Cognitive Outcomes In Patients Research Articles

A Rationale for Music Training to Enhance Executive Functions in Parkinson's Disease: An Overview of the Problem.

Music listening interventions such as Rhythmic Auditory Stimulation can improve mobility, balance, and gait in Parkinson’s Disease (PD). Yet, the impact of music training on executive functions is not yet known. Deficits in executive functions (e.g., attention, processing speed) in patients with PD result in gait interference, deficits in emotional processing, loss of functional capacity (e.g., intellectual activity, social participation), and reduced quality of life. The model of temporal prediction and timing suggests two networks collectively contribute to movement generation and execution: the basal ganglia-thalamocortical network (BGTC) and the cerebellar-thalamocortical network (CTC). Due to decreases in dopamine responsible for the disruption of the BGTC network in adults with PD, it is hypothesized that rhythmic auditory cues assist patients through recruiting an alternate network, the CTC, which extends to the supplementary motor areas (SMA) and the frontal cortices. In piano training, fine motor finger movements activate the cerebellum and SMA, thereby exercising the CTC network. We hypothesize that exercising the CTC network through music training will contribute to enhanced executive functions. Previous research suggested that music training enhances cognitive performance (i.e., working memory and processing speed) in healthy adults and adults with cognitive impairments. This review and rationale provides support for the use of music training to enhance cognitive outcomes in patients with Parkinson’s Disease (PD).

F245. COGNITIVE RESERVE DIFFERENCE IN AFFECTIVE AND NONAFFECTIVE PSYCHOSIS

BackgroundThe cognitive reserve (CR) refers to the capacity of an adult brain to cope with pathology in order to minimize the symptoms (Stern, 2002). Recent studies have shown that CR is associated with clinical, functional and cognitive outcomes in patients with severe mental illness (de la Serna et al., 2013; Forcada et al., 2015; Anaya et al., 2016; Amoretti et al. ., 2016; Grande et al., 2017). Higher CR has been related to a later onset of psychosis, greater adherence and fewer psychotic symptoms (Barnett et al., 2006). However, there are no studies that evaluate longitudinally the role of CR depending on the diagnosis.The objective is to analyze the impact of CR according to the diagnosis and to study whether having a high CR may be associated with better clinical, functional and cognitive outcomes.MethodsWe gathered all the relevant clinical and sociodemographic data. All subjects were assessed clinically, neuropsychologically and functionally at baseline and after a two-year follow-up. To assess CR, three proxies have been integrated: premorbid IQ, years of education-occupation and leisure activities.To determine whether the level of CR was associated with clinical, functional and neuropsychological outcomes and whether it was different between diagnoses, a multivariate analysis of variance was used.Results285 DSM-IV patients with first episode of psychosis (FEP) were enrolled. The sample was divided into affective and non-affective groups.In the non-affective group, those with high CR are older and had a better socioeconomic status, better functioning and cognitive performance and lower symptoms, as well as a shorter duration of untreated psychosis (DUP) and a later age of onset. After 2 years of follow-up, they showed significant differences in all the cognitive domains evaluated, except for the executive functions.In the affective group, the patients with high and low CR showed differences in positive and manic symptoms, as well as in verbal memory at baseline. At 2 years of follow-up the differences were observed in functionality, positive and negative symptoms and in verbal memory. There were no significant differences in terms of age, gender, DUP, or age of onset, although significant differences were found in socioeconomic level (p = 0.038).DiscussionHigher CR can result in better recovery and functioning and in higher cognitive performance in patients with a FEP. Therefore, we propose that early interventions focused on the promotion of neuropsychological abilities and CR could reduce the harmful impact of this disease.However, it is necessary that these interventions should be personalized taking into account that CR plays a differential role according to the diagnosis.

