Poster Presentations: P3P582

of other regions were particularly located in the temporo-parietal and PCC/

precuneus regions (out-going); while amyloid hubs that are being influenced

by a high amount of regions across the brain were located in the lateral and

medial frontal regions (in-coming) (see an example of an individual subject

in Fig. 1,-B and 1-C). Conclusions: Although these findings are promising

to understand the dynamical binding of PIB and network activity of the am-

yloid pathology in preclinical stages of AD, further work is needed in order

to clarify the specific meaning of the temporo-spatial relationships between

amyloid hubs.

Figure 1.

P3-087 TYPE 2 DIABETES IS ASSOCIATEDWITH

ACCELERATEDLONGITUDINALWHITEMATTER

DEGENERATION IN THE ELDERLY

Pauline Maillard1, Owen Carmichael2, Dan Mungas3, Bruce Reed4,

Charles DeCarli5, 1UC Davis, Davis, California, United States; 2University

of California, Davis, Davis, California, United States; 3UC Davis

Alzheimer’s Disease Research Center, Sacramento, California, United

States; 4UC Davis, Martinez, California, United States; 5University of

California at Davis, Sacramento, California, United States.

Contact e-mail: pmaillard@ucdavis.edu

Background: Recent research suggests that diabetes mellitus type II

(DMT2) in the elderly may double risk for dementia and may be associated

with subtle white matter injury on cerebral diffusion tensor imaging (DTI)

scans. However, the time course of white matter change associated with

DMT2 is not well understood. We used longitudinal DTI to determine

whether DMT2 is associated with accelerated microstructuralWM degener-

ation over time in a sample of 162 individuals from the University of Cali-

fornia, Davis Alzheimer’s Disease Center. Methods: A set of 162

participants aged 74.7 6 7.6 years spanning normal cognition, mild cogni-

tive impairment, and dementia (including 50 with DMT2) received a com-

prehensive clinical evaluation and brain DTI on two dates (mean interval

(Dt): 3.6 years). DMT2 was not associated with white matter hyperintensity

volume or summary measures of cognitive performance (p-values>0.1).

Baseline and follow-up FA maps were calculated for each individual from

DTI. Corresponding baseline and follow-up FA maps were aligned using

linear and non-linear transformations, and subtracted to provide maps of in-

dividual FA change (DFA). Baseline FA maps were warped to a common

DTI template, and associated transformation parameters were applied to

DFA maps. This enabled voxel-based linear regressions with DMT2 and

age as predictors of interest, DFA/Dt as the outcome of interest, and clinical

diagnosis (normal, MCI, or dementia), baseline FA, education and gender as

covariates. T maps for the effects of DMT2 and age were corrected for mul-

tiple comparisons. Results: DMT2 was associated with greater decrease in

FA among voxels covering 2cc of the WM. WM tracts most heavily impli-

cated included the corpus callosum (CC) (3.9cc) and the cortico-spinal tract

(2.2cc). Greater age was independently associated with greater decrease in

FA in WM pathways covering 140cc of the WM, with CC (41.7cc) and un-

cinate fasciculus (3.5cc) heavily represented. Conclusions: This is one of

very few studies of longitudinal DTI change in the elderly. DMT2 and

age are independently associated with accelerated WM degeneration in

areas whose integrity is known to be reduced in mild cognitive impairment

and dementia. Future work should clarify the independent role of DMT2 in

accelerating WM degeneration in the aging brain.

P3-088 STAGING OF MICROSTRUCTURALWHITE

MATTER DAMAGE IN EARLYALZHEIMER’S

DISEASE

Lin Zhuang1, Perminder Sachdev1, Julian Trollor1, Simone Reppermund2,

Nicole Kochan1, Henry Brodaty3, Wei Wen1, 1Centre for Healthy Brain

Ageing, School of Psychiatry UNSW Medicine, Sydney, Australia,

Randwick, Australia; 2Centre for Healthy Brain Ageing, School of

Psychiatry UNSW Medicine, Sydney, Australia, Sydney NSW, Australia;3Dementia Collaborative Research Centre, Sydney, NSW, California,

Australia. Contact e-mail: l.zhuang@unsw.edu.au

Background:Alzheimer’s disease (AD) is generally considered to be a dis-

ease of gray matter (GM). Cerebral GM loss develops in a stereotypical pat-

tern, beginning in the medial temporal lobe before spreading to the

association cortices, and then the rest of the brain. However, studies inves-

tigating the evolution of white matter (WM) changes in AD are still lacking.

