03305nas a2200349 4500008004100000022001400041245010700055210006900162260001300231300001100244490000700255520232400262653000902586653002202595653002602617653002402643653001302667653002402680653001102704653001102715653001402726653000902740653002602749100002002775700002102795700002102816700002102837700002102858700001802879700002302897856003502920 2007 eng d a0003-994200aIncidence of dementia in mild cognitive impairment in the cardiovascular health study cognition study.0 aIncidence of dementia in mild cognitive impairment in the cardio c2007 Mar a416-200 v643 a

OBJECTIVES: To examine the incidence of dementia in subjects with mild cognitive impairment (MCI) in the Cardiovascular Health Study Cognition Study.

DESIGN: Prospective epidemiological study.

SETTING: The Cardiovascular Health Study Cognition Study of Pittsburgh, Pa, was conducted from 2002 through 2003 to determine the incidence of dementia in participants classified as having MCI in 1998 and 1999. Subjects There were 136 subjects with MCI. Mild cognitive impairment was subclassified as MCI amnestic type and MCI multiple cognitive deficits type (MCI-MCDT); subjects with MCI-MCDT were also grouped based on the presence of a memory impairment. Subjects with MCI were classified as possible when there were comorbidities that could explain the subjects' cognitive deficits and as probable when there were none. Main Outcome Measure Dementia.

RESULTS: The incidence of all dementias in the subjects with MCI was 147 per 1000 person-years (mean follow-up overall, 4.3 years). Of the 136 subjects with MCI, 69 (51%) in 1998 through 1999 progressed to dementia (57 [83%] to Alzheimer disease [AD]), but 25 (18%) returned to normal. Of the 10 subjects with probable MCI amnestic type, 7 (70%) progressed to dementia (all of them to AD) and none returned to normal, whereas 7 (41%) of the 17 subjects with possible MCI amnestic type became demented (6 [86%] to AD) and 3 (18%) returned to normal. Of the 40 subjects with probable MCI-MCDT, 21 (52%) progressed to dementia (17 [81%] to AD) and 2 (5%) returned to normal. Of the 69 subjects with possible MCI-MCDT, 34 (49%) progressed to dementia (28 [82%] to AD) and 20 (29%) returned to normal. Among the subjects with probable MCI-MCDT, 15 (54%) of 28 with and 6 (50%) of 12 without memory deficits progressed to dementia.

CONCLUSIONS: Subjects with MCI are at high risk for dementia. The probable MCI diagnosis identified individuals in the earliest stages of dementia, usually AD, whereas the possible MCI diagnosis identified a more heterogeneous group. However, this latter group had only a slightly lower rate of conversion to dementia than the group with probable MCI, suggesting that even with comorbid conditions, there is a high likelihood of the presence of a progressive dementing disorder.

10aAged10aAged, 80 and over10aCardiovascular System10aCognition Disorders10aDementia10aDisease Progression10aFemale10aHumans10aIncidence10aMale10aRetrospective Studies1 aLopez, Oscar, L1 aKuller, Lewis, H1 aBecker, James, T1 aDulberg, Corinne1 aSweet, Robert, A1 aGach, Michael1 aDeKosky, Steven, T uhttps://chs-nhlbi.org/node/94703092nas a2200385 4500008004100000022001400041245010000055210006900155260001300224300001100237490000700248520202800255653000902283653002202292653002002314653003202334653001402366653002402380653001102404653002002415653001802435653001102453653001702464653003102481653000902512653001202521653001602533100001702549700002002566700002402586700002102610700002102631700001802652856003602670 2008 eng d a1524-462800aAbnormal regional cerebral blood flow in cognitively normal elderly subjects with hypertension.0 aAbnormal regional cerebral blood flow in cognitively normal elde c2008 Feb a349-540 v393 a

BACKGROUND AND PURPOSE: The purpose of this study was to examine regional cerebral blood flow (rCBF) in normal cognitive-performing subjects with hypertension (HTN) using continuous arterial spin-labeled MRI. The most common explanation for the effect of blood pressure on cognition is that HTN increases the risk of cerebrovascular disease, and it may increase the risk for Alzheimer disease possibly through small vessel disease, ischemia, oxidative stress, and inflammation. However, few studies to date have examined the rCBF of cognitively normal subjects with HTN in population-based cohorts, and none have used continuous arterial spin-labeled MRI. This is a noninvasive technique that does not require either injections or ionizing radiation and can measure absolute rCBF rates over the entire brain.

