Development and assessment of a composite score for memory in the Alzheimer’s Disease Neuroimaging Initiative (ADNI)

We sought to develop and evaluate a composite memory score from the neuropsychological battery used in the Alzheimer’s Disease (AD) Neuroimaging Initiative (ADNI). We used modern psychometric approaches to analyze longitudinal Rey Auditory Verbal Learning Test (RAVLT, 2 versions), AD Assessment Schedule - Cognition (ADAS-Cog, 3 versions), Mini-Mental State Examination (MMSE), and Logical Memory data to develop ADNI-Mem, a composite memory score. We compared RAVLT and ADAS-Cog versions, and compared ADNI-Mem to RAVLT recall sum scores, four ADAS-Cog-derived scores, the MMSE, and the Clinical Dementia Rating Sum of Boxes. We evaluated rates of decline in normal cognition, mild cognitive impairment (MCI), and AD, ability to predict conversion from MCI to AD, strength of association with selected imaging parameters, and ability to differentiate rates of decline between participants with and without AD cerebrospinal fluid (CSF) signatures. The second version of the RAVLT was harder than the first. The ADAS-Cog versions were of similar difficulty. ADNI-Mem was slightly better at detecting change than total RAVLT recall scores. It was as good as or better than all of the other scores at predicting conversion from MCI to AD. It was associated with all our selected imaging parameters for people with MCI and AD. Participants with MCI with an AD CSF signature had somewhat more rapid decline than did those without. This paper illustrates appropriate methods for addressing the different versions of word lists, and demonstrates the additional power to be gleaned with a psychometrically sound composite memory score.     

The effects of intense sound exposure on phase locking in the chick (Gallus domesticus) cochlear nerve

Little is known about changes that occur to phase locking in the auditory nerve following exposure to intense and damaging levels of sound. The present study evaluated synchronization in the discharge patterns of cochlear nerve units collected from two groups of young chicks (Gallus domesticus), one shortly after removal from an exposure to a 120-dB, 900-Hz pure tone for 48 h and the other from a group of non-exposed control animals. Spontaneous activity, the characteristic frequency (CF), CF threshold and a phase-locked peri-stimulus time histogram were obtained for every unit in each group. Vector strength and temporal dispersion were calculated from these peri-stimulus time histograms, and plotted against the unit's CF. All parameters of unit responses were then compared between control and exposed units. The results in exposed units revealed that CF thresholds were elevated by 30-35 dB whereas spontaneous activity declined by 24%. In both control and exposed units a high degree of synchronization was observed in the low frequencies. The level of synchronization above approximately 0.5 kHz then systematically declined. The vector strengths in units recorded shortly after removal from the exposure were identical to those seen in control chicks. The deterioration in discharge activity of exposed units, seen in CF threshold and spontaneous activity, contrasted with the total absence of any overstimulation effect on synchronization. This suggested that synchronization arises from mechanisms unscathed by the acoustic trauma induced by the exposure.     

Electrophysiological correlates of visual affective priming

The present study used event-related potentials (ERPs) to investigate the underlying neural mechanisms of visual affective priming. Eighteen young native English-speakers (6 males, 12 females) participated in the study. Two sets of 720 prime-target pairs (240 affectively congruent, 240 affectively incongruent, and 240 neutral) used either words or pictures as primes and only words as targets. ERPs were recorded from 64 scalp electrodes while participants pressed either "Happy" or "Sad" buttons to indicate target pleasantness. The response time (RT) results confirmed an affective priming effect, with faster responses to affectively congruent trials (659 ms) than affectively incongruent trials (690 ms). Affectively incongruent trials had larger and more negative N200 activation than those to neutral trials. Importantly, a delayed N400 for word prime-target pairs matched the RT results with larger negative amplitudes for incongruent than congruent pairs. This finding suggests that the N400 component is not only sensitive to semantic mismatches, but is also sensitive to affective mismatches for word prime-target pairs.     

Direct and indirect costs of refractory epilepsy in a tertiary epilepsy center in Germany

