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Almitrine-raubasine and cognitive impairment in the elderly: results of a 6-month controlled multicenter study.

Two-hundred four patients between 70 and 85 years of age were included in a double-blind randomized controlled multicenter study (almitrine-raubasine/placebo). Inclusion criteria were a complaint of cognitive disorders and an objective cognitive impairment evaluated by Folstein et al. "Mini-Mental State" (MMS) and by Sandoz Clinical Assessment for Geriatrics (SCAG). Patients were treated for 6 months and evaluations were performed at the beginning of the trial (T0), then 3 (T3) and 6 (T6) months later. Evaluations included a visual analogic self-rating scale and the following psychometric tests: Trail Making A (TMA), Shopping List Task, Word Fluency, Crossing Out Letters, Logical Memory, Digit Span, and Visual Retention. Anxiety and Depression Scales were also used to assess the effects of almitrine-raubasine on affective status. Statistical analysis involving the whole sample did not show any significant difference between the almitrine-raubasine and placebo groups concerning changes in assessment criteria from T0 to T6. However, these results may have been due to the wide heterogeneity of baseline performances in psychometric tests. To prevent this possible bias, further statistical analysis was performed for each psychometric test after patients had been divided into three classes according to baseline score levels. Considering scores on TMA and Digit Span for patients with scores in the intermediate class on TMA, almitrine-raubasine induced a significantly higher improvement in performance from T0 to T6 than that induced by placebo. On the other hand, no side effects were noted with almitrine-raubasine when compared with placebo. These data suggest that almitrine-raubasine enhances concentrated attention in patients with mild to moderate impairment of this function.

Aged↗

Premorbid cognitive testing predicts the onset of dementia and Alzheimer's disease better than and independently of APOE genotype.

OBJECTIVE: To determine whether a cognitive test package can predict the onset of dementia up to 11 years later, and the extent to which this prediction is independent of that provided by APOE genotype. METHODS: Prospective cohort study based on 54 general practices in the UK; 657 survivors of the 1088 participants in the MRC treatment trial of hypertension in older adults were followed for up to 11 years; 370 participants (57% of survivors) were traced, screened for dementia, and genotyped for APOE in 1994. Baseline assessments included trail making test A, paired associated learning test, Raven's progressive matrices, and national adult reading test. At follow up, both mini-mental state examination and CAMCOG were used. Outcome measures were DSM-IIIR dementia and NINCDS-ADRDA possible and probable Alzheimer's disease. RESULTS: All the cognitive tests completed in 1983 predicted onset of dementia and Alzheimer's disease up to 11 years later, as did APOE genotype. Cognitive test performance was not associated with APOE genotype. Addition of cognitive tests increased the area under the ROC curve for the prediction of Alzheimer's disease provided by age, family history, and APOE genotype (0.81 v 0.69, p = 0.048); addition of APOE genotype did not increase the area under the ROC curve for the prediction provided by age, family history, and cognitive tests (0.81 v 0.77, p = 0.28). CONCLUSIONS: Simple tests of cognitive ability provide useful predictive information up to a decade before the onset of dementia. The predictive information provided is independent of, but not enhanced by, the addition of APOE genotype.

Aged↗

Lateralized brain damage and performance on trail making A and B, Digit Span Forward and Backward, and TPT Memory and Location.

The present retrospective study was undertaken to determine whether Trail Making Test A and B, Digit Span Forward and Backward, and TPT Memory and Location scores are differentially sensitive to right or left hemisphere brain damage. Groups of patients with right, left, and generalized cerebral lesions and matched normal controls were compared. Results showed a relative failure for any individual measure, difference, or ratio score to reliably distinguish between right and left hemisphere lesions. Patients with diffuse lesions performed significantly worse than non-neurologic medical controls and right and left lesion groups on Trails A and TPT Memory and Location. Results are discussed in terms of specific methodological variables including chronicity of lesion, the nature of the task demands, and priming effects.

