Distinguishing Between Clinical and Minimal Hepatic Encephalopathy on the Basis of Specific Cognitive Impairment

It is well-known that liver cirrhosis is frequently accompanied by a wide range of neuropsychiatric abnormalities, including general and specific cognitive impairment. The aim of this study was to investigate which cognitive functions are selectively compromised in Hepatic Encephalopathy (HE) and to clarify the relationship between clinically overt or nonovert HE and the different forms and degrees of decay in cognitive deficits. Twenty-two patients without overt HE and 12 patients who showed overt HE at the first level of severity, along with matched control subjects, were compared in several cognitive domains. The results showed significant differences in some measures of attention between patients with minimal HE (mHE) and patients with overt HE. There were also notable differences in verbal short-term memory between patients with mHE and healthy subjects. Thus, we can hypothesize that there is a linear diminution in short-term memory and attentional performance starting from healthy patients, moving toward patients with mHE, and finally progressing toward patients with the first grade of overt HE. There are two types of diminution that we noted: between patients with mHE and the overt form, the decline in the attentional domain was more evident, while between healthy subjects and mHE patients, short-term memory showed a more evident decline.     

Quality of life in patients with minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) represents the mildest type of hepatic encephalopathy (HE). This condition alters the performance of psychometric tests by impairing attention, working memory, psychomotor speed, and visuospatial ability, as well as electrophysiological and other functional brain measures. MHE is a frequent complication of liver disease, affecting up to 80% of tested patients, depending of the diagnostic tools used for the diagnosis. MHE is related to falls, to an impairment in fitness to drive and the development of overt HE, MHE severely affects the lives of patients and caregivers by altering their quality of life (QoL) and their socioeconomic status. MHE is detected in clinically asymptomatic patients through appropriate psychometric tests and neurophysiological methods which highlight neuropsychological alterations such as video-spatial orientation deficits, attention disorders, memory, reaction times, electroencephalogram slowing, prolongation of latency evoked cognitive potentials and reduction in the critical flicker frequency. Several treatments have been proposed for MHE treatment such as non-absorbable disaccharides, poorly absorbable antibiotics such rifaximin, probiotics and branched chain amino acids. However, because of the multiple diagnosis methods, the various endpoints of treatment trials and the variety of agents used in trials, to date the treatment of MHE is not routinely recommended apart from on a case-by-case basis. Aim of this review is analyze the burden of MHE on QoL of patients and provide a brief summary of therapeutic approaches.     

Neuropsychological impairment in patients with chronic hepatitis C

Hepatitis C is the most common cause of chronic liver disease in the United States and it significantly reduces quality of life. The role of cognitive deficits contributing to the morbidity of this disease has not been well characterized. The purpose of this study was to examine cognitive functioning in patients with chronic hepatitis C and to investigate relationships among parameters of disease severity and performance on neuropsychological tests. Sixty-six patients with chronic hepatitis C and 14 patients with other chronic liver diseases were administered a brief battery of neuropsychological tests assessing attention, visuoconstructional ability, learning, memory, and psychomotor speed. Cognitive impairment in patients with chronic hepatitis C ranged from 0% on a visuoconstructional task to 82% on a measure of sustained attention and concentration. Test scores of patients with chronic hepatitis C did not differ from those of patients with other chronic liver diseases. Hence, patients with and without chronic hepatitis C experience cognitive deficits, especially in tasks requiring attention and psychomotor speed. In addition, there was a significant relationship between fibrosis stage and test performance, with greater fibrosis associated with poorer performance. However, both patients with and without cirrhosis exhibited cognitive dysfunction. In conclusion, these findings suggest that progressive hepatic injury may result in cognitive problems even before the development of cirrhosis. Future studies need to determine the effect of this decrease in cognitive function on quality of life.     