PURPOSE: There are only few studies on the costs of epilepsy in Germany. Therefore, we performed a pilot study to estimate the direct and indirect costs of refractory epilepsy in a German epilepsy center. METHODS: A "prevalence-based," cross-sectional convenience sample of adults with active epilepsy attending the outpatient clinic of our tertiary epilepsy center was evaluated. Seizure-free patients and patients presenting with their first seizure were excluded. Direct and indirect costs were prospectively recorded over a three-month period using questionnaires and a patient diary. Cost driving factors were identified. RESULTS: One hundred one patients were included (40.7+/-15.2 years; disease duration: 18.1+/-15.3 years; 6 patients had focal epilepsy with simple partial seizures only, 28 with complex partial seizures, 43 with secondarily generalized tonic-clonic seizures; 20 had idiopathic generalized epilepsy with generalized tonic-clonic seizures). The total costs of epilepsy per patient were in average euro 2610+/-4200 over the three-month period. Direct cost contributed 39% to the total costs. Costs of anticonvulsant medication were the main contributor to the direct costs while indirect costs were caused mainly by losses due to early retirement. Cost driving factors included higher seizure frequency, longer disease duration, ictal falls, and situationally inappropriate complex behavior during or after the seizure. CONCLUSIONS: Indirect costs were higher than direct costs in adult patients with active epilepsy attending a German epilepsy center. Medication contributed the most to the direct costs and early retirement was the main factor for the indirect costs. The costs of poorly controlled epilepsy in this German study were above average of the European costs of epilepsy.     

Widespread subcutaneous haematoma after thrombolytic therapy in stroke patients. Mild falls at stroke onset may be dangerous

Recombinant tissue Plasminogen Activator (rtPA) is one of the more and more often used therapies in ischemic stroke. Main adverse effect of rtPA could be bleeding in different anatomical sites. Onset of the stroke is often associated with falls due to sudden limb weakness. Mild trauma can be not reported by patients and their families and can leave no visible signs on the skin. Thrombolytic therapy given in such cases can cause potentially dangerous complication such as subcutaneous or subfascial hematoma. The article presents two cases of patients with ischemic stroke who received thrombolytic therapy with subsequent complication of wide-spread subcutaneous hematomas.     

Behavioral interventions for agitation in older adults with dementia: an evaluative review

BACKGROUND: Older adults with dementia commonly exhibit agitated behavior that puts them at risk of injury and institutionalization and is associated with caregiver stress. A range of theoretical approaches has produced numerous interventions to manage these behavior problems. This paper critically reviews the empirical literature on behavioral interventions to reduce agitation in older adults with dementia. METHOD: A literature search yielded 23 articles that met inclusion criteria. These articles described interventions that targeted wandering, disruptive vocalization, physical aggression, other agitated behaviors and a combination of these behaviors. Studies are summarized individually and then evaluated. RESULTS: Behavioral interventions targeting agitated behavior exhibited by older adults with dementia show considerable promise. A number of methodological issues must be addressed to advance this research area. Problem areas include inconsistent use of functional assessment techniques, failure to report quantitative findings and inadequate demonstrations of experimental control. CONCLUSIONS: The reviewed studies collectively provide evidence that warrants optimism regarding the application of behavioral principles to the management of agitation among older adults with dementia. Although the results of some studies were mixed and several studies revealed methodological shortcomings, many of them offered innovations that can be used in future, more rigorously designed, intervention studies.     

Daytime sleeping, sleep disturbance, and circadian rhythms in the nursing home.

OBJECTIVE: This study reports the frequency of abnormal daytime sleeping and identifies factors related to daytime sleeping, nighttime sleep disturbance, and circadian rhythm abnormalities among nursing home residents. METHODS: The authors conducted secondary analysis of data collected under usual care conditions within a nonpharmacologic sleep intervention trial. All residents from four Los Angeles nursing homes were screened for daytime sleeping (asleep>or=15% of observations, 9:00 am-5:00 pm). Consenting residents with daytime sleeping had two nights of wrist actigraphy to assess nighttime sleep disturbance (asleep<80%, 10:00 pm-6:00 am). Residents with nighttime sleep disturbance completed an additional 72-hour wrist actigraphy recording to assess circadian activity rhythms and light exposure. RESULTS: Sixty-nine percent of 492 observed residents had daytime sleeping, of whom 60% also had disturbed nighttime sleep. Sleep disturbance and daytime sleeping were rarely documented in medical records. Residents spent one-third of the day in their rooms, typically in bed, and were seldom outdoors or exposed to bright light. More time in bed and less social activity were significant predictors of daytime sleepiness. Ninety-seven percent of residents assessed had abnormal circadian rhythms. More daytime sleeping and less nighttime sleep were associated with weaker circadian activity rhythms. Later circadian rhythm acrophase (peak) was associated with more bright light exposure. CONCLUSION: Daytime sleepiness, nighttime sleep disturbance, and abnormal circadian rhythms were common in nursing home residents. Modifiable factors (e.g., time in bed) are associated with sleep/wake abnormalities. Mental health specialists should consider the complexity of factors causing sleep problems in nursing home residents.     

