Neuropsychometric Tests Research Articles

Easily Screenable Characteristics Associated with Cognitive Improvement and Dysfunction After Carotid Endarterectomy

Carotid endarterectomy (CEA) is an effective treatment for the prevention of stroke in patients with carotid artery stenosis. We aimed to clarify the incidence and risk factors for early cognitive dysfunction (eCD) and early cognitive improvement (eCI), defined as change in cognitive performance ≤24 hours after surgery, using a battery of neuropsychometric tests. In total, 585 patients undergoing CEA were tested with neuropsychometric tests before and after surgery; 155 patients undergoing "simple" spine surgery were the reference group. Patient performance for each test was evaluated by z scores. Cognitive change was defined as eCD (or eCI) if: 1) patients had a z score ≤-2 (or ≥2) in ≥2 cognitive domains or 2) patients had mean z scores across all domains ≤-1.5 (or ≥1.5). Associations between the categorical cognitive outcomes and variables of interest were modeled using the proportional odds model. Of the 585 subjects, 24% had eCD, 6% had eCI, and 70% had "no change." Patients who had eCD were more likely to be statin naïve (odds ratio [OR] 1.23 [1.03-1.48], P=0.02) or women (OR 1.27 [1.06-1.53], P= 0.02). Those with eCI were less likely to have less formal education (OR 0.95 [0.90-1.00], P= 0.04) and less likely to have diabetes mellitus (OR 0.8 [0.65-0.99], P= 0.04). Patients having CEA may develop eCD or eCI postoperatively. Medications likely to be associated with less eCD are statins and aspirin, which correlate most strongly in asymptomatic patients. In addition to confirming previous findings, we found that women were more likely than men to develop eCD. More sex-specific studies and analysis are needed to better explore these findings.

Association of Preclinical Alzheimer Disease With Optical Coherence Tomographic Angiography Findings

Biomarker testing for asymptomatic, preclinical Alzheimer disease (AD) is invasive and expensive. Optical coherence tomographic angiography (OCTA) is a noninvasive technique that allows analysis of retinal and microvascular anatomy, which is altered in early-stage AD. To determine whether OCTA can detect early retinal alterations in cognitively normal study participants with preclinical AD diagnosed by criterion standard biomarker testing. This case-control study included 32 participants recruited from the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St Louis, St Louis, Missouri. Results of extensive neuropsychometric testing determined that all participants were cognitively normal. Participants underwent positron emission tomography and/or cerebral spinal fluid testing to determine biomarker status. Individuals with prior ophthalmic disease, media opacity, diabetes, or uncontrolled hypertension were excluded. Data were collected from July 1, 2016, through September 30, 2017, and analyzed from July 30, 2016, through December 31, 2017. Automated measurements of retinal nerve fiber layer thickness, ganglion cell layer thickness, inner and outer foveal thickness, vascular density, macular volume, and foveal avascular zone were collected using an OCTA system from both eyes of all participants. Separate model III analyses of covariance were used to analyze individual data outcome. Fifty-eight eyes from 30 participants (53% female; mean [SD] age, 74.5 [5.6] years; age range, 62-92 years) were included in the analysis. One participant was African American and 29 were white. Fourteen participants had biomarkers positive for AD and thus a diagnosis of preclinical AD (mean [SD] age, 73.5 [4.7] years); 16 without biomarkers served as a control group (mean [SD] age, 75.4 [6.6] years). The foveal avascular zone was increased in the biomarker-positive group compared with controls (mean [SD], 0.364 [0.095] vs 0.275 [0.060] mm2; P = .002). Mean (SD) inner foveal thickness was decreased in the biomarker-positive group (66.0 [9.9] vs 75.4 [10.6] μm; P = .03). This study suggests that cognitively healthy individuals with preclinical AD have retinal microvascular abnormalities in addition to architectural alterations and that these changes occur at earlier stages of AD than has previously been demonstrated. Longitudinal studies in larger cohorts are needed to determine whether this finding has value in identifying preclinical AD.

