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Metabolic markers of cobalamin deficiency and cognitive function in normal older adults.

OBJECTIVES: To investigate the relationship between metabolic markers of cobalamin deficiency and cognitive function in normal older adults. DESIGN: Cross-sectional study. SETTING: Queen's University and St. Mary's of the Lake Hospital, Kingston, Ontario, Canada. PARTICIPANTS: Two hundred eighty-one cognitively normal, community-dwelling participants aged 65 and older. MEASUREMENTS: Serum cobalamin, red blood cell folate, methylcitric acid, homocysteine, and methylmalonic acid were determined. Cognitive instruments included the California Verbal Learning Test, Mattis Dementia Rating Scale, and the Stroop Neuropsychological Screening Inventory (Stroop). RESULTS: Serum levels of methylcitric acid had a significant negative correlation with recall, learning, and discriminability (factor 1) of the California Verbal Learning Test after adjusting for age and sex (beta=-0.138, P=.019). Subjects with elevated methylcitric acid had significantly lower scores (factor 1) than subjects with normal methylcitric acid (P<.01). Bivariate analysis showed significant correlations between levels of homocysteine and the Stroop score and between cobalamin, methylmalonic acid, and homocysteine and some scores of the California Verbal Learning Test, but these relationships did not remain significant after multivariate analysis. Subjects with high homocysteine (tHcy) had lower Stroop scores than subjects with normal tHcy (P<.05). No biochemical parameters were associated with the Mattis Dementia Rating Scale scores. CONCLUSION: This study indicates that, in normal elderly subjects, some cognitive scores are related to serum methylcitric acid and possibly homocysteine.

Aged↗

Association between attitude toward medication and neurocognitive function in schizophrenia.

OBJECTIVES: A patient's attitude toward medication is important for medication adherence, which is a key determinant of outcome in schizophrenia. This study examined the association between attitude toward antipsychotic medication and clinical status, particularly neurocognitive function, in patients with schizophrenia. METHOD: Ninety-two patients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria for schizophrenia participated in this study. The attitudes of the subjects toward medication were evaluated using the Drug Attitude Inventory (DAI). Clinical characteristics, including psychiatric symptoms and side effects of medication were evaluated. Neurocognitive function was measured using the Mini Mental State Examination and a computerized battery consisting of the Digit Span Test, Verbal Learning Test, Continuous Performance Test, Wisconsin Card Sorting Test, Finger Tapping Test, and Trail Making Test, parts A and B. The associations between attitude toward medication and neurocognitive function and clinical characteristics were analyzed. RESULTS: The scores on the DAI were not significantly correlated with the clinical characteristics, such as psychopathology, subjective well-being, or neuroleptic-induced extrapyramidal side effects. Instead, the scores on the DAI were significantly correlated with the learning index and delayed free recall on the Verbal Learning Test, the number of categories completed on the Wisconsin Card Sorting Test, and omission and commission errors on the Continuous Performance Test; the scores were not significantly correlated with measures on the Mini Mental State Examination, Digit Span Test, Finger Tapping Test, or Trail Making Test. CONCLUSIONS: Our findings indicate that a patient's attitude toward medication is associated with neurocognitive function. Specifically, verbal learning memory, executive functioning, and sustained attention were associated with attitude toward medication.

Adolescent↗

Mechanisms of verbal memory impairment in four neurodevelopmental disorders.

Profiles of verbal learning and memory performance were compared for typically developing children and for four developmental disorders characterized by different patterns of language functioning: specific language impairment, early focal brain damage, Williams Syndrome, and Down Syndrome. A list-learning task was used that allowed a detailed examination of the process of verbal learning, recall, and recognition (California Verbal Learning Test--Children's Version). Distinct patterns of performance characterized the four disorders. These patterns were consistent with the language deficits typically seen in the disorders, with the exception of a dissociation seen in Williams Syndrome.

Adolescent↗

[Neuropsychological profile of patients with bipolar depression in remission].

