Relationships among Cortical Glutathione Levels, Brain Amyloidosis, and Memory in Healthy Older Adults Investigated In Vivo with 1H-MRS and Pittsburgh Compound-B PET.

BACKGROUND AND PURPOSE: Oxidative stress has been implicated as an important pathologic mechanism in the development of Alzheimer disease. The purpose of this study was to assess whether glutathione levels, detected noninvasively with proton MR spectroscopy, are associated with brain amyloidosis and memory in a community-dwelling cohort of healthy older adults. MATERIALS AND METHODS: Fifteen cognitively healthy subjects were prospectively enrolled in this study. All subjects underwent 1H-MR spectroscopy of glutathione, a positron-emission tomography scan with an amyloid tracer, and neuropsychological testing by using the Repeatable Battery for the Assessment of Neuropsychological Status. Associations among glutathione levels, brain amyloidosis, and memory were assessed by using multivariate regression models. RESULTS: Lower glutathione levels were associated with greater brain amyloidosis in the temporal (P = .03) and parietal (P = .05) regions, adjusted for apolipoprotein E ε4 carrier status. There were no significant associations between glutathione levels and cognitive scores. CONCLUSIONS: This study found an association between cortical glutathione levels and brain amyloidosis in healthy older adults, suggesting a potential role for 1H-MR spectroscopy measures of glutathione as a noninvasive biomarker of early Alzheimer disease pathogenesis.

Results of intervention for lupus patients with self-perceived cognitive difficulties.

The authors developed an 8-week psychoeducational group intervention for patients with systemic lupus erythematosus (SLE) who reported cognitive dysfunction but were not globally impaired on neuropsychological testing. Results of a nonrandomized, uncontrolled pilot study of this program in 17 women with SLE suggest that metamemory and memory self-efficacy improve after participation. One hundred percent retention throughout the study further suggests that patients with SLE are willing and capable of successfully completing the program.

Letter and semantic fluency in older adults: effects of mild depressive symptoms and age-stratified normative data.

Depression induced cognitive impairment, also referred to as the dementia syndrome of depression or pseudodementia, has been well characterized, yet the extent to which the more common mild depressive symptoms influence cognition has not been well studied. We sought to identify the influence of mild depressive symptoms on verbal fluency performance in a large sample of healthy community dwelling older adults. Letter and semantic fluency testing was conducted on 188 participants (ages 60-92 years) with no known history of neurologic or psychiatric disease. Depressive symptoms were assessed with the Geriatric Depression Scale (GDS). A total of 39 subjects obtained GDS scores consistent with mild depressive symptoms (GDS=10-19), and 149 subjects were identified as not depressed (GDS<10). ANOVA indicated that subjects with mild depressive symptoms performed significantly worse than normal controls on letter fluency (p<.05), but there was no significant difference between the groups on semantic fluency. Analysis of the nondepressed group stratified into young-old, middle-old, and oldest-old revealed a significant decline in semantic (p<.001) but not letter fluency with age. The nondepressed young-old showed the expected advantage for word list generation to semantic as compared to letter categories, yet this pattern was reversed in the older age groups, where letter fluency scores exceeded semantic fluency scores. Our results suggest that the presence of even mild depressive symptoms may confound using letter versus category discrepancies in the differential diagnosis of dementia. Further, our findings suggest that the commonly used strategy of examining letter-semantic fluency discrepancies may not be relevant for individuals of advanced age. Age-stratified normative data for fluency testing in older adults is also provided.

Relations among indexes of memory disturbance and depression in patients with Lyme borreliosis.

This study examined the relation between complaints of memory disturbance and measures of mood and memory functioning in 55 patients with serological evidence of late-stage Lyme Borreliosis (LB). Patients completed the Self-Ratings of Memory Questionnaire (SRMQ) and the Beck Depression Inventory. Memory functioning was assessed with the California Verbal Learning Test. Depressed patients exhibited more frequent complaints of memory disturbance on the SRMQ, although their pattern of responses did not differ from nondepressed patients. There was a significant correlation between subjective memory ratings and self-reported depression (Spearman rho = -.57, p < .001). No relation was observed between subjective memory ratings and objective memory performance. The results indicate subjective complaints of more severe memory disturbance in patients with LB and depression. Particular attention should be paid to the assessment of depression and subjective symptoms of memory disturbance when administering neuropsychological tests of memory functioning in patients with LB.

