Darren P. O'Neill

Altered Default Mode Network Connectivity in Older Adults with Cognitive Complaints and Amnestic Mild Cognitive Impairment

Default mode network (DMN) disruption has been reported in Alzheimers disease (AD), yet the specific pattern of altered connectivity over the course of prodromal AD remains to be characterized. The aim of this study was to assess DMN connectivity in older adults with informant-verified cognitive complaints (CC) but normal neuropsychological performance compared to individuals with mild cognitive impairment (MCI) and healthy controls (HC). DMN maps were derived from resting-state fMRI using independent component analysis. Group comparisons of DMN connectivity were performed between older adults with MCI (n = 18), CC (n = 23), and HC (n = 16). Both CC and MCI showed decreased DMN connectivity in the right hippocampus compared to HC, with the CC group showing greater connectivity than MCI. These differences survived atrophy correction and correlated with cognitive performance. DMN connectivity appears sensitive to early prodromal neurodegenerative changes associated with AD, notably including pre-MCI individuals with cognitive complaints.

Altered Cerebral Blood Flow One Month after Systemic Chemotherapy for Breast Cancer: A Prospective Study Using Pulsed Arterial Spin Labeling MRI Perfusion

Cerebral structural and functional alterations have been reported after chemotherapy for non-CNS cancers, yet the causative mechanism behind these changes remains unclear. This study employed a novel, non-invasive, MRI-based neuroimaging measure to provide the first direct longitudinal measurement of resting cerebral perfusion in breast cancer patients, which was tested for association with changes in cognitive function and gray matter density. Perfusion was measured using pulsed arterial spin labeling MRI in women with breast cancer treated with (N = 27) or without (N = 26) chemotherapy and matched healthy controls (N = 26) after surgery before other treatments (baseline), and one month after chemotherapy completion or yoked intervals. Voxel-based analysis was employed to assess perfusion in gray matter; changes were examined in relation to overall neuropsychological test performance and frontal gray matter density changes measured by structural MRI. Baseline perfusion was not significantly different across groups. Unlike control groups, chemotherapy-treated patients demonstrated significantly increased perfusion post-treatment relative to baseline, which was statistically significant relative to controls in the right precentral gyrus. This perfusion increase was negatively correlated with baseline overall neuropsychological performance, but was not associated with frontal gray matter density reduction. However, decreased frontal gray matter density was associated with decreased perfusion in bilateral frontal and parietal lobes in the chemotherapy-treated group. These findings indicate that chemotherapy is associated with alterations in cerebral perfusion which are both related to and independent of gray matter changes. This pattern of results suggests the involvement of multiple mechanisms of chemotherapy-induced cognitive dysfunction. Additionally, lower baseline cognitive function may be a risk factor for treatment-associated perfusion dysregulation. Future research is needed to clarify these mechanisms, identify individual differences in susceptibility to treatment-associated changes, and further examine perfusion change over time in survivors.

Teaching NeuroImage: MRI visualization of papilledema associated with cerebral sinovenous thrombosis in a child

A 3-year-old boy with ulcerative colitis and developmental delay presented with a 3-week history of headaches, emesis, and dehydration. His neurologic examination was nonfocal, but MR venogram revealed cerebral sinovenous thrombosis (figure). He was rehydrated and discharged on enoxaparin. Three months later he starting having difficulty reaching for objects and was running into walls. Repeat MRI and MR venogram demonstrated residual thrombosis and interval development of papilledema …

Disparities and guideline adherence in drugs of abuse screening in intracerebral hemorrhage

Objective: To characterize the pattern of urine drug screening in a cohort of intracerebral hemorrhage (ICH) patients at our academic centers. Methods: We identified cases of primary ICH occurring from 2009 to 2011 in our academic centers. Demographic data, imaging characteristics, processes of care, and short-term outcomes were ascertained. We performed logistic regression to identify predictors for screening and evaluated preguideline and postguideline reiteration screening patterns. Results: We identified 610 patients with primary ICH in 2009–2011; 379 (62.1%) were initially evaluated at an outside hospital. Overall, 142/610 (23.3%) patients were screened, with 21 positive for cocaine and 3 for amphetamine. Of patients <55 years of age, only 65/140 (46.4%) were screened. Black patients <55 years of age were screened more than nonblack patients <55 years of age (38/61 [62.3%] vs 27/79 [34.2%]; p = 0.0009). In the best multivariable model, age group (p = 0.0001), black race (p = 0.4529), first Glasgow Coma Scale score (p = 0.0492), current smoking (p < 0.0001), and age group × black race (p = 0.0097) were associated with screening. Guideline reiteration in 2010 did not improve the proportion <55 years of age who were screened: 42/74 (56.8%) were screened before and 23/66 (34.9%) after (p = 0.01). Conclusions: We found disparities in drugs of abuse (DOA) screening and suboptimal guideline adherence. Systematic efforts to improve screening for DOA are warranted. Improved identification of sympathomimetic exposure may improve etiologic classification and influence decision-making and prognosis counseling.