METHODS: rCBF was measured at 1.5 T using continuous arterial spin-labeled MRI in 41 cognitively normal subjects who were participating in the Cardiovascular Health Study Cognition Study. A deformable atrophy-corrected registration method was used to warp the rCBF maps to the standard colin27 brain space. Image and cluster-based statistical analyses were performed between subject groups.

RESULTS: Cognitively normal subjects with HTN (n=19) had decreased rCBF in the putamen, globus pallidus, bilaterally, and in the left hippocampus compared with normotensives (n=22). In addition, decreased rCBF was observed in the right and left anterior cingulate gyrus with extension to the subcallosal region, left posterior cingulate gyrus and medial precuneus, left lateral inferior and superior frontal, and inferior parietal, left orbitofrontal, and left superior temporal cortices.

CONCLUSIONS: rCBF is affected in normal subjects with HTN, not only in the subcortical regions, but also in limbic and paralimbic structures. We hypothesize that the HTN creates a vulnerability state for the development of neurodegenerative disorders, especially Alzheimer disease.

10aAged10aAged, 80 and over10aCerebral Cortex10aCerebrovascular Circulation10aCognition10aCognition Disorders10aFemale10aGlobus Pallidus10aGyrus Cinguli10aHumans10aHypertension10aMagnetic Resonance Imaging10aMale10aPutamen10aSpin Labels1 aDai, Weiying1 aLopez, Oscar, L1 aCarmichael, Owen, T1 aBecker, James, T1 aKuller, Lewis, H1 aGach, Michael uhttps://chs-nhlbi.org/node/100502893nas a2200361 4500008004100000022001400041245015400055210006900209260001300278300001100291490000700302520181400309653002202123653001002145653001002155653001802165653003202183653001102215653001102226653003102237653000902268653003102277653004102308653001602349100001702365700002002382700002102402700001602423700001702439700002102456700001802477856003602495 2009 eng d a1552-656900aImaging cerebral blood flow in the cognitively normal aging brain with arterial spin labeling: implications for imaging of neurodegenerative disease.0 aImaging cerebral blood flow in the cognitively normal aging brai c2009 Oct a344-520 v193 a

INTRODUCTION: Arterial spin labeling (ASL) is a safe, noninvasive imaging method for evaluating cerebral blood flow (rCBF). The purpose of this article is to present ASL imaging features of 38 elderly cognitively normals (CN) with their rCBF values and an averaged profile of targeted anatomic regions rCBF values.

METHODS: Thirty-eight CN underwent MR imaging especially ASL with voxel morphometric techniques fusing the MR anatomical and ASL images to a standard reference brain (colin27). The ASL images were fused to echo planar images, which were then coregistered to high-resolution anatomical SPGR images. rCBF was calculated per region of interest using a modified continuous arterial spin labeling (CASL) convolutional method. Anatomical regions were selected and identified by the Talairach atlas in SPM2.

RESULTS: We identified areas of decreased and increased perfusion (compared to the averaged rCBF of all 38 CN) corresponding to decreased and increased quantified rCBF. The most common sites for decreased perfusion were precuneus (53%), superior temporal (48%), and orbitofrontal (37%), and for increased perfusion the caudate (39%), posterior cingulate (34%), anterior cingulate (32%), and amygdala (32%).

CONCLUSION: There are regional variations in rCBF both increased and decreased with the posterior cingulate and precuneus cortex showing the highest averaged values and signal intensity (bright spots). These variations represent the normal profile of a CN elderly brain, with higher perfusion in areas associated with cognition, memory, and behavior. It is necessary to understand these normal variations in order to determine if there are perfusion changes in ASL detected in neurodegenerative disorders such as Alzheimer's disease.

