Cognitive Abilities Screening Instrument Score Research Articles

Effect of an Anterior Cingulotomy on Pain, Cognition, and Sensory Pathways.

Anterior cingulotomy (AC) was originally used to treat patients with a psychiatric disorder, but it is also useful for treating patients with chronic intractable pain. We reviewed 24 patients at our hospital who underwent AC for chronic intractable pain to determine whether surgery influenced patient cognition and the pain circuit. A visual analog scale (VAS) was used to evaluate patients' pain scale preoperatively, at 1 month and 3-6 months postoperatively, and at the final follow-up. Mini-Mental State Examination (MMSE) and Cognitive Abilities Screening Instrument (CASI) were used to evaluate postoperative cognitive function. The latencies of peaks P20 and P37 of the somatosensory evoked potential (SSEP) conductive time were used to evaluate the intactness of the thalamocortical tract after AC. The median preoperative VAS score was 8,MMSE score was 27, and CASI score was 86.8. Six patients underwent a reoperation because of recurrent pain. Pain was significantly reduced after AC, and the median VAS score at the last follow-up was 5. There was no significant pain improvement in patients who underwent a reoperation. There were no significant changes in MMSE and CASI scores or SSEP after cingulotomy. There were no operation-related complications in the patients. A stereotactic AC was safe and effective in resolving chronic refractory pain. It did notaffect patient cognition or the sensory conductive pathway. However, patients who had recurrent intractable pain after a cingulotomy did not respond well to the reoperation.

Abstract P014: Lower eGFR and Proteinuria Were Independently Associated With Lower Cognitive Abilities in Community-dwelling Men in Japan: SESSA study

Introduction: The relationship between chronic kidney disease (CKD) and cognitive function remains to be determined. Existing studies focused primarily on estimated glomerular filtration rate (eGFR) but not proteinuria in relation to cognitive function. Hypothesis: In a community-based sample, lower eGFR and presence of proteinuria are cross-sectionally independently associated with lower cognition. Methods: The Shiga Epidemiological Study of Subclinical Atherosclerosis (SESSA) randomly recruited and examined participants from Shiga, Japan in 2006-08 at baseline. Among 824 male participants in the follow-up exam (2010-12), we restricted our analyses to those who underwent the Cognitive Abilities Screening Instrument (CASI), age ≥65 years-old, free of stroke, with no missing pertinent covariates. We calculated eGFR (creatinine-based) according to the 2012-guideline by the Japanese Society of Nephrology. We then divided the participants into three groups by eGFR of ≥60, 59-40, and <40 (mL/min/1.73m 2 ), and separately divided into three groups according to proteinuria using urine dipstick: (-), (-/+), and ≥(1+). We defined CKD as either eGFR <60 or proteinuria ≥ (-/+). In linear regression with CASI score being a dependent variable, we computed the score adjusted for age, highest education attained, smoking, drinking, body mass index, hypertension, diabetes, and dyslipidemia. Results: We analyzed 541 men. The mean [standard deviation] of age and unadjusted score were 72.6 [4.3] years and 89.7 [6.0]. Prevalence of CKD was 56%. The score was significantly lower in participants with CKD than those without it (P=0.03). eGFR and proteinuria categories were separately and jointly associated with lower CASI score in a graded fashion (Ps for trend <0.05 in all the models tested. Table 1 ). Conclusions: Lower eGFR and higher degree of proteinuria were independently associated with lower cognitive function in the community-based men. CKD even in its early phase may predispose to lower cognitive function.

Cognitive decline and slower reaction time in elderly individuals with mild cognitive impairment.

