older adults. We studied 311 cognitively normal older adults who participated in the population-based Mayo Clinic Study of Aging from January 2009 through September 2010. Participants underwent (11)C-Pittsburgh compound B (PiB) PET, (1)H MRS from the posterior cingulate gyri, and neuropsychometric testing to assess memory, attention/executive, language, and visual-spatial domain functions within 6 months. Partial Spearman rank order correlations were adjusted for age, sex, and education. Higher PiB retention was associated with abnormal elevations in myoinositol (mI)/creatine (Cr) (partial r(s) = 0.17; p = 0.003) and choline (Cho)/Cr (partial r(s) = 0.13; p = 0.022) ratios. Higher Cho/Cr was associated with worse performance on Auditory Verbal Learning Test Delayed Recall (partial r(s) = -0.12; p = 0.04), Trail Making Test Part B (partial r(s) = 0.12; p = 0.04), Wechsler Adult Intelligence Scale-Revised (WAIS-R) Digit Symbol (partial r(s) = -0.18; p < 0.01), and WAIS-R Block Design (partial r(s) = -0.12; p = 0.03). Associations between (1)H MRS metabolites and cognitive function were not different among participants with high vs low PiB retention. In cognitively normal older adults, the (1)H MRS metabolite ratios mI/Cr and Cho/Cr are associated with the preclinical pathologic processes in the Alzheimer disease cascade. Higher Cho/Cr is associated with worse performance on domain-specific cognitive tests independent of Aβ load, suggesting that Cho/Cr elevation may also be dependent on other preclinical dementia pathologies characterized by Cho/Cr elevation such as Lewy body or ischemic vascular disease in addition to Aβ load.

Effect of Amyloid-Beta load on cognition is modified by the APOE status in a population-based sample of cognitively normal older adults

While 30% of cognitively normal older adults have increased b-amyloid (AB) deposition on PET imaging with amyloid ligand [11C]-Pittsburgh Compound B (PiB), the effects of AB load on cognitive function in cognitively normal individuals has been variable. Our objective was to determine the relationship between ß-amyloid (AB) load as measured by [11C]-Pittsburgh Compound B (PiB) PET and cognitive function in cognitively normal older adults. Because both AB load and APOE e4 increase the risk of AD, we further investigated the effects of APOE e4 allele on the association between AB load and cognitive performance. We studied 279 cognitively normal older adults who participated in the population-based Mayo Clinic Study of Aging (MCSA) from January 2009 through November 2010. The participants underwent amyloid imaging with PiB PET and neuropsychometric testing within 6 months. All partial Spearman rank-order correlations were adjusted for age, sex and education. Voxel-based analysis was performed to determine the pattern of PiB retention that correlates with the global cognitive function in cognitively normal older adults. Higher PiB retention was inversely associated with a measure of overall cognitive performance (r = -0.18; p < 0.01) specifically in the memory and attention/executive function domains in the whole group of participants. The association between PiB retention and cognition was modified by the APOE status in the whole group and in a secondary group analysis matched on PiB retention. In carriers of the APOE e4 allele, higher PiB retention was associated with lower overall cognitive performance (r = -0.46; p < 0.01) specifically in memory, language, attention/executive function and visual-spatial processing. The overall cognitive performance was associated with the AB deposition in the frontal, temporal and parietal lobe association cortices in APOE e4 carriers (Figure). PiB retention was not associated with cognition in APOE e4 non-carriers.Figure. Statistical analyses based on WM tracts in JHU atlas between controls and AD patients. All p < 0.05; red—yellow: 0.05—0 (pvalue). Higher AB load in the frontal, temporal and a parietal lobe association cortex is associated with lower cognitive performance in cognitively normal APOE e4 carriers but not in non-carriers. APOE genotype modifies the influence of AB load on cognitive function in cognitively normal older adults. Associates between global cortical PiB retention and standardized global cognitive scores according to APOE ε4 status (left). Increased PiB retention correlated with global cognitive performance score in the frontal, temporal and parietal association cortices in APOE ε4 carriers as shown in red (right).