In this study, we used diffusion tensor imaging (DTI) fibre tractography to

evaluate the microstructural integrity of limbic WM tracts: the fornix, the

parahippocampal cingulum, the uncinate fasciculus, and two major cor-

tico-cortical association fibre tracts: the inferior longitudinal fasciculus

and superior longitudinal fasciculus, and one projection fibre: the corticospi-

nal tract, at different stages of amnestic mild cognitive impairment (aMCI),

a preclinical stage of AD. We aimed to identify the staging of WM tract de-

generation in early AD.Methods: 155 cognitively normal subjects (CN), 39

early aMCI and 27 late aMCI subjects were involved in the current study. All

participants were recruited from the Sydney Memory and Ageing Study

(MAS), a population-based longitudinal study of non-demented older peo-

ple aged 70-90 in the Eastern Suburbs of Sydney, Australia. 32 directional

DTI scans were acquired on a Philips 3T MRI scanner. Probabilistic diffu-

sion tensor tractography was performed to reconstruct the fibre tracts in

vivo. Fractional anisotropy (FA), axial diffusivity (DA), and radial diffusiv-

ity (RD) were then extracted along the reconstructed fibre tracts. Automated

measurement of hippocampal volume was performed using the FIRST

program.Results: Early aMCI had significantly higher RD and AxD values

of the fornix than that of controls. No significant group difference in the hip-

pocampal volume was found between early aMCI and controls. Late aMCI

showed lower FA values in the left fornix, while RD and AxD values were

significantly greater in the fornix, uncinate fasciculus, and parahippocampal

cingulum, when compared with controls. In addition, hippocampal volumes

were significantly smaller in late aMCI than in controls. Conclusions:

These results suggest that the use of microstructural WM measures by

DTI can provide a more sensitive and earlier detection of brain structural

changes in early AD than conventional GM volumetric measures.

P3-089 INCREASED CEREBRAL BLOOD FLOW IN

COGNITIVELY NORMAL OLDER ADULTS WITH

AMYLOID

Aaron Schultz1,DonaldMcLaren2, Jasmeer Chhatwal1, Karleyton Evans1,

Keith Johnson3, Reisa Sperling4, 1Massachusetts General Hospital,

Charlestown, Massachusetts, United States; 2Massachusetts General

Hospital, Harvard Medical School, Bedford VA Medical Center,

Charlestown, Massachusetts, United States; 3Massachusetts General

Hospital, Boston, Massachusetts, United States; 4Brigham and Women’s

Hospital, Boston, Massachusetts, United States. Contact e-mail: mclaren@

nmr.mgh.harvard.edu

Figure 1.

Figure 2.

Figure 3.

