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