Diffusion tensor imaging and cognitive function in older adults with no dementia

To determine the patterns of diffusivity associated with cognitive domain functions in older adults without dementia. We studied older adults without dementia (n = 220) who underwent neuropsychometric testing and a diffusion tensor imaging (DTI) examination at 3 T in a cross-sectional study. Memory, language, attention/executive function, and visual-spatial processing domains were assessed within 4 months of the MRI examination. A fluid-attenuated inversion recovery-based DTI sequence that enabled uncontaminated cortical diffusion measurements was performed. Associations between cortical mean diffusivity (MD) and cognitive function were tested using voxel-based regression analysis. Association between tract diffusivity and cognitive function was tested with regions of interest drawn on color-coded fractional anisotropy (FA) maps. Memory function was associated with the medial temporal lobe cortical MD on voxel-based analysis (p < 0.001, corrected for multiple comparisons), and inferior longitudinal fasciculus and posterior and anterior cingulum FA on tract-based analysis (p < 0.001). Language function was associated with the left temporal lobe cortical MD (p < 0.001, corrected for multiple comparisons), inferior longitudinal fasciculus, fornix, and posterior cingulum FA (p < 0.05). Attention and executive function was associated with the posterior and anterior cingulum FA, and visual-spatial function was associated with posterior cingulum FA (p < 0.01). Specific cognitive domain functions are associated with distinct patterns of cortical and white matter diffusivity in elderly with no dementia. Posterior cingulum tract FA was associated with all 4 cognitive domain functions, in agreement with the hypothesis that the posterior cingulate cortex is the main connectivity hub for cognitive brain networks. Microstructural changes identified on DTI may be associated with neurodegenerative pathologies underlying cognitive changes in older adults without dementia.

L-Dopa improves Restless Legs Syndrome and periodic limb movements in sleep but not Attention-Deficit-Hyperactivity Disorder in a double-blind trial in children

Background In a previous open-label study, dopaminergic agents improved Restless Legs Syndrome (RLS) and Periodic Limb Movements in Sleep (PLMS), as well as Attention-Deficit-Hyperactivity Disorder (ADHD) in children with both disorders. We therefore conducted a double-blind placebo-controlled trial of l-DOPA in ADHD children with and without RLS/PLMS. Methods Two groups of patients (total n = 29), those with ADHD only or those with ADHD and RLS/PLMS, were randomized to l-DOPA or placebo therapy. At baseline and after therapy patients were assessed with Conners’ parent and teacher rating scales; polysomnography; RLS rating scale; and neuropsychometric measures of memory, learning, attention, and vigilance. Results l-DOPA improved RLS/PLMS symptoms in all patients with those disorders compared with placebo ( p = .007). When assessed by the Conners’ Scales before therapy, ADHD was more severe in children without RLS/PLMS than in children with RLS/PLMS ( p = 0.006). l-DOPA had no effect on Conners’ scales, sleep, or neuropsychometric tests when all patients treated with the drug were compared to those on placebo or when patients with ADHD only were compared to those with ADHD and RLS/PLMS. Conclusions In this first double-blind study of a dopaminergic therapy in children with RLS/PLMS, l-Dopa significantly improved RLS/PLMS but not ADHD. These results, however, should be interpreted carefully since they may have been influenced by the relatively small sample size and the baseline differences in severity of ADHD symptoms. Further work needs to be done to elucidate the relationship between dopamine, ADHD and RLS/PLMS.

Cognitive impairment in type 2 diabetes mellitus

BackgroundType 2 diabetes mellitus (T2DM) is a modern day epidemic. Chronic course of diabetes is detrimental to the cognitive functions. AimTo decipher the pattern of cognitive impairment in relation to the duration of diabetes. Study designCross-sectional. Material and methodsT2DM patients (Group I: ⩽5 years duration of diabetes, n=11; Group II: >5 years duration of diabetes, n=17) without clinical evidence of central nervous system damage and non-diabetic controls (n=18) were studied clinically and P300 event-related potentials (ERPs) recorded using three stimuli oddball paradigm. Subjects were examined with Folstein mini-mental state examination (MMSE) for cognitive function and those showing scores more than 26 (maximum score=30) were enrolled for the study. Patients with known diabetic complications were excluded. ResultsP300 latencies in diabetic group did not relate linearly to the duration of diabetes. Diabetic subgroups with ⩽5 years and >5 years duration of diabetes showed striking differences, patients with over 5 years of disease duration had much prolonged P300 latencies in contrast to patients with 5 years or less disease duration who showed trends similar to that of control group. Differences in P300 amplitudes between groups were non-significant. Hypertensive diabetics showed much prolongation in P300 latencies compared to normotensive diabetics. ConclusionsP300 ERPs revealed cognitive dysfunction which was not detected by neuro-psychometric test (MMSE). Patients with T2DM have decreased cognitive function which is more prominent when the disease duration exceeds 5 years. Co-existence of hypertension with T2DM further increases the risk of cognitive impairment.

