Mild cognitive impairment in prediagnosed Huntington disease.

BACKGROUND: Cognitive decline has been reported in Huntington disease (HD), as well as in the period before diagnosis of motor symptoms (i.e., pre-HD). However, the severity, frequency, and characterization of cognitive difficulties have not been well-described. Applying similar cutoffs to those used in mild cognitive impairment (MCI) research, the current study examined the rates of subtle cognitive dysfunction (e.g., dysfunction that does not meet criteria for dementia) in pre-HD. METHODS: Using baseline data from 160 non-gene-expanded comparison participants, normative data were established for cognitive tests of episodic memory, processing speed, executive functioning, and visuospatial perception. Cutoff scores at 1.5 standard deviations below the mean of the comparison group were then applied to 575 gene-expanded pre-HD participants from the observational study, PREDICT-HD, who were stratified by motor signs and genetic risk for HD. RESULTS: Nearly 40% of pre-HD individuals met criteria for MCI, and individuals closer to HD diagnosis had higher rates of MCI. Nonamnestic MCI was more common than amnestic MCI. Single-domain MCI was more common than multiple-domain MCI. Within the nonamnestic single-domain subtype, impairments in processing speed were most frequent. CONCLUSIONS: Consistent with the Alzheimer disease literature, MCI as a prodromal period is a valid concept in pre-HD, with nearly 40% of individuals showing this level of impairment before diagnosis. Future studies should examine the utility of MCI as a marker of cognitive decline in pre-HD.

Improved executive functioning following repetitive transcranial magnetic stimulation.

The cognitive effects of active and sham repetitive transcranial magnetic stimulation (rTMS) were examined in 19 middle-aged and elderly patients with refractory depression. Patients received either active (n = 9) or sham (n = 10) rTMS targeted at the anterior portion of the left middle frontal gyrus. Patients in the active rTMS group improved significantly on a test of cognitive flexibility and conceptual tracking (Trail Making Test-B).

Unilateral vs. bilateral ultrasound in the monitoring of cerebral microemboli.

We used bilateral transcranial Doppler to monitor the number of microembolic events (ME) in the left and right middle cerebral arteries of 29 patients during cardiac surgery that required extracorporeal circulation. Based on a previously published study, we hypothesized that the commonly used method of doubling unilateral ME counts to obtain an estimated bihemispheric load would result in significant errors of estimation. In our sample, estimated bihemispheric counts were inaccurate by an average of 18% (range 0--80%). Despite this large range of error, calculation of Cronbach's alpha revealed that actual error due to unreliability (4%) was small relative to the large variation in ME counts across subjects in this patient series. These findings suggest that unilateral monitoring is sufficient when the goal is to characterize a given subject's ME load within the context of the other subjects in the sample. However, when precise ME counts are required, bilateral monitoring is essential.

Single photon emission computed tomography, magnetic resonance imaging hyperintensity, and cognitive impairments in patients with vascular dementia.

BACKGROUND: The relationship between subcortical hyperintensity (SH) on magnetic resonance imaging (MRI), cortical perfusion on single photon emission computed tomography (SPECT), and cognitive function is not well understood. The authors examined these relationships in individuals with vascular dementia (VaD), paying particular attention to frontal lobe function to determine whether the presence of SH on MRI was associated with frontal hypoperfusion on SPECT, which in turn would be associated with impairments of executive-attention function. METHODS: Patients with vascular dementia (n = 26) were assessed on neurocognitive tests and brain MRI and SPECT. SH volume was quantified from the axial T2-weighted fluid attenuated inversion recovery MRI. Total counts of activation across voxels for 12 cortical regions of interest were determined from SPECT. Perfusion ratios of both total cortical and frontal activation relative to cerebellum activation were derived, and regression analyses were performed to determine the relationships between cognitive, MRI, and SPECT indices. RESULTS: SH volume on MRI was significantly associated with frontal lobe perfusion, but not with global cortical perfusion as measured by SPECT. Frontal lobe perfusion did not consistently correlate with performance on measures of executive-attention function, although both total and frontal perfusion ratios were significantly associated with other cognitive functions. CONCLUSIONS: These results suggest that a functional "disconnection" between the frontal lobes and subcortical structures does not fully account for the magnitude of global cognitive impairment in VaD. Cortical perfusion as measured by SPECT appears to be associated with cognitive performance, but not specifically executive-attention dysfunction. Additional studies are needed to further examine the relationship between subcortical and cortical function in VaD.