The relationship between declining performance, as measured by changes in reaction time, and declining cognitive function has not been critically studied. The aim of the present study was to investigate the association between reaction time during a task and cognitive ability in elderly Taiwanese individuals. Patients aged 65 years or older with mild cognitive impairment (MCI) (n = 33) and Alzheimer's disease (n = 26) were recruited from the neurology clinic of a regional hospital in southern Taiwan. In addition, 28 healthy controls aged 65 years or older were recruited from the community. The cognitive performance of the study participants was assessed using the Cognitive Abilities Screening Instrument (CASI). A computer-administered simple reaction time (SRT) task and a flanker reaction time (FRT) task were administered to assess participants' cognitive function. A non-parametric Kruskal-Wallis test was performed to compare CASI scores, SRT, and FRT among the three groups. anova was also used to compare CASI scores, inverse-transformed SRT, and inverse-transformed FRT among the three groups, with adjustment for age and years of education. Additionally, Pearson's partial correlation coefficients were used to assess the association of CASI scores with inverse-transformed SRT, and inverse-transformed FRT within each of the three groups. Significant differences in CASI scores, SRT, and FRT were found between the Alzheimer's disease group and the other two groups, either with or without adjustment for age or education. The reaction time of patients with Alzheimer's disease was significantly slower than the other two groups. Moreover, significant correlation between CASI and FRT was found in patients with MCI. Altered performance in a speed task was observed in patients with MCI. The FRT task should further be explored for its role as a marker for cognitive decline in elderly individuals, particularly in those with MCI.

Changes in Frailty Predict Changes inCognition in Older Men: TheHonolulu-Asia Aging Study.

As cognitive decline mostly occurs in late life, where typically it co-exists with many other ailments, it is important to consider frailty in understanding cognitive change. Here, we examined the association of change in frailty status with cognitive trajectories in a well-studied cohort of older Japanese-American men. Using the prospective Honolulu-Asia Aging Study (HAAS), 2,817 men of Japanese descent were followed (aged 71-93 at baseline). Starting in 1991 with follow-up health assessments every two to three years, cognition was measured using the Cognitive Abilities Screening Instrument (CASI). For this study, health data was used to construct an accumulation of deficits frailty index (FI). Using six waves of data, multilevel growth curve analyses were constructed to examine simultaneous changes in cognition in relation to changes in FI, controlling for baseline frailty, age, education, and APOE-ɛ4 status. On average, CASI scores declined by 2.0 points per year (95% confidence interval 1.9-2.1). Across six waves, each 10% within-person increase in frailty from baseline was associated with a 5.0 point reduction in CASI scores (95% confidence interval 4.7-5.2). Baseline frailty and age were associated both with lower initial CASI scores and with greater decline across the five follow-up assessments (p < 0.01). Cognition is adversely affected by impaired health status in old age. Using a multidimensional measure of frailty, both baseline status and within-person changes in frailty were predictive of cognitive trajectories.

Cumulative impact of health deficits, social vulnerabilities, and protective factors on cognitive dynamics in late life: a multistate modeling approach.

IntroductionMany factors influence late-life cognitive changes, and evaluating their joint impact is challenging. Typical approaches focus on average decline and a small number of factors. We used multistate transition models and index variables to look at changes in cognition in relation to frailty (accumulation of health deficits), social vulnerability, and protective factors in the Honolulu-Asia Aging Study (HAAS).MethodsThe HAAS is a prospective cohort study of 3,845 men of Japanese descent, aged 71 to 93 years at baseline. Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI). Baseline index variables were constructed of health deficits (frailty), social vulnerabilities, and protective factors. The chances of improvement/stability/decline in cognitive function and death were simultaneously estimated using multistate transition modeling for 3- and 6-year transitions from baseline.ResultsOn average, CASI scores declined by 5.3 points (standard deviation (SD) = 10.0) over 3 years and 9.5 points (SD = 13.9) over 6 years. After adjusting for education and age, baseline frailty was associated with an increased risk of cognitive decline at 3 years (β = 0.18, 95% confidence interval (CI), 0.08 to 0.29) and 6 years (β = 0.40, 95% CI, 0.27 to 0.54). The social vulnerability index was associated with 3-year changes (β = 0.16, 95% CI, 0.09 to 0.23) and 6-year changes (β = 0.14, 95% CI, 0.05 to 0.24) in CASI scores. The protective index was associated with reductions in cognitive decline over the two intervals (3-year: β = −0.16, 95% CI, −0.24 to −0.09; 6-year: β = −0.21, 95% CI, −0.31 to –0.11,).ConclusionsResearch on cognition in late life needs to consider overall health, the accumulation of protective factors, and the dynamics of cognitive change. Index variables and multistate transition models can enhance understanding of the multifactorial nature of late-life changes in cognition.Electronic supplementary materialThe online version of this article (doi:10.1186/s13195-015-0120-7) contains supplementary material, which is available to authorized users.