Microglial activation correlates in vivo with both tau and amyloid in Alzheimer’s disease

Alzheimer's disease is characterized by the histopathological presence of amyloid-β plaques and tau-containing neurofibrillary tangles. Microglial activation is also a recognized pathological component. The relationship between microglial activation and protein aggregation is still debated. We investigated the relationship between amyloid plaques, tau tangles and activated microglia using PET imaging. Fifty-one subjects (19 healthy controls, 16 mild cognitive impairment and 16 Alzheimer's disease subjects) participated in the study. All subjects had neuropsychometric testing, MRI, amyloid (18F-flutemetamol), and microglial (11C-PBR28) PET. All subjects with mild cognitive impairment and Alzheimer's disease and eight of the controls had tau (18F-AV1451) PET. 11C-PBR28 PET was analysed using Logan graphical analysis with an arterial plasma input function, while 18F-flutemetamol and 18F-AV1451 PET were analysed as target:cerebellar ratios to create parametric standardized uptake value ratio maps. Biological parametric mapping in the Statistical Parametric Mapping platform was used to examine correlations between uptake of tracers at a voxel-level. There were significant widespread clusters of positive correlation between levels of microglial activation and tau aggregation in both the mild cognitive impairment (amyloid-positive and amyloid-negative) and Alzheimer's disease subjects. The correlations were stronger in Alzheimer's disease than in mild cognitive impairment, suggesting that these pathologies increase together as disease progresses. Levels of microglial activation and amyloid deposition were also correlated, although in a different spatial distribution; correlations were stronger in mild cognitive impairment than Alzheimer's subjects, in line with a plateauing of amyloid load with disease progression. Clusters of positive correlations between microglial activation and protein aggregation often targeted similar areas of association cortex, indicating that all three processes are present in specific vulnerable brain areas. For the first time using PET imaging, we show that microglial activation can correlate with both tau aggregation and amyloid deposition. This confirms the complex relationship between these processes. These results suggest that preventative treatment for Alzheimer's disease should target all three processes.

F88. MANIPULATION OF THE GUT MICROBIOTA WITH A PREBIOTIC IN SCHIZOPHRENIA: A DOUBLE-BLINDED RANDOMIZED PLACEBO-CONTROLLED CROSS-OVER STUDY

BackgroundNeurocognitive impairment is increasingly recognized as a fundamental symptomatology in schizophrenia with more than 80% of patients exhibiting significant deficits, even at first episode of illness. Current pharmacotherapies do not alleviate cognitive symptoms, and often cause severe metabolic dysfunction and weight gain that readily become major health concerns. Identifying adjunctive interventions that improve cognition without disrupting the therapeutic actions of anti-psychotic medications, and can mitigate the metabolic side-effects of these drugs, would be highly beneficial to patients and improve prognosis. We have recently demonstrated that the manipulation of the rat gut microbiota with a prebiotic (dietary fibre that grows beneficial enteric bacteria) improves cognitive flexibility and prevents olanzapine-mediated weight gain. We therefore aim to explore whether these actions of the prebiotic translate to medicated stable patients with schizophrenia.MethodsA total of 40 patients with psychosis aged 18–65 will be enrolled in a 24-week maltodextrin-controlled cross-over experimental medicine study. Participants will receive either a 12-week treatment with a prebiotic (active compound) followed by a 12-week maltodextrin supplement (placebo), or in the reverse order. The order of supplements that participants receive is randomized. The primary outcome is to examine the influence of prebiotic supplementation on neurocognitive functioning, which is measured using a tablet-based neuropsychometric test battery. We will also examine the impact on clinical metabolic measures such as total weight and visceral adiposity. The concentration of immune-related serum proteins as well as neuroendocrine hormones will be evaluated. All measurements will take place at baseline, at 12-week cross-over, and at the end of the 24-week study. A within-subjects repeated measures analysis will be performed, and co-variates (gender, weight, medication) identified. This trial is registered with ClinicalTrials.gov, identifier number NCT03153046.ResultsWe have currently screened 36 patients, of whom 30 were eligible for the study (67% male). At baseline, the average age of all recruited was 36.41 ± 11.42. The overall cognitive score was -2.03 ± 0.53 where the subtests included verbal memory (29.09 ± 8.75), digit sequencing (15.41 ± 2.77), token motor (55.74 ± 24.14), semantic fluency (8.83 ± 3.46), letter fluency (11.39 ± 3.65), symbol coding (35.61 ± 9.22) and tower of London (15.1 ± 4.06). There was no difference in overall cognitive between male (14.29 ± 2.46) and female (17.22 ± 2.30) patients. However, long-term associative learning as measured by the digit sequencing subtest appeared to show a significant difference between male (14.29 ± 2.46) and female (17.22 ± 2.33; p=0.008) participants. No significant differences between clinical metabolic measures were observed in baseline BMI (32.25 ± 6.79) and abdominal obesity as measured by hip-to-waist ratio (0.94 ± 0.11). The serum concentrations of immune and endocrine markers will also be presented.DiscussionThis investigation, to our knowledge, is the first clinical study to provide medicated schizophrenia patients with a prebiotic, as a potential means of improving cognition and managing secondary metabolic dysfunction. Although a potential link between commensal enteric bacteria and schizophrenia have been suggested, earlier work with probiotics (live cultures) did not support this association. However, since the current study uses a prebiotic that proliferates multiple species of gut bacteria, it will provide more robust data that will support, or refute, the validity of manipulating the gut microbiome in the treatment of schizophrenia.