Executive function and magnetic resonance imaging subcortical hyperintensities in vascular dementia.

OBJECTIVE: To determine the relation between subcortical hyperintensities (SHs) visible on magnetic resonance imaging and executive function among patients with vascular dementia. BACKGROUND: The relation between SHs and executive dysfunction is not well understood, because studies have varied widely in methodology and have produced conflicting results. METHOD: We examined the relation between SHs (expressed as a percentage of total brain volume, not including ventricular volume) and six tests of executive function in a well-defined group of 24 individuals with vascular dementia. Executive tests were divided in two groups: Attention/Speed and Abstraction/Problem Solving. Bivariate correlations were computed between individual neuropsychological variables and SHs. RESULTS: Results showed significant bivariate correlations between SHs and three of the four tests in the Attention/Speed domain. Subcortical hyperintensities shared virtually no association with performance on tests in the Abstraction/Problem-Solving domain. CONCLUSIONS: The finding that SHs are significantly associated with psychomotor slowing and attentional dysfunction is consistent with what is known about the behavioral manifestations of subcortical disease. More detailed investigations of the regional distribution of SHs as well as measures of atrophy, hypoperfusion, and hypometabolism may be necessary to accurately characterize the complex relation between vascular disease and different aspects of executive dysfunction.

Emotional and personality changes following cingulotomy.

The effects of bilateral anterior cingulate cortex (ACC) lesions on emotional and personality functioning were studied. Patients undergoing cingulotomy for chronic intractable pain were assessed on the Minnesota Multiphasic Personality Inventory (MMPI), the Profile of Mood States (POMS), cognitive tests, and pain ratings, pre- and postsurgically. Patients with intractable pain, not treated with cingulotomy, served as controls. Cingulotomy patients experienced reductions in POMS-Tension, POMS-Anger, and MMPI Scale 7 (Psychasthenia) compared with baseline and the controls. POMS-Tension was significantly correlated with attention-intention performance. The results indicate that the ACC modulates emotional experience, related to self-perceived tension, and that there is relationship between the emotional and the attentional effects of cingulotomy.

Bupropion SR vs. methylphenidate vs. placebo for attention deficit hyperactivity disorder in adults.

Despite the increasing recognition of attention-deficit hyperactivity disorder (ADHD) in adults, there are few controlled trials demonstrating the effectiveness of pharmacological treatments, particularly with nonstimulants. One controlled trial found bupropion SR more effective than placebo in the treatment of ADHD adults. We conducted a controlled study to contrast the effectiveness of bupropion SR and methylphenidate to placebo in ADHD adults. A randomized, double-blind, parallel design was used in this study. Following a 7-day placebo lead-in, 30 ADHD (DSM-IV) subjects (18-60 years old) were randomized to bupropion, methylphenidate, or placebo for 7 weeks. Methylphenidate was titrated over 1 week to a maximum dose of 0.9 mg/kg/d divided into 3 doses while bupropion was titrated over 2 weeks to a maximum dose of 200 mg A.M. and 100 mg P.M. Response rates based on Clinical Global Impression improvement ratings in patients receiving bupropion, methylphenidate, and placebo were 64, 50, and 27%, respectively. The difference in response rates between active treatment and placebo was not statistically significant (p = 0.14). Neuropsychological testing demonstrated trends favoring drug treatment on measures of immediate recall and verbal fluency. While bupropion SR may be a viable clinical alternative for adults with ADHD, further investigation is needed.

Dementia rating scale performance: a comparison of vascular and Alzheimer's dementia.