Neurocognition and Cerebral Lesion Burden in High-Risk Patients Before Undergoing Transcatheter Aortic Valve Replacement: Insights From the SENTINEL Trial

ObjectivesThe authors sought to determine baseline neurocognition before transcatheter aortic valve replacement (TAVR) and its correlations with pre-TAVR brain imaging. BackgroundTAVR studies have not shown a correlation between diffusion-weighted image changes and neurocognition. The authors wanted to determine the extent to which there was already impairment at baseline that correlated with cerebrovascular disease. MethodsSENTINEL (Cerebral Protection in Transcatheter Aortic Valve Replacement) trial patients had cognitive assessments of attention, processing speed, executive function, and verbal and visual memory. Z-scores were based on normative means and SDs, combined into a primary composite z-score. Brain magnetic resonance images were obtained pre-TAVR on 3-T scanners with a T2 fluid-attenuated inversion recovery (FLAIR) sequence. Scores ≤−1.5 SD below the normative mean (7th percentile) were considered impairment. Paired t tests compared within-subject scores, and chi-square goodness-of-fit compared the percentage of subjects below −1.5 SD. Correlation and regression analyses assessed the relationship between neurocognitive z-scores and T2 lesion volume. ResultsAmong 234 patients tested, the mean composite z-score was −0.65 SD below the normative mean. Domain scores ranged from −0.15 SD for attention to −1.32 SD for executive function. On the basis of the ≥1.5 SD normative reference, there were significantly greater percentages of impaired scores in the composite z-score (13.2%; p = 0.019), executive function (41.9%; p < 0.001), verbal memory (p < 0.001), and visual memory (p < 0.001). The regression model between FLAIR lesion volume and baseline cognition showed statistically significant negative correlations. ConclusionsThere was a significant proportion of aortic stenosis patients with impaired cognition before TAVR, with a relationship between baseline cognitive function and lesion burden likely attributable to longstanding cerebrovascular disease. These findings underscore the importance of pre-interventional testing and magnetic resonance imaging in any research investigating post-surgical cognitive outcomes in patients with cardiovascular disease.

Cognitive Outcomes of Patients with Traumatic Bifrontal Contusions.

We aimed to investigate the prevalence and pattern of cognitive dysfunction in patients with traumatic bifrontal contusions and their association with functional outcome. We prospectively recruited patients with bifrontal contusions in a regional neurosurgical center in Hong Kong over a 2-year period. Functional outcome was assessed by modified Rankin Scale (mRS), and cognitive outcomes were assessed by Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and a comprehensive neuropsychological battery. We recruited 34 patients with traumatic bifrontal contusions over a 2-year period. Nine (26%) patients had craniotomy for evacuation of left or right frontal contusions. Functional outcome using mRS was significantly correlated with cognitive outcomes using MMSE or MoCA. The effect of cognitive outcome using MMSE or MoCA persisted after adjustments of age, sex, admission Glasgow Coma Scale, and surgery. In patients who completed the comprehensive neuropsychological assessments, cognitive impairment in at least one of the neuropsychological tests was noted in 73% of them. Cognitive dysfunction had a significant impact on functional outcome, and treatment strategy should be developed to minimize them.

Association Between Inflammatory Markers and Cognitive Outcome in Patients with Acute Brain Dysfunction Due to Sepsis.

Sepsis-induced brain dysfunction (SIBD) has been neglected until recently due to the absence of specific clinical or biological markers. There is increasing evidence that sepsis may pose substantial risks for long term cognitive impairment. To find out clinical and inflammatory factors associated with acute SIBD serum levels of cytokines, complement breakdown products and neurodegeneration markers were measured by ELISA in sera of 86 SIBD patients and 33 healthy controls. Association between these biological markers and cognitive test results was investigated. SIBD patients showed significantly increased IL-6, IL-8, IL-10 and C4 d levels and decreased TNF-α, IL-12, C5a and iC3b levels than healthy controls. No significant alteration was observed in neuronal loss and neurodegeneration marker [neuron specific enolase (NSE), amyloid β, tau] levels. Increased IL-1β, IL-6, IL-8, IL-10, TNF-α and decreased C4 d, C5a and iC3b levels were associated with septic shock, coma and mortality. Transient mild cognitive impairment was observed in 7 of 21 patients who underwent neuropsychological assessment. Cognitive dysfunction and neuronal loss were associated with increased duration of septic shock and delirium but not baseline serum levels of inflammation and neurodegeneration markers. Increased cytokine levels, decreased complement activity and increased neuronal loss are indicators of poor prognosis and adverse events in SIBD. Cognitive dysfunction and neuronal destruction in SIBD do not seem to be associated with systemic inflammation factors and Alzheimer disease-type neurodegeneration but rather with increased duration of neuronal dysfunction and enhanced exposure of the brain to sepsis-inducing pathogens.