Use of computerized assessment to predict neuropsychological functioning and emotional distress in patients with systemic lupus erythematosus

OBJECTIVE: Cognitive dysfunction and neuropsychiatric disturbance are common in systemic lupus erythematosus (SLE). This study addressed the ability of the Automated Neuropsychological Assessment Metrics (ANAM), a computerized cognitive testing battery consisting of cognitive subtests, a sleepiness rating scale, and a mood scale, to predict neuropsychological status in patients with SLE. METHODS: Sixty individuals with SLE and no overt neuropsychiatric symptoms were administered ANAM to determine its validity as a screening measure of cognitive dysfunction and emotional distress in SLE. RESULTS: Performance on ANAM was compared with results of a consecutively administered, 2-hour battery of traditional neuropsychological tests and the Beck Depression Inventory II (BDI-II). Individual ANAM cognitive test scores were significantly correlated with most neuropsychological tests, particularly those measuring psychomotor processing speed and executive functioning. Using logistic regression, ANAM cognitive subtests successfully predicted individuals with SLE who had probable versus no impairment after controlling for premorbid levels of cognitive ability. Sensitivity of group classification was 76.2% and specificity was 82.8%, with 80% correct classification overall. ANAM's ability to predict neuropsychological functioning remained even after controlling for subjective reports of depressed mood and current sleepiness. Further, the ANAM mood scale was significantly correlated with the BDI-II (r = 0.67, P < 0.001), indicating its potential future use as a screening tool for emotional distress. CONCLUSION: ANAM shows promise as a time- and cost-efficient tool for screening and monitoring cognitive and emotional functioning in SLE, and can indicate when a more thorough neuropsychological investigation is warranted.     

Sarcopenia and cognitive impairment in liver cirrhosis: A viewpoint on the clinical impact of minimal hepatic encephalopathy

Minimal hepatic encephalopathy(MHE) represents the mildest type of hepatic encephalopathy(HE). MHE is considered as a preclinical stage of HE and is part of a wide spectrum of typical neurocognitive alterations characteristic of patients with liver cirrhosis, particularly involving the areas of attention, alertness,response inhibition, and executive functions. MHE can be detected by testing the patients' psychometric performance, attention, working memory, psychomotor speed, and visuospatial ability, as well as by means of electrophysiological and other functional brain measures. MHE is very frequent, affecting from 20% up to80% of patients tested, depending of the diagnostic tools used. Although subclinical, MHE is considered to be clinically relevant. In fact, MHE has been related to the patients' falls, fitness to drive, and working ability. As a consequence, MHE affects the patients and caregivers lives by altering their quality of life and even their socioeconomic status. Recently sarcopenia, a very common condition in patients with advanced liver disease, has been shown to be strictly related to both minimal and overt HE. Aim of this review is to summarize the most recently published evidences about the emerging relationship between sarcopenia and cognitive impairment in cirrhotic patients and provide suggestions for future research.     

Impairment of Response Inhibition Precedes Motor Alteration in the Early Stage of Liver Cirrhosis: A Behavioral and Electrophysiological Study

Abnormality in movement initiation may partially explain psychomotor delay of cirrhotic patients, even in the absence of overt hepatic encephalopathy (HE). Therefore, the aim of this study was to determine the mechanisms of psychomotor delay observed in patients with cirrhosis in the absence of overt HE. Fourteen patients with nonalcoholic cirrhosis and 12 healthy matched control subjects underwent the lateralized readiness potential (LRP) measurement elicited by a visuospatial compatibility task (Simon task). Stimulus-triggered LRPonset reflects the time in which response is selected, while response-triggered LRP onset reflects motor execution. Cirrhotic patients showed delayed reaction times (RTs) compared to controls, particularly those with trial-making test A (TMT-A) or electroencephalogram (EEG) alterations. Stimulus-triggered LRP onset was found to be delayedin cirrhotic patients compared to controls, with a significant Group-versus-Condition interaction, showing a reduced cognitive ability to cope with interfering codes, even in patients without minimal HE (MHE). Response-triggered LRP was found to be delayed only in the patients with TMT-A or EEG alterations. In conclusion, cirrhotic patients without overt HE display a psychomotor slowing, depending firstlyon response inhibition and only later accompanied by impaired motor execution.     

