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Dementia of the frontal type: neuropsychological and [99Tc]-HM-PAO SPET features.

Dementia of the frontal type (DFT) is a degenerative disorder with early behavioral and language disturbances and with relative preservation of memory and visuospatial abilities. On neuropathology, DFT lacks the pathologic hallmarks of Alzheimer's disease (AD). We assessed the neuropsychological and SPET imaging features of 11 DFT and 16 AD patients. The two groups had similar performances on verbal learning, while the former had significantly higher nonverbal learning scores. Testing of verbal and nonverbal instrumental abilities showed that this different behavior could be due to poorer verbal fluency of DFT patients, and not necessarily to poorer learning. Neuropsychological data indicated that the often reported sparing of memory in daily functions of DFT patients can also be shown with formal neuropsychological testing of nonverbal learning. SPET showed a comparatively higher perfusion deficit of frontal regions in the left hemisphere of DFT patients, suggesting that this region might be affected more often in the disease.

Aged↗

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.

Female↗

Effects of allergy season on mood and cognitive function.

The study was conducted to evaluate the effects of having allergic reactions (ie, being in allergy seasons without taking medications) on: (1) speed of cognitive processing, (2) psychomotor speed, (3) ability to sustain attention, (4) verbal learning and memory, and (5) mood. Subjects (ten atopic, eight control) were given a neuropsychologic test and mood rating battery in an A-B-A design ie, in, out of, and in allergy seasons. Only atopic subjects exhibited declines in verbal learning, slower decision-making and psychomotor speed on both simple and choice reaction time tests, and lower positive affect during their allergy seasons in comparison to out of allergy seasons. Atopic subjects did not demonstrate declines in ability to sustain attention. Biochemical mechanisms may cause these changes.

Adult↗

Reduction of caudate nucleus volumes in neuroleptic-naïve female subjects with schizotypal personality disorder.

BACKGROUND: The caudate nucleus might contribute to the psychopathological and cognitive deficits observed in schizotypal personality disorder (SPD), a schizophrenia spectrum disorder. Here we focused on female patients, because this group is underrepresented in studies of SPD and schizophrenia, and we might learn more about the caudate and clinical and cognitive impairments that are unique to female patients diagnosed with SPD. METHODS: Magnetic resonance imaging scans, obtained on a 1.5-T magnet with 1.5-mm contiguous slices, were used to measure the caudate in 32 neuroleptic-naïve women with SPD and in 29 female normal comparison subjects. Subjects were group-matched for age, parental socioeconomic status, and intelligence quotient. RESULTS: We found significantly reduced left and right caudate relative volume (8.3%, 7.7%) in female SPD subjects compared with normal comparison subjects. In female SPD subjects, we found significant correlations between smaller total caudate relative volume and worse performance on the Wisconsin Card Sorting test (nonperseverative errors) and on the California Verbal Learning Test (verbal memory and learning), and significant correlations between smaller total caudate relative volume and both positive and negative symptoms on the Structured Interview for Schizotypy. CONCLUSIONS: These findings demonstrate that, for female SPD subjects, smaller caudate volume is associated with poorer cognitive performance and more schizotypal symptomatology.

Adolescent↗

Cognitive function in euthymic bipolar I disorder.

Recent reports have suggested the presence of persistent cognitive impairments in patients diagnosed with Bipolar Disorder even after prolonged euthymic phases. In this work, various domains of cognitive function were examined in asymptomatic patients diagnosed with Bipolar I Disorder (BDI) in comparison with healthy subjects. Fifteen otherwise healthy BDI patients with a prior history of psychosis during mania completed a neuropsychological testing battery after a prolonged asymptomatic remission. Their scores were compared to those of individually matched healthy subjects with unpaired two-tailed t-tests at P<0.01. Relationships between cognitive performance measures and clinical variables related to illness severity were also examined with Pearson correlations, P<0.05. We detected poorer performance on measures of verbal learning, executive functioning and motor coordination in BDI patients compared to control volunteers. Scores on tests of executive functioning were negatively correlated with the number of episodes of mania and depression. Social and occupational scores were also associated with a poorer performance on measures of verbal learning and executive function. Euthymic BDI patients, therefore, demonstrate reductions in specific cognitive domains even after prolonged asymptomatic phases. Some of these deficits appear to be associated with a more severe course of illness and poorer social and occupational functioning.

Adult↗

Striatal dopamine and learning strategy-an (123)I-FP-CIT SPECT study.