Memory Deficits After Aneurysmal Subarachnoid Hemorrhage: A Functional Magnetic Resonance Imaging Study.

Patients who have sustained aneurysmal subarachnoid hemorrhage (aSAH) are thought to have cognitive impairment. However, little is known about the characteristics of functional imaging in patients with aSAH. In this study, we explored whole brain activity patterns in patients with aSAH using amplitude of low-frequency fluctuation (ALFF) and functional connectivity (FC). Fifty patients with aSAH and 30 healthy controls were recruited and subjected to a resting-state functional magnetic resonance imaging scan and cognitive tasks. Abnormalities of ALFF and FC in patients with aSAH and the correlations with cognitive tasks were assessed. The aSAH group exhibited increased ALFF mainly in the left parahippocampal gyrus (PHG), left inferior temporal gyrus (ITG), and left thalamus (THAL). FC and regression analysis showed positive correlations between functional connectivity strength (FCS) and memory performance in several connections in the aSAH group. These included (1) decreased FC between the left PHG and left inferior parietal lobe; (2) decreased FC between the left ITG and bilateral inferior frontal gyrus orbital part (ORBinf), right middle frontal gyrus; and (3) increased FC between the left THAL and right inferior frontal gyrus orbital part (ORBinf), and right inferior frontal gyrus opercular part. Our findings not only demonstrate the unique abnormal cerebral functional topology of patients with aSAH on both local and network levels, but also confirm the correlation between specific FCS and memory function in these patients. In addition, we have identified several potential imaging biomarkers for predicting cognitive outcomes in patients with aSAH.

Effects of deep sedation under mechanical ventilation on cognitive outcome in patients undergoing surgery for oral and maxillofacial cancer and microvascular reconstruction.

Cognitive impairment after intensive care unit (ICU) admission is becoming increasingly recognized. High-dose deep sedation has been suggested to play an important role in the development of cognitive impairment. However, the impact of heavy sedation as a single cause in the development of cognitive impairment in ICU patients remains unclear. In this study we investigated whether a three-day deep sedation protocol could reduce cognitive function in mechanically ventilated non-critical patients. A prospective observational study was carried out. A total of 17 surgical patients were studied. None. Cognitive function before and after ICU admission. Thirty-one patients requiring three days of sedation after microvascular reconstruction were initially enrolled in the study. Sedation in the ICU was maintained with propofol and dexmedetomidine combined with fentanyl. Cognitive function was assessed using a battery of 6 neuropsychological tests two days before surgery and three weeks after surgery. Finally, a total of 17 patients were included in the analysis. Cognitive impairment (defined as a decline of >20% from the pre-admission cognitive evaluation scores in at least two of 6 tests) was observed in 5 of the 17 patients (29%). However, there were no significant differences between the pre- and post-admission cognitive evaluations in 6 tests. Middle-term cognitive function can be impaired in some patients subjected to deep sedation during several days following maxillary-mandibular oral surgery with microvascular reconstruction.

Short- and Long-term Cognitive Outcomes in Patients With Major Depression Treated With Electroconvulsive Therapy.