Journal Article↗

Single voxel proton magnetic resonance spectroscopy in women with and without intimate partner violence-related posttraumatic stress disorder.

Preliminary in vivo proton magnetic spectroscopic ((1)H-MRS) studies of N-acetylaspartate (a putative marker of neuronal viability and function) in combat veterans and maltreated children with posttraumatic stress disorder (PTSD) suggest altered neuronal integrity in anterior cingulate and medial temporal lobe structures. In this study, (1)H-MRS was used to measure N-acetylaspartate (NAA), choline (Cho) and myo-inositol (mI) relative to creatine (Cr) in the anterior cingulate of 16 women with histories of intimate partner violence (7 with a DSM-IV diagnosis of PTSD, 9 without PTSD) and 11 healthy, non-abused comparison subjects. The relationship between anterior cingulate chemistry and performance on the Stroop Color-Word task and Part B of the Trail Making Test was also examined. There were no significant differences in anterior cingulate or occipital gray matter metabolite ratios of NAA/Cr and Cho/Cr between intimate partner violence and healthy comparison subjects. Intimate partner violence subjects with PTSD had significantly higher anterior cingulate Cho/Cr than intimate partner violence subjects without PTSD. There was evidence that the subjects with PTSD suffered more severe intimate partner violence as measured by the Conflict Tactics Scale-Revised. Metabolite ratios were not significantly correlated with performance on the Stroop or Trails B. Our findings, in agreement with earlier studies, showed significant alterations in anterior cingulate chemistry in women with PTSD. In contrast to other studies, we found an increase in Cho/Cr rather than a decrease in NAA/Cr, indicating alterations in glia, instead of neuronal dropout.

Adult↗

Smooth pursuit eye tracking, neuropsychological test performance, and computed tomography in schizophrenia.

Smooth pursuit eye movements (SPEM) were measured in 18 patients who met Research Diagnostic Criteria for schizophrenia. Some degree of SPEM impairment was present in most patients. Deviant eye tracking was not related to ratings of severity of illness, but was related to recurrent episodes of hospitalization, antipsychotic medication, and lower ratings in anxiety and delusions. Worse SPEM tended to be associated with larger lateral ventricles as assessed on computed tomography. Three patients with reversed occipital asymmetry had more deviant eye tracking than the remaining patients. Eye movement impairment was related to worse performance in Finger Tapping and in the Trail-Making Test, and to fewer perceived alternations of a Necker cube, suggesting that frontoparietal disturbances are related to poor pursuit eye tracking in schizophrenia.

Adult↗

Portosystemic encephalopathy after transjugular intrahepatic portosystemic shunt: results of a prospective controlled study.

Portosystemic encephalopathy is a common complication of surgical portacaval shunts. Recently, transjugular intrahepatic portosystemic shunts have been proposed to produce portal decompression in a manner analogous to a side-to-side portacaval shunt, but with less morbidity. The incidence and clinical spectrum of portosystemic encephalopathy after transjugular intrahepatic portosystemic shunts, however, had not been previously prospectively defined. We therefore prospectively studied portosystemic encephalopathy in 30 patients undergoing transjugular intrahepatic portosystemic shunts and compared these findings with 25 patients concurrently undergoing sclerotherapy (controls). At entry, both study groups were comparable. Portosystemic encephalopathy was assessed by examining and grading mental status, asterixis, plasma ammonia and trail making tests. The portosystemic encephalopathy index was calculated from these parameters. Nine of 30 patients with transjugular intrahepatic portosystemic shunts experienced 24 episodes of acute portosystemic encephalopathy during follow-up; 6 of 9 had a history of portosystemic encephalopathy before transjugular intrahepatic portosystemic shunts and 5 of these 6 patients had Child C cirrhosis. Mental status and asterixis scores as well as portosystemic encephalopathy index worsened significantly in the first month after transjugular intrahepatic portosystemic shunts but showed some improvement thereafter. Increasing age, a medical history of portosystemic encephalopathy and trail scores for part B greater than 100 sec were predictors of portosystemic encephalopathy after transjugular intrahepatic portosystemic shunts. Portosystemic encephalopathy could be managed medically in all but one patient who underwent liver transplant. In contrast, there were no significant changes in mental status, asterixis, ammonia or trail scores over time in sclerotherapy controls. Only six episodes of encephalopathy occurred in endoscopic sclerotherapy patients over the duration of the study. Thus, overall risk of portosystemic encephalopathy after transjugular intrahepatic portosystemic shunts was higher than during sclerotherapy.