Postoperative Delirium, Learning, and Anesthetic Neurotoxicity: Some Perspectives and Directions

Evidence of anesthetic neurotoxicity is unequivocal when studied in animal models. These findings have translated poorly to the clinical domain when equated to postoperative delirium (POD) in adults and postoperative cognitive dysfunction (POCD) in either children or the elderly. In this perspective, we examine various reasons for the differences between animal modeling of neurotoxicity and the clinical situation of POD and POCD and make suggestions as to potential directions for ongoing research. We hypothesize that the animal anesthetic neurotoxicity models are limited, in part, due to failed scaling correction of physiological time. We posit that important insights into POCD in children and adults may be gleaned from studies in adults examining alterations in perioperative management designed to limit POD. In this way, POD may be more useful as the proxy for POCD rather than neuronal dropout or behavioral abnormalities that have been used in animal models but which may not be proxies for the human condition. We argue that it is time to move beyond animal models of neurotoxicity to directly examine these problems in well-conducted clinical trials with comprehensive preoperative neuropsychometric and psychiatric testing, high fidelity intraoperative monitoring of physiological parameters during the anesthetic course and postoperative assessment of subthreshold and full classification of POD. In this manner, we can “model ourselves” to better understand these important and poorly understood conditions.

Does Rifaximin Improve EEG and VEP in Egyptian Cirrhotic Patients with Minimal Hepatic Encephalopathy?

Background: Minimal hepatic Encephalopathy (MHE) is defined as HE without symptoms on clinical/neurological examination, but with deficits in some cognitive areas that can only be measured by neuropsychometric testing. However, numerous studies have shown that, although the neurological symptoms are slight, affected patients are markedly impaired in their quality of life and ability to work. Various treatment modalities that have been shown to reverse MHE include lactulose/lactitol, probiotics/synbiotics, L-carnitine but rifaximin has shown a general trend toward better efficacy and better tolerability in patients with overt hepatic encephalopathy (OHE). Objective: Our objective is to assess the diagnostic role of minimental state examination (MMSE), electroencephalography (EEG) and visual evoked potential (VEP) in detection of MHE and to evaluate the efficacy of rifaximin in improving EEG and VEP in patients with MHE. Patients and Methods: Sixty cirrhotic patients were enrolled in the study depending on clinical evidence of stigmata of chronic liver disease, laboratory investigations including liver function tests, ultrasonographic features of liver cirrhosis and with no evidence of overt hepatic encephalopathy. Diagnois of MHE was made depending on minimental state examination (MMSE) and neurophysiological tools including EEG and VEP. A control group of sixty healthy volunteers with age and sex matched were included. The patient group received Rifaximin 550 mg twice daily for 8 weeks then follow up EEG and VEP studies were done. Results: MHE was detected in 36.7%, 48.3%, 51.7% of our series based on MMSE, EEG and VEP respectively. Child Pouph A, B, C was found in 51.7%, 35%, 13.3% respectively. Rifaximin was well tolerated. At the end of treatment, EEG and VEP studies were done which showed signficant changes between pre and post treatment results (P value = 0.03, 0.001, Conclusion: MMSE as well as EEG and VEP were reasonable diagnostic tools for early detection of MHE particularly in countries with low level of education. Rifaximin significantly improves both EEG and VEP in cirrhotic patients with MHE.