AIM: To determine if the patients with bipolar affective disorder, after the depressive phase, would exhibit cognitive impairment in remission. METHODS: Twenty-three euthymic patients with bipolar disorder were matched, on a case-by-case basis, to twenty-one healthy subjects in the control group, for the presence of the symptoms of depression. The patients and the control group were tested with a battery of neuropsychological tests. RESULTS: Impairments were found in the patients compared with the control group in tests of verbal learning and memory and in tests of executive function. Verbal learning and memory, as well as executive functions, did not correlate either with the clinical indices of patients, or with the demographic and baseline clinical measures of depression. CONCLUSION: Impaired verbal learning and memory and executive functions may represent a trait rather than the state variables in bipolar disorder.

Adult↗

Differential impairment of memory in Korsakoff's syndrome.

Groups of Korsakoff, alcoholic and non-alcoholic subjects were given picture-recognition memory (patterns and objects) and verbal learning tasks. Korsakoff subjects were impaired relative to the two control groups on verbal learning and object-picture memory; on pattern memory Korsakoff and alcoholic subjects were comparable but both were inferior to non-alcoholics. These findings gave some support to the idea (Butters and Cermak, 1976) that visuo-spatial functions (represented here by pattern memory) are impaired through chronic alcoholism whilst the development of Korsakoff's syndrome induces an additional impairment in semantic processing of information (represented here by verbal learning and object-picture memory).

Adult↗

The effects of total sleep deprivation on cerebral responses to cognitive performance.

We review the findings from a study utilizing functional magnetic resonance imaging (FMRI) to examine the effects of total sleep deprivation (TSD) on verbal learning, arithmetic, and divided attention. For verbal learning and divided attention, TSD was associated with increased activation in the bilateral prefrontal cortex and parietal lobes. Increased sleepiness after TSD and lower levels of memory impairment were correlated with increased activation in specific regions of the prefrontal cortex and parietal lobes, respectively. The arithmetic task led to significantly decreased activation in the bilateral prefrontal cortex and parietal lobes. Based on this and other data, we hypothesize an adaptive cerebral response during cognitive performance following TSD with the specific pattern of adaptation depending on the specific cognitive processes performed. We discuss the need to test the hypothesis in a variety of ways.

Adaptation, Physiological↗

Differential genetic influence for components of memory in aging adult twins.

OBJECTIVE: To investigate the relative proportion of genetic and environmental contributions to verbal memory in community-dwelling World War II veteran twins. DESIGN: The California Verbal Learning Test (CVLT) was administered to 94 monozygotic (MZ) and 89 dizygotic (DZ) elderly male twin pair participants in the fourth examination of the National Heart, Lung, and Blood Institute Twin Study. SETTING: Subjects voluntarily participated on an outpatient basis at a research or medical center facility in 1 of 4 sites in the United States. PARTICIPANTS: Subjects had a mean age of 71.8 years (SD, 2.9 years), a mean educational level of 13.6 years (SD, 2.8 years), and no history of stroke and/or a Mini-Mental State Examination score of 23 or greater. MAIN OUTCOME MEASURES: Twin pair similarity in performance on 4 factor analytically derived components of the CVLT measuring verbal learning and memory, response discrimination, learning strategy, and recognition memory. RESULTS: The MZ intraclass correlation was significantly larger than the DZ correlation for verbal learning and memory (I<.001) but not for the other 3 components of memory. Using maximum likelihood methods, the best-fitting genetic model indicated that verbal learning and memory has a substantial genetic component (56% of total variance), whereas response discrimination has a much smaller, although still detectable, genetic component (24% of total variance). There is no evidence of genetic influence on learning strategy or recognition memory. CONCLUSION: Differential contribution of genetic and environmental influences to specific components of memory suggest that, in this group of elderly male twin pairs, some components may be more amenable to intervention than others.

Aged↗

Adequacy of language function and verbal memory performance in unilateral temporal lobe epilepsy.