Trajectories of cognitive function in dementia-free subjects: Radiation Effects Research Foundation Adult Health Study

ObjectivesTo investigate associations between age, sex, education, and birth cohort and global cognitive decline among a population that would most likely not progress to dementia. MethodsA total of 1538 dementia-free subjects aged 60 to 80years in 1992 were followed up through 2011 without dementia occurrence. We assessed cognitive function using the Cognitive Ability Screening Instrument (CASI). Using stepwise-like model selection procedure, we built mixed-effects models for initial cognition and longitudinal cognition. ResultsInitial CASI scores for younger age and more years of formal education were higher than those for older and less education. Sex did not show a significant effect. In the longitudinal analysis, cognitive decline became more rapid with increasing age. Sex and education did not modify the degree of deterioration with age. CASI scores were higher for younger cohorts and men due to differences in education levels. ConclusionAmong dementia-free subjects, age is an important predictor of cognitive function level and cognitive decline. Education level affects cognitive function level, but did not affect cognitive decline. The results have implications not only for elucidation of the aging process, but also for reference in dementia screening.

Potential cognitive decline linked to angiotensin-converting enzyme gene but not hypertension: Evidence from cognitive event-related potentials

ObjectivesThe aims of the present study were to investigate the effect of hypertension and angiotensin-converting enzyme (ACE) genotypes on cognitive event-related potentials (ERPs), and whether the impact of ACE genotypes on P300 is related to the influence of hypertension. MethodsUsing the Cognitive Abilities Screening Instrument (CASI), we recruited 97 mentally healthy middle-aged and older adults. Medical histories were collected, and blood pressure, ACE insertion/deletion polymorphisms and ERPs in an auditory oddball task were measured for all participants. ResultsWhen the participants were stratified according to the presence or absence of hypertension, there were no differences in CASI score, percentage of ACE genotypes and ERPs. The subjects with the D/D homozygote displayed lower amplitude and longer latency of P300, although there were no differences in CASI score and the percentage of hypertension. ConclusionsThe subjects with the D/D genotype tended to have decreased amplitude and prolonged latency of P300 ERPs which reflected subtle cognitive impairment. There were no associations between hypertension, CASI score and P300 measurements. SignificanceUsing ERPs, potential cognitive decline was linked to ACE genotypes, independently of the effect of hypertension.

Long-term disability after lacunar stroke: secondary prevention of small subcortical strokes.

To determine whether vascular and demographic factors predict worsening disability up to 8 years after lacunar stroke. SPS3 (Secondary Prevention of Small Subcortical Strokes) was a clinical trial in lacunar stroke patients with annual assessment of disability using the Older Americans Resources and Survey instrumental activities of daily living (IADL) scale (range 0-14). Generalized estimating equations modeled the likelihood of disability (IADL <14) over time, adjusting for demographics, medical risk factors, cognition, mood, stroke location, and geographic region in univariate and multivariable models. IADL assessments after recurrent stroke were censored. We stratified by study region and age quartile. Among 2,820 participants, mean age was 63.4 years (SD 10.8), 63% were male, 36% had diabetes, 90% hypertension, and 10% prior stroke. Mean follow-up was 3.7 years. In multivariable models, female sex, education, diabetes, nonregular alcohol use, prior stroke, Cognitive Abilities Screening Instrument score, depression, mild cognitive impairment, and stroke location were associated with disability. The youngest age quartile had decreased odds of disability over time (odds ratio 0.90 per year, 95% confidence interval 0.85-0.95), whereas the oldest age quartile had increased odds (2.20, 95% confidence interval 1.75-2.75). Americans and Latin Americans had >2-fold greater odds of disability per year compared with Spaniards (p < 0.0001). In lacunar stroke patients, older age was associated with worsening long-term disability, even without recurrence. Worse long-term function was associated with diabetes, cognitive status, and prior stroke, and regional differences may be attributable to variations in health care delivery or scale interpretation.

