03130nas a2200325 4500008004100000022001400041245010800055210006900163260001300232300001100245490000800256520220200264653000902466653002202475653002202497653001002519653003202529653002402561653001102585653001102596653003102607653000902638100001702647700002002664700002402684700002102708700002102729700001802750856003602768 2009 eng d a1527-131500aMild cognitive impairment and alzheimer disease: patterns of altered cerebral blood flow at MR imaging.0 aMild cognitive impairment and alzheimer disease patterns of alte c2009 Mar a856-660 v2503 a

PURPOSE: To examine regional cerebral blood flow (rCBF) in incident mild cognitive impairment (MCI) and Alzheimer disease (AD) by using continuous arterial spin-labeling (CASL) magnetic resonance (MR) imaging.

MATERIALS AND METHODS: This study was approved by the local institutional review board and was compliant with HIPAA regulations. Informed consent was obtained. rCBF was measured in 38 control subjects, 29 MCI patients, and 37 AD patients who were participating in a longitudinal epidemiologic study. Multisection CASL MR imaging with alternating single and double adiabatic inversion pulses and ramp-sampled echo-planar imaging were performed to acquire 19 contiguous axial sections. Voxel-level rCBF was compared among groups by using an analysis of variance design; clusters of voxels with significant group differences were identified. Multiple regression models controlled for age, sex, and presence of hypertension and related the mean rCBF in those clusters to the presence of MCI and AD.

RESULTS: MCI and AD patients had decreased rCBF in the posterior cingulate gyrus (P = .01) with extension to the medial precuneus compared with that in control subjects. MCI patients had increased rCBF in the left hippocampus (P < .001), right amygdala (P = .007), and rostral head of the right caudate nucleus and ventral putamen and globus pallidus (P = .003) compared with that in control subjects. AD patients had decreased rCBF relative to that in control subjects and MCI patients in the left inferior parietal (P = .005), left lateral frontal (P < .001), left superior temporal (P = .001), and left orbitofrontal (P = .003) cortices. AD patients had increased rCBF in the right anterior cingulate gyrus (P = .02) compared with that in control subjects.

CONCLUSION: The transition from normal cognition to AD is associated with dynamic pathologic processes in the brain, and this is reflected by both decreases and increases in rCBF. Increases in rCBF suggest a cellular and vascular compensatory process associated with incipient AD.

SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2503080751/DC1.

10aAged10aAged, 80 and over10aAlzheimer Disease10aBrain10aCerebrovascular Circulation10aCognition Disorders10aFemale10aHumans10aMagnetic Resonance Imaging10aMale1 aDai, Weiying1 aLopez, Oscar, L1 aCarmichael, Owen, T1 aBecker, James, T1 aKuller, Lewis, H1 aGach, Michael uhttps://chs-nhlbi.org/node/107102616nas a2200397 4500008004100000022001400041245013300055210006900188260000900257300001000266490000700276520146100283653001601744653000901760653002201769653002201791653002201813653001001835653003001845653002401875653001901899653001101918653001101929653002401940653003101964653000901995653002602004100002302030700002102053700002002074700002102094700002202115700002402137700002102161856003602182 2012 eng d a1875-890800aMarkers of cholesterol metabolism in the brain show stronger associations with cerebrovascular disease than Alzheimer's disease.0 aMarkers of cholesterol metabolism in the brain show stronger ass c2012 a53-610 v303 a

Cholesterol metabolism is believed to play a role in the development of Alzheimer's disease (AD). Oxysterol metabolites of cholesterol, 24S-hydroxycholesterol (24-OHC, a brain-derived oxysterol) and 27-hydroxycholesterol (27-OHC, a peripherally derived oxysterol) cross the blood brain barrier and have been associated with AD. We investigated whether oxysterols were associated with markers of cerebrovascular disease prior to the onset of cognitive impairment. Oxysterols were quantified in 105 participants (average age: 80 ± 4 years) from the Pittsburgh Cardiovascular Health Study Cognition Study who remained cognitively normal at blood draw in 2002, had MRI in 1992 and 1998, and annual cognitive assessment for incident AD and mild cognitive impairment made by consensus conference between 1998 and 2010. Higher plasma levels of 24-OHC were associated with age, gender, the presence of high grade white matter hyperintensities, and brain infarcts on prior MRI. Participants with higher plasma 24-OHC and a greater ratio of 24-OHC/27-OHC were also more likely to develop incident cognitive impairment over 8 years of follow-up. Higher levels of 24-OHC suggest increased cholesterol metabolism occurring in the brains of participants with cerebrovascular disease prior to the onset of cognitive impairment. Measurement of oxysterols may provide information about cholesterol metabolism and brain disease over the cognitive impairment process.

10aAge Factors10aAged10aAged, 80 and over10aAlzheimer Disease10aApolipoprotein E410aBrain10aCerebrovascular Disorders10aCognition Disorders10aCohort Studies10aFemale10aHumans10aHydroxycholesterols10aMagnetic Resonance Imaging10aMale10aRetrospective Studies1 aHughes, Timothy, M1 aKuller, Lewis, H1 aLopez, Oscar, L1 aBecker, James, T1 aEvans, Rhobert, W1 aSutton-Tyrrell, Kim1 aRosano, Caterina uhttps://chs-nhlbi.org/node/1367