The effect of menopause and perimenopause on the course of epilepsy.

PURPOSE: The purpose of this study was to obtain preliminary information about the effect of menopause and perimenopause on the course of epilepsy, and to determine whether seizure type, use of hormone-replacement therapy (HRT), or a history of catamenial seizure pattern would influence this course. METHODS: We performed a questionnaire study of women with epilepsy currently in menopause and perimenopause, requesting information regarding the course of their epilepsy and treatment. Statistical analysis was performed by using Pearson chi2 with 95% confidence limits. RESULTS: Forty-two menopausal women (ages 41-86 years) responded. Twelve subjects reported no change in seizures at menopause, 17 reported a decrease in seizure frequency, and 13 reported an increase. Sixteen (38%) took synthetic HRT. Sixteen (38%) additional subjects (having some overlap with the HRT group) reported having a catamenial seizure pattern before menopause. HRT was significantly associated with an increase in seizures during perimenopause (p = 0.001). A history of catamenial seizure pattern was significantly associated with a decrease in seizures at menopause (p = 0.013). Thirty-nine perimenopausal women (ages 38-55 years) responded. Nine subjects reported no change in seizures at perimenopause, five reported a decrease in seizure frequency, and 25 reported an increase. Eight (15%) subjects took synthetic HRT, and 28 (72%) reported having a catamenial seizure pattern before menopause. HRT had no significant effect on seizures; however, a history of catamenial seizure pattern was significantly associated with an increase in seizures at perimenopause (p = 0.02). CONCLUSIONS: These pilot data suggest that synthetic HRT may be associated with an increase in seizure frequency in menopausal women with epilepsy. A catamenial seizure pattern may be associated with seizure decrease during menopause but with an increase during perimenopause.

A beneficial effect on mood in partial epilepsy patients treated with gabapentin.

PURPOSE: Antiepileptic drugs (AEDs) are frequently used for their beneficial psychoactive effects on affective disorders. We sought to demonstrate a psychoactive effect of gabapentin (GBP) when used as add-on AED therapy. METHODS: Forty adult patients with partial epilepsy were studied in a prospective, non-randomized fashion with interviewer-rated and self-rated scales of mood and anxiety: the Cornell Dysthymia Rating Scale (CDRS), Beck Depression Inventory (BDI), and Hamilton Depression (Ham-D) and Anxiety (Ham-A) Scales. After completion of baseline mood and anxiety scales (time 1), 20 of the 40 patients were prescribed add-on GBP (treated group). The remaining 20 patients served as a control group. Both groups were similar in age and sex distribution. Follow-up mood and anxiety scales were performed in all patients approximately 3 months later (time 2). The average GBP dose at time 2 was 1,615 mg/day. All patients were taking stable doses of one to four AEDs at baseline and throughout the study. Seizure frequency was monitored throughout. Statistical significance was assessed by analysis of variance (ANOVA) by using a two-factor repeated-measures model. RESULTS: The GBP-treated group had a significant decrease in CDRS score over time compared with the control group (p = 0.04). No significant differences between the control and the treated groups were found for any of the remaining mood scales (BDI, p = 0.58; Ham-D, p = 0.59; Ham-A, p = 0.93). There was no significant difference or change in seizure frequency between groups. CONCLUSIONS: GBP treatment is associated with mood improvement as measured by the CDRS. This improvement was not accounted for by seizure improvement.

Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing.

