The goal of this proposal is to develop and validate an early, non-invasive, quantitative marker for the pre-clinical stage of Alzheimer's disease (risk marker) using functional magnetic resonance imaging (fMRI). Such a sensitive marker for AD will have significant advantages in identifying people at risk, facilitating early assessment and providing effective disease management. Recent developments in fMRI technology allow us to indirectly observe neuronal activity with high spatial and temporal resolution. We and others have observed spontaneous low frequency (SLF) fluctuations in the BOLD contrast-weighted neurophysiological signal in subjects at rest. We have developed an index, the COSLOF index, to quantify changes of SLF signal. The results of numerous published neuropathological studies suggest that the hippocampal formation is the initial locus in the disease processes of AD. In addition, the progression of neurodegenerative changes is remarkably uniform across individuals, is predictable, and shows little inter-patient variation. In AD, the lesions eventually lead to severe damage to the hippocampus (referred to as the """"""""floor effect"""""""") and clinical expression of dementia. Our preliminary results demonstrate that the COSLOF index has the ability to distinguish between probable/possible AD patients and cognitively healthy controls. Based on all these results, we propose a prospective and longitudinal study to test the hypothesis that the COSLOF index in the hippocampal formation can predict the onset of AD dementia in subjects with mild cognitive impairment (MCI). We chose to study MCI subjects because of their high incidence (yearly 10-12 percent) of AD development. At the end of the five-year period, we can determine retrospectively the sensitivity of the COSLOF index to predict the pre-clinical onset of AD progression and to distinguish those MCI subjects who are destined to develop AD from those who are undergoing normal aging processes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG020279-02
Application #
6640352
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Buckholtz, Neil
Project Start
2002-07-01
Project End
2007-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
2
Fiscal Year
2003
Total Cost
$356,250
Indirect Cost
Name
Medical College of Wisconsin
Department
Biophysics
Type
Schools of Medicine
DUNS #
937639060
City
Milwaukee
State
WI
Country
United States
Zip Code
53226
Li, Wenjun; Wang, Yang; Ward, B Douglas et al. (2017) Intrinsic inter-network brain dysfunction correlates with symptom dimensions in late-life depression. J Psychiatr Res 87:71-80
Chen, Guangyu; Shu, Hao; Chen, Gang et al. (2016) Staging Alzheimer's Disease Risk by Sequencing Brain Function and Structure, Cerebrospinal Fluid, and Cognition Biomarkers. J Alzheimers Dis 54:983-993
Shu, Hao; Shi, Yongmei; Chen, Gang et al. (2016) Opposite Neural Trajectories of Apolipoprotein E ?4 and ?2 Alleles with Aging Associated with Different Risks of Alzheimer's Disease. Cereb Cortex 26:1421-1429
Li, Wenjun; Ward, B Douglas; Xie, Chunming et al. (2015) Amygdala network dysfunction in late-life depression phenotypes: Relationships with symptom dimensions. J Psychiatr Res 70:121-9
Li, Wenjun; Douglas Ward, B; Liu, Xiaolin et al. (2015) Disrupted small world topology and modular organisation of functional networks in late-life depression with and without amnestic mild cognitive impairment. J Neurol Neurosurg Psychiatry 86:1097-105
Li, Wenjun; Muftuler, L Tugan; Chen, Gang et al. (2014) Effects of the coexistence of late-life depression and mild cognitive impairment on white matter microstructure. J Neurol Sci 338:46-56
Li, Wenjun; Antuono, Piero G; Xie, Chunming et al. (2014) Aberrant functional connectivity in Papez circuit correlates with memory performance in cognitively intact middle-aged APOE4 carriers. Cortex 57:167-76
Shu, Hao; Yuan, Yonggui; Xie, Chunming et al. (2014) Imbalanced hippocampal functional networks associated with remitted geriatric depression and apolipoprotein E ?4 allele in nondemented elderly: a preliminary study. J Affect Disord 164:5-13
Xie, Chunming; Li, Wenjun; Chen, Gang et al. (2013) Late-life depression, mild cognitive impairment and hippocampal functional network architecture. Neuroimage Clin 3:311-20
Chen, Guangyu; Zhang, Hong-Ying; Xie, Chunming et al. (2013) Modular reorganization of brain resting state networks and its independent validation in Alzheimer's disease patients. Front Hum Neurosci 7:456

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