Poster Presentations: P3 P583

Background: Substantial work in preclinical Alzheimer’s disease (AD) has

been focused on understanding the relationships between amyloid, cogni-

tion, atrophy and neural activity; however, there have been limited investi-

gations of cerebral blood flow (CBF) to date. Recently, CBF, as measured

with pulsed arterial spinning labeling (pASL), has been shown to be a reli-

able marker of blood flow in cognitively normal older adults (CN) and may

have potential as an early AD biomarker. The objective of the present study

is to a ssess the effect of amyloid burden, APOE ε4 carrier status and age on

CBF using pASL. Methods: 84 CN participants (CDR¼0) in the Harvard

Aging Brain Study had a pASL scan that passed quality control, a PiB-

PET scan, and APOE genotyping. pASL images were motion corrected

and entered into the UPenn ASL Toolbox to compute CBF maps. The

CBF maps were then normalized to MNI space and additionally smoothed

(Fig 1). Mean cortical (mc) DVR PiB values were obtained from the PiB-

PET scans. Regional CBF from fcMRI networks derived using a factor anal-

ysis were analyzed with general linear models with PiB status (mcPiB+ de-

fined as mcPiB>1.4), APOE genotype (ε 3/ε 3 vs ε 3/ε 4), age and their

interactions as predictors. Forward and backward model selection methods

were used to select the final model for each region. Results: Amyloid pos-

itive CN had significantly higher CBF in the DMN (p¼0.0315, Fig 2,), lat-

eral visual network (p¼0.045), medial visual network (p¼0.011), and dorsal

attention network (p¼0.002). Significant decreases with age were found in

the both visual networks (p<0.001) and the dorsal attention network

(p¼0.002). Interestingly, we found that ε 4 carriers had greater age-related

decreases in the DMN (p¼0.008, Fig 3) and association network (p¼0.007).

Conclusions: Consistent with reports from longitudinal studies, we found

that amyloid burden is associated with increased cerebral blood flow

cross-sectionally in our sample. The amyloid-related increases might repre-

sent the brains response to initial stages of neuronal damage. Furthermore,

the increased age-related decline in ε4 carriers extends previous work com-

paring young and old ε 4 carriers. These results support the potential of CBF

as a biomarker to detect early functional change in the DMN, specifically

related to amyloid deposition.

P3-090 STRATEGIC BRAIN AREAS FOR COGNITIVE

DECLINE IN SUBCORTICALVASCULAR

COGNITIVE IMPAIRMENT: A DIFFUSION-

TENSOR IMAGING AND PET STUDY

Min-Jeong Kim1, Kyoung-Min Lee2, Young-Don Son3, Hyeon-Ae Jeon4,

Sejin Yoo5, Young-Bo Kim3, Zang-Hee Cho3, 1Department of Neurology,

Seoul National University Hospital Healthcare System Gangnam Center,

Seoul, South Korea; 2Seoul National University Hospital, Seoul, South

Korea; 3Neuroscience Research Institute, GachonMedical School, Incheon,

South Korea; 4Department of Neuropsychology, Max Planck Institute for

Human Cognitive and Brain Sciences, Leipzig, Germany; 5Interdisciplinary

Program in Cognitive Science, Seoul National University, Seoul, South

Korea. Contact e-mail: kmjchh@gmail.com

Background: Subcortical vascular cognitive impairment is known to be

caused by subcortical ischemic changes that are presented as white mat-

ter hyperintensities, lacunar infarcts, and microbleeds on MRI. However,

the specific brain area which is critical for clinical cognitive decline has

not been revealed yet in subcortical vascular cognitive impairment. Here

we aimed to investigate the difference of affected brain areas between

those with and without clinical cognitive impairment in patients having

subcortical ischemic changes on conventional MRI by using diffusion

tensor imaging (DTI) and [18F]-Fluorodeoxygucose (FDG)-PET.

Methods: 17 patients with both of subcortical vascular ischemic changes

and clinical cognitive impairment, 12 patients with subcortical vascular

changes but without cognitive impairment, and 10 normal healthy subjects

underwent DTI and FDG-PET. Frational anisotropy (FA) of whole brain

areas was compared among the groups by using tract-based spatial statis-

tics. Cortical glucose metabolism was also compared among the groups by

using 3-dimensional MRI-PET co-registration and spatial normalization.

The statistical maps for significantly different areas were constructed.

Results: Those with both subcortical ischemia and cognitive impairment

showed significantly decreased FA value in the periventricular white mat-

ters including the superior longitudinal fasciculus, the inferior longitudi-

nal fasciculus, and the corpus callosum compared to those without

cognitive impairment. Those with cognitive impairment also showed sig-

nificant cortical hypometabolism in the bilateral dorsal and ventral inferior

frontal, the left dorsal inferior temporal areas compared to those without

cognitive impairment. Comparison between normal control subjects and

those with subcortical ischemia showed significant difference in more ex-

tensive and non-specific areas: white matter tracts including both