CONTEXT: Given the similarities between Alzheimer disease and dementia pugilistica, we evaluated the relationship between apolipoprotein E (APOE) genotype and chronic traumatic brain injury (CTBI) in boxers to determine whether there is a genetic susceptibility to the effects of head trauma. OBJECTIVE: To assess the relationship between CTBI and APOE genotype in boxers. DESIGN AND SETTING: Clinical characterization of 24 volunteer and 6 referred boxers in an outpatient setting. PARTICIPANTS: Thirty professional boxers aged 23 to 76 years underwent neurologic and behavioral assessment in conjunction with APOE genotyping. MAIN OUTCOME MEASURES: Apolipoprotein E genotype was examined in relationship to measures of CTBI. A 10-point clinical rating scale (0-9), the Chronic Brain Injury (CBI) scale, was devised to assess the severity of traumatic encephalopathy associated with boxing. Boxers with abnormal CTBI scores were further classified on the basis of whether their impairments were possibly or probably related to boxing. Scores were analyzed in relation to boxing exposure (number of bouts) and APOE genotype. RESULTS: Among the 30 boxers, 11 were found to be normal (CBI score=0), 12 showed mild deficits (CBI score=1-2), 4 were moderately impaired (CBI score=3-4), and 3 showed signs of severe impairment (CBI score > 4). High-exposure boxers (ie, those with > or = 12 professional bouts) had significantly higher CBI scores (mean [SD], 2.6 [1.9]) than low-exposure boxers (mean [SD], 0.3 [0.7]) (P<.001), indicating that neurologic impairment as measured by the CBI scale seems related to boxing exposure. The APOE genotype frequencies of the study population were approximately the same as those found in the general population. Boxers with low exposure had mean CBI scores of 0.33, irrespective of APOE genotype. However, high-exposure boxers with an APOE epsilon4 allele had significantly greater CBI scores (mean [SD], 3.9 [2.3]) than high-exposure boxers without APOE epsilon4 (mean [SD], 1.8 [1.2]) (P=.04). All boxers with severe impairment possessed at least 1 APOE epsilon4 allele. The tendency for greater CTBI among those with both high exposure and an epsilon4 allele was statistically significant at the P<.001 level. CONCLUSIONS: These preliminary findings suggest that possession of an APOE epsilon4 allele may be associated with increased severity of chronic neurologic deficits in high-exposure boxers.

Serial recovery of language during the intracarotid amobarbital procedure.

There is considerable variability among epilepsy centers in the methods and interpretations of the intracarotid amobarbital procedure. Prominent among these differences is the determination of language representation and assessment of language functions. Some centers rely on speech arrest following amobarbital injection as a marker for language representation, whereas other centers examine verbal output for the presence of aphasic errors. The present study assessed the pattern of language recovery following amobarbital injection in epilepsy patients who were candidates for temporal lobectomy. Language recovery from dominant hemisphere injection (left or right) followed a stereotypical progression, with 71.8% of patients showing return of vocalization followed by return of naming and comprehension. Repetition deficits with paraphasic errors persisted the longest (mean = 12'30"), with a conduction aphasia persisting after the acute global aphasia resolved. Although two patients interpreted as left hemisphere language dominant were mute following right hemisphere injection, all language functions were intact immediately upon resumption of vocalization and they showed no other signs of aphasia such as paraphasias or anomia. Possible explanations for serial language recovery and persistent conduction aphasia are discussed. These findings have significant implications for the determination of cerebral language dominance.

Clinical features of neocortical temporal lobe epilepsy.

Few studies have examined the clinical features of neocortical temporal lobe epilepsy (NTLE) in carefully selected patients. We reviewed records from 21 patients with NTLE, defined by intracranial electroencephalogram (EEG), who have been seizure free for 1 year or more following temporal lobectomy. The mean age of onset at the time of first seizure was 14 years (range, 1-41 years). Febrile seizures were reported in only 2 patients (9.5%). In contrast to prior mesial temporal lobe epilepsy (MTLE) studies, seizure-free intervals between the initial cerebral insult or first seizure and habitual seizures were uncommon. Possible or known risk factors for epilepsy were reported in 13 of 21 patients (62%). Fifteen (71%) patients reported auras, with experiential phenomena being the most common type. Magnetic resonance imaging was normal or nonspecific in 15 patients, revealed mild hippocampal atrophy in 2, tumors in 2, and heterotopic gray matter and hippocampal atrophy in 1, and cortical dysgenesis in 1. Neuropsychological testing showed deficits consistent with the seizure focus in 13 patients (62%), and Wada test showed ipsilateral memory deficits in 10 (48%). The most common behavioral manifestation was a motionless stare at ictal onset (48%). In contrast to prior studies of MTLE, only 1 NTLE patient had frequent independent, contralateral temporal lobe epileptiform spikes on scalp EEG.

