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COMT Val 158 Met polymorphism is associated with nonverbal cognition following mild traumatic brain injury.
Winkler, EA, Yue, JK, McAllister, TW, Temkin, NR, Oh, SS, Burchard, EG, Hu, D, Ferguson, AR, Lingsma, HF, Burke, JF, et al
Neurogenetics. 2016;(1):31-41
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Abstract
Mild traumatic brain injury (mTBI) results in variable clinical outcomes, which may be influenced by genetic variation. A single-nucleotide polymorphism in catechol-o-methyltransferase (COMT), an enzyme which degrades catecholamine neurotransmitters, may influence cognitive deficits following moderate and/or severe head trauma. However, this has been disputed, and its role in mTBI has not been studied. Here, we utilize the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) study to investigate whether the COMT Val (158) Met polymorphism influences outcome on a cognitive battery 6 months following mTBI--Wechsler Adult Intelligence Test Processing Speed Index Composite Score (WAIS-PSI), Trail Making Test (TMT) Trail B minus Trail A time, and California Verbal Learning Test, Second Edition Trial 1-5 Standard Score (CVLT-II). All patients had an emergency department Glasgow Coma Scale (GCS) of 13-15, no acute intracranial pathology on head CT, and no polytrauma as defined by an Abbreviated Injury Scale (AIS) score of ≥3 in any extracranial region. Results in 100 subjects aged 40.9 (SD 15.2) years (COMT Met (158) /Met (158) 29 %, Met (158) /Val (158) 47 %, Val (158) /Val (158) 24 %) show that the COMT Met (158) allele (mean 101.6 ± SE 2.1) associates with higher nonverbal processing speed on the WAIS-PSI when compared to Val (158) /Val (158) homozygotes (93.8 ± SE 3.0) after controlling for demographics and injury severity (mean increase 7.9 points, 95 % CI [1.4 to 14.3], p = 0.017). The COMT Val (158) Met polymorphism did not associate with mental flexibility on the TMT or with verbal learning on the CVLT-II. Hence, COMT Val (158) Met may preferentially modulate nonverbal cognition following uncomplicated mTBI.Registry: ClinicalTrials.gov Identifier NCT01565551.
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Accumulation of geriatric conditions is associated with poor nutritional status in dependent older people living in the community and in nursing homes.
Hirose, T, Hasegawa, J, Izawa, S, Enoki, H, Suzuki, Y, Kuzuya, M
Geriatrics & gerontology international. 2014;(1):198-205
Abstract
AIM: To clarify the association between nutritional status and the prevalence of geriatric conditions in dependent older adults. METHODS A cross-sectional observational study of dependent older adults aged 65years or older who were living either in the community (n = 511, mean age 81.2years) or in nursing homes (n = 587, mean age 85.2years) was carried out. Data included the participants' demographic characteristics, basic activities of daily living, Charlson Comorbidity Index and the prevalence of eight geriatric conditions (visual impairment, hearing impairment, falls, bladder control problems, cognitive impairment, impaired mobility, swallowing disturbance and loss of appetite). Nutritional status was assessed by the Mini Nutritional Assessment short form (MNA-SF). RESULTS Of 1098 participants, 21.4% (n = 235) were categorized as "malnourished", according to the MNA-SF classification. Participants in the "malnourished" group had a greater number of geriatric conditions than those in the other two groups. A higher prevalence of all the geriatric conditions except for falls was detected in the group with poorer nutritional status. Multivariate logistic regression analysis showed that malnutrition was associated with the number of geriatric conditions, but not with that of comorbidities, even after controlling for confounders. CONCLUSIONS Malnutrition was confirmed to have significant associations with geriatric conditions in dependent older adults.
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Faciobrachial dystonic seizures: the influence of immunotherapy on seizure control and prevention of cognitive impairment in a broadening phenotype.