10aAged, 80 and over10aAging10aBrain10aBrain Mapping10aCerebrovascular Circulation10aFemale10aHumans10aMagnetic Resonance Imaging10aMale10aNeurodegenerative Diseases10aSignal Processing, Computer-Assisted10aSpin Labels1 aLee, Charles1 aLopez, Oscar, L1 aBecker, James, T1 aRaji, Cyrus1 aDai, Weiying1 aKuller, Lewis, H1 aGach, Michael uhttps://chs-nhlbi.org/node/108603130nas 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/107102532nas a2200469 4500008004100000022001400041245008400055210006900139260001300208300001400221490000700235520120900242653000901451653002201460653001001482653002201492653001001514653002401524653001101548653001101559653003101570653001801601653002501619653003101644653000901675653002101684653002701705653002901732653002401761653002601785100001901811700002001830700002101850700002401871700002701895700001801922700001901940700002401959700002201983700002102005856003602026 2012 eng d a1558-149700aWhite matter lesions and brain gray matter volume in cognitively normal elders.0 aWhite matter lesions and brain gray matter volume in cognitively c2012 Apr a834.e7-160 v333 a

Cerebral white matter lesions (WMLs) reflect small vessel disease, are common in elderly individuals, and are associated with cognitive impairment. We sought to determine the relationships between WMLs, age, gray matter (GM) volume, and cognition in the Cardiovascular Health Study (CHS). From the Cardiovascular Health Study we selected 740 cognitively normal controls with a 1.5 T magnetic resonance imaging (MRI) scan of the brain and a detailed diagnostic evaluation. WML severity was determined using a standardized visual rating system. GM volumes were analyzed using voxel-based morphometry implemented in the Statistical Parametric Mapping software. WMLs were inversely correlated with GM volume, with the greatest volume loss in the frontal cortex. Age-related atrophy was observed in the hippocampus and posterior cingulate cortex. Regression analyses revealed links among age, APOE*4 allele, hypertension, WMLs, GM volume, and digit symbol substitution test scores. Both advancing age and hypertension predict higher WML load, which is itself associated with GM atrophy. Longitudinal data are needed to confirm the temporal sequence of events leading to a decline in cognitive function.

10aAged10aAged, 80 and over10aAging10aApolipoprotein E410aBrain10aCognition Disorders10aFemale10aHumans10aImaging, Three-Dimensional10aLeukoaraiosis10aLongitudinal Studies10aMagnetic Resonance Imaging10aMale10aMemory Disorders10aMental Status Schedule10aNeuropsychological Tests10aRegression Analysis10aRetrospective Studies1 aRaji, Cyrus, A1 aLopez, Oscar, L1 aKuller, Lewis, H1 aCarmichael, Owen, T1 aLongstreth, William, T1 aGach, Michael1 aBoardman, John1 aBernick, Charles, B1 aThompson, Paul, M1 aBecker, James, T uhttps://chs-nhlbi.org/node/133302971nas a2200421 4500008004100000022001400041245006900055210006700124260001300191300001100204490000700215520185500222653000902077653002202086653001202108653001002120653002802130653000902158653002502167653001102192653001102203653001602214653001102230653001502241653003102256653000902287653002402296653003102320100001902351700002202370700002002392700002102412700001802433700002202451700001902473700002102492856003602513 2014 eng d a1873-260700aRegular fish consumption and age-related brain gray matter loss.0 aRegular fish consumption and agerelated brain gray matter loss c2014 Oct a444-510 v473 a

BACKGROUND: Brain health may be affected by modifiable lifestyle factors; consuming fish and antioxidative omega-3 fatty acids may reduce brain structural abnormality risk.

PURPOSE: To determine whether dietary fish consumption is related to brain structural integrity among cognitively normal elders.

METHODS: Data were analyzed from 260 cognitively normal individuals from the Cardiovascular Health Study with information on fish consumption from the National Cancer Institute Food Frequency Questionnaire and brain magnetic resonance imaging (MRI). The relationship between fish consumption data collected in 1989-1990 and brain structural MRI obtained in 1998-1999 was assessed using voxel-based morphometry in multiple regression analyses in 2012. Covariates were age, gender, race, education, white matter lesions, MRI-identified infarcts, waist-hip ratio, and physical activity as assessed by the number of city blocks walked in 1 week. Volumetric changes were further modeled with omega-3 fatty acid estimates to better understand the mechanistic link between fish consumption, brain health, and Alzheimer disease.