Esophageal and Gastric Varices↗

Relationships between measures of auditory verbal learning and executive functioning.

Relationships between performance on the California Verbal Learning Test (CVLT) and executive abilities were examined. In a sample of 115 neurological cases principal components factor analysis produced five theoretically and clinically meaningful CVLT factors. The five CVLT factors reflected general verbal learning (CVLT1), response discrimination (CVLT2), a proactive interference effect or "working memory" (CVLT3), serial learning strategy (CVLT4), and a retroactive interference effect (CVLT5). Canonical correlation between executive function measures and the five CVLT factor scores yielded one significant canonical variable accounting for 29 percent of the variance in the data. Two CVLT factors (CVLT1 and CVLT3), the Trail Making Test Part B, and Digit Span were significantly correlated with the canonical variate. Higher levels of memory performance were associated with better attention and mental tracking. Based on the present findings, attentional aspects of executive abilities appear to play a role in learning and working memory. Other aspects of executive abilities (abstraction, problem-solving, planning) appear to have minimal relationships with memory processes.

Adolescent↗

Association of executive function and performance of dual-task physical tests among older adults: analyses from the InChianti study.

BACKGROUND: previous studies have reported an association between cognitive function and physical performance, particularly among older adults. OBJECTIVE: to examine the association between executive function and performance difference on complex versus usual walking tasks in a sample of non-demented older adults. DESIGN: population-based epidemiological study of older people residing in the Chianti area (Tuscany, Italy). PARTICIPANTS: 737 community-dwelling individuals aged 65 years and older. METHODS: gait speed (m/s) was measured during the performance of complex walking tasks (walking/talking, walking/picking-up an object, walking/carrying a large package, walking over obstacles, walking with a weighted vest) and reference walking tasks (7 m usual pace, 7 m fast pace and 60 m fast pace). Executive function was assessed using the Trail Making Test (TMT). Other measures included Mini-Mental State Examination (MMSE), sociodemographic characteristics and selected physiological impairments. RESULTS: gait speed for the selected reference and complex walk tasks was consistently lower among participants with poor executive function. Per cent decline in gait speed compared with the reference task differed by executive function for certain tasks (e.g. walking/obstacles: 30 versus 24% decline in low versus high executive function respectively, P = 0.0006) but not for others. CONCLUSIONS: poor executive function is associated with measures of gait, including specific challenges. Overall, the results showed that the cost associated with the addition of a challenge to the basic walking task differs by executive function and the nature of the task. Further research is needed to determine whether improvement in executive function abilities translates to better performance on selected complex walking tasks.

Activities of Daily Living↗

Neuropsychological function in nondemented carriers of presenilin-1 mutations.

