Munro Cullum

Bifrontal, bitemporal and right unilateral electrode placement in ECT: randomised trial

BACKGROUND Electroconvulsive therapy (ECT) is an effective treatment for major depression. Optimising efficacy and minimising cognitive impairment are goals of ongoing technical refinements. AIMS To compare the efficacy and cognitive effects of a novel electrode placement, bifrontal, with two standard electrode placements, bitemporal and right unilateral in ECT. METHOD This multicentre randomised, double-blind, controlled trial (NCT00069407) was carried out from 2001 to 2006. A total of 230 individuals with major depression, bipolar and unipolar, were randomly assigned to one of three electrode placements during a course of ECT: bifrontal at one and a half times seizure threshold, bitemporal at one and a half times seizure threshold and right unilateral at six times seizure threshold. RESULTS All three electrode placements resulted in both clinically and statistically significant antidepressant outcomes. Remission rates were 55% (95% CI 43-66%) with right unilateral, 61% with bifrontal (95% CI 50-71%) and 64% (95% CI 53-75%) with bitemporal. Bitemporal resulted in a more rapid decline in symptom ratings over the early course of treatment. Cognitive data revealed few differences between the electrode placements on a variety of neuropsychological instruments. CONCLUSIONS Each electrode placement is a very effective antidepressant treatment when given with appropriate electrical dosing. Bitemporal leads to more rapid symptom reduction and should be considered the preferred placement for urgent clinical situations. The cognitive profile of bifrontal is not substantially different from that of bitemporal.

Cognitive endophenotypes of psychosis within dimension and diagnosis

This study sought to characterize the psychosis phenotype, contrasting cognitive features within traditional diagnosis and psychosis dimension in a family sample containing both schizophrenia and psychotic bipolar I disorder. Seventy-six probands with psychosis [44 probands with schizophrenia, 32 probands with psychotic bipolar I disorder] and 55 first-degree relatives [30 relatives of schizophrenia probands, 25 relatives of bipolar probands] were recruited. Standardized clinical and neuropsychological measures were administered. No differences in cognitive performance emerged between probands with schizophrenia and probands with psychotic bipolar disorder, or between relatives of probands with schizophrenia and relatives of probands with bipolar disorder in the domains of working and declarative memory, executive function and attention. Relatives overall showed higher cognitive performance compared to probands, as expected. However, when we segmented the probands and relatives along a psychosis dimension, independent of diagnostic groups, results revealed lower cognitive performance in probands compared to relatives without psychosis spectrum disorders, whereas relatives with psychosis spectrum disorders showed an intermediate level of performance across all cognitive domains. In this study, cognitive performance did not distinguish either probands or their first-degree relatives within traditional diagnostic groups (schizophrenia and psychotic bipolar disorder), but distinguished probands and relatives with and without lifetime psychosis manifestations independent of diagnostic categories. These data support the notion that schizophrenia and psychotic bipolar disorder present a clinical continuum with overlapping cognitive features defining the psychosis phenotype.

Normative data for the Montreal Cognitive Assessment (MoCA) in a population-based sampleAuthor Response

# {#article-title-2} Rossetti et al.1 reported a population-based study of scores on the Montreal Cognitive Assessment (MoCA) in Texas. Compared to our study2 in Montreal, the Caucasian group of normal controls in the Rossetti et al. study was considerably younger (52.9 vs 72.8 years) and had slightly lower mean MoCA scores (25.6 vs 26.9). In the other ethnic groups, they found substantial effects of age and education on their MoCA scores. Subjects in our study were excluded if they had subjective complaints …

Altered Neural Cholinergic Receptor Systems in Cocaine-Addicted Subjects

Changes in the brains cholinergic receptor systems underlie several neuropsychiatric disorders, including Alzheimers disease, schizophrenia, and depression. An emerging preclinical literature also reveals that acetylcoholine may have an important function in addictive processes, including reward, learning, and memory. This study was designed to assess alterations in cholinergic receptor systems in limbic regions of abstinent cocaine-addicted subjects compared with healthy controls. On three separate days, 23 1- to 6-week abstinent, cocaine- (and mostly nicotine-) addicted subjects and 22 sex-, age-, and race-matched control subjects were administered the muscarinic and nicotinic cholinergic agonist physostigmine, the muscarinic antagonist scopolamine, and saline. Regional cerebral blood flow (rCBF) after each infusion was determined using single photon emission-computed tomography. Both cholinergic probes induced rCBF changes (p<0.005) in relatively distinct, cholinergic-rich, limbic brain regions. After physostigmine, cocaine-addicted subjects showed altered rCBF, relative to controls, in limbic regions, including the left hippocampus, left amygdala, and right insula. Group differences in the right dorsolateral prefrontal cortex, posterior cingulate, and middle temporal gyrus were also evident. Scopolamine also revealed group differences in the left hippocampus and right insula as well as the posterior cingulate and middle temporal gyrus. Cocaine addicted and controls differ in their subcortical, limbic, and cortical response to cholinergic probes in areas relevant to craving, learning, and memory. Cholinergic systems may offer a pharmacologic target for cocaine addiction treatment.