The risk of cognitive impairment is a concern for patients with major depressive disorder receiving electroconvulsive therapy (ECT). Here, we evaluate the acute, short-term and long-term effects of ECT on tests of processing speed, executive function, memory, and attention. Forty-four patients with major depressive disorder receiving ECT (61% right unilateral, 39% mixed right unilateral-bitemporal, left unilateral, and/or bitemporal lead placement) underwent a cognitive battery prior to ECT (T1), after 2 sessions (T2), and at the end of the index (T3). Thirty-two patients returned for a 6-month follow-up (T4). Thirty-three control subjects were assessed at 2 times approximately 4 weeks apart (C1 and C2). At baseline, patients showed deficits in processing speed, executive function, and memory compared with control subjects. Including depression severity and lead placement covariates, linear mixed-model analysis showed significant improvement in only processing speed between T1 and T3 and between T1 and T4 in patients. An acute decline in attention and verbal memory was observed at T2, but performance returned to baseline levels at T3. Longitudinal cognitive outcomes did not differ in patients defined as ECT responders/nonresponders. Episodic memory was not measured, and medications were not controlled between T3 and T4. Control subjects also showed improvements in processing speed, suggesting practice effects for some measures. In this naturalistic ECT treatment study, results show that the initiation of ECT may transiently affect memory and executive function, but cognition is largely unaffected during and after ECT. Whereas some functions might improve, others will at least remain stable up to 6 months following the ECT index.

NCOG-11. COGNITIVE FUNCTIONS AND VARIANTS IN GENES ASSOCIATED WITH AGING AND INFLAMMATION IN BRAIN TUMOR PATIENTS

AbstractBACKGROUNDCognitive dysfunction is common in patients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT). We reported previously that single nucleotide polymorphisms (SNPs) in the APOE, COMT and BDNF genes may influence cognitive outcome in this clinical population. In this study, we assessed whether additional genes with known associations with aging, Alzheimer’s disease and inflammation may contribute to cognitive dysfunction in brain tumor survivors.METHODSOne hundred and fifty patients with brain tumors participated in the study: ninety had been treated with RT ± CT, fifty-seven had CT alone, and three had no therapy. All patients completed neuropsychological tests of attention, executive functions and memory, and provided a blood sample for genotyping. We used a Bayesian penalized multivariate regression approach to estimate the associations between the SNPs and cognitive outcome, adjusting for age, education, tumor location, treatment with RT ± CT, time since treatment completion, and APOE epsilon є-4 allele. We quantified the strength of association between a SNP and a cognitive test score using a novel measure referred to as the posterior association summary (PAS) that takes value between 0 (= no association) and 1 (= very strong association).RESULTSSeveral SNPs previously reported in association with age-related cognitive decline and Alzheimer’s disease (PDE7A rs10808746, CD2AP rs9349407, ABCC1 rs8187858, APOE rs405697) and inflammation (IL-1A rs1800587, IL-1 rs1143634, IL-6 rs1474348) were strongly associated with tests of attention, executive functions and memory (PAS ≥ 0.95). Several additional SNPs that mapped to the ABCA7, CD33, COMT, IL-6, MS4A4E, PDE7A, PICALM, SERPINA3 and SORC1 genes were also associated with tests of attention and executive functions with PAS ≥ 0.90.CONCLUSIONThe findings provide new evidence that polymorphisms in genes associated with aging, Alzheimer’s disease and inflammation may be functionally relevant and influence cognitive outcome in patients with brain tumors.

Cognition in multiple sclerosis.

Cognition in multiple sclerosis.

Does supplementation with carnosine improve cardiometabolic health and cognitive function in patients with pre-diabetes and type 2 diabetes? study protocol for a randomised, double-blind, placebo-controlled trial

IntroductionCarnosine, an over-the-counter food supplement, has a promising potential for the prevention and treatment of chronic diseases such as type 2 diabetes (T2DM), cardiovascular and neurodegenerative diseases through its anti-inflammatory,...