UNLABELLED: Patients with Parkinson's disease (PD) have difficulty in processing learning tasks that lack external guidelines and, consequently, necessitate the subjects to generate their own problem-solving strategy. While the contribution of striatal dopaminergic deficiency to PD-specific motor symptoms is well established, its role in the PD-characteristic deviant learning style remains unclear. The aim of this study was to assess the relation between striatal dopamine activity as revealed by single photon emission computed tomography (SPECT) with (123)I-FP-CIT, a ligand for the dopamine transporter (DaT), and type of learning strategy, as identified by the California Verbal Learning Task (CVLT) in 19 patients with probable PD. The results showed a robust inverse correlation between striatal dopamine DaT binding and the externally guided, serial learning strategy: the lower the DaT in caudate nucleus as well as in putamen, the more the patient group appeared to rely on externally structured learning. Additionally, a significant positive correlation was found between caudatal DaT activity and the internally generated, semantic learning strategy. Unlike these strategic learning characteristics, IQ equivalent and recall total score appeared to vary independently from striatal DaT availability. CONCLUSION: our findings provide direct evidence that striatal dopaminergic activity is specifically involved in the regulation of strategic learning processes.

Adult↗

Motor deficits and recovery during the first year following mild closed head injury.

OBJECTIVE: This study examined motor impairments over 1 year following mild closed head injury (CHI). It is the first study to serially assess long-term oculomotor and upper-limb visuomotor function following mild head trauma. METHODS: Thirty-seven patients with mild CHI and 37 matched controls were compared at 1 week, 3 months and 6 months and 31 available pairs at 12 months post-injury on measures of saccades, oculomotor smooth pursuit, upper-limb visuomotor function and neuropsychological performance. Symptomatic recovery was sampled using the Rivermead Postconcussion Symptoms Questionnaire. RESULTS: At 1 week, the group with CHI reported high levels of post-concussional symptoms and exhibited prolonged saccade latencies, increased directional errors, decreased saccade accuracy and impaired fast sinusoidal smooth pursuit concomitant with increased arm movement reaction time, decreased arm movement speed and decreased motor accuracy on upper-limb visuomotor tracking tasks. Neuropsychological testing identified deficits only in verbal learning and speed of processing while attention, short-term/working memory and general cognitive performance were preserved. At 3 and 6 months, the group with CHI continued to show deficits on several oculomotor and upper-limb visuomotor measures in combination with some deficits on verbal learning and improved, yet abnormal, levels of post-concussional symptoms. At 12 months, the group with CHI had no cognitive impairment but residual deficits in eye and arm motor function and continued to show elevated levels of post-concussional symptoms. CONCLUSIONS: The findings indicate that multiple motor systems are measurably impaired up to 12 months following mild CHI and that instrumented motor assessment may provide sensitive and objective markers of cerebral dysfunction during recovery from mild head trauma independent of neuropsychological assessment and patient self-report.

Adolescent↗

Epidemiology and predictors of post-concussive syndrome after minor head injury in an emergency population.

OBJECTIVE: To determine if clinical variables or neurobehavioural test (NBT) scores obtained in the ED within 24 hours of minor head injury (MHI) predict the development of postconcussive syndrome (PCS). METHODS: Prospective, observational study of 71 MHI patients and 60 orthopaedic controls. MHI defined as loss of consciousness < 10 minutes or amnesia, GCS 15, no skull fracture or new neurologic focality on PE, and no brain injury on CT (if done). All patients received a seven part NBT battery in the ED. Telephone follow-up was done at 1, 3 and 6 months to determine if patients met the DSM IV definition of PCS. ANALYSIS: Stepwise, multivariate, logistic regression. RESULTS: Predictors of PCS at 1 month were female gender (OR = 7.8; 95% CI = 41.6, 1.98), presence of both retrograde and anterograde amnesia (OR = 0.055; CI = 0.002, 0.47), Digit Span Forward Scores (OR = 0.748; CI = 0.52, 1.03) and Hopkins Verbal Learning A scores (OR = 0.786; CI = 0.65, 0.91); at 3 months, presence of both retrograde and anterograde amnesia (OR = 0.13; CI = 0.0, 0.93), Digit Span Forward Scores (OR = 0.744; CI = 0.58, 0.94). No variables fit the model at 6 months. 92% of males scoring > 25 on Hopkins Verbal Learning A did not have PCS at 1 month, and 89% of females scoring < 9 on Digit Span Forward did have PCS at 1 month. CONCLUSIONS: Gender and two NBTs can help predict PCS after MHI.

Adult↗

[Memory processes in endogenous depression].