The Performance of Australian Children and Adolescents on Rey's Tangled Lines Test

ObjectiveThe study aimed to generate preliminary Australian normative data for the performance of individuals aged 8–15 years on the Rey Tangled Lines Test (Rey TLT), and to chronicle age‐related trends in the acquisition of processing speed and accuracy. The Rey TLT is a neuropsychometric test that queries processing speed and was intended to assist in the differentiation of problems in fine eye tracking from wider cognitive disorders. This instrument does not require verbal or motor responses and may be administered in less than 10 min. To date, it has been unavailable for inclusion in a child or adolescent cognitive assessment battery due to the absence of normative data for this population.MethodsN = 120 children aged 8–15 years (68 females and 52 males) were recruited to establish four, 2‐year chronological age groups (i.e., 8–9, 10–11, 12–13, and 14–15 years) with n = 30 participants per group. The Rey TLT was administered to each participant in a single session. Response time and accuracy were documented.ResultsSets of normative data for Australian children's performance on the Rey TLT were collected. Completion time decreased and task accuracy increased with age; younger children generally performed more slowly and less accurately than older children.ConclusionsThe Rey TLT appears to be sensitive to changes in age of children and is quick and simple to administer. It holds promise for inclusion in a battery of psychological tests to examine processing speed and fine eye tracking.

Failed epilepsy surgery deserves a second chance

ObjectivesResective epilepsy surgery has been shown to have up to 70–80% success rates in patients with intractable seizure disorder. Around 20–30% of patients with Engel Classification III and IV will require reevaluation for further surgery. Common reasons for first surgery failures include incomplete resection of seizure focus, incorrect identification of seizure focus and recurrence of tumor. Patient and methodsClinical chart review of seventeen patients from a single adult comprehensive epilepsy program who underwent reoperation from 2007 to 2014 was performed. High resolution Brain MRI, FDG-PET, Neuropsychometric testing were completed in all cases in both the original surgery and the second procedure. Postoperative outcomes were confirmed by prospective telephone follow up and verified by review of the patient’s electronic medical records. Outcomes were classified according to the modified Engel classification system: Engel classes I and II are considered good outcomes. ResultsA total of seventeen patients (involving 10 females) were included in the study. The average age of patients at second surgery was 42 (range 23–64 years). Reasons for reoperation included: incomplete first resection (n=13) and recurrence of tumor (n=4). Median time between the first and second surgery was 60 months. After the second surgery, ten of the seventeen patients (58.8%) achieved seizure freedom (Engel Class I), in agreement with other published reports. Of the ten patients who were Engel Class I, seven required extension of the previous resection margins, while three had surgery for recurrence of previously partially resected tumor. ConclusionsWe conclude that since the risk of complications from reoperation is low and the outcome, for some, is excellent, consideration of repeat surgery is justified.

Late-onset Tay–Sachs disease

We discuss the assessment and differential diagnoses of a young adult Hungarian man with a 1-year history of a progressive and symmetric amyotrophic lateral sclerosis-like syndrome, along with irregular action...

Attention-memory training yields behavioral and academic improvements in children diagnosed with attention-deficit hyperactivity disorder comorbid with a learning disorder.