Attention Deficits in Minimal Hepatic Encephalopathy

Minimal hepatic encephalopathy (HE) is characterized by a decrease of psychomotor speed, and deficits in visual perception, visuo-spatial orientation, and visuo-constructive abilities. Attention deficits have also been proposed to be part of the syndrome. Several attempts were made in the past to elaborate suitable psychometric means for the assessment of minimal HE. However, there is still no gold standard for the diagnosis of minimal HE. We recently evaluated the so called PSE-Test for the assessment of minimal HE, a test battery which does not include a test predominantly aimed at the assessment of attention. We therefore presented a battery of attention tests in addition to the PSE-Test to a group of cirrhotics without clinical signs of HE compared to a healthy control group matched for age and education to determine whether the addition of special attention tests would increase the diagnostic sensitivity of the PSE-Test. It was shown that the patients with a pathological PSE-Test result differed significantly from controls in all attention tests applied, while the patients with normal PSE-Test results achieved attention test results similar to that of the controls. Thus, the PSE-Test results represent attention deficits as well as deficits in motor skills, visuo-spatial orientation, and visual construction.     

Cognitive function in patients with liver cirrhosis without overt hepatic encephalopathy: Assessment using an automated neuropsychological test battery

Background and study aimsA wide range of neuropsychiatric disorders occur in patients with liver cirrhosis without overt hepatic encephalopathy. Cognitive dysfunctions do occur and these tend to impair patients’ vocational and social life as well as activities of daily living. The aim of this study is to evaluate cognitive functions in patients with liver cirrhosis without overt HE in Nigeria.Patients and methodsThirty-four patients with liver cirrhosis and 41 normal subjects as control were studied. Medical history and general physical/neurological examinations were carried out on all the subjects. Blood samples were obtained for viral serological markers and liver functions tests. The ‘Fepsy’ automated neuropsychological test battery was performed for the assessment of auditory reaction time (psychomotor speed). Recognition memory test (memory), binary choice reaction task (psychomotor speed/attention) and vigilance task were also administered. The data were analysed with the aid of Statistical Package for Social Sciences (SPSS) version 15.0 software.ResultsThe mean age of patients with liver cirrhosis was 45.00 ± 13.83 years, while that of control subjects was 41.88 ± 139.49 years. The visual/auditory reaction time, binary choice reaction time and computerised visual reaction time were prolonged in patients with liver cirrhosis when compared with control subjects. However, there were differences in the recognition memory test and vigilance performances between the two groups. The patients with liver cirrhosis who had hepatitis C virus infection had poor psychomotor speed when compared with patients who were hepatitis C virus negative, but there was no statistical significant correlation between other aspects of liver function tests and cognitive functions in patients with cirrhosis.ConclusionPatients with liver cirrhosis had similar cognitive functions on measures of memory and vigilance when compared with normal control subjects. However, there were significant differences in other aspects of cognitive functions between the two groups.     

Minimal hepatic encephalopathy

Minimal hepatic encephalopathy (MHE) is the mildest form of spectrum of hepatic encephalopathy (HE). Patients with MHE have no recognizable clinical symptoms of HE but have mild cognitive and psychomotor deficits. The prevalence of MHE is high in patients with cirrhosis of liver and varies between 30% and 84%; it is higher in patients with poor liver function. The diagnostic criteria for MHE have not been standardized but rest on careful patient history and physical examination, normal mental status examination, demonstration of abnormalities in cognition and/or neurophysiological function, and exclusion of concomitant neurological disorders. MHE is associated with impaired health-related quality of life, predicts the development of overt HE and is associated with poor survival. Hence, screening all patients with cirrhosis for MHE using psychometric tests, and treatment of those patients diagnosed to have MHE has been recommended. Ammonia plays a key role in the pathogenesis of MHE, which is thought to be similar to that of overt HE. Thus, ammonia-lowering agents such as lactulose and probiotics have been tried. These agents have been shown to improve cognitive and psychometric deficits, and have good safety profile. Future studies will better define the role of other drugs, such as rifaximin, acetyl L-carnitine and L-ornithine L-aspartate.     