We examined adequacy of language functions, their influence on verbal learning and memory performance, and the relative effects of language function and laterality of seizure focus on the memory performance of 99 left-hemisphere dominant patients with invasively verified epilepsy of left (N = 47) or right (N = 52) temporal lobe origin. Patients with left temporal lobe epilepsy (TLE) scored significantly lower than the right TLE group on several aphasia battery subtests (Visual Naming, Sentence Repetition, Token Test, Reading Comprehension, Aural Comprehension). Adequacy of language function (nominal speech) was significantly related to verbal learning and memory performance for both left and right TLE groups. Finally, comparison of the predictive significance of laterality of TLE and adequacy of language function indicated that language functions (Visual Naming and Aural Comprehension), but not laterality of TLE, were significant predictors for verbal learning and memory performance. It is concluded that: 1) adequacy of basic language functions is particularly compromised in left TLE, 2) there is a significant relationship between adequacy of language function and several aspects of verbal learning and memory ability in both left and right temporal lobe groups, and 3) clinical assessment and theoretical models of memory need to consider these relationships.

Adolescent↗

Relations between verbal and nonverbal memory performance: evidence of confounding effects particularly in patients with right temporal lobe epilepsy.

Confounding left hemisphere verbalization strategies can be suggested as being a major problem in the evaluation of the assumed involvement of right temporo-limbic structures in "nonverbal" visual/figural memory processing. We addressed this issue by evaluating the easily-verbalized Benton-visual-retention-test in 60 patients with either left (LTLE) or right temporal lobe epilepsy (RTLE) and 30 healthy controls. We formally estimated the informational (verbal) content of each item which hypothetically would be needed to solely retain the item from verbal memory. The results indicated confounding of verbal learning and figural memory only in the presence of right temporal lobe dysfunctions. Selective visual/figural learning deficits in RTLE patients became obvious when the verbal load of the figural material exceeded their verbal learning capacity. Instead of excluding verbalization by the use of abstract figural items, its inclusion provides a possibility to control compensatory strategies which overshadow the presence of visual/figural memory deficits.

Adult↗

Changes in alpha rhythm asymmetry during learning of verbal and visuospatial tasks.

Alpha activity in the two cortical hemispheres was examined during learning and overlearning of a verbal and a visuospatial task. Compared to a pretask baseline condition, the amount of alpha activity during the tasks was decreased. An increase in alpha activity was found from learning to overlearning in both tasks. A greater amount of alpha was found in the right hemisphere for both tasks. In addition, no difference in the degree of alpha asymmetry was found between the tasks. This was discussed in light of prior contrary findings. A significant positive correlation was found between change in learning rate and change in alpha asymmetry during the verbal task. An interpretation of this finding was offered in terms of the level of hemispheric activation reflecting the degree of task engagement.

Alpha Rhythm↗

Declarative and procedural learning in individuals with subclinical obsessive-compulsive symptoms.

Previous neuropsychological research suggests that psychometrically defined subclinical obsessive-compulsive (OC) individuals perform worse than non-OC controls on specific tests of executive functioning. This study aimed to extend these findings by comparing the performance of 25 subclinical OC and 28 non-OC control subjects on measures of declarative learning (Rey Auditory Verbal Learning Test), motor procedural learning (star maze), spatial problem solving (single administration of the 3-disk version of the Tower of Hanoi; TH3), and "cognitive" procedural learning (repeated administrations of the 4-disk version of the Tower of Hanoi; TH4). In addition, the subjects were administered measures of general intelligence, anxiety and depression. No between-group differences were observed on measures of declarative and motor procedural learning. Subclinical OC subjects needed significantly more moves than controls to solve TH3, suggesting poorer spatial problem solving ability. A significant group x trial interaction on the TH4 suggested reduced cognitive skill acquisition in the subclinical OC group. However, performance on TH3 and TH4 was significantly correlated in the OC group but not in the control group, suggesting that the suboptimal acquisition of cognitive skills among subclinical OC subjects is more likely to be related to inefficient spatial problem solving strategies than to a cognitive procedural learning deficit per se. These results replicate and expand upon previous findings and support a dimensional model of Obsessive-Compulsive Disorder.

Adolescent↗

Neurocognitive function in HIV-infected patients with low weight and weight loss.