A prospective cohort study evaluating associations among delirium, postoperative cognitive dysfunction, and apolipoprotein E genotype following open aortic repair

Patients undergoing major vascular surgery are at high risk of postoperative delirium and postoperative cognitive dysfunction (POCD). Apolipoprotein E (APOE) is involved in central acetylcholine synthesis, and patients bearing the ε4 genotype (APOE-ε4) are at increased risk of both vascular dementia and peripheral vascular disease. The purpose of this study was to evaluate the associations among delirium, POCD, and APOE-ε4 in patients undergoing open aortic repair. Following Research Ethics Board approval and written informed consent, we recruited a cohort of patients ≥ 60 yr of age undergoing open aortic repair. Apolipoprotein E genotyping and a battery of nine neuropsychometric (NP) tests were performed prior to surgery. Delirium was assessed on postoperative days two, four, and discharge using the Confusion Assessment Method. Neuropsychometric testing was repeated at discharge and again three months following surgery. A group of non-surgical patients was used to adjust NP scores using reliable change index methodology. Logistic regression was used to evaluate independent predictors of both delirium and POCD. Eighty-eight patients underwent surgery, 78 completed NP testing on discharge, and sixty-nine completed NP testing at three months. Delirium was noted in 36% of patients after surgery, while POCD was noted in 62% at discharge and 6% at three months. Delirium predicted POCD at discharge (odds ratio 2.86; 95% confidence intervals 0.99 to 8.27) but not at three months. Apolipoprotein E-ε4 genotype was not associated with either delirium or POCD following adjustment for covariates. Both delirium and POCD are common following open aortic repair; however, the APOE genotype did not predict either condition. This trial has been registered with ClinicalTrials.gov (NCT00911677).

The clock drawing test is a poor screening tool for postoperative delirium and cognitive dysfunction after aortic repair

The Clock Drawing Test (CDT) is a screening tool for dementia that tests a variety of cognitive domains. The CDT takes a maximum of two minutes to complete and might be helpful in identifying postoperative cognitive disorders at the bedside. The objective of this study was to evaluate the accuracy of the CDT in a population at high risk for postoperative cognitive disorders In this prospective observational cohort study, patients were recruited who were≥60yr of age and scheduled for elective open repair of the abdominal aorta. Delirium was assessed using the Confusion Assessment Method (CAM) on postoperative days (POD) 2 and 4 and at discharge. Cognitive function was assessed with neuropsychometric tests before surgery and at discharge. Postoperative cognitive dysfunction (POCD) was determined using the Reliable Change Index. Clock Drawing Tests were administered at all time points. Agreement between the CDT and test for delirium or POCD was assessed with Cohen's Kappa statistic. Delirium was noted in 30 of 83 patients (36%; 95% confidence interval [CI] 26 to 46%) during their hospital stay, while POCD was noted in 48 of 78 patients (60%; 95% CI 51 to 72%) at discharge. Agreement between the CDT and CAM was poor at three intervals (Kappa 0.06 to 0.29), as was POCD at discharge (Kappa 0.46). Sensitivity of the CDT was <0.71 for both delirium and POCD at all intervals. False positives and negatives were common. Agreement between CDT and tests for delirium and POCD was poor; sensitivity was inadequate for a screening test. (ClinicalTrials.gov number, NCT00911677).

Rifaximin Improves Psychometric Performance and Health-Related Quality of Life in Patients With Minimal Hepatic Encephalopathy (The RIME Trial)

Cirrhotics with minimal hepatic encephalopathy (MHE) have a poor health-related quality of life (HRQOL). Treatment of MHE is still evolving. The aim of this double-blind randomized pilot study was to assess the efficacy of rifaximin in improving neuropsychometric (NP) test performance and HRQOL in patients with MHE. MHE was diagnosed if any two NP tests (number and figure connection tests, picture completion, digit symbol, and block design tests) were deranged beyond 2 s.d. of normal. HRQOL was assessed using the sickness impact profile (SIP) questionnaire. A total of 486 patients with cirrhosis were screened and 284 were found eligible. Out of these 115 (40.9%) had MHE, of which 21 refused consent and 94 were randomized to receive placebo (n=45) and rifaximin (n=49; 1200 mg/day) for 8 weeks. At the end of treatment, significantly more number of patients in rifaximin group showed reversal of MHE (75.5% (37/49) vs. 20% (9/45) in placebo group; P<0.0001). Rifaximin group also showed significant reduction in mean number of abnormal NP tests (baseline, 2.35 (95% confidence interval (CI), 2.17-2.53); 2 weeks, 1.29 (95% CI, 1.02-1.56), P=0.002; 8 weeks, 0.81 (95% CI, 0.61-1.02), P=0.000), compared with placebo group (baseline, 2.31 (95% CI, 2.03-2.59); 2 weeks, 2.03 (95% CI, 1.74-2.31); 8 weeks, 1.97 (95% CI, 1.69-2.25), P>0.05). The mean total SIP score also improved significantly in rifaximin group (baseline, 11.67 (95% CI, 10.31-13.03); 8 weeks, 6.45 (95% CI, 5.59-7.30); P=0.000) compared with placebo group (baseline, 9.86 (95% CI, 8.66-11.06); 8 weeks, 8.51 (95% CI, 7.35-9.67); P=0.82). Improvement in HRQOL correlated with improvement in NP tests. Rifaximin was well tolerated. Rifaximin significantly improves both cognitive functions and HRQOL in patients with MHE.

