Carla Back-Madruga

Apathy and executive function in Alzheimer's disease.

Apathy is a common behavioral disturbance in patients with Alzheimers disease (AD). Recent studies have linked the presence of apathy to alterations in frontal lobe functions, but few studies have explored the relationship using standard neuropsychological measures in patients with AD. We administered a comprehensive battery of neuropsychological tests and a behavior rating scale to 80 patients with AD. We explored the relationship of apathy to executive dysfunction. AD patients with apathy performed significantly worse on tests of executive function (WAIS-R Digit Symbol, Trail-Making, Stroop Color Interference Test) than AD patients without apathy. The presence of dysphoria did not modify these results and no significant relationships were found between tests of executive functions and dysphoria. Performance on executive measures as a group were effective in correctly classifying patients as apathetic or nonapathetic with 75% accuracy. Neuropsychological measures not dependent on executive functions were unrelated to apathy. Apathy is associated with executive dysfunction and not with other neuropsychological deficits. Apathy is distinct from dysphoria.

Relational Integration and Executive Function in Alzheimer's Disease.

Executive functions depend on the ability to represent relations between objects and events, and the prefrontal cortex provides the neural substrate for this capacity. Patients with probable Alzheimers disease (AD) and control participants were administered measures of working memory and reasoning that varied systematically in their relational complexity. AD patients showed impairment on reasoning measures that required the online integration of relations but performed as well as control participants on nonrelational items and items requiring the processing of only single relations. When AD patients were divided into subgroups based on their performance on relational reasoning measures, the subgroup that showed significant impairment on relational integration measures exhibited a neuropsychological profile consistent with prefrontal cortical dysfunction.

Neuropsychological Effects of 3,4-Methylenedioxymethamphetamine (MDMA or Ecstasy) in Recreational Users

While neuropsychological studies on 3,4-methylenedioxymethamphetamine (MDMA or ecstasy) users have been emerging, results have been inconsistent, possibly due to methodological issues. The current study examined the performance of 22 recreational MDMA users compared to 28 age, education, and IQ comparable normal control subjects on a comprehensive battery of neuropsychological tests. Results revealed no significant differences in cognitive functioning between the MDMA users and normal controls. However, greater use of MDMA was associated with poorer scores on several measures of nonverbal memory, and greater frequency users (=50 times) evidenced significantly lower scores on 2 of 3 nonverbal memory tests compared to lesser frequency users (<50 times). Our results suggest that a subgroup of MDMA patients, specifically heavy MDMA users, evidence declines in nonverbal (visual) memory, however, other cognitive areas appear to be spared.

Changes in Mood States and Biomarkers during Peginterferon and Ribavirin Treatment of Chronic Hepatitis C

OBJECTIVE:u2003Depression is a frequent side effect of interferon therapy in patients with chronic hepatitis C (CHC). The aim of this study was to identify baseline and on-treatment predictors of depression in CHC patients receiving peginterferon and ribavirin.METHODS:u2003In total, 201 prior nonresponders with advanced fibrosis were treated with peginterferon alfa-2a and ribavirin for 24 wk in the Hepatitis C Antiviral Long-term Treatment against Cirrhosis trial. Of these, 74 continued on antiviral therapy through week 48. Mood states were assessed with the Beck Depression Inventory II and the Composite International Diagnostic Interview. Plasma cortisol and whole blood serotonin levels were measured in 101 subjects at weeks 0, 4, 24, 48, and 72.RESULTS:u2003The incidence of interferon-induced depression was 23% and 42% at weeks 24 and 48, respectively. Although 22% of patients had baseline depression, the absence of a week 20 virological response was the only independent predictor of interferon-induced depression at week 24 (P= 0.0009). Plasma cortisol levels did not change during treatment nor correlate with depression. In contrast, whole blood serotonin/platelet levels significantly decreased during treatment, but did not correlate with interferon-induced depression through week 24 (P= 0.35), nor through week 48 (P= 0.51).CONCLUSION:u2003Depression during peginterferon and ribavirin therapy was associated with a lower antiviral response. The significant reduction in whole blood serotonin levels over time suggest that further studies of the serotonergic pathway are warranted to identify the mediators of interferon-induced depression.