Differences in the pattern of neuropsychological dysfunction associated with Alzheimer's disease (AD) and vascular dementia (VaD) were examined using the Dementia Rating Scale (DRS). We examined three groups of patients: (1) Patients with AD; (2) patients with single stroke (CVA); and (3) patients with multiple cerebral infarctions (MI). Comparisons of cognitive dysfunction were conducted on patients that met the DRS criteria for dementia. Dementia groups were similar in age, education, and severity of dementia. Comparisons of the AD and two VaD groups across the specific DRS-scales (Attention, Conceptualization, Construction, Initiation/Perseveration, and Memory) indicated that patients with AD were more impaired on the DRS-Memory while the patients with VaD were more impaired on the DRS-Construction. Additionally, patients with VaD related to MI scored lower on the DRS-Initiation/Perseveration as compared to patients with AD, and patients with AD scored lower on the DRS-Conceptualization as compared to patients with VaD related to CVA. These results are indicative of qualitative differences in the pattern of cognitive deficits associated with the two types of dementia.

Electroencephalographic, volumetric, and neuropsychological indicators of seizure focus lateralization in temporal lobe epilepsy.

CONTEXT: Anterior temporal lobectomy is an effective treatment for medically intractable temporal lobe seizures. Identification of seizure focus is essential to surgical success. OBJECTIVE: To examine the usefulness of presurgical electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychological data in the lateralization of seizure focus. DESIGN: Presurgical EEG, MRI, and neuropsychological data were entered, independently and in combination, as indicators of seizure focus lateralization in discriminant function analyses, yielding correct seizure lateralization rates for each set of indicators. SETTING: Comprehensive Epilepsy Program, Shands Teaching Hospital, University of Florida, Gainesville. PATIENTS: Forty-four right-handed adult patients who ultimately underwent successful anterior temporal lobectomy. Left-handed patients, those with less-than-optimal surgical outcome, and any patients with a history of neurological insult unrelated to seizure disorder were excluded from this study. MAIN OUTCOME MEASURES: For each patient presurgical EEG was represented as a seizure lateralization index reflecting the numbers of seizures originating in the left hemisphere, right hemisphere, and those unable to be lateralized. Magnetic resonance imaging data were represented as left-right difference in hippocampal volume. Neuropsychological data consisted of mean scores in each of 5 cognitive domains. RESULTS: The EEG was a better indicator of lateralization (89% correct) than MRI (86%), although not significantly. The EEG and MRI were significantly superior to neuropsychological data (66%) (P=.02 and .04, respectively). Combining EEG and MRI yielded a significantly higher lateralization rate (93%) than EEG alone (P<.01). Adding neuropsychological data improved this slightly (95%). CONCLUSIONS: The EEG and MRI were of high lateralization value, while neuropsychological data were of limited use in this regard. Combining EEG, MRI, and neuropsychological improved focus lateralization relative to using these data independently.

Alteration of intention and self-initiated action associated with bilateral anterior cingulotomy.

Neuropsychological manifestations of bilateral anterior cingulate cortex lesions were studied in patients treated with cingulotomy for chronic intractable pain. Cingulotomy patients more than 1 year postsurgery were contrasted with nonsurgical chronic pain patients. Patients were assessed on a neuropsychological battery, including measures of response intention, initiation, generation, and persistence. Cingulotomy patients were intact across most cognitive domains, but they showed deficits of focused and sustained attention as well as mild executive dysfunction. Self-initiated responding--including spontaneous verbal utterances and unstructured design fluency--was most impaired. Results indicate that the greatest impact of cingulotomy lesions is on response intention and self-initiated behavior, with reduced behavioral spontaneity.

Impairments of attention after cingulotomy.

