Laura Jastrzab

Prescription opioid analgesics rapidly change the human brain

&NA; Chronic opioid exposure is known to produce neuroplastic changes in animals; however, it is not known if opioids used over short periods of time and at analgesic dosages can similarly change brain structure in humans. In this longitudinal, magnetic resonance imaging study, 10 individuals with chronic low back pain were administered oral morphine daily for 1 month. High‐resolution anatomical images of the brain were acquired immediately before and after the morphine administration period. Regional changes in gray matter volume were assessed on the whole brain using tensor‐based morphometry, and those significant regional changes were then independently tested for correlation with morphine dosage. Thirteen regions evidenced significant volumetric change, and degree of change in several of the regions was correlated with morphine dosage. Dosage‐correlated volumetric decrease was observed primarily in the right amygdala. Dosage‐correlated volumetric increase was seen in the right hypothalamus, left inferior frontal gyrus, right ventral posterior cingulate, and right caudal pons. Follow‐up scans that were conducted an average of 4.7 months after cessation of opioids demonstrated many of the morphine‐induced changes to be persistent. In a separate study, 9 individuals consuming blinded placebo capsules for 6 weeks evidenced no significant morphologic changes over time. The results add to a growing body of literature showing that opioid exposure causes structural and functional changes in reward‐ and affect‐processing circuitry. Morphologic changes occur rapidly in humans during new exposure to prescription opioid analgesics. Further research is needed to determine the clinical impact of those opioid‐induced gray matter changes. After 1 month of daily opioid analgesic consumption, chronic pain patients showed morphologic changes in several reward‐processing and limbic areas of the brain.

MCP-1 and eotaxin-1 selectively and negatively associate with memory in MCI and Alzheimer's disease dementia phenotypes.

MCP‐1 and eotaxin‐1 are encoded on chromosome 17 and have been shown to reduce hippocampal neurogenesis in mice. We investigated whether these chemokines selectively associate with memory in individuals with mild cognitive impairment (MCI) and Alzheimers disease (AD) dementia.

The Role of Carotid Intima-Media Thickness in Predicting Longitudinal Cognitive Function in an Older Adult Cohort

Background and Purpose: Carotid atherosclerosis is a risk factor for cerebrovascular disease in older adults. Although age-related cognitive decline has been associated with cerebrovascular disease, not much is known about the consequences of carotid atherosclerosis on longitudinal cognitive function. This study examines the longitudinal relationship between atherosclerosis and cognition in a sample of non-demented older subjects using baseline measurements of carotid intima media thickness (CIMT) and annual cognitive measures of executive function (EXEC) and verbal memory (MEM). Methods: Baseline measurements included CIMT derived from B-mode carotid artery ultrasound, structural T1-weighted images of white matter hypointensities (WMH), white matter lesions (WML), and cerebral infarct. Hypertension, low-density lipoprotein (LDL), diabetes, and waist to hip ratios (WHR) were included as covariates in our models to control for cerebrovascular risks and central adiposity. Annual composite scores of EXEC and MEM functions were derived from item response theory. Linear mixed models were used to model longitudinal cognitive change. Results: A significant inverse relationship was found between baseline CIMT and annual EXEC score, but not annual MEM score. Subjects included in the highest 4th quartile of CIMT showed a rate of annual decline in EXEC score that was significant relative to subjects in lower quartile groups (p < 0.01). The relationship between the 4th quartile of CIMT and annual EXEC score remained significant after independently adjusting for imaging measures of white matter injury and cerebral infarct. Conclusions: Older adult subjects with the highest index of CIMT showed an annual decline in EXEC scores that was significant relative to subjects with lower quartile measurements of CIMT, independent of our measures of white matter injury and cerebral infarct. Our findings suggest that elevated measures of CIMT may mark an atherosclerotic state, resulting in a decline in executive function and not memory in non-demented older adults. i 2014 S. Karger AG, Basel

Memory profiles in pathology or biomarker confirmed Alzheimer disease and frontotemporal dementia.

Objective:We examined verbal list memory in participants with pathology-confirmed or biomarker-supported diagnoses to clarify inconsistencies in comparative memory performance. We hypothesized that Alzheimer disease (AD) participants would show more rapid forgetting, whereas behavioral-variant frontotemporal dementia (bvFTD) participants would show a more dysexecutive pattern. We also explored differences in medial temporal volumes, and relative frontal and medial temporal area contributions to memory consolidation. Participants and Methods:Participants had clinical diagnoses of AD and bvFTD who were pathologically confirmed at autopsy or supported with Pittsburgh compound B amyloid imaging. We used cognitive and imaging data collected at baseline visits for a sample of 26 participants with AD (mean age=63.7, education=16.2, Clinical Dementia Rating=0.8), 25 participants with bvFTD (mean age=60.7; education=15.7; CRD=1.1), and 25 healthy controls (mean age=65.6; education=17.5; Clinical Dementia Rating=0.2). Results and Conclusions:AD participants showed more rapid forgetting than bvFTD, and both groups showed more rapid forgetting than controls. In contrast, bvFTD did not conform to a more dysexecutive pattern of performance as patient groups committed similar number of intrusion errors and showed comparably low rates of improvement on cued recall and recognition trials. For patients with neuroimaging, there were no group differences in medial temporal volumes, which was the only significant predictor of consolidation for both dementia groups.