RESULTS: Weekly consumption of baked or broiled fish was positively associated with gray matter volumes in the hippocampus, precuneus, posterior cingulate, and orbital frontal cortex even after adjusting for covariates. These results did not change when including omega-3 fatty acid estimates in the analysis.

CONCLUSIONS: Dietary consumption of baked or broiled fish is related to larger gray matter volumes independent of omega-3 fatty acid content. These findings suggest that a confluence of lifestyle factors influence brain health, adding to the growing body of evidence that prevention strategies for late-life brain health need to begin decades earlier.

10aAged10aAged, 80 and over10aAnimals10aBrain10aCross-Sectional Studies10aDiet10aFatty Acids, Omega-310aFemale10aFishes10aGray Matter10aHumans10aLife Style10aMagnetic Resonance Imaging10aMale10aRegression Analysis10aSurveys and Questionnaires1 aRaji, Cyrus, A1 aErickson, Kirk, I1 aLopez, Oscar, L1 aKuller, Lewis, H1 aGach, Michael1 aThompson, Paul, M1 aRiverol, Mario1 aBecker, James, T uhttps://chs-nhlbi.org/node/659202557nas a2200469 4500008004100000022001400041245008200055210006900137260001300206300001400219490001500233520125500248653000901503653002201512653001001534653002201544653001201566653001501578653002001593653001001613653002601623653002801649653004101677653001101718653001101729653003101740653000901771653001901780653001701799100002401816700001901840700002201859700002001881700002101901700001801922700002001940700002401960700002101984700002402005700002202029856003602051 2015 eng d a1558-149700aPhysical activity, body mass index, and brain atrophy in Alzheimer's disease.0 aPhysical activity body mass index and brain atrophy in Alzheimer c2015 Jan aS194-S2020 v36 Suppl 13 a

The purpose of this study was to use a novel imaging biomarker to assess associations between physical activity (PA), body mass index (BMI), and brain structure in normal aging, mild cognitive impairment, and Alzheimer's dementia. We studied 963 participants (mean age: 74.1 ± 4.4 years) from the multisite Cardiovascular Health Study including healthy controls (n = 724), Alzheimer's dementia patients (n = 104), and people with mild cognitive impairment (n = 135). Volumetric brain images were processed using tensor-based morphometry to analyze regional brain volumes. We regressed the local brain tissue volume on reported PA and computed BMI, and performed conjunction analyses using both variables. Covariates included age, sex, and study site. PA was independently associated with greater whole brain and regional brain volumes and reduced ventricular dilation. People with higher BMI had lower whole brain and regional brain volumes. A PA-BMI conjunction analysis showed brain preservation with PA and volume loss with increased BMI in overlapping brain regions. In one of the largest voxel-based cross-sectional studies to date, PA and lower BMI may be beneficial to the brain across the spectrum of aging and neurodegeneration.

10aAged10aAged, 80 and over10aAging10aAlzheimer Disease10aAtrophy10aBiomarkers10aBody Mass Index10aBrain10aCognitive Dysfunction10aCross-Sectional Studies10aDiffusion Magnetic Resonance Imaging10aFemale10aHumans10aMagnetic Resonance Imaging10aMale10aMotor Activity10aNeuroimaging1 aBoyle, Christina, P1 aRaji, Cyrus, A1 aErickson, Kirk, I1 aLopez, Oscar, L1 aBecker, James, T1 aGach, Michael1 aLongstreth, W T1 aTeverovskiy, Leonid1 aKuller, Lewis, H1 aCarmichael, Owen, T1 aThompson, Paul, M uhttps://chs-nhlbi.org/node/654002967nas a2200457 4500008004100000022001400041245012500055210006900180260000900249300001100258490000700269520161400276653000901890653002201899653002501921653001001946653003001956653001101986653001101997653004002008653002002048653003102068653000902099653002902108653003302137653003002170653002602200653001702226100001902243700002102262700002002283700001902303700002202322700002402344700001802368700002702386700001702413700002202430700002102452856003602473 2015 eng d a1875-890800aRelationship between Systemic and Cerebral Vascular Disease and Brain Structure Integrity in Normal Elderly Individuals.0 aRelationship between Systemic and Cerebral Vascular Disease and  c2015 a319-280 v443 a