BackgroundRecent studies have suggested that children with attention-deficit hyperactivity disorder (ADHD) may benefit from computerized cognitive training. Therapy implementation is especially complicated when ADHD is associated with learning disorders (LDs). This study tested the efficacy of a computer-based cognitive training program, namely, computerized cognitive training (CCT), in children with ADHD comorbid with an LD (ADHD-LD), with or without psychostimulant medication.Materials and methodsAfter diagnostic evaluations, 27 children with ADHD-LD (8 unmedicated and 19 medicated) participated in CCT, which is intended to improve attention, memory, reasoning, visual processing, and executive functioning. The participants completed 24 1-hour sessions over 3 months. Neuropsychometric and standardized academic test results before and after training were compared to assess treatment efficacy. Shapiro–Wilk normality tests were applied, and subsequent Wilcoxon tests were used to identify significant differences in pre-versus post-training performance.ResultsAfter CAT, children diagnosed with ADHD-LD showed 1) improvements in trained skills, measured directly within the software and indirectly by external psychometric tests; 2) improvements in attention, memory, and some executive functioning; 3) improvements in academic performance, particularly in mathematics; and 4) reductions in maladaptive behavioral features.ConclusionThe present findings suggest that cognitive training programs should be explored further as potential adjunctive therapies to improve outcomes in children with ADHD-LD.

FT11. Plaque Prolapse Prevention in Carotid Artery Stenting (3PCAS) Randomized Controlled Trial: Assessment of Subclinical Brain Lesions in CAS by Diffusion-Weighted Magnetic Resonance Imaging (DWMRI), Neuropsychometric Tests, and Neurobiomarkers Increase

FT11. Plaque Prolapse Prevention in Carotid Artery Stenting (3PCAS) Randomized Controlled Trial: Assessment of Subclinical Brain Lesions in CAS by Diffusion-Weighted Magnetic Resonance Imaging (DWMRI), Neuropsychometric Tests, and Neurobiomarkers Increase

Brain Microstructural Correlates of Cognitive Dysfunction in Clinically and Biochemically Normal Hepatitis C Virus Infection

This study examined correlates of the brain's neurocognitive performance among clinically and biochemically normal adult patient with hepatitis C virus (HCV). We hypothesized that anti-HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using diffusion tensor tractrography (DTT) metrics. Anti-HCV positive patient (n=40), and healthy controls (n=31), fulfilling inclusion criteria (incidentally detected anti-HCV positive) and able to provide informed consent were screened and recruited for the study. All these subjects and controls underwent subjective assessment of their quality of life related symptoms, neuropsychometric tests (NPT) and magnetic resonance imaging. The patients were subjected to neuroimaging as well as psychological testing. There was no significant difference in basic laboratory parameters in these two groups. Independent t-test reveals significantly lower neuropsychological functioning as compared to healthy control. A significantly decreased FA values and myoinsitol were observed in HCV subjects on sensory, inferior longitudinal fascicules, and STR fiber bundles as compared to healthy control. Bivariate correlation analysis reveals that neuropsychological scores are significantly positive. Our result show that HCV positive individuals would demonstrate structural brain abnormalities and neurocognitive dysfunction as well as the changes in cell component and extracellular space in the white matter regions of brain in asymptomatic HCV infection by using DTT metrics.

Simple screening for neurocognitive impairment in routine HIV outpatient care: is it deliverable?