Effects of long-term blood pressure lowering and dual antiplatelet treatment on cognitive function in patients with recent lacunar stroke: a secondary analysis from the SPS3 randomised trial

The primary outcome results for the SPS3 trial suggested that a lower systolic target blood pressure (<130 mm Hg) might be beneficial for reducing the risk of recurrent stroke compared with a higher target (130-149 mm Hg), but that the addition of clopidogrel to aspirin was not beneficial compared with aspirin plus placebo. In this prespecified secondary outcome analysis of the SPS3 trial, we aimed to assess whether blood pressure reduction and dual antiplatelet treatment affect changes in cognitive function over time in patients with cerebral small vessel disease. In the SPS3 trial, patients with recent (within 6 months) symptomatic lacunar infarcts from 81 centres in North America, Latin America, and Spain were randomly assigned, in a two-by-two factorial design, to target levels of systolic blood pressure (1:1; 130-149 mm Hg vs <130 mm Hg; open-label) and to a once-daily antiplatelet treatment (1:1; aspirin 325 mg plus clopidogrel 75 mg vs aspirin 325 mg plus placebo; double-blind). For this analysis, the main cognitive outcome was change in Cognitive Abilities Screening Instrument (CASI) during follow-up. Patients were tested annually for up to 5 years, during which time the mean difference in systolic blood pressure was 11 mm Hg (SD 16) between the two targets (138 mm Hg vs 127 mm Hg at 1 year). We used linear mixed models to compare changes in CASI Z scores over time. The SPS3 trial is registered with ClinicalTrials.gov, number NCT00059306. The study took place between March 23, 2003, and April 30, 2012. 2916 of 3020 SPS3 participants (mean age 63 years [SD 11]) with CASI scores at study entry were included in the analysis, with a median follow-up of 3·0 years (IQR 1·0-4·9). Mean changes in CASI Z scores from study entry to assessment at years 1 (n=2472), 2 (n=1968), 3 (n=1521), 4 (n=1135), and 5 (n=803) were 0·12 (SD 0·83), 0·15 (0·84), 0·16 (0·95), 0·19 (0·99), and 0·14 (1·09), respectively. Changes in CASI Z scores over time did not differ between assigned antiplatelet groups (p=0·858) or between assigned blood pressure target groups (p=0·520). There was no interaction between assigned antiplatelet groups and assigned blood pressure target groups and change over time (p=0·196). Cognitive function is not affected by short-term dual antiplatelet treatment or blood pressure reduction in fairly young patients with recent lacunar stroke. Future studies of cognitive function after stroke should be of longer duration or focus on patients with higher rates of cognitive decline. US National Institute of Neurological Disorders and Stroke.

Minimal hepatic encephalopathy in patients with liver cirrhosis: Magnetic resonance spectroscopic brain findings versus neuropsychological changes

Background and study aimMinimal hepatic encephalopathy (MHE) is a subtle complication of cirrhosis that may have a detrimental effect on daily functioning and may progress to overt hepatic encephalopathy (HE). The aims of this study were to identify MHE and assess neuropsychological changes in those patients. Patients and methodsA case–control study was conducted in 35 cirrhotic patients. MHE was identified by brain (hydrogen-1) magnetic resonance spectroscopy (1H-MRS). Neuropsychological changes were evaluated using cognitive abilities screening instrument (CASI) test, Hamilton depression scale, and soft neurological sign assessment. ResultsOf the patients, 16 (45.7%) had significant brain 1H-MRS findings suggesting MHE in the form of decreased myo-Inositol/creatine (mI/Cr) and choline/creatine (Cho/Cr) ratios and increased glutamine–glutamate/creatine (Glx/Cr) ratios in white and grey matters compared to patients without MHE and healthy controls. Patients with MHE had significantly lower abstract thinking subset and total CASI score in comparison to patients without MHE (p=0.03 and p=0.05, respectively) and controls (p=0.003 and p=0.02, respectively). No statistically significant differences were observed amongst different groups regarding other CASI subsets, depression, and soft neurological assessment in spite of a tendency towards increased values in patients with MHE. ConclusionMHE associated with neurophysiological changes demonstrated by 1H-MRS preceded neuropsychological changes. Thus, 1H-MRS may be considered as a potential tool for diagnosis of cirrhosis-associated cerebral dysfunction and a promising method for prioritisation of subjects awaiting liver transplantation.

