Old age and possession of the APOE-4 allele are the two main risk factors for developing later onset Alzheimer's Disease (AD). Carriers of the APOE-4 allele have known differences in intrinsic functional brain network activity across the life span. These individuals also demonstrate specific regional differences in gray and white matter gross structure. However, the relationship of these variations to whole brain structural network connectivity remains unclear. We performed diffusion tensor imaging (DTI), T1 structural imaging, and cognitive testing on aging APOE-4 noncarriers (n = 30; mean age = 63.8±8.3) and APOE-4 carriers (n = 25; mean age = 60.8 ±9.7). Fiber tractography was used to derive whole brain structural graphs, and graph theory was applied to assess structural network properties. Network communication efficiency was determined for each network by quantifying local interconnectivity, global integration, and the balance between these, the small worldness. Relative to noncarriers, APOE-4 carriers demonstrated an accelerated age-related loss of mean local interconnectivity (r = −0.64, P ≤ 0.01) and regional local interconnectivity decreases in the precuneus (r = −0.64), medial orbitofrontal cortex (r = −0.5), and lateral parietal cortex (r = −0.54). APOE-4 carriers also showed significant agerelated loss in mean cortical thickness (r = −0.52, P < 0.05). Cognitively, APOE-4 carriers had significant negative correlations of age and performance on two episodic memory tasks (P < 0.05). This genotype-specific pattern of structural connectivity change with age thus appears related to changes in gross cortical structure and cognition, potentially affecting the rate and/or spatial distribution of AD-related pathology.complex network | genetics A lthough increasing age is the primary risk factor for developing Alzheimer's disease (AD), the disease also has known genetic risk factors. The sole confirmed genetic variant is the apolipoprotein E epsilon 4 allele (APOE-4) (1) of which 15-20% of the Caucasian population carries at least one copy. Individuals in this group are three to four times more likely to develop AD and have a younger mean age at onset than APOE-4 noncarriers (2). The APOE protein functions as the principal cholesterol transporter in the brain and affects diverse cellular processes including development, plasticity, and repair in both gray and white matter (3). Neuroimaging studies of APOE-4 carriers and APOE-4 noncarriers (APOE-4 NCs) have revealed numerous structural and functional brain differences across the life span (4). Whereas APOE-4 carriers have been shown to exhibit earlier signs of cognitive decline with aging (5), some genotype-specific brain differences appear before cognitive decline (6-9). APOE-4 carriers aged ≥60 y are at elevated risk for developing AD (2) and are thus a critical target for identifying neuroimaging biomarkers of AD risk that accompany cognitive decline associated with disease risk.Neuronal atrophy is known to follow a characteristic trajectory in AD, originatin...

Amyloid-β-related angiitis (ABRA) is a rare complication of cerebral amyloid angiopathy in which amyloid-β deposition in the leptomeningeal and cortical vessels is associated with vasculitis characterized by transmural lymphohistiocytic, often granulomatous, inflammation. Patients usually present with acute to subacute cognitive dysfunction, headaches, and focal neurologic deficits. We report 2 cases of ABRA with unusual clinical presentations, including one case with fatal cerebral edema leading to herniation and Duret hemorrhages, and another associated with both lobar and deep parenchymal hemorrhages with intraventricular extension as well as hypercoagulability. Both showed extensive vascular amyloid-β deposition associated with granulomatous angiitis and foreign body-type multinucleated giant cells. One of our cases demonstrates the likely effects of ABRA on impairment of fluid regulation leading to severe cerebral edema, which is an uncommon manifestation of ABRA, and may be a result of impaired blood-brain barrier function or malfunction of the neurovascular unit.

Background Deficits in lexical retrieval, present in approximately 40% of HIV+ patients, are thought to reflect disruptions to frontal-striatal functions and may worsen with immunosuppression. Coupling frontal-striatal tasks such as lexical retrieval with functional neuroimaging may help delineate the pathophysiologic mechanisms underlying HIV-associated neurological dysfunction. Objective We examined whether HIV infection confers brain functional changes during lexical access and retrieval. It was expected that HIV+ individuals would demonstrate greater brain activity in frontal-subcortical regions despite only minimal differences between groups on neuropsychological testing. Within the HIV+ sample, we examined associations between indices of immunosuppression (recent and nadir CD4+ count) and task-related signal change in frontostriatal structures. Method 16 HIV+ participants and 12 HIV− controls underwent fMRI while engaged in phonemic/letter and semantic fluency tasks. Participants also completed standardized measures of verbal fluency. Results HIV status groups performed similarly on phonemic and semantic fluency tasks prior to being scanned. fMRI results demonstrated activation differences during the phonemic fluency task as a function of HIV status, with HIV+ individuals demonstrating significantly greater activation in BG structures than HIV− individuals. There were no significant differences in frontal brain activation between HIV status groups during the phonemic fluency task, nor were there significant brain activation differences during the semantic fluency task. Within the HIV+ group, current CD4+ count, though not nadir, was positively correlated with increased activity in the inferior frontal gyrus and basal ganglia. Conclusion During phonemic fluency performance, HIV+ patients recruit subcortical structures to a greater degree than HIV− controls despite similar task performances suggesting that fMRI may be sensitive to neurocompromise before overt cognitive declines can be detected. Among HIV+ individuals, reduced activity in the frontal-subcortical structures was associated with lower CD4+ count.