Improved cognitive outcomes in patients with relapsing–remitting multiple sclerosis treated with daclizumab beta: Results from the DECIDE study

Background: Cognitive impairment is common in multiple sclerosis (MS), with cognitive processing speed being the most frequently affected domain. Objective: Examine the effects of daclizumab beta versus intramuscular (IM) interferon (IFN) beta-1a on cognitive processing speed as assessed by Symbol Digit Modalities Test (SDMT). Methods: In DECIDE, patients with relapsing–remitting multiple sclerosis (RRMS) (age: 18–55 years; Expanded Disability Status Scale (EDSS) score 0–5.0) were randomized to daclizumab beta (n = 919) or IM IFN beta-1a (n = 922) for 96–144 weeks. SDMT was administered at baseline and at 24-week intervals. Results: At week 96, significantly greater mean improvement from baseline in SDMT was observed with daclizumab beta versus IM IFN beta-1a (p = 0.0274). Significantly more patients treated with daclizumab beta showed clinically meaningful improvement in SDMT (increase from baseline of ⩾3 points (p = 0.0153) or ⩾4 points (p = 0.0366)), and significantly fewer patients showed clinically meaningful worsening (decrease from baseline of ⩾3 points (p = 0.0103)). Odds representing risk of worsening versus stability or improvement on SDMT were significantly smaller for daclizumab beta (p = 0.0088 (3-point threshold); p = 0.0267 (4-point threshold)). In patients completing 144 weeks of treatment, the effects of daclizumab beta were generally sustained. Conclusion: These results provide evidence for a benefit of daclizumab beta versus IM IFN beta-1a on cognitive processing speed in RRMS. Trial registration: ClinicalTrials.gov identifier NCT01064401 (Efficacy and Safety of BIIB019 (Daclizumab High Yield Process) Versus Interferon β 1a in Participants With Relapsing-Remitting Multiple Sclerosis (DECIDE)): https://clinicaltrials.gov/ct2/show/NCT01064401.

ARTEMIDA Trial (A Randomized Trial of Efficacy, 12 Months International Double-Blind Actovegin): A Randomized Controlled Trial to Assess the Efficacy of Actovegin in Poststroke Cognitive Impairment.

Poststroke cognitive impairment is a debilitating consequence of stroke. The aim of this study was to assess whether Actovegin confers cognitive benefit in patients who have had an ischemic stroke. This was a 12-month, parallel-group, randomized, multicenter, double-blind, placebo-controlled study. Eligible patients were ≥60 years of age with a Montreal Cognitive Assessment test score of ≤25 points. Patients were randomized into 2 groups within 1 week of acute supratentorial ischemic stroke in a 1:1 ratio: Actovegin (a deproteinized hemoderivative of calf blood, 2000 mg/d for ≤20 intravenous infusions followed by 1200 mg/d orally) or placebo for 6 months. Patients were treated in accordance with standard clinical practice for a further 6 months. The primary end point was the change from baseline in Alzheimer's Disease Assessment Scale, cognitive subscale, extended version at 6 months. Two-hundred forty-eight patients were randomized to Actovegin and 255 patients to placebo. At month 6, the least squares mean change from baseline in Alzheimer's Disease Assessment Scale, cognitive subscale, extended version was -6.8 for Actovegin and -4.6 for placebo; the estimated treatment difference was -2.3 (95% confidence interval, -3.9, -0.7; P=0.005). Recurrent ischemic stroke was the most frequently reported serious adverse event, with a nonsignificantly higher number for Actovegin versus placebo. Actovegin had a beneficial effect on cognitive outcomes in patients with poststroke cognitive impairment. The safety experience was consistent with the known safety and tolerability profile of the drug. These results warrant confirmation in additional robustly designed studies. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01582854.

Intensive versus Guideline Blood Pressure and Lipid Lowering in Patients with Previous Stroke: Main Results from the Pilot 'Prevention of Decline in Cognition after Stroke Trial' (PODCAST) Randomised Controlled Trial.