Cognitive function does not worsen during pegylated interferon and ribavirin retreatment of chronic hepatitis C

Treatment of chronic hepatitis C with pegylated interferon (peginterferon) and ribavirin can cause or exacerbate depression but its effects on cognitive function are largely unknown. The aim of this study was to determine whether treatment with peginterferon and ribavirin adversely impacts cognitive function in patients with chronic hepatitis C. Prior nonresponders to interferon were retreated with peginterferon alfa‐2a and ribavirin for 24 (n = 177) or 48 weeks (n = 57) in the Hepatitis C Antiviral Long‐term Treatment Against Cirrhosis trial. Cognitive function was prospectively assessed using a battery of 10 standardized neuropsychological tests at weeks 0, 24, 48, and 72. Cognitive impairment was defined based upon a global deficit score. The Beck Depression Inventory and Brief Symptom Inventory were used to assess mood status. The 57 subjects who completed 48 weeks of antiviral therapy reported significant increases in difficulty concentrating, emotional distress, and symptoms of depression, all of which improved after cessation of therapy [P < 0.0001, analysis of variance (ANOVA)]. Nonetheless, the frequency of cognitive impairment did not increase during the first 24 weeks of treatment in 177 patients (34% versus 32%, P = 0.64) nor in the 57 patients completing 48 weeks of treatment (P = 0.48, ANOVA). Conclusion: Retreatment of prior non‐responders with peginterferon and ribavirin was not associated with objective evidence of cognitive impairment as measured by a comprehensive battery of neuropsychological tests. The lack of cognitive impairment is reassuring and suggests that self‐reported symptoms of cognitive dysfunction are more likely related to the systemic and psychiatric side effects of antiviral treatment rather than measurable changes in cognition. (HEPATOLOGY 2007;45:1154–1163.)

Functional ability in executive variant Alzheimer's disease and typical Alzheimer's disease

A frontal, or executive, variant of Alzheimers disease (EAD) has been described in the literature in which frontal dysfunction accompanies temporal and parietal changes in the early stages of the illness. However, no study has empirically investigated associated aspects, such as neuropsychiatric symptoms, instrumental activities of daily living, or caregiver burden in this EAD subgroup. We compared the performance of two subgroups of mild Alzheimers disease patients (e.g., EAD and typical Alzheimers disease; TAD) on neuropsychological and associated measures. Results revealed that the EAD group, selected based on poor executive scores, did not significantly differ from the TAD group on nonexecutive neuropsychological tests of intelligence, language, verbal and nonverbal memory, or visual-spatial abilities. However, the EAD group evidenced more severe neuropsychiatric symptoms, impaired activities of daily living, and greater caregiver distress than the TAD group. Thus, the EAD subgroup is characterized by executive dysfunction, neuropsychiatric symptoms, and functional disability in excess of that seen in TAD. Whether our EAD subgroup represents an actual frontal variant of Alzheimers disease awaits replication in a larger sample including neuroimaging and pathological confirmation, as well as longitudinal assessment of cognition and neuropsychiatric symptoms.

Clinical relevance of cognitive scores in hepatitis C patients with advanced fibrosis.