Memory functioning in Lyme borreliosis.

BACKGROUND: To objectively measure memory functioning in patients with Lyme borreliosis and examine the relationship between subjective reports of memory dysfunction and actual impairment. METHOD: A prospective pretreatment study of patients with Lyme borreliosis (N = 21), a patient control group (osteomyelitis, N = 21), and healthy controls (N = 21) was conducted by using tests of verbal memory functioning (California Verbal Learning Test) and self-reported depression (Beck Depression Inventory-Cognitive Index), fatigue (Fatigue Severity Scale), and subjective ratings of memory abilities (Self-Rating Scale of Memory Functions). RESULTS: Patients with Lyme borreliosis performed worse than healthy controls on verbal memory testing, but did not perform significantly differently from patient controls. Lyme borreliosis patients reported increased fatigue, which was correlated with poorer memory performance. Although the Lyme borreliosis patients rated their memory as more impaired, subjective complaints were not correlated with objective memory scores. CONCLUSION: These findings suggest impaired memory performance is not specific to Lyme borreliosis and may be a result of evaluating cognitive functioning in patients with physical illness and somatic complaints. Fatigue is a prominent presenting complaint in patients with Lyme borreliosis and needs to be controlled for since it is known to influence neuropsychological performance. Subjective complaints are not correlated with objective memory assessment, so self-report of memory impairment should not be the criterion for inclusion in studies investigating cognitive manifestations of Lyme borreliosis.

Sleep quality in Lyme disease.

Complaints of chronic fatigue as well as sleep disturbances are prevalent in Lyme disease. We compared polysomnographic measures of sleep in patients with documented Lyme disease with those of a group of age-matched normal control subjects. Eleven patients meeting Centers for Disease Control criteria for late Lyme disease with serologic confirmation by enzyme-linked immunosorbent assay and Western blot without a history of other medical or psychiatric illness and 10 age-matched control subjects were studied. Lyme disease patients and controls underwent 2 nights of polysomnography. Multiple sleep latency testing (MSLT) was performed in the patients. Sleep was staged by standard criteria, and continuity of sleep was assessed for each stage of frequency analysis of consecutive epochs. All patients studied reported sleep-related complaints, including difficulty initiating sleep (27%), frequent nocturnal awakenings (27%), excessive daytime somnolence (73%) and restless legs/nocturnal leg jerking (9%). Greater sleep latency, decreased sleep efficiency and a greater arousal index were noted in Lyme patients. The median length of uninterrupted occurrences of stage 2 and stage 4 non-rapid eye movement (NREM) sleep was less in Lyme patients (6.3 +/- 3.0 epochs in patients vs. 11.4 +/- 4.4 epochs in controls for stage 2, p < 0.01, and 4.3 +/- 4.4 epochs in patients vs. 11.2 +/- 6.3 epochs in controls for stage 4, p < 0.01), indicating greater sleep fragmentation. Mean sleep onset latency during the MSLT was normal (12.7 +/- 5.6 minutes). Three patients demonstrated alpha-wave intrusion into NREM sleep. These sleep abnormalities may contribute to the fatigue and sleep complaints common in this disease.

Cognitive remediation in schizophrenia: should we attempt it?

Subtle cognitive deficits persist in schizophrenia even after active periods of psychosis subside. Even though early attempts to ameliorate cognitive impairments were relatively successful, the endeavor was abandoned nearly 30 years ago. We contrast this state of affairs with that of closed-head injury, in which less well-designed and less successful attempts to treat similar impairments have been greeted with much enthusiasm. Objections to cognitive remediation in schizophrenia are evaluated and the attempt is encouraged.