OBJECTIVE: To determine neurocognitive function in HIV-infected subjects with low weight and weight loss. DESIGN: Cross-sectional cohort. METHODS: Baseline data from male and female participants in longitudinal treatment studies of AIDS wasting were analyzed. Fifty-seven HIV-infected women (age: 38 +/- 5 years, education level: 12.3 +/- 2.3 years) and 24 HIV-infected men (age: 37 +/- 5 years, education level: 13.5 +/- 2.9 years) with weight <90% IBW or loss of >10% of preillness weight maximum underwent standardized neurocognitive testing to measure intellectual functioning, attention, memory, and fine motor dexterity. The z scores were determined using age- and gender-specific normative data. RESULTS: Among women, IQ (87 +/- 13, z score: -0.8 +/- 0.8 SD) and executive functioning scores (-0.7 +/- 1.2 SD) were below average but within normal limits. In contrast, performance (z scores) on measures of verbal learning (-2.5 +/- 1.5 SD), visuospatial abilities (-2.5 +/- 2.0 SD), and motor coordination (-2.3 +/- 3.3 SD) fell significantly below normal limits. Among men, IQ score was 96 +/- 13 SD (z score: -0.3 +/- 0.8 SD). Performance was below average on measures of verbal learning (-1.0 +/- 1.7 SD) and visual construction (-1.6 +/- 1.7 SD) but within normal limits on executive functioning (-0.1 +/- 1.0 SD). CONCLUSIONS: HIV-infected women at low weight demonstrate significantly reduced verbal learning, memory, and motor function, whereas HIV-infected men at low weight demonstrate more moderate impairment in verbal learning and other measures of neurocognitive function.

Adolescent↗

The effects of clozapine, risperidone, and olanzapine on cognitive function in schizophrenia.

Cognitive function is markedly impaired in most patients with schizophrenia. Antecedents of this impairment are evident in childhood. The cognitive disability is nearly fully developed at the first episode of psychosis in most patients. The contribution of cognitive impairment to outcome in schizophrenia, especially work function, has been established. Preliminary results indicate that cognitive function, along with disorganization symptoms, discriminate schizophrenia patients who are able to work full-time from those who are not. Typical neuroleptic drugs lack the ability to improve the various domains of cognitive function impaired in schizophrenia. Atypical antipsychotic drugs pharmacologically related to clozapine-quetiapine, olanzapine, risperidone, sertindole, and ziprasidone--share the ability to produce fewer extrapyramidal symptoms than typical neuroleptic drugs and more potent antagonism of serotonin2a relative to dopamine2 receptors. However, they have a number of different clinical effects. We have identified all the studies of clozapine, olanzapine, and risperidone that provide data on their effects on cognition in schizophrenia. Data for each drug are reviewed separately in order to identify differences among them in their effects on cognition. Twelve studies that report cognitive effects of clozapine are reviewed. These studies provide (1) strong evidence that clozapine improves attention and verbal fluency and (2) moderate evidence that clozapine improves some types of executive function. However, results of the effects of clozapine on working memory and secondary verbal and spatial memory were inconclusive. Risperidone has relatively consistent positive effects on working memory, executive functioning, and attention, whereas improvement in verbal learning and memory was inconsistent. Preliminary evidence presented here suggests that olanzapine improves verbal learning and memory, verbal fluency, and executive function, but not attention, working memory, or visual learning and memory. Thus, atypical antipsychotic drugs as a group appear to be superior to typical neuroleptics with regard to cognitive function. However, available data suggest that these drugs produce significant differences in specific cognitive functions. These differences may be valuable adjunctive guides for their use in clinical practice if cognitive improvements reach clinical significance. The effects of the atypical antipsychotic drugs on cholinergic and 5-HT2a-mediated neurotransmission as the possible basis for their ability to improve cognition are discussed. It is suggested that the development of drugs for schizophrenia should focus on improving the key cognitive deficits in schizophrenia: executive function, verbal fluency, working memory, verbal and visual learning and memory, and attention.

Antipsychotic Agents↗

Jian Nao Ning for treatment of memory impairment in patients with mild or moderate multi-infarct dementia.

Forty patients with multi-infarct dementia (MID) were randomly assigned to the treatment group (25 cases) treated with Jian Nao Ning (JNN) and the duxil control group (15 cases). Memory function were assessed at baseline and endpoint using memory subscales of a battery of New Psychometric Tests (Chinese version) including mini-mental state examination (MMSE), verbal memory, and non-verbal memory, etc. After treatment, the mean scores of verbal memory in the Hopkins Verbal Learning Test (P<0.05) and total memory scores of memory items (P<0.001) in JNN group increased significantly; and improvement in episodic memory function including story recall (immediate and delayed), delayed word recall, verbal learning and verbal recognition and visual recognition in the JNN group was better than that in the duxil control group, suggesting that JNN can obviously improve memory function for the patients with mild or moderate multi-infarct dementia.