Characteristics of neuropsychological functions in inpatients with poorly‐controlled type 2 diabetes mellitus

Aims/Introduction: It has been suggested that type 2 diabetes is associated with cognitive impairment. We investigated the neuropsychological profile of inpatients with poorly controlled type 2 diabetes and assessed the effects of clinical factors on neuropsychological functions. Materials and Methods: Forty‐two patients with type 2 diabetes and 32 non diabetic control subjects were matched for age, sex ratio, and level of education. Attention & working memory, processing speed, verbal memory, visuospatial memory, visuoconstruction, and executive function were tested. Information about physical function, alcohol use, hypertension, dyslipidemia, and myocardial infarction was retrieved from personal interviews and medical records. Results: Diabetic patients demonstrated mild cognitive deterioration in attention & working memory, processing speed, verbal memory, and executive function. In particular, neuropsychological decline became prominent when tasks related with speed and verbal stimuli became unstructured and complex. Age was significantly associated with the majority of neuropsychological tests, whereas tasks dealing with working memory and executive function were associated with age only in the diabetic group. Duration of diabetes was associated with Backward Digit Span. Conclusions: Accelerated aging had a major influence on cognitive decline in the diabetic group, whereas diminished performance in working memory and executive function might have been more related to diabetes‐related cognitive impairment. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2011.00170.x, 2011)     

Neuropsychological abnormalities in cirrhosis include learning impairment

BACKGROUND/AIMS: Minimal hepatic encephalopathy is a neurocognitive disorder secondary to liver failure that is characterized by a pattern of subcortical impairment. The most conspicuous neuropsychological abnormalities are on attention and psychomotor tests; memory has been inconsistently implicated. We designed a study to assess the presence of memory abnormalities in cirrhotic patients and the effects of liver transplantation. METHODS: Ninety-seven cirrhotics without overt hepatic encephalopathy underwent neuropsychological assessment, including the Auditory Verbal Learning Memory Test. The results were compared to those of healthy controls (n=75) and the assessment was repeated at one year of follow-up (n=33) or after liver transplantation (n=23). RESULTS: Cirrhotic patients exhibited multiple neuropsychological abnormalities, including several disturbances of the Auditory Verbal Learning memory test: learning, long-term memory and recognition. Abnormalities of long-term memory and recognition were corrected after adjusting for learning impairment. Memory abnormalities correlated to attention impairment and to parameters of liver function. Neuropsychological indexes following liver transplantation did not differ from controls. Repeated testing did not have a major effect on neuropsychological tests in healthy subjects and in non-transplanted cirrhotics. CONCLUSIONS: Learning impairment is present in cirrhotic patients with neuropsychological abnormalities. This abnormality is consistent with attention deficit secondary to minimal hepatic encephalopathy.     

Outcome of patients with HIV-1-related cognitive impairment on highly active antiretroviral therapy

OBJECTIVE: To examine the impact of highly active antiretroviral therapy (HAART) on the outcome of HIV-1-related cognitive impairments using a neuropsychological (NP) battery to assess separately the psychomotor, executive function and memory fields. DESIGN: A longitudinal study of HIV-1-infected patients based on serial NP tests in a Paris University Hospital. METHODS: A group of 91 HIV-1-infected patients, of whom 47 were already taking HAART at their first NP examination, were initially categorized as cognitively impaired (n = 53) or non-impaired (n = 38) and underwent one to six serial NP batteries (mean follow-up 12.3+/-8.3 months). Generalized estimating equations (GEE) were used to evaluate performance in a given NP test according to the number of days on HAART. RESULTS: Despite a 25% mortality rate among patients who had cognitive impairment at their first NP examination, GEE showed a positive relationship between the duration of HAART and cognitive performance. Performance in psychomotor tests (e.g. Purdue Pegboard dominant hand) improved continuously during the study period, while memory test performance (e.g. Grober and Buschke free recall) tended to reach a plateau. CONCLUSIONS: HAART improves subcortical cognitive functions during the first year of treatment. Distinct neuropathological mechanisms appear to underlie psychomotor and memory dysfunctions in AIDS.     