BACKGROUND: Prospective and case-control studies have demonstrated that memory loss and executive dysfunction occur early in Alzheimer disease (AD). OBJECTIVE: To investigate these observations by the study of persons at risk for autosomal dominant forms of AD. METHODS: Neuropsychological and genetic tests were performed on 51 nondemented at-risk members of 10 Mexican families with two distinct presenilin-1 (PS1) mutations. Test scores were compared between PS1 mutation carriers (MCs; n = 30) and noncarriers (NCs; n = 21) by analyses of variance, co-varying for family and specific mutation. Regression analyses were performed, taking into account age relative to the median age at dementia diagnosis in the family (adjusted age), gender, Beck Depression Inventory (BDI) scores, education, and number of APOE epsilon4 alleles. Subjects were divided into age tertiles and scores compared within these groups. Composite scores for Verbal Memory, Executive Function/Working Memory, Language, and Visuospatial Function were created, and these scores compared between MCs and NCs. RESULTS: MCs performed worse than NCs on the Mini-Mental State Examination, Trails Making Tests A and B, Delayed Recall of a 10-Word List, and Wechsler Adult Intelligence Scale WAIS Block Design. In multiple linear regression analyses, BDI score, gender, and number of APOE epsilon4 alleles did not consistently affect test scores. The differences seen between MCs and NCs were due to differences in the oldest tertile. MCs had lower Visuospatial and Executive Function/Working Memory but not Verbal Memory or Language composite scores. CONCLUSIONS: This study is consistent with findings in sporadic Alzheimer disease of early problems with memory, visuospatial function, and particularly with executive function in PS1 mutation carriers. Depression, gender, and presence of an APOE epsilon4 allele did not demonstrate large influences on neuropsychological performance.

Adolescent↗

Cognitive differences in dementia patients with autopsy-verified AD, Lewy body pathology, or both.

OBJECTIVE: To examine the neuropsychological profile of dementia patients from a community-based autopsy sample of dementia, comparing Alzheimer disease (AD), Lewy body pathology (LBP) alone, and LBP with coexistent AD (AD/LBP). METHODS: The authors reviewed 135 subjects from a community-based study of dementia for whom autopsy and brain tissue was available. Diagnostic groups were determined according to standard neuropathologic methods and criteria, and the presence of LBs was determined using alpha-synuclein immunostaining. Neuropathologically defined diagnostic groups of AD, AD/LBP, and LBP were examined for differences on neuropsychological test performance at the time of initial study enrollment. RESULTS: There were 48 patients with AD alone, 65 with LB and AD pathology (AD/LBP), and 22 with LBP alone (LBP alone). There were no significant differences between groups demographically or on performance of enrollment Mini-Mental State Examination (MMSE) or Dementia Rating Scale (DRS). AD patients performed worse than the LBP patients on memory measures (Fuld Object Memory Evaluation Delayed Recall, Wechsler Memory Scale Logical Memory Immediate and Delayed Recall; p < 0.05) and a naming task (Consortium to Establish a Registry for Alzheimer's Disease Naming; p < 0.05). LBP patients were more impaired than AD patients on executive function (Trail Making Test Part B; p < 0.05) and attention tasks (Wechsler Adult Intelligence Scale-Revised Digit Span; p < 0.05). Decline in MMSE and DRS scores over time were greatest in the patients with AD/LBP. CONCLUSIONS: In a community-based sample of older, medically complicated patients with dementia, there are neuropsychological differences between dementia subtypes at the time of diagnosis. In particular, patients with Alzheimer disease (AD) alone and AD/Lewy body pathology (LBP) had more severe memory impairment than patients with LBP. LBP alone was associated with more severe executive dysfunction. Patients with AD/LBP had the most rapid rate of cognitive decline.

Age of Onset↗

[Duxil and cognitive deficiency in the elderly. Results of a 6-month controlled multicenter study].