ASSOCIATION BETWEEN N-BACK WORKING MEMORY ACTIVATION ON FMRI AND COGNITIVE ASSESSMENT OF EXECUTIVE FUNCTION

right hippocampi (r1⁄4-0.66,p<0.002; r1⁄4-0.68,p<0.002 respectively) as well as the left and right thalami (r1⁄4-0.66,p<0.002; r1⁄4-0.68,p<0.002 respectively). A weaker but similar relationship was observed in the control group, possibly due to a smaller population size (see Table 1). Figures 1.a,c show correlation coefficients overlaid on ICBM template for ventricular regions for the ex-CFL and control groups. Figure 1.b shows the significant FDR corrected p-value map for the ex-CFL cohort. Figures 2.a-c show similar images for subcortical regions. The color-coded bars in Figures 1.a-c and 2.a-c represent correlation coefficients values: warm colors correspond to regions of enlargement with age i.e. ventricles; cold colors correspond to areas negatively correlated with age i.e. hippocampi and thalami. Figure 2.b shows the significant regions after FDR correction in the ex-CFL. Table 1 shows correlation coefficients and FDR corrected p-values for the two groups for areas indicated by arrows. The uncorrected p-values for the control group did not survive FDR correction. Conclusions: Our results revealed extensive changes associated with age in the ex-CFL population. The changes predominantly involved volume decreases in the hippocampi and thalami, and volume increases in the ventricles. DBM may be a sensitive measure for detecting focal brain atrophy in patients that have suffered multiple concussions. IC-P-094 ASSOCIATION BETWEEN N-BACK WORKING MEMORYACTIVATION ON FMRI AND COGNITIVE ASSESSMENT OF EXECUTIVE FUNCTION John D. West, Shannon L. Risacher, Pratik K. Gandhi, YuChien Wu, Eileen F. Tallman, Brenna C. McDonald, Liana G. Apostolova, Martin R. Farlow, Jared R. Brosch, Darren P. O’Neill, Sujuan Gao, Steven A. Brown, Bradley S. Glazier, Frederick W. Unverzagt, Andy J. Saykin, 1 Indiana University School of Medicine, Indianapolis, IN, USA; 2 Indiana Alzheimer Disease Center, Indianapolis, IN, USA. Contact e-mail: jdwest@ iupui.edu

ASSOCIATION OF THE COGNITIVE CHANGE INDEX WITH HIPPOCAMPAL SUBFIELD VOLUMES

related to lower memory performance at baseline, whereas thinner temporal cortex was associated to subsequent decline of executive function (table 1). Conclusions: We found that thinner cortex in fronto-temporo-parietal regions is associated with subtle lower scores on memory function, while thinner temporal cortex is associated with an increased rate of decline in executive function. These findings suggest that subtle changes in the cortical mantle may precede clinical manifestation of AD.

SCENE ENCODING FMRI IN SUBJECTIVE COGNITIVE DECLINE

elwise analyses revealed widespread areas of hypometabolism (in lateral frontal, temporal, and parietal lobes) that were associated with less cognitive activity, and these regions overlapped partially the meta ROIs. Hippocampal volume was not correlated with cognitive activity in any age epoch. Conclusions: Cognitive engagement in early and midlife is associated with reduced amyloid, while current cognitive engagement is associated with reduced hypometabolism. These findings are consistent with proposed effects of early/midlife cognitive engagement on neural efficiency, but suggest that late life effects reflect other factors, such as cognitive reserve or reverse causation.

Characterization of regional cerebral blood flow in people with mild cognitive impairment and older adults with cognitive complaints

or AD, 12 were normotensive and 18 were hypertensive and treated with at least one anti-hypertensive agent. The groups did not differ by age. Participants underwent cognitive testing and brain MRI including DTI and mcDESPOT, a new method of quantifying myelin integrity (Deoni et al., 2008). Myelin integrity is represented as a metric called myelin water fraction (MWF; higher values indicate greater integrity). We calculated 4 DTI metrics: mean, axial, and radial diffusivity, and fractional anisotropy. Cognitive test scores were summarized into attention, processing speed, executive, and memory composite scores. Results: In the whole group, MWF but not DTI metrics in NAWMwas significantly correlated with age (r1⁄4 -0.58, p < 0.01). The hypertensive and normotensive groups did not differ significantly by volume measures (NAWM,WMH, or grey matter volume), white matter or myelin integrity (DTI metrics orMWF), or cognitive performance. In the hypertensive group, there were no significant correlations between cognitive composite scores and either MWF or DTI metrics. In the normotensive group, however, MWF was significantly correlated with attention and processing speed composite measures (all r >0.64, p < 0.035) but not with either executive or memory composites. The association remained significant after controlling for age. By contrast, DTI metrics did not correlate with any of the composite measures. Conclusions: We found that myelin integrity in NAWM is associated with attention and processing speed in MCI and AD patients among normotensives but not hypertensives. Hypertension in MCI and AD may mask or disrupt associations between myelin integrity and cognitive functions seen in normotensive individuals.