The thesis aims to answer the questions about the profile of mental ability in endogenous depression and to decide whether self-estimation of depressive symptoms influences the results achieved by patients in memory tests. Fifty six patients suffering from endogenous depression have been examined. The following methods have been applied: Mini Mental State Examination, Benton Visual Retention Test, Beck Depression Inventory, hold tests: Vocabulary, Information, Comprehension and Digit Span of Wechsler Adult Intelligence Scale (WAIS), Rey-Osterrieth Complex Figure, Auditory Verbal Learning Test, DCS Weidlich. General status of cognitive functions correlates with the profile of specific kinds of memory results, particularly with delayed memory. Self-estimation of depressive symptoms intensity is mostly influenced by memory capacity, visuomotorial factor, functions of perception and lingual factor. High correlation between verbal and non verbal learning shows uniform influence of depression on the process of learning.

Depressive Disorder↗

Klinefelter's syndrome as a model of anomalous cerebral laterality: testing gene dosage in the X chromosome pseudoautosomal region using a DNA microarray.

Consistent handedness and language laterality are two of the most striking behavioral and cognitive asymmetries observed in humans. Alterations in the typical pattern of cerebral laterality, termed "anomalous dominance," is observed in left-handers and some patients with verbal learning disabilities. We undertook the study of a genetically distinct group of subjects, XXY males (Klinefelter's syndrome; KS), who demonstrate anomalous dominance in a variety of testing paradigms in order to begin to elucidate the molecular basis of anomalous dominance in this population. KS subjects manifest specific verbal learning disability, evidence of altered functional laterality for phonologic processing, and an increase in left-handedness when measured by skill. It is proposed that an alteration in gene dosage in the pseudoautosomal region (PAR) of the sex chromosomes is the most likely explanation for anomalous dominance in these patients. This is especially intriguing in light of previously described genetic models of cerebral laterality that suggest a contributing locus in the PAR, or adjacent high homology regions of the X chromosome. We have developed an ordered DNA microarray covering the X chromosome PAR at high resolution for hybridization with two-color fluorescently labeled probes. We demonstrate the ability to detect changes in hybridization signal that will facilitate efficient large-scale screening of this region for alterations in gene dosage associated with features of anomalous dominance and other cognitive or behavioral phenotypes.

Case-Control Studies↗

Associative interference between cues and between outcomes presented together and presented apart: an integration.

In recent years, 'stimulus competition' in the study of acquired behavior has referred exclusively to (a) associative competition between cues trained in compound (e.g. overshadowing and blocking). Rarely cited are older experiments cast in the verbal learning tradition, now complemented with data from humans and rats in Pavlovian preparations, that demonstrate (b) competition between cues separately trained with a common outcome (i.e. proactive and retroactive interference). Similarly neglected are numerous examples of (c) competition between outcomes separately trained with a common cue within the verbal learning literature (also proactive and retroactive interference) as well as within the Pavlovian literature (i.e. counterconditioning). Recent data demonstrate (d) competition between outcomes trained in compound, thereby completing the four cells of a 2x2 matrix (competing stimuli trained together vs. trained apart and the competing stimuli being cues or outcomes) which highlights the ubiquitous nature of associative stimulus interference/competition. Most contemporary theories of acquired behavior can account for the phenomena in one or at most two cells of this matrix. Whether a common mechanism underlies the phenomena in all four cells of the matrix is currently unclear, but until such time as data preclude a common mechanism, parsimony encourages efforts to develop a model that encompasses all four cells. Here we offer a tentative model that addresses all four cells, albeit with two processes.

Journal Article↗

Cognitive performance after cardiac operation: implications of regression toward the mean.

OBJECTIVE: The purpose of this study was to assess the influence of regression toward the mean on different definitions of cognitive dysfunction after coronary artery bypass graft operation. METHODS: A total of 120 patients who underwent nonemergency coronary bypass operation and who were involved in a randomized trial of an anti-inflammatory agent were assessed prospectively with a battery of 10 psychometric tests covering a variety of cognitive domains. The battery was administered before the operation and 5 days and 3 months after the operation. Data from 2 representative tests, the Rey Auditory Verbal Learning Test and the Trail Making Test (part A), were used. The influence of regression toward the mean on 3 commonly used single-case definitions of cognitive impairment (1 SD method; one-half SD method; 20% method) was analyzed. RESULTS: Group mean performance deteriorated on the Rey Auditory Verbal Learning Test at the discharge assessment (P <.001) and remained below baseline at 3 months (P =.03). Mean performance on the Trail Making Test (part A) showed a near-significant decline at discharge (P =. 06), followed by improvement at 3 months (P <.01). Regression toward the mean was demonstrated on both tests by classifying the preoperative scores into low, moderate, and high-performance categories. Applying the different definitions of dysfunction resulted in substantially larger numbers of patients in the high-performance group being classified as impaired. CONCLUSION: Single-case definitions of cognitive dysfunction are influenced strongly by regression toward the mean. Disproportionate numbers of high-baseline performers are classified as impaired, thereby questioning the validity of established definitions. Group mean analysis with controls is potentially the most reliable method for detecting real change or differences.