Parallel Improvement of Cognitive Functions and P300 Latency Following Donepezil Treatment in Patients With Alzheimer's Disease

To evaluate the effect of donepezil, one of the cholinesterase inhibitors, on P300 measurements in patients with Alzheimer's disease (AD) and investigate the relationship between the subfactors of cognitive performance and P300 components. One hundred outpatients with AD were evaluated for cognitive function (cognitive ability screening instrument) and event-related potentials before and after 22 to 23 weeks of treatment with donepezil (5 mg/day). Twenty age-matched normal control subjects were recruited. The patients with AD showed prolonged P300 and N200 latency, no significant differences in N100 and P200 components, and poor performance in neuropsychological assessments compared with control subjects at baseline. After donepezil treatment, the patients with AD had reduction in P300 latency at Pz lead, which was associated with a parallel improvement in cognitive function in terms of remote memory, recent memory, visual instruction, and orientation. The pre-post treatment difference of P300 latency significantly correlated with the cognitive ability screening instrument score difference and recent memory score difference, respectively. The patients with AD still had intact early sensory processing but impaired higher-level cognitive processes that could influence behavior deviation. The donepezil treatment, which enhances higher-level cognitive processing time, revealed that P300 latency decreases as cognitive capability increases, especially improved in recent memory.

Clinical utility of the Functional Independence Measure for assessment of patients with Alzheimer's disease and vascular dementia

The aim of this study was to investigate the clinical utility of the Functional Independence Measure (FIM), and especially FIM-Cognition (FIM-C) scores, in patients with Alzheimer's disease (AD) and vascular dementia (VaD), and to determine the influence of behavioural and psychological symptoms of dementia (BPSD) on FIM-C scores. This was a cross-sectional survey of 37 AD and 40 VaD patients. Cognitive function was assessed with the Cognitive Abilities Screening Instrument. Activities of daily living were evaluated with the FIM and the Barthel Index. BPSD were assessed with the Behavioural Pathology in Alzheimer's Disease Frequency Weighted Severity Scale. For both groups, Spearman's correlations were found between FIM-Motor and Barthel Index scores and between FIM-C and Mini Mental State Examination scores. Each FIM-C subscore was correlated with Cognitive Abilities Screening Instrument scores in both groups, except for the FIM-C Social interaction subscore in VaD. VaD patients showing Activity Disturbance and Aggressiveness on the Behavioural Pathology in Alzheimer's Disease Frequency Weighted Severity Scale had significantly lower FIM-C Memory and Social interaction subscores than those without BPSD. The results suggest that the FIM-Motor and FIM-C scales are useful measures of physical and cognitive disabilities in patients with AD and VaD. The FIM-C profile of AD may reflect global cognitive function, while that of VaD may be more influenced by BPSD.

Interleukin-1 alpha (rs1800587) genetic polymorphism is associated with specific cognitive functions but not depression or loneliness in elderly males without dementia