BackgroundStroke is associated with the development of cognitive impairment and dementia. We assessed the effect of intensive blood pressure (BP) and/or lipid lowering on cognitive outcomes in patients with recent stroke in a pilot trial.MethodsIn a multicentre, partial-factorial trial, patients with recent stroke, absence of dementia, and systolic BP (SBP) 125–170 mmHg were assigned randomly to at least 6 months of intensive (target SBP <125 mmHg) or guideline (target SBP <140 mmHg) BP lowering. The subset of patients with ischaemic stroke and total cholesterol 3.0–8.0 mmol/l were also assigned randomly to intensive (target LDL-cholesterol <1.3 mmol/l) or guideline (target LDL-c <3.0 mmol/l) lipid lowering. The primary outcome was the Addenbrooke’s Cognitive Examination-Revised (ACE-R).ResultsWe enrolled 83 patients, mean age 74.0 (6.8) years, and median 4.5 months after stroke. The median follow-up was 24 months (range 1–48). Mean BP was significantly reduced with intensive compared to guideline treatment (difference –10·6/–5·5 mmHg; p<0·01), as was total/LDL-cholesterol with intensive lipid lowering compared to guideline (difference –0·54/–0·44 mmol/l; p<0·01). The ACE-R score during treatment did not differ for either treatment comparison; mean difference for BP lowering -3.6 (95% CI -9.7 to 2.4), and lipid lowering 4.4 (95% CI -2.1 to 10.9). However, intensive lipid lowering therapy was significantly associated with improved scores for ACE-R at 6 months, trail making A, modified Rankin Scale and Euro-Qol Visual Analogue Scale. There was no difference in rates of dementia or serious adverse events for either comparison.ConclusionIn patients with recent stroke and normal cognition, intensive BP and lipid lowering were feasible and safe, but did not alter cognition over two years. The association between intensive lipid lowering and improved scores for some secondary outcomes suggests further trials are warranted.Trial RegistrationISRCTN ISRCTN85562386

Impact of mass effect, tumor location, age, and surgery on the cognitive outcome of patients with high-grade gliomas: a longitudinal study

High-grade gliomas are the most frequently occurring brain tumors and carry unfavorable prognosis. Literature is controversial regarding the effects of surgery on cognitive functions. We analyzed a homogenous population of 30 patients with high-grade glioma who underwent complete resection. Patients underwent extensive neuropsychological analysis before surgery, 7 days after surgery, and approximately 40 days after surgery, before adjuvant treatments. Thirty-four neuropsychological tests were administered in the language, memory, attention, executive functions, and praxis domains. The preoperative percentage of patients with impairment in the considered tests ranged from 0% to 53.3% (mean 20.9%). Despite a general worsening at early follow-up, a significant recovery was observed at late follow-up. Preoperative performances in language and verbal memory tasks depended on the joint effect of tumor volume, volume of surrounding edema, and tumor localization, with major deficits in patients with left lateralized tumor, especially insular and temporal. Preoperative performances in attention and constructive abilities tasks depended on the joint effect of tumor volume, volume of surrounding edema, and patient age, with major deficits in patients ≥ 65 years old. Recovery at late follow-up depended on the volume of resected tumor, edema resorption, and patient age. Longitudinal neuropsychological performance of patients affected by high-grade glioma depends, among other factors, on the complex interplay of tumor volume, volume of surrounding edema, tumor localization, and patient age. Reported results support the definition of criteria for surgical indication based on the above factors. They may be used to propose more customized surgical, oncological, and rehabilitative strategies.

Cognitive Outcome in Childhood-Onset Epilepsy: A Five-Decade Prospective Cohort Study.