Cognitive functioning and well-being in euthyroid patients on thyroxine replacement therapy for primary hypothyroidism

OBJECTIVE: Hypothyroidism is associated with neurocognitive impairment. Sparse data suggest that treatment of hypothyroidism, resulting in a return to euthyroidism, may be associated with only partial recovery of overall neurocognitive functioning. The aim of this study was to assess neurocognitive functioning and well-being in euthyroid patients with primary hypothyroidism on adequate thyroxine (T4) treatment. We also investigated whether serum TSH and thyroid antibodies are determinants of neurocognitive functioning and well-being. DESIGN: We assessed neurocognitive functioning and well-being in 141 patients with primary hypothyroidism. METHODS: Neurocognitive test results and scores on questionnaires measuring well-being of 141 patients were compared with the reference values for these tests as published and used in Dutch clinical neuropsychological practice. Assessment of neurocognitive functioning included tests for cognitive or psychomotor speed, attention, working memory as well as learning and memory. Well-being was measured with the Symptom Check List-90 total score and the Rand 36-item Health Survey subscales for 'mental health' and 'vitality'. RESULTS: Patients showed poor performance on various domains of neurocognitive functioning compared with mean standard reference values, especially on a complex attention task and on verbal memory tests. Levels of well-being were significantly lower for patients compared with those of the general population. Neither serum TSH nor thyroid antibodies were determinants of neurocognitive functioning and well-being. CONCLUSION: The results of this study suggest that neurocognitive functioning as well as psychological well-being may not be completely restored in patients with hypothyroidism, despite T4 treatment.     

Memory function in early hepatic encephalopathy

BACKGROUND: Early hepatic encephalopathy (HE) is characterized by deficits in motor performance, visual perception, visuo-constructive abilities and attention. Whether defective memory is a feature of early HE is controversial. AIMS: To analyze memory function in patients with early HE. METHODS: Memory tests were applied to cirrhotic patients with grade 0 HE, minimal HE and grade I HE (n=45) and controls (n=52). The battery included short and long term memory tests requiring free recall or recognition. Minimal HE was diagnosed by assessing the psychometric hepatic encephalopathy score using the PSE-Syndrom-Test and by carrying out a neurological examination. Group differences of the test results were analyzed using analysis of covariance. RESULTS: HE 0 patients achieved test results similar to the controls in all but two tests. Patients with early HE (minimal and grade I HE) scored lower than the controls in all tests applied. A detailed analysis of test performance showed that the patients' deficits were in attention and visual perception, rather than memory. CONCLUSIONS: Patients with early HE score lower than controls in memory tasks predominantly because of deficits in attention and visual perception.     

Lateralized cognitive dysfunction in patients with systemic lupus erythematosus

This study was designed to determine whether there is a lateralized pattern of cognitive dysfunction in patients with systemic lupus erythematosus (SLE). Fifty right-handed patients with SLE, but no history of cerebrovascular disease participated in the study. Thirty right-handed healthy subjects matched for age and education served as controls. SLE and healthy control subjects underwent a three-hour neuropsychological evaluation designed to measure attention, memory, visual spatial skills, verbal skills reasoning, psychomotor speed, and motor function. A cognitive disability index was created to identify cognitive impairment. Percentile tables based on the performance of all subjects were constructed for 20 component scores. Any subject with five or more component scores below the 25th percentile was designated impaired. Using this criterion, cognitive impairment was identified in 50% of patients with SLE and 20% of healthy controls. Patients with SLE were impaired on measures of psychomotor speed/fluency, verbal speed/fluency and verbal memory. This pattern of performance on neuropsycholgical testing was consistent with left hemisphere brain dysfunction. The observed deficits were not clearly attributable to vascular lesions and suggest immune-mediated effects on specific brain regions in a subgroup of patients with SLE.     