Mild neuropsychological impairment has previously been reported in chronic hepatitis C (CHC) patients. The aim of this study was to assess the presence and severity of cognitive impairment among a cohort of CHC patients with advanced fibrosis using clinician ratings compared to classification based upon statistical methods. In addition, we set out to determine the relationship between cognitive scores and functional status. Two experienced neuropsychologists provided “clinician ratings” on a battery of 10 neuropsychological tests performed in 100 randomly selected patients participating in the HALT-C clinical trial. The overall kappa between the 2 graders on level of impairment was 0.59. Clinician ratings (the gold standard) were similarly sensitive to identifying cognitive impairment as was classification based on standard scores (44% vs. 40%). Global Deficit Scores (GDS), derived from pooling standard scores, also identified 44% of patients as having mild impairment and were highly correlated with clinician ratings (r = .81 p = < 0.0001). Neither clinician ratings nor deficit scores correlated with SF-36 subscale or summary scores but did correlate with depression scores (p < .0007). In summary, clinician ratings and deficit scores identified a similar prevalence of cognitive impairment amongst CHC patients with advanced fibrosis. There was a significant correlation between cognitive impairment and self-reported depression.

Cognitive reserve and neuropsychological functioning in patients infected with hepatitis C

This study evaluated the influence of cognitive reserve on neuropsychological test performance in 198 patients infected with the hepatitis C virus. IQ scores, educational level, and occupational rating were combined to calculate a Cognitive Reserve Score (CRS) for each patient. Similar to studies of infection with the human immunodeficiency virus, there was a significantly increased risk of impairment in neuropsychological test performance in individuals with lower CRSs. It is important to account for CRS when assessing cognitive findings in large-scale clinical trials.

Cognitive function does not worsen during long-term low-dose peginterferon therapy in patients with chronic hepatitis C.

OBJECTIVES:Neuropsychiatric toxicity is a common dose-limiting side effect of interferon therapy. The primary aim of this study was to determine whether patients receiving long-term low-dose peginterferon therapy had a higher incidence of cognitive side effects compared with untreated patients enrolled in the Hepatitis C Antiviral Long-Term treatment against Cirrhosis (HALT-C) Trial.METHODS:A total of 129 patients with chronic hepatitis C and advanced fibrosis completed a battery of 10 neuropsychological tests and the Beck Depression Inventory at pretreatment baseline and at months 12, 24, 36, and 48 while receiving long-term peginterferonα2a (90u2009μg/week) or no therapy during the randomized phase of the HALT-C Trial. Cognitive impairment was defined as a global deficit score (GDS) ≥1.0.RESULTS:The mean age was 51.2 years, 67% were male, and 42% had cirrhosis. After accounting for baseline GDS scores, the mean GDS scores did not significantly change over time (P=0.46) nor with treatment group (P=0.49). Cognitive function was also not influenced by medication adherence in the 66 patients receiving maintenance peginterferon (P=0.14) after controlling for baseline GDS scores and time. Beck Depression scores did not significantly increase over time (P=0.60), nor did they vary by treatment group (P=0.74). Although 32% of patients experienced objective worsening of their liver disease during follow-up, the frequency and severity of cognitive impairment did not differ in those with and without disease progression (P=0.71).CONCLUSIONS:Measures of cognitive function were neither influenced by low-dose peginterferon treatment nor with objective evidence of liver disease progression in patients with advanced chronic hepatitis C prospectively followed up for 3.5 years.

Has the Rolling Uterus Finally Gathered Moss? Somatization and Malingering of Cognitive Deficit in Six Cases of “Toxic Mold” Exposure

This article reports six cases of litigants claiming neuropsychiatric impairment due to toxic mold exposure. In spite of recent growth in personal injury claims due to mold, numerous reviews of the literature have failed to find an association between environmental exposure to mold and neuropsychiatric and/or neuropsychological damage. We report data on six patients claiming harm, 4 of whom revealed a long history of somatization by history and psychological testing, and 2 of whom were shown to be malingering based on multiple indicators of non-credible performance. Of the 6 patients, only the 2 somatoform patients who were also depressed showed credible evidence of neuropsychological dysfunction. We review two other studies that have examined the link between mold exposure and cognitive impairment and discuss their limitations in view of the presenting behaviors of these 6 patients. Until the literature has established a credible link between mold and neuropsychiatric/neuropsychological impairment, jurists and clinicians must consider the ethics and potential harm of exposing somatoform patients to multiple unwarranted medical evaluations. Principles for forensic evaluations in this special population are reviewed.