Irani, SR, Stagg, CJ, Schott, JM, Rosenthal, CR, Schneider, SA, Pettingill, P, Pettingill, R, Waters, P, Thomas, A, Voets, NL, et al
Brain : a journal of neurology. 2013;(Pt 10):3151-62
Abstract
Voltage-gated potassium channel complex antibodies, particularly those directed against leucine-rich glioma inactivated 1, are associated with a common form of limbic encephalitis that presents with cognitive impairment and seizures. Faciobrachial dystonic seizures have recently been reported as immunotherapy-responsive, brief, frequent events that often predate the cognitive impairment associated with this limbic encephalitis. However, these observations were made from a retrospective study without serial cognitive assessments. Here, we undertook the first prospective study of faciobrachial dystonic seizures with serial assessments of seizure frequencies, cognition and antibodies in 10 cases identified over 20 months. We hypothesized that (i) faciobrachial dystonic seizures would show a differential response to anti-epileptic drugs and immunotherapy; and that (ii) effective treatment of faciobrachial dystonic seizures would accelerate recovery and prevent the development of cognitive impairment. The 10 cases expand both the known age at onset (28 to 92 years, median 68) and clinical features, with events of longer duration, simultaneously bilateral events, prominent automatisms, sensory aura, and post-ictal fear and speech arrest. Ictal epileptiform electroencephalographic changes were present in three cases. All 10 cases were positive for voltage-gated potassium channel-complex antibodies (346-4515 pM): nine showed specificity for leucine-rich glioma inactivated 1. Seven cases had normal clinical magnetic resonance imaging, and the cerebrospinal fluid examination was unremarkable in all seven tested. Faciobrachial dystonic seizures were controlled more effectively with immunotherapy than anti-epileptic drugs (P = 0.006). Strikingly, in the nine cases who remained anti-epileptic drug refractory for a median of 30 days (range 11-200), the addition of corticosteroids was associated with cessation of faciobrachial dystonic seizures within 1 week in three and within 2 months in six cases. Voltage-gated potassium channel-complex antibodies persisted in the four cases with relapses of faciobrachial dystonic seizures during corticosteroid withdrawal. Time to recovery of baseline function was positively correlated with time to immunotherapy (r = 0.74; P = 0.03) but not time to anti-epileptic drug administration (r = 0.55; P = 0.10). Of 10 cases, the eight cases who received anti-epileptic drugs (n = 3) or no treatment (n = 5) all developed cognitive impairment. By contrast, the two who did not develop cognitive impairment received immunotherapy to treat their faciobrachial dystonic seizures (P = 0.02). In eight cases without clinical magnetic resonance imaging evidence of hippocampal signal change, cross-sectional volumetric magnetic resonance imaging post-recovery, after accounting for age and head size, revealed cases (n = 8) had smaller brain volumes than healthy controls (n = 13) (P < 0.001). In conclusion, faciobrachial dystonic seizures can be prospectively identified as a form of epilepsy with an expanding phenotype. Immunotherapy is associated with excellent control of the frequently anti-epileptic drug refractory seizures, hastens time to recovery, and may prevent the subsequent development of cognitive impairment observed in this study.
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Predictors of short-term neurocognitive outcome following coronary revascularisation (CABG) depending on the use of cardiopulmonary bypass.
Lazibat, I, Sutlić, Z, Brkić, K, Nevajda, B, Sikić, J, Mestrović, AH
Collegium antropologicum. 2012;(3):827-33
Abstract
The purpose of our study was to investigate the association between perioperative cerebral microembolization, expressed as high-intensity transient signals (HITS) and postoperative dynamics of the neuromarker S100P in patients operated using cardiopulmonary bypass, and to assess their impact upon the neurocognitive function in the early postoperative stage. The study involved 62 consecutive male patients aged 60 or above, alls scheduled for elective aortocoronary bypass. The patients were recruited from two groups with respect to the use of CPB: on-pump group (CPB+, N = 30) and off-pump group (CPB-, N = 32). In all patients we performed intraoperative monitoring of cerebral haemodynamics using transcranial Doppler, with the goal of quantifying perioperative cerebral microembolization. The serum levels of the neuromarker S100l were measured immediately after surgery, and then 12, 24 and 48 hours after the surgery. Neurocognitive status was assessed before and after the surgery and in three cognitive domains. Results of the study have shown that with respect to the short-term postoperative neurocognitive outcome there is no significant difference between the on-pump and off-pump surgical technique of coronary revascularization'. Perioperative cerebral microembolization was significantly more pronounced in the on-pump group yet it did not affect early postoperative neurocognitive function, while the increase in the neuromarker S100beta serum level 48 hours after surgery may have prognostic value as a predictor of postoperative neurocognitive dysfunction.