Cognition↗

Neuropsychological outcome after unilateral pallidotomy for the treatment of Parkinson's disease.

OBJECTIVE: To assess the long term cognitive outcome of unilateral posteroventral pallidotomy (PVP) and the overall efficacy of the surgery. METHODS: Forty two (29 left and 13 right PVP) patients with Parkinson's disease underwent neurological and neuropsychological testing before PVP and at 3 and 12 months after PVP. The neuropsychological testing battery emphasised measures of verbal learning and memory, visuospatial abilities, speed of information processing, executive functioning, and affective functioning. RESULTS: All patients demonstrated motor improvements after surgery during their off state, and 86% of patients also showed improvements in motor functioning in their on state. Repeated measures ANOVA showed significant improvements in confrontational naming, visuospatial organisation, and affective functioning 3 months and 12 months after surgery, with inconsistent improvements in executive functioning 12 months post-PVP. Patients demonstrated a transient impairment in verbal memory, with verbal learning performance returning to baseline 12 months post-PVP after a significant decline 3 months after PVP. When three patients with lesions extending outside of the PVP were excluded from the analysis, a decline in verbal fluency performance after PVP was not found to be significant. Differences due to side of lesion placement were not found on any of the cognitive measures. CONCLUSIONS: In the largest long term follow up study reported to date, the cognitive changes found up to a year after PVP are minimal compared with the robust improvements in motor function. The findings highlight the need to investigate the relation between the specific fibre tracts affected by the lesions and cognitive outcome.

Activities of Daily Living↗

Systolic blood pressure tracking over 25 to 30 years and cognitive performance in older adults.

OBJECTIVE: To determine the extent to which individual changes in systolic blood pressure (SBP) over a 30-year interval are associated with differential neuropsychological outcomes in old age. METHODS: Seven hundred seventeen survivors from the Western Collaborative Group Study, a longitudinal study of cardiovascular risk factors now in its 38th year of follow-up, with blood pressures measured in middle age (mean=45 years) and in old age (mean=75 years) and neuropsychological tests administered at follow-up were included in this analysis. Participants were grouped according to 30-year change in SBP (increased, decreased, or "normal"). Analyses focused on comparisons of neuropsychological performance of "high SBP trackers" (ie, those with persistent SBP>/=140 mm Hg throughout adult life) and of SBP "decreasers" with the performance of those whose SBP was either stable or changed in an expected way over time. RESULTS: Only 7.5% of participants had elevated SBP in middle age, but 43.8% of participants had elevated SBP in old age. After adjustment for age, education, depression, clinically defined stroke, and use of antihypertensive medications and after exclusion of individuals with impaired cognitive performance at follow-up, high SBP trackers, 5.0% (n=36), performed consistently less well than the "normal" SBP subgroups on a composite measure of verbal learning and memory (P=0.04). When compared with the "normal" SBP subgroup, the SBP decreasers, 5.3% (n=38), performed less well on speeded performance (P=0.03). CONCLUSIONS: There is a relatively small group of people who maintain elevated SBP throughout their adult lives. These persons are at increased risk for reduced verbal learning and memory function. There is also a group of individuals who experience a decrease in SBP and who are at risk for decreased psychomotor speed. Delineation of these 2 SBP subgroups may lead to further clarification of the effects of SBP on neurobehavioral function in older adults.

Adult↗

Cognitive and brain function in schizotypal personality disorder.

