Low-PIB Intermediate-PIB High-PIB

Verbal episodic memory versus:

Composite [18F]FDG MetaROI -0.14 0.68** 0.33

Right angular gyrus -0.10 0.80** 0.31

Left angular gyrus -0.10 0.68* 0.44

PCC -0.16 0.28 -0.10

Poster Presentations: P2P392

and non-carriers suggests that ε4 accelerates volume loss not in medial tem-

poral structures but in posterior cingulate gyrus in cognitively normal el-

derly subjects.

P2-127 IS VERBAL EPISODIC MEMORY IN ELDERLY

Right inferior temporal gyrus -0.11 0.59 0.57*

Left inferior temporal gyrus -0.01 0.52 0.36

INDIVIDUALS WITH AMYLOID DEPOSITS

PRESERVED THROUGH ALTERED NEURONAL

FUNCTION?

Rik Ossenkoppele1, Cindee Madison2, Hwameeh Oh2, Miranka Wirth3,

Bart van Berckel4, William Jagust5, 1VU University Medical Center,

Amsterdam, Massachusetts, Netherlands; 2Helen Wills Neuroscience

Institute, Berkeley, California, United States; 3UC Berkeley, Berkeley,

California, United States; 4VU University Medical Center, Amsterdam,

Netherlands; 5University of California, Berkeley, Berkeley, California,

United States. Contact e-mail: r.ossenkoppele@vumc.nl

Background: Approximately 30% of the elderly come to autopsy with sig-

nificant cerebral amyloid pathology but themechanisms that enable intellec-

tual preservation in individuals supposedly on the path to ADare not yet

fully understood.Methods: In the present study we explored the inter-rela-

tionships between amyloid deposition, glucose metabolism and cognitive

performance in 81 cognitively normal elderly (mean age: 75 6 7, MMSE:

29 6 1). Subjects were divided into low-amyloid (n¼53), intermediate-

amyloid (n¼13) and high-amyloid (n¼15) groups as defined by their [11

C]PIB status. To assess glucose metabolism in highly vulnerable AD re-

gions, pons normalized standardized uptake value ratios of [18 F]FDG im-

ages we extractedusing aMetaROImask that includes theposterior cingulate

cortexand bilateral angular and inferior temporal gyri . Previously validated

factor scores for verbal and visual episodic memory, semantic memory,

working memory and executive functioning were used to evaluate cognitive

performance in detail.Results: Linear regression analysis, adjusted for age,

education and APOE, showed an association between precuneus [11 C]PIB

retention and compositie MetaROI [18 F]FDG uptake at trend level (b: 0.21,

p¼0.10)that became significant after additional adjustment for cortical gray

matter volume (b: 0.28, p<0.05). Precuneus [11 C]PIB was negatively cor-

related with visual episodic memory (b: -0.30, p<0.05), but this finding did

not survive adjustment for age, education and APOE genotype. Across all

subjects, composite and regional [18 F]FDG uptake were not associated

with cognitive performance. Within the intermediate-amyloid group, how-

ever, verbal episodic memory performance correlated positively with com-

posite(b: 0.68) andright (b: 0.80)andleft (b: 0.68)angular gyrus [18 F]FDG

uptake (all p<0.05). Conclusions: There are at least two mechanisms that

may account for increased glucose metabolism in elderly with elevated

[11 C]PIB retention. First, it may reflect compensatory activation of the

brain to counteract neurotoxic effects of amyloid-beta. Second, there is ev-

idence that synaptic activity increases the deposition of amyloid pathology.

The positive association between verbal episodic memory performance and

metabolic activity in subjects with elevated amyloid levels seems in favor of

the "compensation hypothesis". Altogether, these findings suggest that

asymptomatic elderly with cerebral amyloidosis are, at least temporarily,

able to preserve cognitive function through altered neuronal function.

P2-128 BODY MASS ANDWHITE MATTER INTEGRITY:

THE ROLE OF VASCULAR AND INFLAMMATORY

FACTORS IN HEALTHYAGING

Brianne Bettcher1, Christine Walsh2, Christa Watson2, Joshua Miller3,

Ralph Green4, Nihar Patel2, BruceMiller2, Kristine Yaffe5, Joel H. Kramer2,1UCSF Memory and Aging Center, San Francisco, California, United

States; 2UCSF, San Francisco, California, United States; 3Rutgers

University, New Brunswick, New Jersey, United States; 4UC Davis Medical

Center, Sacramento, California, United States; 5University of California

San Francisco, San Francisco, California, United States.

Contact e-mail: bbettcher@memory.ucsf.edu

Background: High adiposity is deleteriously associated with brain health,

and may disproportionately affect white matter integrity; however, limited

information exists regarding the neuroanatomic specificity of these alter-

ations, as well as themechanisms bolstering the association between adipos-

ity and white matter integrity. The present study evaluated whether vascular

and inflammatory markers modulate the relationship between body mass in-

dex (BMI) and corpus callosum (CC) integrity, a region shown to be vulner-

able to the aging process, in a healthy older adult cohort. Methods: All

participants (n¼110) underwent diffusion tensor imaging (DTI), provided

blood samples, and participated in a general health evaluation. DTI was pro-

cessed using tract-based spatial statistics (TBSS), and fractional anisotropy

was calculated for our primary regions of interest (genu, body, and splenium

of the corpus callosum) based on the Johns Hopkins University ICBM-DTI-

81 white matter atlas. Vascular and inflammatory blood markers were ana-

lyzed (i.e. high sensitivity c-reactive protein, interleukin-6, homocysteine,

HOMA-IR, HDL, LDL), and vascular risk factors were documented (i.e.

smoking history, hypertension).Results:Hierarchical regressions indicated

that higher BMIwas associated with lower white matter integrity in the genu

(r p ¼-.37, p <.0001), body (r p ¼-.30, p ¼.001), and splenium (r p ¼-.31,

p ¼.001) of the CC (see Figure 1). Vascular and inflammatory factors

partially modulated the association between BMI and CC fractional anisot-

ropy. Specifically, BMI was independently associated with the genu fibers

(b ¼-.29; p ¼.03), even after controlling for vascular risk factors and blood

markers. In contrast, BMI was no longer associated with the body (b -.18;

p¼.16) and splenium (b¼-.24; p¼.09) of the CC after controlling for these

markers. Conclusions: The complex and noxious connection between BMI

and white matter integrity is modified in part by traditional vascular and in-

flammatory markers; however, regional variability also suggests the role of

additional mechanisms that may drive the relationship between BMI and

corpus callosum integrity. Extensive knowledge of these mechanisms will