Comparison of the CERAD and CVLT list-learning tasks in Alzheimer's disease.

This investigation examined the relationship of the word list from the CERAD neuropsychological battery to the California Verbal Learning Test (CVLT) in a sample of 138 subjects with Probable Alzheimer’s disease (AD). Results revealed modest but statistically significant associations between the two measures on many key variables. Total words learned showed the strongest association, with lower correlations for delayed recall, intrusion errors, and recognition variables. As expected, the CERAD and CVLT assess similar aspects of verbal learning in patients with AD. However, the modest level of many of the correlations suggests that caution should be exercised in applying the same interpretive strategies derived on more comprehensive measures to shorter ones.

Reduced global brain metabolism but maintained vascular function in amnestic mild cognitive impairment.

Amnestic mild cognitive impairment represents an early stage of Alzheimer’s disease, and characterization of physiological alterations in mild cognitive impairment is an important step toward accurate diagnosis and intervention of this condition. To investigate the extent of neurodegeneration in patients with mild cognitive impairment, whole-brain cerebral metabolic rate of oxygen in absolute units of µmol O2/min/100 g was quantified in 44 amnestic mild cognitive impairment and 28 elderly controls using a novel, non-invasive magnetic resonance imaging method. We found a 12.9% reduction (p = 0.004) in cerebral metabolic rate of oxygen in mild cognitive impairment, which was primarily attributed to a reduction in the oxygen extraction fraction, by 10% (p = 0.016). Global cerebral blood flow was not found to be different between groups. Another aspect of vascular function, cerebrovascular reactivity, was measured by CO2-inhalation magnetic resonance imaging and was found to be equivalent between groups. Therefore, there seems to be a global, diffuse diminishment in neural function in mild cognitive impairment, while their vascular function did not show a significant reduction.

Poster 265 Relationship Between Severe Headache and Elevated Depression and Anxiety Scores after Sports-Related Concussion

Design: Retrospective chart review using Mayo’s Advanced Cohort Explorer (ACE) program. Setting: Tertiary care hospital. Participants: 120 subjects ages 18-60 with a history of depression who then went on to sustain a concussion were included in the study. 60 were on pharmacologic treatment of depression at the time of concussion and 60 were not on pharmacologic depression treatment at the time of concussion. Exclusion criteria included prior concussion, history of migraine, or intracranial bleed at time of head injury. Interventions: Not applicable. Main Outcome Measures: Number of clinician visits (physician, neuropsychologist, therapist) for post-concussion symptoms (symptoms not present prior to concussion) were counted via review of medical record and recorded at 3, 6, and 12 months. Results: In treated group, mean number of clinician visits for postconcussion symptoms was 1.91.5 at 3 months, 2.43.4 at 6 months, and 2.85.3 at 12 months. In untreated group, mean number of visits was 6.13.8 at 3 months, 10.811.3 at 6 months, and 15.818.8 at 12 months. The treated group had statistically significant (P<.001) fewer visits than the untreated group at 3, 6, and 12 months. Conclusions: In patients that have a history of depression and then sustain a concussion, pharmacologic treatment of depression at the time of concussion results in a significantly fewer clinician visits for post-concussion symptoms compared to depressed patients not pharmacologically treated for their depression at the time of sustaining a concussion. Furthermore, fewer clinician visits represents a decrease in healthcare utilization. A prospective study would be the next step to confirm this association and investigate role of starting pharmacologic treatment after concussion. Level of Evidence: Level III

Odorant Item Specific Olfactory Identification Deficit May Differentiate Alzheimer Disease From Aging