Cerebral white matter lesions (WMLs) are considered a reflection of cerebral and systemic small vessel disease (SVD), and are associated with reductions in brain volume. Like the brain, the kidney is also sensitive to factors that affect vasculature. Glomerular dysfunction due to renal vascular damage can be measured with different biochemical parameters, such as creatinine or cystatin C, although cystatin C is considered to be more accurate than creatinine in the elderly. The purpose of the study was to determine whether manifestations of SVD in the kidney can predict SVD-based damage to the brain. We examined the relationship between glomerular dysfunction as a measure of SVD on WMLs, gray matter (GM) volume, and cognition in 735 cognitively normal participants from the Cardiovascular Health Study Cognition Study. The multivariate analyses controlled for demographic characteristics, hypertension, heart disease, diabetes, Apolipoprotein 4 allele, C reactive protein, lipids, physical activity, smoking, and body mass index (BMI). Elevated cystatin C levels were associated with lower neuropsychological test scores, the presence of MRI-identified brain infarcts, the severity of WMLs, and GM atrophy five years later. In adjusted models, GM volume was significantly associated with cystatin-C only until BMI and severity of WMLs were added to the model, meaning that the effect of SVD on GM volume is mediated by these two variables. These findings suggest that age-related SVD is a process that leads to altered brain structure, and creates a vulnerability state for cognitive decline.

10aAged10aAged, 80 and over10aAnalysis of Variance10aBrain10aCerebrovascular Disorders10aFemale10aHumans10aImage Processing, Computer-Assisted10aLogistic Models10aMagnetic Resonance Imaging10aMale10aNeuropsychological Tests10aPeripheral Vascular Diseases10aPredictive Value of Tests10aRetrospective Studies10aWhite Matter1 aRiverol, Mario1 aBecker, James, T1 aLopez, Oscar, L1 aRaji, Cyrus, A1 aThompson, Paul, M1 aCarmichael, Owen, T1 aGach, Michael1 aLongstreth, William, T1 aFried, Linda1 aTracy, Russell, P1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/659302782nas a2200289 4500008004100000022001400041245011100055210006900166260000900235300001100244490000700255520193000262100001902192700002202211700001702233700001902250700001902269700002202288700002002310700002102330700002402351700001802375700002202393700002002415700002102435856003602456 2016 eng d a1875-890800aLongitudinal Relationships between Caloric Expenditure and Gray Matter in the Cardiovascular Health Study.0 aLongitudinal Relationships between Caloric Expenditure and Gray  c2016 a719-290 v523 a

BACKGROUND: Physical activity (PA) can be neuroprotective and reduce the risk for Alzheimer's disease (AD). In assessing physical activity, caloric expenditure is a proxy marker reflecting the sum total of multiple physical activity types conducted by an individual.

OBJECTIVE: To assess caloric expenditure, as a proxy marker of PA, as a predictive measure of gray matter (GM) volumes in the normal and cognitively impaired elderly persons.

METHODS: All subjects in this study were recruited from the Institutional Review Board approved Cardiovascular Health Study (CHS), a multisite population-based longitudinal study in persons aged 65 and older. We analyzed a sub-sample of CHS participants 876 subjects (mean age 78.3, 57.5% F, 42.5% M) who had i) energy output assessed as kilocalories (kcal) per week using the standardized Minnesota Leisure-Time Activities questionnaire, ii) cognitive assessments for clinical classification of normal cognition, mild cognitive impairment (MCI), and AD, and iii) volumetric MR imaging of the brain. Voxel-based morphometry modeled the relationship between kcal/week and GM volumes while accounting for standard covariates including head size, age, sex, white matter hyperintensity lesions, MCI or AD status, and site. Multiple comparisons were controlled using a False Discovery Rate of 5 percent.

RESULTS: Higher energy output, from a variety of physical activity types, was associated with larger GM volumes in frontal, temporal, and parietal lobes, as well as hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis.

