abnormal connectivity of the hippocampus in amnestic mild cognitive impairment: a diffusion tensor...

Poster Presentations P4S748

Two additional variables were included as covariates into the analysis as to

account for differences among subjects in task performanceand in grey-mat-

ter atrophy. Results: In the control and MCI groups,increased activation

during both the encoding and retrieval phases of the memory task was

revealed in the posterior hippocampus bilaterally. Instead, theAD group

showed increased activation only in occipital and motor regions andde-

creased activation in precuneus and hippocampus bilaterally. Comparison

betweengroups showed no significant differences between controls and

MCI, although, at the uncorrected level, the extent and the intensity of acti-

vation in the hippocampal regions were greater in the MCI patients than in

controls. Inaddition, there was greater activation in the control and MCI

groups relativeto the AD group in the hippocampus bilaterally, in both

encoding and retrieval. Conclusions: Results from task-related fMRI are

consistent with previous studies on memory in patients with AD and

MCI. The greater medial temporal activation in MCI patients compared to

controls andAD support their hypothesis that MCI patients engage compen-

satory mechanisms thatare not available anymore to AD patients. Further

results from resting fMRI will be presented and compared to the results

of task-related fMRI. Additional analyses will be presented to clarify the

role of performance and atrophy onresting and task-related functional data

P4-124 ABNORMAL CONNECTIVITY OF THE

HIPPOCAMPUS IN AMNESTIC MILD COGNITIVE

IMPAIRMENT: A DIFFUSION TENSOR

TRACTOGRAPHY STUDY

Lin Zhuang*1, Wei Wen2, Julian Trollor2, Nicole Kochan2,

Simone Reppermund2, Henry Brodaty3, Perminder Sachdev2, 1The

University of New South Wales, Sydney, Australia; 2University of New South

Wales, Sydney, Australia; 3Dementia Collaborative Research Centre,

Sydney, NSW, Australia.

Background: The fornix is a major outflow white matter tract of the hippo-

campus, and is critical for episodic memory retrieval. Since the hippocam-

pal formation is the earliest and primary site affected by the pathology of

Alzheimer’s disease (AD), it seems likely that the fornix may also be vulner-

able to the disease process, which in turn could disconnect the hippocampus

and cause memory impairment. This study used diffusion tensor imaging

(DTI) and fibre tractography to evaluate whether microstructural integrity

of the fornix is altered in amnestic mild cognitive impairment (aMCI),

and aimed to improve our understanding of memory deficits in the prodro-

mal stage of AD. Methods: We studied 206 cognitively normal controls

(CN), 76 aMCI subjects. All participants were recruited from of the Sydney

Memory and Ageing Study (MAS), a population-based longitudinal study of

non-demented older people aged 70-90 in the Eastern Suburbs of Sydney,

Australia. 32 directional DTI scans were acquired on a Philips 3TMRI scan-

ner. Probabilistic diffusion tensor tractographywas performed to reconstruct

the fornix in vivo using tools from the FMRIB’s Software Library (FSL) pro-

gram. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity

(DA), and radial diffusivity (RD) values of the fornix were then extracted

along the reconstructed fornix. Hippocampal volumes were also measured

using deformation-based morphometry.Results:Compared to controls, sig-

nificant FA reductions, MD and RD increases of the bilateral fornix, and bi-

lateral hippocampal atrophy were observed in aMCI. In addition,

microstructural abnormalities of the fornix correlated with hippocampal

atrophy. Furthermore, in aMCI, the left fornix microstructural measures

correlated with verbal memory performance, while the right fornix micro-

structural features were associated with visual memory function. Although

hippocampal volumes also correlated with verbal memory in aMCI, regres-

sions analysis showed that MD and RD measures of the left fornix were the

only predictors of verbal memory dysfunction in aMCI. Conclusions: The

microstructural alterations of the fornix already occurred in the prodromal

stage of Alzheimer’s disease (AD), and DTI measures of the fornix may

serve as a more sensitive biomarker than hippocampal volumes in detecting

early memory dysfunction in the preclinical stage of the dementia.

