Shannon Buckley

We compared the predictive value of cerebral perfusion as measured by arterial-spin labeling magnetic resonance imaging (ASL-MRI) with MRI-derived hippocampal volume for determining future cognitive and functional decline and subsequent conversion from mild cognitive impairment to dementia. Forty-eight mild cognitive impairment subjects received structural and ASL-MRI scans at baseline and clinical and neuropsychologic assessments annually. Thirteen subjects became demented during the period of longitudinal observation (2.7+/-1.0 y). Cox regression analyses suggest that baseline hippocampal volume [relative risk (RR)=0.99, P=0.004], baseline right inferior parietal (RR=0.64, P=0.01) and right middle frontal (RR=0.73, P=0.01) perfusion were associated with conversion to dementia. Results from linear mixed effects modeling suggest that baseline perfusion from the right precuneus predicted subsequent declines in Clinical Dementia Rating Sum of Boxes (P=0.002), Functional Activates Questionnaire (P=0.01), and selective attention (ie, Stroop switching, P=0.009) whereas baseline perfusion from the right middle frontal cortex predicted subsequent episodic memory decline (ie, total recognition discriminability score from the California Verbal Learning Test, P=0.03). These results suggest that hypoperfusion as detected by ASL-MRI can predict subsequent clinical, functional, and cognitive decline and may be useful for identifying candidates for future Alzheimer disease treatment trials.

BACKGROUND: At least 60% of those treated for an alcohol use disorder will relapse. Empirical study of the integrity of the brain reward system (BRS) is critical to understanding the mechanisms of relapse as this collection of circuits is implicated in the development and maintenance of all forms of addictive disorders. This study compared thickness, surface area, and volume in neocortical components of the BRS among nonsmoking light-drinking controls (controls), individuals who remained abstinent and those who relapsed after treatment. METHODS: Seventy-five treatment-seeking alcohol-dependent individuals (abstinent for 7±3 days) and 43 controls completed 1.5T proton magnetic resonance imaging studies. Parcellated morphological data were obtained for following bilateral components of the BRS: rostral and caudal anterior cingulate cortex, insula, medial and lateral orbitofrontal cortex (OFC), rostral and caudal middle and superior frontal gyri, amygdala and hippocampus as well as for 26 other bilateral neocortical regions. Alcohol-dependent participants were followed over 12-months after baseline study and were classified as abstainers (no alcohol consumption; n=24) and relapsers (any alcohol consumption; n=51) at follow-up. RESULTS: Relapsers and abstainers demonstrated lower cortical thickness in the vast majority of BRS regions as well as lower global thickness compared to controls. Relapsers had lower total BRS surface area than both controls and abstainers, but abstainers were not significantly different from controls on any surface area measure. Relapsers demonstrated lower volumes than controls in the majority of regions, while abstainers showed lower volumes than controls in the superior frontal gyrus, insula, amygdala, and hippocampus, bilaterally. Relapsers exhibited smaller volumes than abstainers in the right rostral middle and caudal middle frontal gyri and the lateral OFC, bilaterally. In relapsers, lower baseline volumes and surface areas in multiple regions were associated with a greater magnitude of post-treatment alcohol consumption. CONCLUSIONS: Results suggest relapsers demonstrated morphological abnormalities in regions involved in the "top down" regulation/modulation of internal drive states, emotions, reward processing, and behavior, which may impart increased risk for the relapse/remit cycle that afflicts many with an alcohol use disorder. Results also highlight the importance of examining both cortical thickness and surface area to better understand the nature of regional volume loss frequently observed in alcohol use disorders. Results from this report are consistent with previous research implicating plastic neurobiological changes in the BRS in the maintenance of addictive disorders.

OBJECTIVE: To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease. DESIGN: Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxyglucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers. SETTING: Academic medical center. PARTICIPANTS: A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. MAIN OUTCOME MEASURES: The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume. RESULTS: Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P = .60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P = .001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r = 0.29, P = .0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P < .05, determined by use of pairwise Fisher z tests). CONCLUSIONS: Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or metabolism in cognitively normal persons at increased genetic risk for Alzheimer disease.

PURPOSE: In temporal lobe epilepsy (TLE) with evidence of hippocampal sclerosis (TLE-MTS) volumetric gray (GM) and white (WM) matter abnormalities are not restricted to the hippocampus but also are found in extrahippocampal structures. Less is known about extrahippocampal volumetric abnormalities in TLE without hippocampal sclerosis (TLE-no). In this study, we used optimized voxel-based morphometry (VBM) with and without modulation with the following aims: (a) to identify WM and GM abnormalities beyond the hippocampus in TLE-MTS and TLE-no; and (b) to determine whether extratemporal WM and GM abnormalities differ between TLE-MTS and TLE-no. METHODS: Optimized VBM of GM and WM with and without modulation was performed in 26 TLE-MTS (mean age, 35.6 +/- 9.7 years), 17 TLE-no (mean age, 35.6 +/- 11.1 years), and 30 healthy controls (mean age, 30.3 +/- 11.1 years). RESULTS: In TLE-MTS, GM/WM volume and concentration reductions were found in the ipsilateral limbic system, ipsi- and contralateral neocortical regions, thalamus, cerebellum, internal capsule, and brainstem when compared with controls. In contrast, no differences of GM/WM volumes/concentrations were found between TLE-no and controls or between TLE-no and TLE-MTS. CONCLUSIONS: In TLE-MTS, optimized VBM showed extensive GM and WM volume reductions in the ipsilateral hippocampus and in ipsi- and contralateral extrahippocampal regions. In contrast, no GM/WM volume or concentration reductions were found in TLE-no. This further supports the hypothesis that TLE-no is a distinct clinicopathologic entity from TLE-MTS and probably heterogeneous in itself.