Two hundred and four patients, 70-85 years old, were included in a double-blind (Duxil/placebo), controlled, multicentric study. The inclusion criteria were a subjective complaint of a cognitive deficiency and a cognitive deficit objectively determined using the Folstein mini-mental state test and the Sandoz geriatric clinical evaluation score. The patients, treated for 6 months, were examined at the onset of the study (T0), then 3 (T3) and 6 months (T6) later. The assessment criteria included: a visual self-evaluation test measuring cognitive function and the following psychometric tests: trail making A (TMA), memorization of a shopping list, verbal fluidity, letter identification, repetition of a story, immediate recall of numbers and immediate visual memory. Anxiety and depression evaluations were also used to assess the effects of Duxil on the affective state. Statistical analysis of the observations made on the entire population did not reveal a significant difference between the treated group and the control placebo group, in terms of assessment criteria, between T0 and T6. However, this lack of a difference could be explained, in part, by the very wide variation in the initial psychometric performance scores of the subjects. In an attempt to control this possible bias, another statistical analysis was made for each psychometric test, after the patients had been divided into 3 classes based on their initial performance scores. The results of this second analysis showed that Duxil was able to improve memory performances in TMA and number retention better than the placebo. However, this effect was limited to the group of patients whose initial scores were in the intermediate class for TMA. These findings suggest that Duxil improves the concentrating ability of patients with light to moderate deficits in this function.

Aged↗

Thalamus and language: interface with attention, memory and executive functions.

Subcortical structures are in a strategic functional position within the cognitive networks. Their lesion can interfere with a great number of functions. We studied six patients with thalamic vascular lesions (three left sided, two right sided and one bilateral), to characterize their repercussion in the communicative abilities and the interface between language alterations and other cognitive abilities, as attention, memory and frontal executive. All patients were evaluated through a functional interview (discourse analysis), and the following batteries: Boston Diagnostic Aphasia Examination, Boston Naming Test, Token Test, Benton Visual Retention Test, Trail Making, Wisconsin Card Sorting and frontal scripts. All patients performed MRI and five underwent SPECT. Results show that these patients present impairment in several cognitive domains, especially attention and executive functions (working memory, planning and self-monitoring); those with right lesions have an additional visuospatial impairment. Such alterations interfere with language abilities, and this fact must be considered in the rehabilitation efforts.

Adult↗

The relationship between neuropsychologic function and level of caregiver supervision at 1 year after traumatic brain injury.

OBJECTIVES: To evaluate distribution of levels of caregiver supervision at 1 year after traumatic brain injury, and to determine neuropsychologic predictors of supervision level. DESIGN: Prospective longitudinal design, concurrent measurement of neuropsychologic function and supervision level. SETTING: Seventeen Traumatic Brain Injury Model Systems centers. PARTICIPANTS: A total of 563 adults tested at 1 year postinjury; and a subgroup of 452 studied for neuropsychologic function in the absence of impairment in mobility or basic self-care, as assessed by high FIM instrument motor scores. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Supervision level measured by scores on Supervision Rating Scale (SRS). RESULTS: Two thirds (69%) of the sample was rated as independent of supervision. Participants without significant dysfunction on motor FIM were grouped into supervision groups differing in intensity of time commitment from caregiver (independent, moderate supervision, heavy supervision). In univariate analyses, groups differed on demographic variables (education, race, productivity prior to injury), duration of altered consciousness, and all but 1 neuropsychologic measure. A binomial regression model (complementary log-log model) revealed that supervision at 1 year was predicted by education and scores on the Trail Making Test Part B and digits backward. CONCLUSIONS: Findings confirm the importance of preinjury status and measures of working memory and cognitive flexibility in predicting functional independence after TBI. The SRS appears prone to ceiling effects in persons followed prospectively after moderate to severe TBI.

Adolescent↗

Selected neurocognitive test data and work attendance for chronic psychiatric patients.

The relationship between work attendance-absence and selected measures of executive (Wisconsin Card Sorting Test, Trail Making B) and motor (Purdue Pegboard) function was explored in a sample of 42 chronic psychiatric patients at a sheltered workshop setting. Work attendance was unrelated to intelligence but correlated with several executive and motor variables. A stepwise regression analysis produced a three-variable model which accounted for 40% of the variance. However, the direction of the relationships suggested that high attendance was most likely for older, more cognitively rigid patients, with less manual dexterity than other patients. These findings are discussed in terms of the need to consider jointly neurocognitive and environmental constraints on ecological functioning.

Adolescent↗

Relationship between concussion and neuropsychological performance in college football players.