Schizotypal personality disorder, a diagnosis defined partially in terms of a genetic relatedness to schizophrenia, has begun to receive extensive investigative study. While the exact etiologic relationship between schizotypal personality disorder and schizophrenia remains to be determined, three models have been considered: (1) the two may be distinct disorders, (2) they may be essentially identical disorders but expressed with different degrees of severity, or (3) they may be related disorders with a partially overlapping etiology that might account for the many similarities yet the lack of psychosis or severe deficits in schizotypal individuals. Some of the recent research in the structural and functional neuroanatomy, neurochemistry, cognitive function, and pharmacology of schizotypal personality disorder is reviewed with citation of the most recent findings from our laboratory and others. Both schizotypal and schizophrenic subjects appear to show abnormalities in temporal lobe volume, but schizotypal subjects do not appear to show the volumetric decreases in frontal cortex that schizophrenic patients evidence. Abnormalities in thalamic nuclei parallel these findings-the pulvinar, which projects to temporal association and sensory cortices, is reduced in both disorders, but the mediodorsal nucleus, which projects extensively to the frontal cortex, is reduced in schizophrenic patients but not in schizotypal patients. Functional imaging studies suggest that there may be abnormalities in frontal activation in both disorders, but that schizotypal individuals can recruit alternative regions to accomplish tasks requiring frontal lobe activation that may help compensate. Imaging studies of the subcortex including FDG/PET imaging of metabolic activity during a verbal learning task, SPECT imaging studies which measure binding of IBZM and its displacement following amphetamine administration, and plasma HVA determinations following 2-deoxyglucose administration all suggest the possibility of relatively reduced dopaminergic subcortical activity in schizotypal individuals compared to schizophrenic patients. Cognitive function is also impaired in the areas of working memory, verbal learning, and attention in schizotypal patients, as in schizophrenic patients, and they may be particularly susceptible to cognitive tasks with high context dependence, as in schizophrenia. Preliminary trials of catecholaminergic agents suggest that these agents may be able to improve these impaired cognitive functions.

Benzamides↗

Investigation of the laterality of hostility, cardiovascular regulation, and auditory recognition.

This experiment tested a hypothesis linking the right cerebral regulation of hostility and cardiovascular arousal. First, replication of previous research supporting heightened cardiovascular (systolic blood pressure [SBP] and diastolic blood pressure [DBP]) reactivity among high hostile participants was partially successful. Second, dynamic variations in functional cerebral asymmetry in response to emotional linguistic processing was measured. Thirty low- and high-hostile, undergraduate volunteer participants (n = 30) were identified using the Cook Medley Hostility Scale (CMHS). Only healthy, right-handed male participants completed the experiment. All participants completed the negative affective auditory verbal learning test (AAVLT). Cardiovascular measures (SBP and DBP) were recorded and dichotic listening procedures were administered before and after the cognitive affective stressor. The results support greater left cerebral activation among both groups following the dichotic phoneme listening tasks and greater right cerebral activation among both groups following an emotional linguistic (affective verbal learning) cognitive stressor.

Affect↗

Memory for verbal information in individuals with HIV-associated dementia complex. HNRC Group.

Patterns of memory performance were examined for 9 participants with HIV-associated dementia (HAD), 15 HIV-seropositive participants without dementia, and 15 HIV-seronegative controls. Episodic and semantic memory were assessed using the California Verbal Learning Test, the Boston Naming Test, and Verbal Fluency tests. The HAD group showed deficits in episodic memory, with relative sparing of semantic memory. In addition, results suggest a retrieval deficit in HAD rather than a deficit in retention of information. This pattern is consistent with the presence of a subcortical dementing process and supports findings from previous neuropathological, neuroimaging, and neuropsychological studies suggesting that subcortical brain dysfunction is frequently associated with HIV disease (e.g., Navia, Jordan, & Price, 1986).

AIDS Dementia Complex↗

Neurocognitive dysfunction in first-episode psychosis: correlates with symptoms, premorbid adjustment, and duration of untreated psychosis.

OBJECTIVE: The authors examined the relationship of neurocognitive function with duration of untreated psychosis, premorbid illness factors, and clinical symptoms to determine whether long duration of untreated psychosis independently compromises cognitive function. METHOD: Patients recruited to a study of the effect of an early detection program on the duration of untreated first-episode psychosis in two catchment areas were compared to patients in a similar treatment program in two other catchment areas without an early detection program. The median duration of untreated psychosis was 10.5 weeks for all patients. A total of 301 patients entered the study, and 207 completed a comprehensive neuropsychological test battery that assessed working memory/fluency, executive function, verbal learning, impulsivity, and motor speed. The median time from start of treatment to neuropsychological testing was 108 days; all patients were tested within 9 months. RESULTS: No significant association was found between duration of untreated psychosis and any of the cognitive measures. Strong associations were demonstrated between poorer premorbid school functioning and neurocognitive deficits, especially in verbal learning and working memory. No relationship was found between neurocognitive functions and clinical measures, except for an inverse correlation of Positive and Negative Syndrome Scale negative symptoms and working memory and a positive correlation between positive symptoms and motor speed. CONCLUSIONS: The data contribute to a disconfirmation of the hypothesis of an association between duration of untreated psychosis and neurocognitive performance at baseline.

Adult↗