Inflammatory process is considered to be a pathway that results in neurodegeneration, and numerous plasma cytokines have been examined for their association with cognitive function and depression. Interleukin-1 alpha (IL-1A) genetic polymorphism (rs1800587) has been found to be associated with Alzheimer's disease susceptibility. The aim of this study was to investigate the effect of IL-1A rs1800587 genetic effects on cognitive functions, loneliness and depression severity in elderly males without dementia or major depression. 192 non-demented Chinese elderly male were recruited and underwent Cognitive Abilities Screening Instrument (CASI), Wechsler Digit Span Task, Geriatric Depression Scale-short form, and UCLA Loneliness Scale assessment. IL-1A rs1800587 is a C to T transition at position −889. Compared to the C/C carriers, the T allele carriers had significantly overall higher CASI score (p=0.017) after using age and total education years as co-variates. This was especially true in the four distinct domains of long-term memory (p<0.001), orientation (p=0.017), visual construction (p=0.003), and list-generating fluency (p=0.020). This polymorphism is not associated with Geriatric Depression Scale-short form or UCLA Loneliness Scale. Our data supports that the T allele of IL-1A rs1800587 genetic polymorphism is associated with better cognitive function in the elderly. Further research will be needed to better understand the molecular mechanism for IL-1A genetic effects on cognitive function in the elderly.

Antihypertensive medication use and risk of cognitive impairment

To determine the associations between classes of antihypertensive medication use and the risk of cognitive impairment among elderly hypertensive men. The Honolulu-Asia Aging Study is a prospective, community-based cohort study of Japanese American men conducted in Honolulu, Hawaii. We examined 2,197 participants (mean age 77 years at cohort entry, 1991-1993, followed through September 2010) with hypertension and without dementia or cognitive impairment at baseline, who provided information on medication use. Cognitive function was assessed at 7 standardized examinations using the Cognitive Abilities Screening Instrument (CASI). Cognitive impairment was defined as a CASI score <74. A total of 854 men developed cognitive impairment (median follow-up, 5.8 years). β-Blocker use as the sole antihypertensive drug at baseline was consistently associated with a lower risk of cognitive impairment (incidence rate ratio [IRR] 0.69; 95% confidence interval [CI] 0.50-0.94), as compared with men not taking any antihypertensive medications, adjusting for multiple potential confounders. The use of diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors, or vasodilators alone was not significantly associated with cognitive impairment. Results were similar excluding those with cardiovascular disease or <1 year of follow-up, and additionally adjusting for pulse pressure, heart rate, baseline and midlife systolic blood pressure, and midlife antihypertensive treatment (IRR 0.65; 95% CI 0.45-0.94). The association between β-blocker use and cognitive impairment was stronger among men with diabetes, men aged >75 years, and those with pulse pressure ≥70 mm Hg. β-blocker use is associated with a lower risk of developing cognitive impairment in elderly Japanese American men.

Cerebrolysin enhances cognitive recovery of mild traumatic brain injury patients: double-blind, placebo-controlled, randomized study

In adults, mild traumatic brain injury (MTBI) frequently results in impairments of cognitive functions which would lead to psychological consequences in the future. Cerebrolysin is a nootropic drug, and can significantly improve cognitive function in patients with Alzheimer's disease and stroke. The purpose of this study was to investigate how Cerebrolysin therapy enhances cognitive recovery for mild traumatic brain injury patients using a double-blinded, placebo-controlled, randomized phase II pilot study. Patients having head injury within 24 h sent to our hospital were screened and recruited if patients were alert and conscious, and had intracranial contusion haemorrhage. From July 2009 to June 2010, totally, thirty-two patients were recruited in the double-blinded, placebo-controlled, and randomized study. Patients were randomized to receive Cerebrolysin (Group A, once daily intravenous infusion of 30 mL Cerebrolysin over a 60-min period for 5 days) or placebo (Group B, same dosage and administration of normal saline as Group A). The primary outcome measures were differences of cognitive function including Mini-Mental Status Examination (MMSE), and Cognitive Abilities Screening Instrument (CASI) scores between baseline and week 1, between baseline and week 4, and between baseline and week 12. Thirty-two patients completed the trial. For Group A, the CASI score difference between baseline and week 12 was 21.0 ± 20.4, a significantly greater change than that of Group B (7.6 ± 12.1) (p = 0.0461). Besides, drawing function (one of the domains of CASI; p = 0.0066) on week 4 and both drawing function (p = 0.0472) and long-term memory (one of the domains of CASI; p = 0.0256) on week 12were also found to be significantly improved in the patients receiving Cerebrolysin treatment. Our results suggest that Cerebrolysin improves the cognitive function of the MTBI in patients at 3rd month after injury, especially for long-term memory and drawing function.