CONTEXT: Despite the high prevalence and potentially serious outcomes associated with concussion in athletes, there is little systematic research examining risk factors and short- and long-term outcomes. OBJECTIVES: To assess the relationship between concussion history and learning disability (LD) and the association of these variables with neuropsychological performance and to evaluate postconcussion recovery in a sample of college football players. DESIGN, SETTING, AND PARTICIPANTS: A total of 393 athletes from 4 university football programs across the United States received preseason baseline evaluations between May 1997 and February 1999. Subjects who had subsequent football-related acute concussions (n = 16) underwent neuropsychological comparison with matched control athletes from within the sample (n = 10). MAIN OUTCOME MEASURES: Clinical interview, 8 neuropsychological measures, and concussion symptom scale ratings at baseline and after concussion. RESULTS: Of the 393 players, 129 (34%) had experienced 1 previous concussion and 79 (20%) had experienced 2 or more concussions. Multivariate analysis of variance yielded significant main effects for both LD (P<.001) and concussion history (P=.009), resulting in lowered baseline neuropsychological performance. A significant interaction was found between LD and history of multiple concussions and LD on 2 neuropsychological measures (Trail-Making Test, Form B [P=.007] and Symbol Digit Modalities Test [P=.009]), indicating poorer performance for the group with LD and multiple concussions compared with other groups. A discriminant function analysis using neuropsychological testing of athletes 24 hours after acute in-season concussion compared with controls resulted in an overall 89.5% correct classification rate. CONCLUSIONS: Our study suggests that neuropsychological assessment is a useful indicator of cognitive functioning in athletes and that both history of multiple concussions and LD are associated with reduced cognitive performance. These variables may be detrimentally synergistic and should receive further study.

Adolescent↗

Test complexity and brain damage at different educational levels.

This investigation attempted to determine whether the complexity (problem-solving component) of selected tests of the Reitan-Halstead Neuropsychological Test Battery was related to their ability to discriminate groups of brain-damaged and non-brain-damaged adults at different educational levels. Twenty tests from the Wechsler-Bellevue and the Reitan-Halstead Battery were administered to 51 brain-damaged and 51 non-brain-damaged adults at three educational levels (grade school, high school, university). Spearman rank-order correlations were obtained for the relationship of task complexity with global scores that reflected the effects of education and brain damage for each variable and with the differences between group means for each education level. The ability of these measures to discriminate the groups was correlated significantly with problem-solving level, whereas the effects of education were correlated negatively with this dimension.

Adult↗

Long-term neuropsychological deficits after traumatic head injury with comatosis.

Studied neuropsychological deficits in a population who had sustained traumatic head injuries of the concussive type. Experimental Ss were 48 adults who had been comatose and hospitalized during the 3-year period that preceded the study. Control Ss (N = 16) had been hospitalized due to other types of injuries and had not been comatose. Ss were recalled and administered the Halstead-Reitan Battery, Trail Making Test, WAIS, and various questionnaires. Significant differences between experimental and control Ss were found that indicated persistence of neuropsychological dysfunctions. Groups of Ss who had sustained long comas performed more poorly than those who had short comas, which indicated that duration of coma was an important factor.

Adolescent↗

Screening for learning disabilities: a neuropsychological approach.

The ability of the Trail Making Test (TMT) and Tactual Performance Test (TPT) to discriminate between learning-disabled and normal children was examined. Twenty children aged 9 to 14 years who recently had been classified as learning disabled and 20 matched controls were administered individually the TPT, TMT, and two experimental forms of the TMT (parts X and Y). The data from the two groups were analyzed with a discriminant analysis. An overall accuracy rate of 82.5% was obtained when the measures were used to predict the classification status of individual children. A stepwise discriminant analysis procedure revealed an experimental form of the TMT (part X), Tactual Performance Test total time, and Tactual Performance Test localization to be the most sensitive measures. The use of such measures to screen for learning disabilities is discussed.

Achievement↗