OBJECTIVES To explore whether the ability to recognize specific odorant items is differentially affected in aging versus Alzheimer disease (AD); to refine olfactory identification deficit (OID) as a biomarker of prodromal and early AD. DESIGN Prospective multicenter cross-sectional study with a longitudinal arm. SETTING Outpatient memory diagnostic clinics in New York and Texas. PARTICIPANTS Adults aged 65 and older with amnestic mild cognitive impairment (aMCI) and AD and healthy aging (HA) subjects in the comparison group. MEASUREMENTS Participants completed the University of Pennsylvania Smell Identification Test (UPSIT) and neuropsychological testing. AD-associated odorants (AD-10) were selected based on a model of ordinal logistic regression. Age-associated odorants (Age-10) were identified using a linear model. RESULTS For the 841 participants (234 HA, 192 aMCI, 415 AD), AD-10 was superior to Age-10 in separating HA and AD. AD-10 was associated with a more widespread cognitive deficit across multiple domains, in contrast to Age-10. The disease- and age-associated odorants clustered separately in age and AD. AD-10 predicted conversion from aMCI to AD. CONCLUSIONS Nonoverlapping UPSIT items were identified that were individually associated with age and disease. Despite a modest predictive value of the AD-specific items for conversion to AD, the AD-specific items may be useful in enriching samples to better identify those at risk for AD. Further studies are needed with monomolecular and unilateral stimulation and orthogonal biomarker validation to further refine disease- and age-associated signals.

Valid but invalid: suboptimal impact© baseline performance in university athletes

Objective To investigate the frequency of valid yet suboptimal ImPACT© performance in college athletes. Design Descriptive. Setting Research Laboratory. Participants Division 1 University athletes (n=769) from 22 different sports. Intervention The Immediate Postconcussion Assessment and Cognitive Test (ImPACT) was administered to participants per the institution’s concussion management protocol at baseline in groups <2. Participants who scored <16th percentile compared to ImPACT normative data on any neurocognitive index (potentially suggesting suboptimal effort) were re-administered ImPACT up to two additional times. Outcome measures Descriptive analyses were used to examine validity indicators and individual Verbal and Visual Memory, Visual Motor Speed and Reaction Time ImPACT composite scores in initial and subsequent administrations. Main results Based on ImPACT’s validity criteria, 1% (9/769) of administrations were invalid and 14.6% (112/769) had one or more composite scores <16th percentile but were considered valid. After one re-administration 71.4% (80/112) achieved scores >16th percentile and an additional 18/32 scored >16th percentile after a third administration. Conclusions Approximately 16% of ImPACT records were flagged as invalid or had one or more composite scores <16th percentile, potentially indicative of suboptimal performance. Upon readministration, 88% of those participants scored >16th percentile. Clinicians must be aware of suboptimal ImPACT performance as it limits the clinical utility of the baseline assessment. Further research is needed to address factors leading to “valid” but invalid baseline performance. Competing interests None.

Poster 147 Gender Differences in Symptom Reporting within Student-Athletes from the North Texas Sports Concussion Registry (ConTex)

Disclosures: Kathleen Bell: Consulting fees or other remuneration (payment) Avanir Pharmaceutical Objective: To examine gender differences in post-injury symptom reporting for adolescents enrolled in the ConTex study, a longitudinal concussion registry in North Texas. Design: Consecutive enrollment of clinical cohort using self-report. Setting: Four outpatient concussion or sports medicine clinics in North Texas. Participants: Subjects were 56 female and 47 male full-time students aged 13-19 years (M1⁄415.2, SD1⁄41.6) who consecutively presented 0-110 days (M1⁄417.7, SD1⁄420.0) after sports-related concussion. Interventions: Not applicable. Main Outcome Measures: Generalized Anxiety Disorders-7 (GAD-7), Patient Health Questionnaire (PHQ-9), and a Concussion Symptom Log. Results: Across 31 individual anxiety, depression, and concussion items examined, females tended to endorse symptoms somewhat more often, but only two items were significantly different by gender: 1) “Not being able to stop or control worrying” and 2) “Feeling bad about yourselfeor that you are a failure or have let yourself or your family down” (P1⁄4.024 and .046, respectively), with higher frequency endorsement by females (29% vs 11% and 20% vs 6%, respectively). No significant gender differences were found in total anxiety, depression or concussion symptom log scores (P>.05). Conclusions: Using global anxiety and depression self-report scores, we found no significant differences between the level of symptom reporting in females and males. However, females reported two items with greater frequency, suggesting the possibility of different psychological sequelae post sports concussion in female versus male adolescents. Level of Evidence: Level I