ABSTRACTRoutine screening for psychological and cognitive difficulties is recommended in BHIVA guidelines but screening questions are not specified and studies give varied recommendations. Our aim was to see if simple screening in the routine clinic could help better direct our referrals to psychology and highlight those patients requiring, and likely to benefit from, further assessment. We introduced brief questions to assess neurocognitive impairment (NCI) and mood into routine HIV visits, with an onward referral pathway for further investigation for those screening positive. Routine attendees to HIV outpatient care over 12 weeks completed brief screening for depression (PHQ-2) and anxiety (GAD-2) and answered three short questions to screen for possible neurocognitive impairment (NCI-3Q). Patients screening positive underwent further screening via our psychologists and/or referral for neuropsychometric testing. Patient demographics, HIV markers and treatment history were recorded. 97 HIV outpatients were screened; 44 (45%) initially screened positive for NCI and/or mood. 29/44 (66%) were referred for further screening and/or psychological assessment and 21/29 (72%) of those engaged. The Montreal Cognitive Assessment (MoCA) and International HIV Dementia Scale (IHDS) were conducted on seven patients; four of these received full neuropsychometric testing. A detectable viral load was associated with positive neurocognitive screening. Rates of NCI and mood disorder among those who were tested were consistent with previous studies. The PHQ-2 and GAD-2 did detect mood problems; however, our results suggest the NCI-3Q questions alone are not good at detecting those with possible NCI. Screening for NCI remains practically difficult in the routine outpatient setting and this pilot supports the need for clearer guidelines on detecting HIV related NCI.

P054 The evaluation of transcranial magnetic stimulation rTMS in corticobasal degeneration (CBD): PET, QEEG and neuropsychological correlates

Background CBD is a neurodegenerative disorder characterized by asymmetric motor parkinsonism symptomatology and impairment in language, personality and affective functions that are related to frontoparietal atrophy. To date, there is still no effective treatment for CBD. In this respect, TMS may be a novel therapeutic candidate for CBS. Considering all of this evidence, we aimed to evaluate the pre and post-treatment electrophysiological, neurometabolic and neuropsychometric correlates of TMS application in four CBS patients. Methods We have evaluated the pre and post treatment EEG, FDG-PET and detailed clinical behavioral and neuropsychometric test correlates of TMS in four CBD patients who were admitted to our dementia outpatient at the University of Medipol-Istanbul. The following detailed neuropsychometric test procedures were applied to patients; Digit Span (Forward/Back) Test, Verbal Fluency Test, Lexical Fluency Test, Clock Drawing Test, Similarities and Comprehension test, Verbal Learning Test (SBSTTA-Oktem), Wechsler Memory Scale (WMS-Logical Memory Test), Benton Face Recognition Test (BFR), Line Orientation Identification Test (BLOT), Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS), Frontal Behavioral Inventory Test (FBI), Standardized Mini Mental State Examination (MMSE) and Clinical Dementia Rating-Scale (CDR). Results & conclusion We have found that increased pretreatment theta activity was significantly decreased after the TMS treatment in frontal, central and parietal regions that was associated with the normalized glucose metabolism and neurobehavioral test scores after the TMS treatment.

Topiramate in Migraine Prevention: A 2016 Perspective.