Attention and executive functioning profiles in children following perinatal arterial ischemic stroke

ABSTRACT Perinatal arterial ischemic stroke (PAIS) is a form of childhood stroke; the majority of those affected experience neurologic sequelae, including motor, language and neurocognitive impairments. This study examines the attention and executive functioning (EF) profiles of children following PAIS, as well as the impact of age and sex. In this single-center cross-sectional study, 40 children aged 3 to 16 years (median age 7.2 years; 58% male) who have suffered a PAIS underwent a comprehensive neuropsychological battery to assess attention and EF. Parents completed behavioral questionnaires regarding real-world functioning. Composite scores were calculated for seven attention and EF domains (Attention, Working Memory, Verbal Retrieval, Inhibitory Control, Flexibility/Shifting, Planning/Organization, and Processing Speed). The results for all measured domains of attention and EF are significantly lower in the participants compared to the normative samples (p < .001), with the exception of Working Memory. However, increasing difficulty with Working Memory is associated with developing age. Older age at time of testing is also associated with a higher incidence of clinically-elevated attention deficit hyperactivity disorder (ADHD) symptoms. Sex is not associated with performance measures or parental report of functioning. The participants demonstrate mild-to-moderate attention and EF impairment compared to the normative population. Clinicians, families, and educators should be informed about the neurocognitive sequelae of PAIS and the need for close developmental surveillance in this population to identify vulnerable children and initiate appropriate therapeutic interventions in a timely fashion.

Incidence and predictors of epilepsy after pediatric arterial ischemic stroke.

Objective: To determine the cumulative incidence and clinical predictors of remote symptomatic seizures and epilepsy after pediatric arterial ischemic stroke (AIS). Methods: We performed a retrospective analysis of 218 participants with neonatal AIS (NAIS), presumed perinatal AIS (PPAIS), and childhood AIS (CAIS) from a single-center prospective consecutive cohort enrolled from 2006 to 2014. Medical records were reviewed for timing, semiology, and treatment of acute symptomatic seizures, remote symptomatic seizures (RSS), and epilepsy. Cumulative incidence of RSS and epilepsy were assessed using survival analysis. Results: Acute symptomatic seizures occurred in 94% of NAIS (n = 70/74) and 17% of CAIS (n = 18/105). Younger children were more likely to present with seizures at stroke ictus, and acute symptomatic seizures were predictive of later RSS and epilepsy in CAIS. Median follow-up for the entire cohort was 34 months, interquartile range 44.9 months (16.3–61.2). Estimated cumulative incidence of RSS at 2 years was 19% in NAIS, 24% in PPAIS, and 7% in CAIS. Estimated cumulative incidence of epilepsy at 2 years was 11% in NAIS, 19% in PPAIS, and 7% in CAIS. The median time to these outcomes was <2 years in all stroke subtypes. Among participants developing epilepsy (n = 34), seizures were often well-controlled at last follow-up with median Engel class of ≤2 (<1 seizure/month). Conclusions: RSS and epilepsy are important neurologic sequelae of pediatric AIS. Children with perinatal stroke and CAIS with acute symptomatic seizures are at increased risk of these outcomes. These cohorts need further study to identify biomarkers and potential therapeutic targets for epileptogenesis.

Triglycerides Are Negatively Correlated With Cognitive Function in Nondemented Aging Adults

Objective: Vascular risk factors like hyperlipidemia may adversely affect brain function. We hypothesized that increased serum triglycerides are associated with decreased executive function and memory in nondemented elderly subjects. We also researched possible vascular mediators and white matter microstructure as assessed with diffusion tensor imaging (DTI). Design/Method: Participants were 251 nondemented elderly adults (54% male) with a mean age of 78 (SD = 6.4; range: 62–94) years and a mean education of 15.6 (SD = 2.9; range: 8–23) years. Fasting blood samples were used to detect serum triglyceride and low-density lipoprotein (LDL) levels along with ApoE4 status. DTI was used to determine whole brain fractional anisotropy (FA). Composite executive and memory scores were derived from item response theory. Clinical Dementia Rating (CDR) scores provided informant-based measures of daily functioning. Results: Triglyceride levels were inversely correlated with executive function, but there was no relationship with memory. Controlling for age, gender, and education did not affect this correlation. This relationship persisted after controlling for vascular risk factors like LDL, total cholesterol, CDR and ApoE4 status. Lastly, adding whole-brain FA to the model did not affect the correlation between triglycerides and executive function. Conclusion: Triglyceride levels are inversely correlated with executive function in nondemented elderly adults after controlling for age, education, gender, total cholesterol, LDL, ApoE4 status, CDR, and white-matter microstructure. The fact that the effect of triglycerides on cognition was not clearly mediated by vascular risks or cerebrovascular injury raises questions about widely held assumptions of how triglycerides might impact cognition function.