1. Background:
The default mode network (DMN) is a set of interconnected brain
regions remaining active under task free conditions preferentially
affected by Alzheimer’s disease (AD). Decreases in its connectivity
have been shown to be associated with the increased risk of AD
(Buckner et. al 2008). Separately, some recent studies suggested
abnormal glucose levels also contributed to AD risk (Burns et. al
2013). Using resting-state fMRI data, this study examined the
association between the increased serum glucose levels and the
reduced DMN connectivity in cognitively normal (CN) elderly subjects
encompassing all ApoE genotype combinations.
Understanding the Relationship between Fasting Blood Serum Glucose Levels and Default Mode Network Connectivity
E. R. Peshkin1
, C. A. Dunbar2
, I. R. Beck3,4
, A. Roontiva3,4
, R. J. Bauer III3,4
, J. Lou3,4
, V. Devadas3,4
, E. M. Reiman3,4,5,6
, K. Chen3,4,7
1
Duke University, 2
Columbia University, 3
Banner Alzheimer’s Institute, 4
Arizona Alzheimer’s Consortium, 5
TGen, 6
University of Arizona, 7
Arizona State University.
REFERENCES :
[1]Buckner, R. L., Annals of the New York Academy of Sciences 1124.1 (2008): 1-38. Web.
[2] Burns, C. M., American Academy of Neurology, 2013
[3] Kim, Insub, Journal of Alzheimer's Disease 19: 1371-1376. Web.
[4] Chao-Gan Y, DPARSF: A MATLAB Toolbox for “Pipeline” Data Analysis of Resting-State fMRI. Front Syst Neurosci. 2010;5:1–7.
Conclusions
Our results demonstrated the negative impact of serum glucose level
on brain DMN connectivity. Further studies are needed to confirm our
findings and to investigate the ε4 effects on the serum glucose and
DMN associations.
Objectives:
1. Evaluate the effect of elevated blood serum glucose levels
in cognitively normal elderly subjects on default mode network
connectivity.
2. Explore the relationship between elevated glucose levels
and DMN connectivity after accounting for variation in ApoE e4
genotypes.
Methods:
Subjects and data (Table 1)
100 cognitively normal subjects, all participants in our NIH-
sponsored APOE risk investigation, with no prior blood serum
glucose related conditions
57 ApoE e4 noncarriers (NC)
27ApoE e4 heterozygous (HT)
16 ApoE e4 homozygous (HM)
Results:
Overall, we found that glucose level was negatively associated with the DMN
connectivity at the hippocampus, parahippocampal formation, fusiform gyrus,
posterior cingulum, and medial temporal lobe. Furthermore, separate examina
tions showed such association was common to ε4 NC, HT and HM groups.
Table 1. Subject Demographics and Neuropsychological Scores
ACKNOWLEDGMENTS :
NIH APOE (Grant R01AG031581), State of Arizona, Arizona
Alzheimer’s Research Consortium, and the Swiss National
Science Foundation
Image pre-processing
Discarded first 10 volumes to obtain steady state
magnetization
Slice time correction, realignment, normalization to SPM8
EPI template, smoothing with 4 mm full-width half maximum
Gaussian kernel
Linear detrending to correct for signal drift, and 0.01–0.08
Hz bandpass filtering to reduce non-neuronal contributions
to blood-oxygenation-level-dependent (BOLD) signal
fluctuations. (Jones et al.).
Statistical analysis
DMN map for each individual subject was created using the
posterior cingulate cortex (PCC) as the seed ROI. Then, at
the group level, we generated voxel-wise serum glucose/
DMN association map based on a general linear model
approach for simple comparison and for covariating our ApoE
e4 effects. Significance was not corrected for multiple
comparisons at the p=0.005 level.
Fig 1 and Table 2: Overall Negative Correlation between Fasting Serum Glucose Level
and Posterior Cingulate seed ROI based DMN connectivity
[5] Jones, D., and Gunter, J., ADNI. Version 1.1. Mayo Clinic, 2012. Web. 16 July 2014. <http://adni.bitbucket.org/>.
[6] Statistical Parametric Mapping (www.fil.ion.uclac.uk/spm)
Fig 2 and Table 3: Negative Correlation between elevated serum glucose levels and DMN
connectivity in Non-carriers, Heterozygotes, and
Homozygotes
NC
HT
HM
Note: The hippocampus seemed affected by glucose independently of
ApoE.
Toil
etApp
roved
Brain Region X-Coordinate Y-Coordinate Z-Coordinate t-Value p-Value
Hippocampus 32 -34 13 3.8 1.4e-04
Left Precuneus -22 -46 10 3.7 2.0e-04
Right Transverse Temporal 30 -34 16 3.6 2.3e-04
Right Precuneus 24 -46 10 3.5 3.1e-04
Amygdala -22 -6 -10 3.4 4.4e-04
Right Inferior Temporal
Lobe 48 -19 -23 3.4 5.2e-04
Left Inferior Temporal Lobe -53 -40 -15 3.2 9.2e-04
Left Parahippocampus 2 1 -24 2.9 2.2e-03
Right Parahippocampus 6 1 -20 2.8 2.7e-03
Left Superior Temporal Pole -34 10 -24 2.8 3.3e-03
Brain Region X Y Z t-Score p-Value
Non-Carriers (NC)
Hippocampus 32 -34 13 3.7 1.8e-04
Precuneus -22 -46 10 3.6 2.4e-04
Amygdala -24 -6 -13 3.6 2.8e-04
Inferior Temporal Lobe 48 -19 -23 3.5 3.5e-04
Parahippocampus 2 1 -24 3.0 1.8e-03
Heterozygous (HT)
Hippocampus 32 -34 13 4.0 6.4e-05
Precuneus -22 -46 10 3.7 2.1e-04
Amygdala -22 -6 -10 3.5 4.2e-04
Inferior Temporal Lobe 48 -19 -23 3.2 1.0e-03
Fusiform Gyrus 38 -11 -26 3.0 1.9e-03
Parahippocampus 6 1 -20 2.8 3.0e-03
Homozygous (HM)
Hippocampus 32 -34 13 4.2 3.3e-05
Precuneus -22 -46 10 3.9 8.5e-05
Inferior Temporal Lobe 48 -19 -23 3.9 8.8e-05
Transverse Temporal
Gyrus 32 -34 16 3.8 1.4e-04
Angular Gyrus -30 -45 24 2.9 2.2e-03
NC HT HM p-value
Number of subjects (n=57) (n=27) (n=16)
Age (years) 64.5±6.6 66.3±5.5 62.9±5.8 0.23
Gender (F/M) 33/24 18/9 10/6 0.73
Education (years) 16.2±2.2 16.0±2.7 16.6±2.4 0.73
Fasting Time (hours) 11.1±5.1 9.0±4.5 10.1±5.2 0.21
Mini-Mental State Examina-
tion score 29.6±0.8 29.8±0.4 29.9±0.5 0.40
Auditory Verbal Learning Test
Total Learning 49.0±8.4 48.0±8.5 49.1±8.3 0.87
Long Term Memory 9.4±3.2 9.7±3.1 9.3±3.6 0.88
Short Term Memory 10.4±2.8 10.4±3.2 10.1±3.3 0.92
Fasting Serum Glucose 92.7±8.4 92.2±10.4 91.1±12.3 0.83