P4-125 CORTICAL AMYLOID DEPOSITION AND

GLUCOSE METABOLISM IN CLINICALLY

DIFFERENT STAGES OFALZHEIMER’S DISEASE

Shizuo Hatashita*1, 1Shonan-Atsugi Hospital, Atsugi, Japan.

Background: We have demonstrated that the diagnostic framework with

amyloid deposition allows for an earlier and more specific AD diagnosis

with [11C]-PIB PET. We clarify the association between cortical amyloid

deposition, glucose metabolism and cognitive function in clinically differ-

ent stages of Alzheimer’s disease (AD). Methods: The 114 patients with

AD, 93 with mild cognitive impairment (MCI) and 127 healthy control

(HC) subjects were studied. All subjects underwent cognitive testing, 60-

min dynamic [11C]-PIB PET and 20-min static [18F]-FDG PET. [11C]-

PIB data was acquired from 35-60 min after injection. Regions of interest

(ROI) were defined on co-registered MRI. PIB distribution volume ratios

(DVR) were calculated using Logan graphical analysis. Quantitative analy-

sis for [18F]-FDG used the standardized uptake value ratio (SUVR) values

of same regions. Results: All AD patients showed increase in PIB retention

in cortical regions and reduction in glucosemetabolism.MeanDVR value in

14 patients with moderate AD (CDR: 2.0) was significantly higher (2.17 60.37, p < 0.01). The DVR value in 36 patients with very mild AD (CDR:

0.5) and 64 patients with mild AD (CDR: 1.0) were similar to moderate

AD. Mean value of FDG SUVR in moderate AD (0.86 6 0.05, p < 0.05)

was significantly lower than that in very mild AD (0.92 6 0.05). However,

increased PIB retention did not correlate to comparable metabolic decrease

in any cortical region. In contrast, 42 (45%) of 93 MCI patients showed in-

crease in DVR value (2.07 6 0.31) while decrease in FDG value (0.94 60.06). Further, 24 (18%) of 127 HC subjects had increase in DVR value

of 1.97 6 0.27, similar to very mild AD. However, no significant changes

in FDG value were observed in any cortical region. In 180 patients with in-

creased PIB retention, there was no correlation between DVR and FDG

values in whole cortical regions. FDG values correlated strongly with the

MMSE (r¼ 0.46, P< 0.001) or CDR SB scores (r¼ 0.44, P< 0.001).Con-

clusions: Prodromal AD andAD dementia are identified, based on cognitive

function and amyloid deposition. Further, the cortical amyloid deposition is

detected at pre-symptomatic stage. The cerebral glucose metabolism starts

to decrease in prodromal AD, and its greater decrease correlates with greater

cognitive impairment along the continuum from prodromal to AD dementia.

P4-126 DISRUPTED EFFECTIVE CONNECTIVITY IN THE

POSTERIOR CINGULATE IS COMPENSATED BY

THE TEMPORO-PARIETAL NETWORK IN EARLY

ALZHEIMER’S DISEASE

Heidi Jacobs1, Martin VanBoxtel1, Armin Heinecke2, Ed Gronenschild1,

Walter Backes3, Inez Ramakers1, Jelle Jolles4, Frans R. J. Verhey1,1Maastricht University, Maastricht, Netherlands; 2BrainInnovation,

Maastricht, Netherlands; 3Maastricht University Medical Centre,

Maastricht, Netherlands; 4AZIRE Research Institute, Faculty of Psychology

and Education, VU University, Amsterdam, Netherlands.

Background: Parietal lobe dysfunctions in early Alzheimer’s Disease (AD)

has been investigated using different neuroimaging methods. Conflicting

parietal activation patterns have been found using visuospatialtask para-

digms, which may reflect either compensatory, dedifferentiation