Cognitive correlates with functional outcomes after anoxic brain injury: A case-controlled comparison with traumatic brain injury

Objectives: To assess the effectiveness of inpatient rehabilitation in adults who have sustained an anoxic brain injury (AnBI). Secondly, to identify areas of cognition that predict functional outcomes at discharge.Design: Retrospective, matched case-controlled study.Methods: Ten patients with moderate-to-severe AnBI and 10 patients with traumatic brain injury (TBI), treated in an inpatient neurorehabilitation programme, were matched on age, acute care length of stay and admission Functional Independence Measure (FIM). Functional outcome was assessed using the FIM and Disability Rating Scale (DRS).Results: Patients with AnBI performed worse on all measures of functional outcome relative to patients with TBI. Patients with AnBI achieved significantly lower FIM motor and cognitive gain compared with patients with TBI (11.5, SD 13.6 vs. 31.0, SD 19.7 and 2.4, SD 3.9 vs. 7.5, SD 4.2, respectively (p < 0.02)). DRS data showed similar trends of functional improvement between the groups. Several neuropsychometric tests correlated with functional outcome (p < 0.01).Conclusions: Patients with AnBI had worse functional outcomes following rehabilitation than patients with TBI, confirming the results of previous reports. Poor cognitive function predicted poor functional outcomes on the FIM and somewhat on the DRS. Research is needed to assess why these differences occur and to improve or develop new effective rehabilitation treatments for AnBI.

Cognitive functions correlate with diffusion tensor imaging metrics in patients with spina bifida cystica

Spina bifida cystica (SBC) is a group of neurodevelopmental defects caused by improper neural tube closure, which may be responsible for deficits in cognitive functions. The purpose of this study was to examine changes in normal appearing deep gray and white matter brain regions in SBC patients compared with controls through diffusion tensor imaging (DTI) and correlate these changes with neuropsychometric tests. Conventional magnetic resonance imaging and neuropsychometric tests were performed on 13 patients and ten controls. DTI-derived fractional anisotropy (FA) and mean diffusivity (MD) were quantified in different brain regions in controls and patients. Significantly decreased FA was observed in caudate nuclei, putamen, genu, splenium, and increased FA was found in middle cerebellar peduncle (MCP) in patients compared with controls. We observed significantly increased MD in genu and splenium. However, increased MD was found in fornix of patients compared with controls. Majority of neuropsychological tests were found to be significantly impaired and some of these showed significant correlation with DTI metrics in genu, splenium, and MCP in these patients. We conclude that DTI metrics are significantly abnormal in deep gray matter nuclei, genu, splenium, and MCP in SBC patients and may provide microstructural basis for neuropsychological abnormalities in these patients.

Poster 5: Cognitive Correlates With Functional Outcome After Anoxic Brain Injury: A Case-Controlled Comparison With Traumatic Brain Injury

Objectives: To assess the effectiveness of inpatient rehabilitation in adults who have sustained an anoxic brain injury (AnBI). Secondly, to identify areas of cognition that predict functional outcomes at discharge. Design: Retrospective, matched case-controlled study. Methods: Ten patients with moderate-to-severe AnBI and 10 patients with traumatic brain injury (TBI), treated in an inpatient neurorehabilitation programme, were matched on age, acute care length of stay and admission Functional Independence Measure (FIM). Functional outcome was assessed using the FIM and Disability Rating Scale (DRS). Results: Patients with AnBI performed worse on all measures of functional outcome relative to patients with TBI. Patients with AnBI achieved significantly lower FIM motor and cognitive gain compared with patients with TBI (11.5, SD 13.6 vs. 31.0, SD 19.7 and 2.4, SD 3.9 vs. 7.5, SD 4.2, respectively (p < 0.02)). DRS data showed similar trends of functional improvement between the groups. Several neuropsychometric tests correlated with functional outcome (p < 0.01). Conclusions: Patients with AnBI had worse functional outcomes following rehabilitation than patients with TBI, confirming the results of previous reports. Poor cognitive function predicted poor functional outcomes on the FIM and somewhat on the DRS. Research is needed to assess why these differences occur and to improve or develop new effective rehabilitation treatments for AnBI.