Little is known about the very long-term cognitive outcome in patients with childhood-onset epilepsy. The aim of this unique prospective population-based cohort study was to examine cognitive outcomes in aging participants with childhood-onset epilepsy (mean onset age=5.3 years) five decades later (mean age at follow-up=56.5 years). The sample consisted of 48 participants with childhood-onset epilepsy and 48 age-matched healthy controls aged 48-63 years. Thirty-six epilepsy participants were in remission and 12 continued to have seizures. Cognitive function was examined with 11 neuropsychological tests measuring language and semantic function, episodic memory, and learning, visuomotor function, executive function, and working memory. The risk of cognitive impairment was very high in participants with continuing seizures; odds ratio (OR)=11.7 (95% confidence interval [CI] (2.8, 49.6), p=.0008). They exhibited worse performances across measures of language and semantic function, and visuomotor function compared to participants with remitted epilepsy and healthy controls. In the participants with remitted epilepsy, the risk of cognitive impairment was somewhat elevated, but not statistically significant; OR=2.6 (95% CI [0.9, 7.5], p=.08). Our results showed that the distinction of continued versus discontinued seizures was critical for determining long-term cognitive outcome in childhood-onset epilepsy. Few participants in remission exhibited marked cognitive impairment compared to age-matched peers. However, a subgroup of participants with decades long active epilepsy, continuous seizure activity and anti-epileptic drug (AED) medication, showed clinically significant cognitive impairment and are thus in a more precarious position when entering older age. (JINS, 2017, 23, 332-340).

Neurocognitive Trajectory of Patients with Childhood Cerebral Adrenoleukodystrophy Who Received Allogeneic Hematopoietic Cell Transplantation at an Early Stage of Cerebral Disease

Adrenoleukodystrophy (ALD) is an X-linked disorder of very long chain fatty acid metabolism which may manifest with adrenal gland and/or central nervous system disease. Thirty-five percent of affected boys develop cerebral involvement (cALD) during childhood. Characterized by progressive cerebral demyelination and resulting in devastating neurological and cognitive decline, cALD is usually fatal within years of clinically-evident disease. The only treatment known to enhance long-term survival and stabilize cerebral disease for boys with cALD is hematopoietic cell transplantation (HCT). It is well-established that the risk for negative long-term outcomes is significantly lower when HCT occurs at an earlier stage of cerebral white matter disease (ALD MRI severity score [Loes score] < 10). Nevertheless, there is limited knowledge of broad-based neurocognitive outcomes of patients transplanted with early-disease cALD. We studied all patients who underwent HCT for cALD at the University of Minnesota between January 1, 1991 and October 20, 2014. HCT preparative regimens varied with time, although most patients underwent myeloablative conditioning. Transplant allograft sources varied. Neurocognitive data were available for 63 patients who had a pre-transplant Loes MRI severity score < 10. Within this cohort, patients with less extensive cerebral disease (Loes ≤ 4) at the time of HCT had significantly higher scores on baseline tests of intellectual functioning than those with more cerebral involvement (Loes >4). This difference was particularly apparent on measures of nonverbal (visual) reasoning and processing speed. Furthermore, patients with more MRI-evident white matter disease at HCT showed more dramatic declines in neurocognitive test performance over time. In a subset of 20 patients who were followed for at least 4 years post-transplant, 15 patients (75%) demonstrated significant neurocognitive deficits (>1.5 SD below the mean) in at least one of the following domains: overall intellectual functioning (30%), attention (39%), verbal memory (33%), visual-motor integration (40%) and fine motor skills (58%). Results of this study provide evidence that within this patient group (boys undergoing HCT for cALD with Loes score < 10), patients have better neurocognitive outcomes when minimal cerebral disease is evident on neuroimaging prior to transplant. These data represent the largest analysis of cognitive outcomes in patients with early-disease cALD who underwent HCT. Our findings provide a benchmark for comparison to alternative or additional interventions for patients with cALD. Opportunities to enhance standard methods of detecting early cerebral disease and to intervene at the earliest possible stage of cALD should be explored. The emergence of newborn screening for adrenoleukodystrophy will provide avenues for improved pre-transplant monitoring and timing of intervention to preserve cognitive functioning and quality of life among patients with cALD. DisclosuresNo relevant conflicts of interest to declare.