In evidence-based guidelines published in 2000, topiramate was a third-tier migraine preventive with no scientific evidence of efficacy; recommendation for its use reflected consensus opinion and clinical experience. Its neurostabilizing activity, coupled with its favorable weight profile, made topiramate an attractive alternative to other migraine preventives that caused weight gain. When guidelines for migraine prevention in episodic migraine were published in 2012, topiramate was included as a first-line option based on double-blind, randomized controlled trials involving nearly 3000 patients. The scientific and clinical interest in topiramate has generated a large body of data from randomized controlled trials, meta-analyses, patient registries, cohort studies, and claims data analyses that have more fully characterized its role as a migraine preventive. This article will review the profile of topiramate that has emerged out of the past decade of research and clinical use in migraine prophylaxis. It will also address the rationale for extended-release (XR) formulations in optimizing topiramate therapy in migraine. Topiramate has activity at multiple molecular targets, which may account for why it is effective in migraine and most other, more specific, anticonvulsants are not. Based on randomized controlled trials, topiramate reduces migraine frequency and acute medication use, improves quality of life, and reduces disability in patients with episodic migraine and in those with chronic migraine with or without medication overuse headache. Its efficacy in chronic migraine is not improved by the addition of propranolol. Topiramate's ability to prevent progression from high-frequency episodic migraine to chronic migraine remains unclear. Consistent with clinicians' perceptions, migraineurs are more sensitive to topiramate-associated side effects than patients with epilepsy. Paresthesia is a common occurrence early in treatment but is rarely cause for terminating topiramate treatment. Cognitive problems occur much less frequently than paresthesia but are more troublesome in terms of treatment discontinuation. Cognitive complaints can often be managed by slowly increasing the topiramate dose in small increments to allow habituation. As with other carbonic anhydrase inhibitors, topiramate has metabolic effects that favor the development of metabolic acidosis and possibly renal stones. Because migraineurs have an increased risk of renal stones independent of topiramate exposure, clinicians should counsel all migraine patients to maintain hydration. Abrupt onset of blurring, other visual disturbances, and/or ocular pain following topiramate's initiation should be evaluated promptly since this may indicate rare but potentially sight-threatening idiosyncratic events. Postmarketing evidence has shown that first-trimester exposure to topiramate monotherapy is associated with increased occurrence of cleft lip with or without cleft palate (Pregnancy Category D). Even though topiramate's long half-life would seemingly support q.d. dosing, randomized controlled migraine trials used b.i.d. administration of immediate-release (IR) topiramate, which has more favorable plasma concentration-time profile (ie, lower peak concentrations and higher trough concentrations) than q.d. IR dosing. Given the sensitivity of migraineurs to topiramate-related adverse events, particularly cognitive effects, pharmacokinetic profiles should be considered when optimizing migraine outcomes. The extended-release (XR) formulations Qudexy® XR (Upsher-Smith Laboratories) and Trokendi XR® (Supernus Pharmaceuticals) were specifically designed to achieve the adherence benefits of q.d. dosing but with more favorable (ie, more constant) steady-state plasma concentrations over the 24-hour dosing interval vs IR topiramate b.i.d. Intriguing results from a study in healthy volunteers showed consistently less impairment in neuropsychometric tests of verbal fluency and mental processing speed with an XR topiramate formulation (Trokendi XR) vs IR topiramate b.i.d. These findings suggest a pharmacodynamic effect associated with significantly reducing plasma concentration fluctuation when topiramate absorption is slowed. Results of retrospective studies in migraineurs treated with XR topiramate appear to support a clinically meaningful benefit of XR topiramate vs IR topiramate in terms of significantly fewer cognitive effects, improved adherence, and overall better outcomes of migraine prophylaxis with topiramate.

MCI Patients in Europe: Medication and Comorbidities. The DESCRIPA Study

The main objective of the present study was to investigate the prevalence and type of medication taken by MCI patients in the DECRIPA cohort. A secondary objective was to assess the cognitive function of these patients and the relationship between the results of neuropsychometric tests and medication use. We selected 880 subjects (375 males, 505 females) who were older than 55 years without obvious causes of cognitive impairment. A complete history was obtained for all patients. In addition, demographical data were collected and several factors were studied, including the types and dosages of the medications taken. Comparisons between groups were statistically analyzed in relation to the number of medications. Most patients (85.7%, n=754) were taking at least one medication during the study period. The median (interquartile range-IQ) number of medications per participant was 3 (1-5), whereas 40% of the patients took at least 4 medications. The types of medications that were most often taken were cardiovascular drugs (62.0%), antidepressants (16.8%), sedatives (14.6%), thyroid drugs (10.0%) and anti-diabetic drugs (7.6%). On average, MCI patients take three medications for the prevention or treatment of an average of two medical conditions. The most prevalent types of medications were cardiovascular drugs, antidepressants, sedatives and thyroid drugs. Significant differences in the number of medications taken were observed for gender and age.