CONCLUSION: Increasing energy output from a variety of physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status.

1 aRaji, Cyrus, A1 aMerrill, David, A1 aEyre, Harris1 aMallam, Sravya1 aTorosyan, Nare1 aErickson, Kirk, I1 aLopez, Oscar, L1 aBecker, James, T1 aCarmichael, Owen, T1 aGach, Michael1 aThompson, Paul, M1 aLongstreth, W T1 aKuller, Lewis, H uhttps://chs-nhlbi.org/node/700002655nas a2200253 4500008004100000022001400041245010600055210006900161260000900230300001400239490000700253520189200260100001602152700002302168700003102191700002302222700002302245700002102268700002102289700002002310700001802330700001702348856003602365 2020 eng d a1875-890800aCerebral Blood Flow Is Associated with Diagnostic Class and Cognitive Decline in Alzheimer's Disease.0 aCerebral Blood Flow Is Associated with Diagnostic Class and Cogn c2020 a1103-11200 v763 a

BACKGROUND: Reliable cerebral blood flow (CBF) biomarkers using a noninvasive imaging technique are sought to facilitate early diagnosis and intervention in early Alzheimer's disease (AD).

OBJECTIVE: We aim to identify brain regions in which CBF values are affected and related to cognitive decline in early AD using a large cohort.

METHODS: Perfusion MRIs using continuous arterial spin labeling were acquired at 1.5 T in 58 normal controls (NC), 50 mild cognitive impairments (MCI), and 40 AD subjects from the Cardiovascular Health Study Cognition Study. Regional absolute CBF and normalized CBF (nCBF) values, without and with correction of partial volume effects, were compared across three groups. Association between regional CBF values and Modified Mini-Mental State Examination (3MSE) were investigated by multiple linear regression analyses adjusted for cardiovascular risk factors.

RESULTS: After correcting for partial volume effects and cardiovascular risk factors, ADs exhibited decreased nCBF with the strongest reduction in the bilateral posterior cingulate & precuneus region (p < 0.001) compared to NCs, and the strongest reduction in the bilateral superior medial frontal region (p < 0.001) compared to MCIs. MCIs exhibited the strongest nCBF decrease in the left hippocampus and nCBF increase in the right inferior frontal and insular region. The 3MSE scores within the symptomatic subjects were significantly associated with nCBF in the bilateral posterior and middle cingulate and parietal (p < 0.001), bilateral superior medial frontal (p < 0.001), bilateral temporoparietal (p < 0.02), and right hippocampus (p = 0.02) regions.

CONCLUSION: Noninvasive perfusion MRI can detect functional changes across diagnostic class and serve as a staging biomarker of cognitive status.

1 aDuan, Wenna1 aSehrawat, Parshant1 aBalachandrasekaran, Arvind1 aBhumkar, Ashish, B1 aBoraste, Paresh, B1 aBecker, James, T1 aKuller, Lewis, H1 aLopez, Oscar, L1 aGach, Michael1 aDai, Weiying uhttps://chs-nhlbi.org/node/838202391nas a2200241 4500008004100000022001400041245007000055210006700125260001600192520166500208100002401873700001901897700002201916700002001938700002101958700001801979700002101997700002402018700002402042700002502066700002202091856003602113 2020 eng d a1097-019300aEstrogen, brain structure, and cognition in postmenopausal women.0 aEstrogen brain structure and cognition in postmenopausal women c2020 Sep 103 a

Declining estrogen levels before, during, and after menopause can affect memory and risk for Alzheimer's disease. Undesirable side effects of hormone variations emphasize a role for hormone therapy (HT) where possible benefits include a delay in the onset of dementia-yet findings are inconsistent. Effects of HT may be mediated by estrogen receptors found throughout the brain. Effects may also depend on lifestyle factors, timing of use, and genetic risk. We studied the impact of self-reported HT use on brain volume in 562 elderly women (71-94 years) with mixed cognitive status while adjusting for aforementioned factors. Covariate-adjusted voxelwise linear regression analyses using a model with 16 predictors showed HT use as positively associated with regional brain volumes, regardless of cognitive status. Examinations of other factors related to menopause, oophorectomy and hysterectomy status independently yielded positive effects on brain volume when added to our model. One interaction term, HTxBMI, out of several examined, revealed significant negative association with overall brain volume, suggesting a greater reduction in brain volume than BMI alone. Our main findings relating HT to regional brain volume were as hypothesized, but some exploratory analyses were not in line with existing hypotheses. Studies suggest lower levels of estrogen resulting from oophorectomy and hysterectomy affect brain volume negatively, and the addition of HT modifies the relation between BMI and brain volume positively. Effects of HT may depend on the age range assessed, motivating studies with a wider age range as well as a randomized design.