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[Effect of cytoflavin on the recovery of cognitive function after the cardiaс surgery with artificial blood circulation].
Kardash, OF, Shestakova, LG, Krachak, DI, Chernookiĭ, OG, Zasetskiĭ, AE, Ostrovskiĭ, IuP
Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova. 2011;(7):76-9
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Cholesterol and cognitive performance in normal controls and the influence of elective statin use after conversion to mild cognitive impairment: results in a clinical trial cohort.
Sparks, DL, Kryscio, RJ, Connor, DJ, Sabbagh, MN, Sparks, LM, Lin, Y, Liebsack, C
Neuro-degenerative diseases. 2010;(1-3):183-6
Abstract
BACKGROUND We reported a significant 67% reduction in the hazard risk of incident Alzheimer's disease (AD) with elective statin use in the AD Anti-inflammatory Prevention Trial (ADAPT), without a reduction in risk of incident mild cognitive impairment (MCI). OBJECTIVE To assess if cholesterol levels are associated with cognitive performance and determine if statin use alters cognitive performance after onset of MCI. DESIGN Fractionated cholesterol levels, neurological and cognitive status were evaluated annually. Comparisons of non-LLA (lipid-lowering agent) users or statin-LLA users were performed blind to the ADAPT medication randomization. Pearson's correlations were validated using a time-dependent linear mixed model. RESULTS The MMSE performance significantly declined over time in non-LLA users, and, after adjusting for this, a significant positive correlation between MMSE and HDL was identified (p = 0.0002). A negative correlation between total and LDL cholesterol, and immediate and delayed recall of the Rivermead paragraph was significant (total cholesterol, p < 0.003; LDL, p < 0.02). Pilot data suggest a positive signal on delayed recall of both the Hopkins word list and Rivermead paragraph with deterioration in the non-LLA users and improvement in the statin users after conversion to MCI. CONCLUSION Cholesterol levels may be associated with differential performance on the MMSE and measures of learning or memory. The trend for improved delayed recall in statin users with MCI compared to non-LLA users with MCI may have contributed to the reduced hazards risk of incident AD without reducing the risk of MCI.
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Effects of quetiapine on cognitive functions in schizophrenic patients: a preliminary single-trial ERP analysis.
Zhang, Y, Lehmann, M, Shobeiry, A, Höfer, D, Johannes, S, Emrich, HM, Dietrich, DE
Pharmacopsychiatry. 2009;(4):129-34
Abstract
AIM: The study aimed to explore by means of single-trial event-related potentials (ERPs), whether and how the medication change from older neuroleptics to quetiapine in schizophrenic patients led to a significant cognitive enhancement. This single-trial ERP analysis helps to investigate attention and memory processes in the single patient before and after treatment. PATIENTS AND METHODS Thirteen schizophrenic patients (mean age: 40.1+/-13.5 years) were followed up for 16 weeks and assessed for changes of clinical symptoms and ERP components P300 representing target detection processes and N400 indexing context integration in word recognition processes. Three subjects had to be excluded from the ERP recording sessions because of excessive blink artefacts and movements. RESULTS Regarding the P300 components of the target detection, there were significant increases of amplitudes in 5 of 10 patients (50%) at week 16 comparing with week 0. Regarding the N400 components of the word recognition, there were significant increases of amplitudes in 4 of 10 patients (40%) at week 16 comparing with week 0. DISCUSSION The mean scores of PANSS, MADRS, Bf-S, SCL-90 and CGI-S at the end of study (week 16) showed significant improvements compared to the baselines (week 0) (p<0.05). During the study, no extrapyramidal symptoms as well as akathisia were reported after quetiapine treatment. These preliminary data suggest that quetiapine might partially improve the cognitive functions in the context integration and target detection processing in these patients. This technical procedure (single-trial ERP) may help to differentially assess cognitive enhancements in each single patient under treatment.