Hope and coping in family members of patients with obsessive-compulsive disorder

Obsessive-compulsive disorder (OCD) affects approximately 2-4% of the adult population. Despite the practical and emotional demands of having a family member with OCD, few systematic attempts have been made to assess the coping strategies used by relatives of individuals with such diagnoses. In this study we examined the relationships between hope, coping strategies, and depressive symptoms in a heterogeneous sample of 67 spouses/primary caregivers of individuals with a history of OCD. In support of our hypotheses, hope was negatively related to depressive symptoms, symptom severity, and denial disengagement coping strategies, and positively related to active reframing and social support coping strategies. Active, Reframing, Social Support, and Religiosity were negatively related to depressive symptoms. Denial/Disengagement was positively associated with depressive symptoms. Coping mediated the relationship between hope and depressive symptoms. Given the importance of family members in treatment, clinical implications of these findings are discussed.     

Age and gender effects in EEG coherence: III. Girls with attention-deficit/hyperactivity disorder.

OBJECTIVE: This study investigated intrahemispheric and interhemispheric EEG coherences as a function of age in girls with different DSM-IV subtypes of Attention-Deficit/Hyperactivity Disorder (AD/HD). It completes a series of 3 studies aimed at clarifying developmental and gender impacts on the coupling between brain regions in this disorder. METHODS: Three groups of 40 children (AD/HD combined type, AD/HD inattentive type, and normal controls) participated. Each group contained 8 females in each of 5, 1-year age bands from 8 to 12 years. EEG was recorded from 21 sites during an eyes-closed resting condition. Wave-shape coherence was calculated for 8 intrahemispheric electrode pairs (4 in each hemisphere), and 8 interhemispheric electrode pairs, within each of the delta, theta, alpha and beta bands. RESULTS: Developmental effects in intrahemispheric coherences at shorter and longer inter-electrode distances were not as predicted by Thatcher's two-compartment model, contrary to previous findings in boys. Females with AD/HD showed evidence of developmental delay and widespread anomalous elevations in coherence. Girls with AD/HD of the combined type showed similar but greater anomalies than girls with AD/HD of the inattentive type. CONCLUSIONS: Girls with AD/HD show coherence anomalies relative to age- and gender-matched controls, which differ substantially from those shown by boys with AD/HD. These coherence anomalies did not differ in nature between girls with different DSM-IV subtypes of AD/HD, suggesting that subtype differences in girls reflect only symptom severity. SIGNIFICANCE: The data reported here indicate qualitative differences in EEG coherences in girls with AD/HD compared with controls, and quantitative differences between girls with different subtypes of AD/HD. Both sets of effects differ in nature from those previously found in boys with AD/HD, showing the need to carefully consider gender in future studies of AD/HD.     

The Yield of Multimodal Computed Tomography among Emergency Department Patients with Suspected Large Vessel Occlusion Stroke

Objectives: Endovascular therapy (EVT) improves outcomes for appropriately selected acute ischemic stroke patients. Guidelines suggest rapid acquisition of noninvasive vascular imaging to screen suspected ischemic stroke patients for large vessel occlusion (LVO) and candidacy for EVT. We sought to quantify the yield of an LVO stroke screening process in an undifferentiated emergency department (ED) suspected stroke population as well as identify predictors of successful EVT. Methods: We identified a cohort of consecutive ED patients who received CT angiography and brain perfusion (CTA/P) imaging to determine candidacy for EVT during 2016. In keeping with the guidelines at that time, hospital protocol directed physicians to obtain CTA/P studies if time from the onset of symptoms was less than or equal to 6 hours, and the National Institute of Health Stroke Scale (NIHSS) more than or equal to 6 or if recommended by the consulting stroke neurologist. Final discharge diagnoses, EVT attempts, and successful reperfusion (TICI 2b or better) were recorded. Yield of CTA/P was compared among patients based on NIHSS and duration of symptoms. Results: Over a 12-month period, 406 suspected stroke patients were screened with CTA/P; 273 (67%) received a final diagnosis of ischemic stroke. Among cases screened, 53 (13%) underwent attempted EVT; 35 (9%) achieved successful reperfusion. Only 1 of 113 (1%) patients with an NIHSS less than 6 was successfully treated with EVT compared to 34 of 285 (12%) with higher NIHSS (p = 0.001). The probability of successful EVT declined with increasing symptom duration (p = 0.009 for trend). In multivariable analysis, NIHSS more than or equal to 6 was associated with successful EVT (odds ratio [OR] 4.0 [1.6 to 9.9]) but presentation within 6 hours of onset was not (OR 2.3 [0.8 to 6.7]). Conclusions: EVT candidates were common among suspected stroke patients screened with CTA/P in the ED, however, patients with NIHSS less than 6 rarely received successful EVT.