White matter structural network abnormalities underlie executive dysfunction in amyotrophic lateral sclerosis

Research in amyotrophic lateral sclerosis (ALS) suggests that executive dysfunction, a prevalent cognitive feature of the disease, is associated with abnormal structural connectivity and white matter integrity. In this exploratory study, we investigated the white matter constructs of executive dysfunction, and attempted to detect structural abnormalities specific to cognitively impaired ALS patients. Eighteen ALS patients and 22 age and education matched healthy controls underwent magnetic resonance imaging on a 4.7 Tesla scanner and completed neuropsychometric testing. ALS patients were categorized into ALS cognitively impaired (ALSci, n = 9) and ALS cognitively competent (ALScc, n = 5) groups. Tract-based spatial statistics and connectomics were used to compare white matter integrity and structural connectivity of ALSci and ALScc patients. Executive function performance was correlated with white matter FA and network metrics within the ALS group. Executive function performance in the ALS group correlated with global and local network properties, as well as FA, in regions throughout the brain, with a high predilection for the frontal lobe. ALSci patients displayed altered local connectivity and structural integrity in these same frontal regions that correlated with executive dysfunction. Our results suggest that executive dysfunction in ALS is related to frontal network disconnectivity, which potentially mediates domain-specific, or generalized cognitive impairment, depending on the degree of global network disruption. Furthermore, reported co-localization of decreased network connectivity and diminished white matter integrity suggests white matter pathology underlies this topological disruption. We conclude that executive dysfunction in ALSci is associated with frontal and global network disconnectivity, underlined by diminished white matter integrity. Hum Brain Mapp 38:1249-1268, 2017. © 2016 Wiley Periodicals, Inc.

Response: Commentary: Correlation between Patent Foramen Ovale, Cerebral "Lesions" and Neuropsychometric Testing in Experienced Sports Divers: Does Diving Damage the Brain?

Response: Commentary: Correlation between Patent Foramen Ovale, Cerebral "Lesions" and Neuropsychometric Testing in Experienced Sports Divers: Does Diving Damage the Brain?

Relationship between impulsivity and obsession types in obsessive-compulsive disorder

Objective: Impulsivity is an important aspect of obsessive-compulsive disorder (OCD) which is classified under a new heading in DSM-5 with other impulsivity related disorders like trichotillomania. Due to its heterogeneous nature, different obsessions may be linked to varying impulsivity profiles. Aim of this study was to investigate the impulsivity traits and their relationship with obsession types by comparing OCD subjects who display sexual, religious and aggressive obsessions or other obsessions to healthy controls.Methods: Outpatients with OCD (n = 146) and healthy controls (n = 80) were evaluated with Sociodemographic Data Form, SCID-I, SCID non-patient version, Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Barratt Impulsiveness Scale (BIS-11).Results: BIS-11 attention scores of the OCD group were significantly higher than healthy subjects. In patients with sexual, aggressive, religious obsessions, BIS-11 attention scores were significantly higher than those who have other obsession types and that of controls.Conclusions: Higher levels of attentional impulsivity, particularly in patients suffering from sexual, aggressive or religious obsessions suggest a common diathesis for a dysfunction in neural correlates corresponding to these symptoms. The results of our study may promote further studies conducted with more advanced and objective neuropsychometric tests evaluating features of the clinical course, neurobiology and the response to OCD treatment.

Heterogeneous multimodal biomarkers analysis for Alzheimer's disease via Bayesian network.

By 2050, it is estimated that the number of worldwide Alzheimer’s disease (AD) patients will quadruple from the current number of 36 million, while no proven disease-modifying treatments are available. At present, the underlying disease mechanisms remain under investigation, and recent studies suggest that the disease involves multiple etiological pathways. To better understand the disease and develop treatment strategies, a number of ongoing studies including the Alzheimer’s Disease Neuroimaging Initiative (ADNI) enroll many study participants and acquire a large number of biomarkers from various modalities including demographic, genotyping, fluid biomarkers, neuroimaging, neuropsychometric test, and clinical assessments. However, a systematic approach that can integrate all the collected data is lacking. The overarching goal of our study is to use machine learning techniques to understand the relationships among different biomarkers and to establish a system-level model that can better describe the interactions among biomarkers and provide superior diagnostic and prognostic information. In this pilot study, we use Bayesian network (BN) to analyze multimodal data from ADNI, including demographics, volumetric MRI, PET, genotypes, and neuropsychometric measurements and demonstrate our approach to have superior prediction accuracy.