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Stress-induced blood pressure elevation in subjects with mild cognitive impairment: effects of the dual-type calcium channel blocker, cilnidipine.
Kawashima, Y, Akishita, M, Hasegawa, H, Kozaki, K, Toba, K
Geriatrics & gerontology international. 2008;(4):278-83
Abstract
AIM: We investigated whether mental stress-induced blood pressure elevation was related to cognitive function in the elderly, and further examined the effects of the dual-type calcium channel blocker, cilnidipine, on stress induced hypertension in subjects with mild cognitive impairment. METHODS In study I, 39 consecutive outpatients (mean age +/- standard deviation, 77 +/- 8 years), who were referred to our memory clinic and were not taking any medications, were studied. They were divided into three groups according to cognitive function on the Hasegawa Dementia Scale-Revised (HDSR): group 1 (n = 8), 28 points or more; group 2 (n = 18), 21-27 points; and group 3 (n = 13), 20 points or less. In study II, 14 outpatients with hypertension and mild cognitive impairment (aged 79 +/- 8 years; HDSR score, 24 +/- 4) were assigned to receive cilnidipine (10-20 mg/day). The control group (n = 10) matched for age, HDSR and blood pressure was followed without cilnidipine. RESULTS In study I, although age and basal blood pressure were similar among the three groups, the blood pressure response to a mental arithmetic test was twice as large in group 2 (26 +/- 12 mmHg in systolic pressure and 11 +/- 8 mmHg in diastolic pressure) as those in groups 1 and 3. In study II, after 4 weeks, cilnidipine treatment significantly decreased the blood pressure responses to the mental arithmetic test compared to the baseline as well as to those of the control group. CONCLUSIONS Stress-induced blood pressure elevations are exaggerated in subjects with mild cognitive impairment. Cilnidipine may have inhibitory effects on stress-induced hypertension.
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Vitamin B(12) supplementation did not improve cognition but reduced delirium in demented patients with vitamin B(12) deficiency.
Kwok, T, Lee, J, Lam, L, Woo, J
Archives of gerontology and geriatrics. 2008;(3):273-82
Abstract
To examine the effects of vitamin B(12) supplementation on the cognitive function, delirium, and neuropsychiatric symptoms of mild to moderate dementia patients with vitamin B(12) deficiency. Thirty consecutive mild to moderate dementia cases aged over 60 years with low serum B(12) (< 200 pmol/l) were given vitamin B(12) supplementation for 40 weeks. The Mattis Dementia Rating Scale (MDRS), Category Verbal Fluency Test (CVFT), Delirium Rating Scale (DRS), Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory (NPI) were performed at baseline, and after 6, 16, and 40 weeks. No significant changes in cognitive function and behavioral symptoms were detected between baseline and 40 weeks. DRS scores decreased significantly at 6 and 40 weeks (median change of -1 at both follow-ups, p=0.006 and 0.04, respectively). Cognitive function of mild to moderately demented older people with vitamin B(12) deficiency did not significantly change with vitamin B(12) supplementation over a 10-month period. The supplementation reduced delirium associated with dementia.
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Glutamate/aspartate supplementation during cardiopulmonary bypass: effect on postoperative neurocognitive function.
Erol, DD, Ibis, HA
The heart surgery forum. 2008;(1):E17-20
Abstract
In this randomized trial, we investigated the effect of glutamate/aspartate-containing cardioplegia on neurocognitive function in 70 patients undergoing first-time elective coronary artery bypass graft surgery. Half of the patients received glutamate/aspartate, and the other 35 patients served as controls and received crystalloid cardioplegia. Neurocognitive function after surgery was assessed with the Mini-Mental State Examination performed before surgery and again on postoperative day 3. Although patients in both groups scored slightly lower postoperatively (17 versus 18 of a total of 30 points), no significant group differences were found. Our results indicate that glutamate/aspartate supplementation had no impact on neurocognitive function after coronary artery bypass graft surgery.