Neurocognitive performance and quality of life in patients with HIV infection

We examined the relationship of HIV-related cognitive impairment and health-related quality of life (QoL). Subjects were administered measures of cognitive function (a battery of 17 neuropsychological tests) and of QoL (the MOS-HIV questionnaire). Study measures also included comprehensive clinical and neurological evaluation, laboratory testing, and brain imaging studies in patients with impaired neuropsychological evaluation. One-hundred and eleven subjects were examined. Cognitively impaired patients (33.3%) reported poorer QoL scores in all domains (p < 0.05): physical health summary score (PHS) (44.6 vs. 49.9), mental health summary score (MHS) (37.7 vs. 44.4), pain (67.6 vs. 79.4), physical functioning (75.9 vs. 87.7), role functioning (32.4 vs. 41.5), social functioning (70.3 vs. 83.5), mental health (48.2 vs. 61.0), energy (53.1 vs. 63.0), health distress (60.8 vs. 75.5), cognitive functioning (CF) (60.5 vs. 71.8), general health perceptions (29.2 vs. 43.4), and QoL (36.5 vs. 47.0). The number of altered neuropsychological tests correlated significantly with MHS (p < 0.001), PHS (p < 0.03), CF (p < 0.02), and QoL (p < 0.02) scores. A correlation between seven of seven neuropsychological measures exploring speed of mental processing, three of four exploring mental flexibility, four of six exploring memory, and two of two exploring fine motor functioning and MHS, PHS, CF, or QoL scores was also found. Poor performance on the Digit Symbol test was most strongly associated with poor MHS (OR 1.04, 95% CI 1.01-1.08, p < 0.009) and PHS (OR 1.04, 95% CI 1.01-1.08, p < 0.01) scores, controlling for CD4 count, previous AIDS diagnosis, receiving HAART, and drug abuse. Cognitive impairment is associated with poor QoL. People with more severe cognitive impairment have the highest probability of having a poor QoL. Cognitive impairment in any cognitive domain explored in our battery is also associated with poor QoL. Poor performance on the Digit Symbol Test is the strongest predictor of poor QoL.     

Memory Dysfunction,Psychomotor Slowing,and Decreased Executive Function Predict Mortality in Patients With Heart Failure and Low Ejection Fraction

BackgroundThe purpose of this study was to evaluate whether dysfunction of specific cognitive abilities is a predictor of impending mortality in adults with systolic heart failure (HF).MethodsA total of 166 stable outpatients with HF completed cognitive function evaluation in language, working memory, memory, visuospatial ability, psychomotor speed, and executive function using a neuropsychological test battery. Demographic and clinical variables, comorbidity, depressive symptoms, and health-related quality of life were also measured. Patients were followed for 12 months to determine all-cause mortality.ResultsThere were 145 survivors and 21 deaths. In logistic regression analyses, significant predictors of mortality were lower left ventricular ejection fraction (LVEF) and poorer scores on measures of global congnitive function Mini-Mental State Examination [MMSE], working memory, memory, psychomotor speed, and executive function. Memory loss was the most predictive cognitive function variable (overall χ² = 17.97, df = 2, P < .001; Nagelkerke R² = 0.20). Gender was a significant covariate in 2 models, with men more likely to die. Age, comorbidity, depressive symptoms, and health-related quality of life were not significant predictors. In further analyses, significant predictors of mortality were lower systolic blood pressure and poorer global cognitive function, working memory, memory, psychomotor speed, and executive function, with memory being the most predictive.ConclusionsAs hypothesized, lower LVEF and memory dysfunction predicted mortality. Poorer global cognitive score as determined by the MMSE, working memory, psychomotor speed, and executive function were also significant predictors. LVEF or systolic blood pressure had similar predictive values. Interventions are urgently needed to prevent and manage memory loss in HF.     

Cognitive impairment in alcoholic and nonalcoholic cirrhotic patients

Cognitive impairment is common in patients with advanced liver disease. It has been suggested that patients with alcoholic liver disease (ALD) have more impaired cognition than nonalcoholics. The objective of this study was to characterize any differences in cognitive functions between alcoholic cirrhotic patients and non-alcoholic cirrhotic patients of similar age, education, and severity of liver disease. We assessed cognitive functions in 117 patients with alcoholic cirrhosis and 163 patients with nonalcoholic cirrhosis using a brief battery of neuropsychological tests. In addition, all patients had standard psychiatric examinations to assess the effect of the disease severity, alcoholism, anxiety, and depression on the test scores. The study showed a higher proportion of patients with cognitive impairment in the alcoholic group. Alcoholics performed poorly in tests of memory and motor speed compared with nonalcoholics, despite similar premorbid IQ and education. Because patients with alcoholic cirrhosis had more severe liver disease (Child-Pugh score 8.5 +/- 2.2 vs. 7.6 +/- 2.2, P =.03) than nonalcoholics, the results were reanalyzed after adjusting for the linear effects of Child-Pugh score on cognitive test scores. We also used two-way analysis of variance to examine the interaction between Child class and alcoholism. Finally, the test scores were compared within each Child class. These analyses revealed no primary or interaction effect of alcoholism and confirmed that the differences in the test scores observed in alcoholics reflect the greater severity of their liver disease. The severity of cognitive impairment is similar in both alcoholic and non-alcoholic cirrhotic patients when adjusted for the severity of liver disease.     