Cognitive deficits after aneurysmal and angiographically negative subarachnoid hemorrhage: Memory, attention, executive functioning, and emotion recognition.

The authors' aim was to investigate cognitive outcome in patients with aneurysmal and angiographically negative subarachnoid hemorrhage (aSAH and anSAH), by comparing them to healthy controls and to each other. Besides investigating cognitive functions as memory and attention, they focused on higher-order prefrontal functions, namely executive functioning (EF) and emotion recognition. Patients and healthy controls were assessed with tests measuring memory (15 Words Test, Digit Span), attention and processing speed (Trail Making Test A and B), EF (Zoo Map, Letter Fluency, Dysexecutive Questionnaire), and emotion recognition (Facial Expressions of Emotion Stimuli and Tests). Between-groups comparisons of test performances were made. Patients with aSAH scored significantly lower than healthy controls on measures of memory, processing speed, and attention, but anSAH patients did not. In the higher-order prefrontal functions (EF and emotion recognition), aSAH patients were clearly impaired when compared to healthy controls. However, anSAH patients did not perform significantly better than aSAH patients on the majority of the tests. In the subacute phase after SAH, cognitive functions, including the higher-order prefrontal functions EF and emotion recognition, were clearly impaired in aSAH patients. Patients with anSAH did not perform better than aSAH patients, which indicates that these functions may also be affected to some extent in anSAH patients. Considering the importance of these higher-order prefrontal functions for daily life functioning, and following the results of the present study, tests that measure emotion recognition and EF should be part of the standard neuropsychological assessment after SAH. (PsycINFO Database Record

Review of the Utility of Prophylactic Anticonvulsant Use in Critically Ill Patients With Intracerebral Hemorrhage

Spontaneous atraumatic intracerebral hemorrhage (sICH) accounts for 10% to 15% of strokes a year and results in significant morbidity and mortality for survivors. The sICH-related, 30-day mortality is 30% to 50% with a significant proportion occurring in the acute phase, often in the first 48 hours,1 which may be a reflection of early withdrawal of life-sustaining therapy based on perceived poor neurological prognosis.2,3 Cerebrovascular disease, including sICH, is the most common cause of acute symptomatic seizures and localization-related epilepsy in adults, accounting for ≈3.2% to 10.7% of epilepsy.4–6 Spontaneous ICH patients typically develop seizures early after their hemorrhage,7–9 but the association between early seizures and late seizures/epilepsy remains uncertain. Our understanding of risk factors for developing seizures and epilepsy, and the role of antiseizure medications in preventing poststroke seizures and epilepsy, is based mainly on retrospective analyses. To date, there are limited data on the impact of seizures, epilepsy, and antiseizure medications on functional and cognitive outcomes in patients with sICH. The goal of this nonsystematic review is to summarize the available literature, focusing on the role of seizure prophylaxis in the immediate and long-term post-sICH periods. To identify key articles for inclusion, MEDLINE on the Ovid platform (through February 14, 2016) and Embase and newer (unindexed/in process) articles from PubMed were searched using the following terms or combination of terms Anticonvulsants, Seizures, Cerebral Hemorrhage, Intracranial Hemorrhage, Nontraumatic, Spontaneous and Critical Care. All identified references were then cross-referenced to select further articles for inclusion. Non-English studies and studies isolated to infants and children were excluded. ### Definitions Seizures occur at various time points after sICH, from onset to weeks, months, and years afterward. Onset or immediate seizures occur either at ictus or within 24 hours of injury and may in fact be …

PREDICTING LONG-TERM COGNITIVE OUTCOME IN PATIENTS RECEIVING ALZHEIMER’S DISEASE MEDICATIONS

PREDICTING LONG-TERM COGNITIVE OUTCOME IN PATIENTS RECEIVING ALZHEIMER’S DISEASE MEDICATIONS