1 aBoyle, Christina, P1 aRaji, Cyrus, A1 aErickson, Kirk, I1 aLopez, Oscar, L1 aBecker, James, T1 aGach, Michael1 aKuller, Lewis, H1 aLongstreth, William1 aCarmichael, Owen, T1 aRiedel, Brandalyn, C1 aThompson, Paul, M uhttps://chs-nhlbi.org/node/847902708nas a2200253 4500008004100000022001400041245016400055210006900219260000900288300001200297490000700309520189300316100001602209700001902225700003102244700002302275700002302298700002102321700002102342700002002363700001802383700001702401856003602418 2021 eng d a1875-890800aCerebral Blood Flow Predicts Conversion of Mild Cognitive Impairment into Alzheimer's Disease and Cognitive Decline: An Arterial Spin Labeling Follow-up Study.0 aCerebral Blood Flow Predicts Conversion of Mild Cognitive Impair c2021 a293-3050 v823 a

BACKGROUND: This is the first longitudinal study to assess regional cerebral blood flow (rCBF) changes during the progression from normal control (NC) through mild cognitive impairment (MCI) and Alzheimer's disease (AD).

OBJECTIVE: We aim to determine if perfusion MRI biomarkers, derived from our prior cross-sectional study, can predict the onset and cognitive decline of AD.

METHODS: Perfusion MRIs using arterial spin labeling (ASL) were acquired in 15 stable-NC, 14 NC-to-MCI, 16 stable-MCI, and 18 MCI/AD-to-AD participants from the Cardiovascular Health Study (CHS) cognition study. Group comparisons, predictions of AD conversion and time to conversion, and Modified Mini-Mental State Examination (3MSE) from rCBF were performed.

RESULTS: Compared to the stable-NC group: 1) the stable-MCI group exhibited rCBF decreases in the right temporoparietal (p = 0.00010) and right inferior frontal and insula (p = 0.0094) regions; and 2) the MCI/AD-to-AD group exhibited rCBF decreases in the bilateral temporoparietal regions (p = 0.00062 and 0.0035). Compared to the NC-to-MCI group, the stable-MCI group exhibited a rCBF decrease in the right hippocampus region (p = 0.0053). The baseline rCBF values in the posterior cingulate cortex (PCC) (p = 0.0043), bilateral superior medial frontal regions (BSMF) (p = 0.012), and left inferior frontal (p = 0.010) regions predicted the 3MSE scores for all the participants at follow-up. The baseline rCBF in the PCC and BSMF regions predicted the conversion and time to conversion from MCI to AD (p < 0.05; not significant after multiple corrections).

CONCLUSION: We demonstrated the feasibility of ASL in detecting rCBF changes in the typical AD-affected regions and the predictive value of baseline rCBF on AD conversion and cognitive decline.

1 aDuan, Wenna1 aZhou, Grace, D1 aBalachandrasekaran, Arvind1 aBhumkar, Ashish, B1 aBoraste, Paresh, B1 aBecker, James, T1 aKuller, Lewis, H1 aLopez, Oscar, L1 aGach, Michael1 aDai, Weiying uhttps://chs-nhlbi.org/node/877302245nas a2200193 4500008004100000022001400041245007500055210006900130260001600199520166700215100001601882700002301898700001801921700002101939700002001960700001801980700001701998856003602015 2022 eng d a1875-890800aPattern of Altered Magnetization Transfer Rate in Alzheimer's Disease.0 aPattern of Altered Magnetization Transfer Rate in Alzheimers Dis c2022 Jun 093 a

BACKGROUND: Biomarkers for Alzheimer's disease (AD) are crucial for early diagnosis and treatment monitoring once disease modifying therapies become available.