Impact of homocysteine on cortical perfusion and cognitive decline in mild Alzheimer's dementia

Elevated plasma total homocysteine level (tHcy) is associated with increased risk of dementia via increased white matter changes or reduction in cortical volume. Whether tHcy has an independent impact on regional perfusion and if it can predict a more rapid cognitive decline in mild Alzheimer dementia (AD) warrants investigation. Eighty AD patients with a clinical dementia rating of 1 were enrolled. Their Cognitive Ability Screening Instrument (CASI) scores on enrolment and after 1 year of follow-up as well as their perfusion index (PI) from single photon emission computed tomography upon enrolment were analyzed. In cross-sectional analysis, elevated tHcy was associated with lower frontal PI independent of cerebrovascular risk factors (β = -0.35, P = 0.009). The CASI scores correlated with temporo-parietal PI (Pearson r range 0.3-0.39, P < 0.01) but not with tHcy or frontal PI. By longitudinal analysis, only tHcy level was related to a more rapid cognitive decline (odds ratio for executive function score 1.82; odds ratio for total CASI score 1.74). Cognitive performance in mild AD can be reflected by hypo-perfusion of the temporo-parietal region while frontal hypo-perfusion may be mediated by tHcy. tHcy level is an independent risk factor for rapid cognitive decline, especially in the executive function.

Connectivity of default-mode network is associated with cerebral edema in hepatic encephalopathy.

Cerebral edema, a well-known feature of acute liver disease, can occur in cirrhotic patients regardless of hepatic encephalopathy (HE) and adversely affect prognosis. This study characterized and correlated functional HE abnormalities in the brain to cerebral edema using resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). Forty-one cirrhotic patients (16 without HE, 14 minimal HE, 11 overt HE) and 32 healthy controls were assessed. The HE grade in cirrhotic patients was evaluated by the West Haven criteria and neuro-psychological examinations. Functional connectivity correlation coefficient (fc-CC) of the default mode network (DMN) was determined by rs-fMRI, while the corresponding mean diffusivity (MD) was obtained from DTI. Correlations among inter-cortical fc-CC, DTI indices, Cognitive Ability Screening Instrument scores, and laboratory tests were also analyzed. Results showed that gradual reductions of HE-related consciousness levels, from “without HE” or “minimal HE” to “overt HE”, correlated with decreased anterior-posterior fc-CC in DMN [F(4.415), p = 0.000)]. The MD values from regions with anterior-posterior fc-CC differences in DMN revealed significant differences between the overt HE group and other groups. Increased MD in this network was inversely associated with decreased fc-CC in DMN and linearly correlated with poor cognitive performance. In conclusion, cerebral edema can be linked to altered cerebral temporal architecture that modifies both within- and between-network connectivity in HE. Reduced fc-CC in DMN is associated with behavior and consciousness deterioration. Through appropriate targets, rs-fMRI technology may provide relevant supplemental information for monitoring HE and serve as a new biomarker for clinical diagnosis.

Impaired memory and executive function associated with decreased medial temporal and prefrontal blood flow in Clinical Dementia Rating 0.5 status: the Osaki‐Tajiri project