BACKGROUND: Outcome studies have generally not indicated significant cognitive disturbances after cingulotomy. There is now considerable evidence that the cingulate may play an important role in emotional behavior and attention. OBJECTIVE: To characterize impairments of attention associated with bilateral lesions of the anterior cingulate cortex produced by cingulotomy. METHODS: Twelve patients who underwent cingulotomy for treatment of intractable pain were administered tests of attention, executive functions, response intention and production, and a broad range of other neurocognitive functions before surgery and again 3 and 12 months after surgery. Data from this within-subjects repeated-measures design were analyzed by multivariate analysis of variance procedures. RESULTS: After cingulotomy, patients initially had executive and attentional impairments. By 12 months, these had resolved into more circumscribed deficits, with greatest impairments on tasks requiring intention and spontaneous response production, and milder impairments of focused and sustained attention. Other aspects of attention and other cognitive functions were generally unaffected. CONCLUSION: The anterior cingulate cortex modulates response intention and focused attention.

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.

Neurocognitive functioning and improvement in quality of life following participation in cardiac rehabilitation.

We investigated the relationship between neurocognitive functioning and quality of life/self-perceived health status (QOL) among cardiac rehabilitation (CR) patients to determine whether level of neurocognitive functioning is related to baseline QOL and improvement following CR. CR patients (n = 35) were given a neurocognitive screening before participation in CR, and also completed a behavioral inventory (SF-36) before and after CR to measure QOL associated with medical illness. At baseline, CR patients obtained relatively low SF-36 scores compared with published norms, and as reported previously, demonstrated inferior neurocognitive performance compared with healthy controls. Furthermore, neurocognitive performance was strongly positively correlated to SF-36 scores. Significant improvements were evident on many of the SF-36 subscales following rehabilitation. These improvements were relatively greater among SF-36 indexes of physical health status compared with SF-36 indexes of mental health status. Baseline neurocognitive performance also correlated strongly to the degree of improvement in SF-36 scores following rehabilitation. These findings indicate a strong relationship between baseline neurocognitive functioning and QOL before CR, and the degree to which QOL improves following this intervention.

Neuropsychological functioning among cardiac rehabilitation patients.

PURPOSE: The underlying pathophysiology contributing to coronary heart disease also predisposes patients to cerebrovascular disease and associated cognitive disorders. Although prior studies have focused on the neuropsychological sequelae of specific cardiac problems, few have examined the associated cognitive capacities and limitations of typical cardiac patients. The current study was designed to examine neuropsychological functioning among a sample of cardiac rehabilitation (CR) patients. METHODS: Using neuropsychological instruments, patients were compared in a CR program to age-matched outpatient control subjects who had no known history of cardiac or neurologic disease. Cardiac rehabilitation patients were then divided into dichotomous subgroups based on whether they had undergone coronary artery bypass grafting, had experienced a myocardial infarction, had hypertension, or had impaired ejection fraction. Neuropsychological functioning was examined relative to each of these factors. RESULTS: Cardiac rehabilitation patients had poorer neuropsychological test performance than did control subjects, with subtle relative deficits on measures of response generation, memory, and verbal abstraction, and particularly verbal fluency. Low ejection fraction, hypertension, and prior coronary artery bypass graft were associated with greater relative neuropsychological impairments. CONCLUSIONS: Although CR patients were not grossly neuropsychologically impaired as a group, it appears highly likely that many within a given program exhibit some degree of neuropsychological dysfunction. Including neuropsychological screening as part of pre-CR testing would help to identify such patients. This information may help staff to impart health care information in a manner that is most effective for the individual patient and may also be useful in the formation of realistic goals.

Reduplicative paramnesia: longitudinal neurobehavioral and neuroimaging analysis.

Reduplicative paramnesia (RP) is a delusion in which the patient perceives familiar places, objects, or events to have been duplicated. The current case describes the development of RP in an 81-year-old male following a large right frontal lobe infarction. As the patient had been hospitalized previously with hemorrhagic contusions, neurologic, neuropsychological, and neuroimaging data were obtained both prior to and following RP onset. Psychophysiologic data were obtained following the development of the delusion. Both premorbidly and at follow-up, neuropsychological functioning was characterized by significant impairments of learning and memory and frontal-executive functions. Language and visuospatial skills and motor speed were intact both before and after RP onset. The case is described within the context of preexisting theories of RP, and it is surmised that the delusion is secondary to temporal-limbic-frontal dysfunction giving rise to a distorted sense of familiarity and impaired ability to resolve the delusion via reasoning.