Impaired executive function is associated with delirium after coronary artery bypass graft surgery

OBJECTIVES: To determine the extent to which preoperative performance on tests of executive function and memory was associated with delirium after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective observational cohort study. SETTING: Two academic medical centers and one Department of Veterans Affairs medical center in Massachusetts. PARTICIPANTS: Eighty subjects without preoperative delirium undergoing CABG or CABG-valve surgery completed baseline neuropsychological assessments with validated measures of memory and executive function. MEASUREMENTS: Beginning on postoperative Day 2, a battery to diagnose delirium was administered daily. Confirmatory factor analysis (CFA) was used to define two cognitive domain composites (memory and executive function). The loading pattern of neuropsychological measures onto the latent cognitive domains was determined a priori. Poisson regression was used to model the association between neuropsychological performance and cognitive domain composite scores and risk of postoperative delirium. The association was expressed as the difference between impaired (0.5 standard deviations (SDs) below mean) and nonimpaired (0.5 SDs above mean) performers. RESULTS: Forty subjects (50%) developed delirium. Measures of memory function were not significantly related to delirium. Of the executive function measures, verbal fluency, category fluency, Hopkins Verbal Learning Test learning, and backward recounting of days and months were significantly related to delirium. Preoperative mental status was a strong predictor of postoperative delirium. After controlling for age, sex, education, medical comorbidity, mental status, and the other cognitive domain, CFA cognitive domain composites suggest that risk for delirium is specific for executive functioning impairment (relative risk (RR) = 2.77, 95% confidence interval (CI) = 1.12-6.87) but not for memory impairment (RR = 0.49, 95% CI = 0.19-1.25). CONCLUSION: Worse preoperative performance in executive function was independently associated with greater risk of developing delirium after CABG.     

Cognitive impairment and MRI correlates in the elderly patients with type 2 diabetes mellitus

BACKGROUND: exact mechanisms underlying cognitive dysfunction in diabetes mellitus (DM) remain unclear. Imaging studies of the brain could help to identify possible structural brain lesions underlying cognitive dysfunction. OBJECTIVE: to describe a detailed neuropsychological profile in patients functioning independently with type 2 DM. Secondly, correlations were studied between cognitive impairment and brain lesions on magnetic resonance imaging (MRI), i.e. periventricular hyperintensities (PVH), deep white matter lesions (DWML), medial temporal lobe atrophy (MTA), cerebral atrophy and lacunar infarcts. In addition, the influence of relevant disease variables of DM was studied. METHODS: 92 patients with type 2 DM (mean age 73.2 +/- 5.7 years, mean duration 13.8 +/- 10.8 years) and 44 control subjects (mean age 72.9 +/- 5.3 years) were included and underwent an extensive neuropsychological test battery and an MRI of the brain. RESULTS: neuropsychological scores were worse for each cognitive domain except for memory functions after adjustment for hypertension in a group of elderly patients with type 2 DM compared to healthy control subjects. Only PVH were independently associated with motor speed, whereas all other MRI measures were not independently associated with cognitive impairment. Interactions between the different MRI measures were not present. Glycosylated haemoglobin (HbA(1c)) and duration of DM were significantly associated with cognitive dysfunction. CONCLUSIONS: the data of this cross-sectional study show that type 2 DM is associated with diminished cognitive function in different cognitive domains, while memory is less affected after adjustment for hypertension. The association of cognitive impairment with MRI measures is equivocal, whereas HbA(1c) and duration of DM were significantly associated with cognitive dysfunction.