Aged↗

A double-blind study of combination of clozapine with risperidone in patients with schizophrenia: effects on cognition.

BACKGROUND: Atypical antipsychotic drugs produce improvement in some domains of cognition as well as psychopathology in patients with schizophrenia. However, the effect of combinations of atypical antipsychotic drugs on cognitive function is unknown. The aim of this study was to compare the effect of risperidone or placebo on cognitive function in patients with schizophrenia who were previously treated with clozapine monotherapy. METHOD: This prospective, randomized, double-blind, placebo-controlled, 6-week study included 30 patients with DSM-IV schizophrenia. Patients whose psychopathology was no more than partially responsive to clozapine treatment were randomly assigned to receive adjunctive treatment with risperidone (N = 16) up to 6 mg/day or placebo (N = 14). Cognitive test scores for verbal learning and memory, verbal fluency, attention, executive function, verbal working memory, and motor function were the primary outcome measures. Secondary outcome measures included assessment of psychopathology, extrapyramidal side effects, and global functioning. Data were collected between November 2001 and July 2003. RESULTS: Significant improvement was found in both treatment groups in a variety of cognitive measures, but there was significantly greater improvement in the placebo-augmented group on measures of initial learning acquisition and attention. The improvement in cognition was not correlated with improvement in psychopathology. There were significant correlations between improvement in verbal working memory, verbal learning and memory, and attention and quality of life and global functioning in the placebo-augmented but not the risperidone-augmented group. CONCLUSION: Adjunctive treatment with risperidone for 6 weeks in patients with schizophrenia who had received chronic treatment with clozapine does not significantly improve cognitive function.

Adult↗

Neuropsychological performance of patients following mold exposure.

UNLABELLED: This study investigated the effects of mold exposure (ME) on human cognition by analyzing neuropsychological data from patients who were exposed to mold in their homes or workplaces. Compared to normative data, ME patients were impaired (<10th percentile) on a number of cognitive measures, with the most consistent deficits in visuospatial learning, visuospatial memory, verbal learning, and psychomotor speed. We also examined emotional functioning and found that a number of ME patients showed evidence of both Axis I and Axis II pathology. Interestingly, there was a significant correlation among patients' scores on the Beck Depression Inventory-Second Edition and the number of neuropsychological tests falling within the impaired range. Given the limited understanding of ME and its effect on the human central nervous system, we provide a working model that attempts to capture the complex interactions of impaired cognition, psychosocial stressors, poor physical health, and emotional functioning in patients following ME. KEYWORDS: mold exposure, mild traumatic brain injury, toxic exposure

Adult↗

Verbal memory performance during subchronic challenge with a selective serotonergic and a mixed action antidepressant.

OBJECTIVES: Effects of escitalopram 10-20 mg/day and mirtazapine 30-45 mg/day on verbal memory of 18 healthy participants were assessed in a randomized, double-blind, placebo-controlled, three-way crossover trial. METHOD: Each treatment period lasted for 15 days and was separated from the next period by a washout period of at least 13 days. Participants received an evening dose of escitalopram 10 mg, mirtazapine 30 mg, or placebo from days 1 to 7 and an evening dose of escitalopram 20 mg, mirtazapine 45 mg, or placebo from days 8 to 15. On days 2, 9, and 16 a visual verbal memory task was performed measuring drug effects during the acute phase, after dose increase and at steady state. RESULTS: Escitalopram did not affect immediate or delayed verbal memory score throughout treatment. During mirtazapine treatment, participants performed less well in the overall immediate recall score compared to placebo. This impairment was most pronounced in the final trial of the visual verbal learning task. CONCLUSION: Verbal memory was not affected by acute and subchronic escitalopram treatment in healthy participants. Overall immediate verbal memory was slightly but significantly impaired throughout mirtazapine treatment, probably due to a general reduction in overall arousal caused by H1 blockade.

Adult↗