The Clinical Dementia Rating (CDR) is an assessment of dementia severity based on observations of activities of daily living, and a CDR of 0.5 (CDR 0.5) represents questionable dementia. A combination of the Cognitive Abilities Screening Instrument (CASI) and the Trail Making Test (TMT) scores discriminated CDR 0.5 subjects from healthy participants with a high degree of accuracy. We investigated the neurological background of CDR 0.5 subjects by correlating CASI and TMT scores with regional cerebral blood flow (rCBF) as measured by single photon emission computed tomography (SPECT). From a community-based cohort, 22 CDR 0.5 participants were recruited. CASI and TMT scores, rCBF measure using [(123) I]-N-isopropyl-p-iodoamphetamine and SPECT were obtained. We evaluated the relationships between the CASI domain scores, between TMT scores and rCBF in a regions-of-interest-based analysis, and voxel-based analysis using Statistical Parametric Mapping 5 software. We found that lower rCBF in the left medial temporal cortex correlated with a decreased CASI domain recent memory score both in the regions-of-interest and statistical parametric mapping analysis. In both the regions-of-interest and statistical parametric mapping analysis, the rCBF in the left prefrontal cortex correlated with CASI domain remote memory and mental manipulation and concentration. Our results indicate that some CDR 0.5 subjects have functional impairments in the medial temporal lobe as well as in the prefrontal cortex, as reflected in the cognitive decline measured by CASI and TMT.

Abstract 2781: Prevalence and Characterization of Cerebral Microbleeds in Lacunar Stroke Patients: Observations from the Secondary Prevention Small Subcortical Strokes (SPS3) Trial

Background: The prevalence of cerebral microbleeds (CMBs) has been reported to be high in patients with cerebrovascular disease and particularly in those with cerebral small vessel disease; i.e. lacunar strokes. However, methodological limitations of previous studies imposed by small sample sizes and the absence of a clear classification of stroke subtypes hampers the conclusions regarding prevalence and characterization of CMBs in lacunar stroke patients. Methods: SPS3 is a multi-center international randomized trial including a well-defined cohort of MRI proven lacunar stroke patients. We investigated patients within this population who had an axial T2*- GRE sequence available as part of their baseline clinical MRI. The Brain Observer MicroBleed Scale was used to rate the presence and topography of CMBs. CMB severity was graded as either absent, 1-2 CMBs or &gt;2 CMBs. We compared baseline characteristics and vascular risk factors between patients with CMBs and those without and between the defined CMB severity grades. Results: Of the 651 MRIs analyzed, 237 (36%) had CMBs. Patients with CMBs were more often male (73% vs 62%, p&lt;0.01) and Hispanic (49% vs 39%, p=0.02), were more likely to have hypertension (95% vs 90%, p=0.01) and prior lacunar stroke (13% vs 7%, p=0.01), and had lower baseline mean Cognitive Abilities Screening Instrument (CASI) scores (80 vs 86, p&lt;0.01). Male gender [OR 1.85 (95% CI, 1.26 to 2.70)], prior lacunar stroke [OR 2.19 (95% CI, 1.19 to 4.03)] and lower baseline CASI scores [OR 0.97 (95% CI, 0.95 to 0.98)] remained significant following multivariate analysis. A significant association was found between increasing CMB severity and decreasing CASI scores (p&lt;0.01), an increased presence of multiple lacunar infarcts (p&lt;0.0001) and moderate-severe white matter hyperintensities on MRI (p&lt;0.0001). Conclusions: Preliminary results of this large and well-defined cohort of lacunar stroke suggest a high prevalence of CMBs. A significant association was observed between CMBs and gender and a history of lacunar stroke. CMB severity was associated with multiple infarcts and severity of white matter disease on MRI, as well as lower cognitive function. Ongoing data from SPS3 will likely elucidate whether prognosis and response to therapy differ in patients with CMBs.

Effect of cholesterol and CYP46 polymorphism on cognitive event-related potentials

The integrated effect of the cholesterol and CYP46 genotypes on the risk of cognitive decline needs to be determined. Using the Cognitive Abilities Screening Instrument (CASI), 145 mentally healthy middle-aged and older adults were recruited to investigate the influence of cholesterol and CYP46 genotypes on cognitive event-related potentials (ERPs). The subjects with a high low-density lipoprotein cholesterol (LDL-C) level displayed significantly lower amplitude ERPs, although the CASI scores showed no difference. There was no association between the CYP46 genotypes, CASI scores, cholesterol levels, and measures of ERPs. No interaction between LDL-C level and CYP46 genotypes was noted. The LDL-C level is an independent predictor of low P300 amplitude. Prevention and treatment of high cholesterol may be of potential benefit in reducing cognitive impairment.