OBJECTIVE: This study aims to quantify the forward magnetization transfer rate (kfor) map from brain tissue water to macromolecular protons and use it to identify the brain regions with abnormal kfor in AD and AD progression.

METHODS: From the Cardiovascular Health Study (CHS) cognition study, magnetization transfer imaging (MTI) was acquired at baseline from 63 participants, including 20 normal controls (NC), 18 with mild cognitive impairment (MCI), and 25 AD subjects. Of those, 53 participants completed a follow-up MRI scan and were divided into four groups: 15 stable NC, 12 NC-to-MCI, 12 stable MCI, and 14 MCI/AD-to-AD subjects. kfor maps were compared across NC, MCI, and AD groups at baseline for the cross-sectional study and across four longitudinal groups for the longitudinal study.

RESULTS: We found a lower kfor in the frontal gray matter (GM), parietal GM, frontal corona radiata (CR) white matter (WM) tracts, frontal and parietal superior longitudinal fasciculus (SLF) WM tracts in AD relative to both NC and MCI. Further, we observed progressive decreases of kfor in the frontal GM, parietal GM, frontal and parietal CR WM tracts, and parietal SLF WM tracts in stable MCI. In the parietal GM, parietal CR WM tracts, and parietal SLF WM tracts, we found trend differences between MCI/AD-to-AD and stable NC.

CONCLUSION: Forward magnetization transfer rate is a promising biomarker for AD diagnosis and progression.

1 aDuan, Wenna1 aSehrawat, Parshant1 aZhou, Tony, D1 aBecker, James, T1 aLopez, Oscar, L1 aGach, Michael1 aDai, Weiying uhttps://chs-nhlbi.org/node/908802317nas a2200229 4500008004100000022001400041245011300055210006900168260001600237520160000253100001801853700001901871700003101890700001901921700002101940700002101961700001401982700002001996700001702016700001802033856003602051 2023 eng d a2152-525000aProspective Longitudinal Perfusion in Probable Alzheimer's Disease Correlated with Atrophy in Temporal Lobe.0 aProspective Longitudinal Perfusion in Probable Alzheimers Diseas c2023 May 093 a

Reduced cerebral blood flow (CBF) in the temporoparietal region and gray matter volumes (GMVs) in the temporal lobe were previously reported in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, the temporal relationship between reductions in CBF and GMVs requires further investigation. This study sought to determine if reduced CBF is associated with reduced GMVs, or vice versa. Data came from 148 volunteers of the Cardiovascular Health Study Cognition Study (CHS-CS), including 58 normal controls (NC), 50 MCI, and 40 AD who had perfusion and structural MRIs during 2002-2003 (Time 2). Sixty-three of the 148 volunteers had follow-up perfusion and structural MRIs (Time 3). Forty out of the 63 volunteers received prior structural MRIs during 1997-1999 (Time 1). The relationships between GMVs and subsequent CBF changes, and between CBF and subsequent GMV changes were investigated. At Time 2, we observed smaller GMVs (p<0.05) in the temporal pole region in AD compared to NC and MCI. We also found associations between: (1) temporal pole GMVs at Time 2 and subsequent declines in CBF in this region (p=0.0014) and in the temporoparietal region (p=0.0032); (2) hippocampal GMVs at Time 2 and subsequent declines in CBF in the temporoparietal region (p=0.012); and (3) temporal pole CBF at Time 2 and subsequent changes in GMV in this region (p = 0.011). Therefore, hypoperfusion in the temporal pole may be an early event driving its atrophy. Perfusion declines in the temporoparietal and temporal pole follow atrophy in this temporal pole region.

1 aZhou, Tony, D1 aZhang, Zongpai1 aBalachandrasekaran, Arvind1 aRaji, Cyrus, A1 aBecker, James, T1 aKuller, Lewis, H1 aGe, Yulin1 aLopez, Oscar, L1 aDai, Weiying1 aGach, Michael uhttps://chs-nhlbi.org/node/9389