A recently identified variant within the fat mass and obesity-associated ( FTO ) gene is carried by 46% of Western Europeans and is associated with an ~1.2 kg higher weight, on average, in adults and an ~1 cm greater waist circumference. With >1 billion overweight and 300 million obese persons worldwide, it is crucial to understand the implications of carrying this very common allele for the health of our aging population. FTO is highly expressed in the brain and elevated body mass index (BMI) is associated with brain atrophy, but it is unknown how the obesity-associated risk allele affects human brain structure. We therefore generated 3D maps of regional brain volume differences in 206 healthy elderly subjects scanned with MRI and genotyped as part of the Alzheimer's Disease Neuroimaging Initiative. We found a pattern of systematic brain volume deficits in carriers of the obesity-associated risk allele versus noncarriers. Relative to structure volumes in the mean template, FTO risk allele carriers versus noncarriers had an average brain volume difference of ~8% in the frontal lobes and 12% in the occipital lobes—these regions also showed significant volume deficits in subjects with higher BMI. These brain differences were not attributable to differences in cholesterol levels, hypertension, or the volume of white matter hyperintensities; which were not detectably higher in FTO risk allele carriers versus noncarriers. These brain maps reveal that a commonly carried susceptibility allele for obesity is associated with structural brain atrophy, with implications for the health of the elderly.

Regions of the temporal and parietal lobes are particularly damaged in Alzheimer's disease (AD), and this leads to a predictable pattern of brain atrophy. In vivo quantification of subregional atrophy, such as changes in cortical thickness or structure volume, could lead to improved diagnosis and better assessment of the neuroprotective effects of a therapy. Toward this end, we have developed a fast and robust method for accurately quantifying cerebral structural changes in several cortical and subcortical regions using serial MRI scans. In 169 healthy controls, 299 subjects with mild cognitive impairment (MCI), and 129 subjects with AD, we measured rates of subregional cerebral volume change for each cohort and performed power calculations to identify regions that would provide the most sensitive outcome measures in clinical trials of disease-modifying agents. Consistent with regional specificity of AD, temporal-lobe cortical regions showed the greatest disease-related changes and significantly outperformed any of the clinical or cognitive measures examined for both AD and MCI. Global measures of change in brain structure, including whole-brain and ventricular volumes, were also elevated in AD and MCI, but were less salient when compared to changes in normal subjects. Therefore, these biomarkers are less powerful for quantifying disease-modifying effects of compounds that target AD pathology. The findings indicate that regional temporal lobe cortical changes would have great utility as outcome measures in clinical trials and may also have utility in clinical practice for aiding early diagnosis of neurodegenerative disease.

Objective To determine the prevalence, characteristics, risk factors and temporal profile of concurrent ischemic lesions in patients with acute primary intracerebral hemorrhage (ICH). Methods Patients were recruited within a prospective, longitudinal, magnetic resonance imaging (MRI) based study of primary ICH. Clinical, demographic, and MRI data were collected on all subjects at baseline and 1 month. Results Of the 138 patients enrolled, mean age was 59 years, 54% were male, 73% black, and 84% had a history of hypertension. At baseline, ischemic lesions on diffusion-weighted imaging (DWI) were found in 35% of patients. At 1 month, lesions were present in 27%, and of these lesions, 83% were new and not present at baseline. ICH volume (p=0.025), intraventricular hemorrhage (p=0.019), presence of microbleeds (p=0.024), and large, early reductions in mean arterial pressure (p=0.003) were independent predictors of baseline DWI lesions. A multivariate logistical model predicting the presence of 1 month DWI lesions included history of any prior stroke (p=0.012), presence of 1 or more microbleeds (p=0.04), black race (p=0.641), and presence of a DWI lesion at baseline (p=0.007) Interpretation This study demonstrates that more than 1/3 of patients with primary ICH have active cerebral ischemia at baseline remote from the index hematoma, and 1/4 of patients experience ongoing, acute ischemic events at 1 month. Multivariate analyses implicate blood pressure reductions in the setting of an active vasculopathy as a potential underlying mechanism. Further studies are needed to determine the impact of these lesions on outcome and optimal management strategies to arrest vascular damage.

Background Some prior studies have shown that racial disparities exist in intravenous tissue plasminogen activator (IV tPA) utilization for acute ischemic stroke. We sought to determine whether race was associated with tPA treatment for stroke in a predominantly black urban population. Methods Systematic chart abstraction was performed on consecutive hospitalized ischemic stroke patients from all seven acute care hospitals in the District of Columbia from Feb 1, 2008 to Jan 31, 2009. Results Of 1044 ischemic stroke patients, 74%% were black, 19% non-Hispanic white, 5% received IV tPA. Blacks were one third less likely than whites to receive IV tPA (3% vs. 10%, p<0.001). However, blacks were also less likely than whites to present within 3 hours of symptom onset (13% vs. 21%, p=0.004) and also less likely to be tPA-eligible (5% vs. 13%, p<0.001). Of those who presented within 3 hours, blacks were almost half as likely to be treated with IV tPA than whites (27% vs. 46%, p=0.023). The treatment rate for tPA-eligible patients was similar for blacks and whites (70% vs. 76%, p=0.62). Conclusions In this predominantly black urban population hospitalized for acute ischemic stroke, blacks were significantly less likely to be treated with IV tPA due to contraindications to treatment, delayed presentation, and stroke severity. Effective interventions designed to increase treatment in this population need to focus on culturally relevant education programs designed to address barriers specific to this population.