Parental History of Alzheimer Disease Predicts Abnormal White Matter in Cognitively Normal Elderly Individuals

DT-MRI was performed on cognitively normal adults with and without a family history of dementia of the Alzheimer’s type (DAT). Regional differences were identified in the corpus callosum and parietal white matter in those individuals with confirmed parental history of DAT. These findings support the hypothesis that white matter abnormalities precede the clinically apparent onset of dementia, representing either early pathophysiological changes or fundamental differences in white matter integrity which may place individuals at risk for subsequent development of Alzheimer Disease.

These specific perfusion patterns measured by ASL-MRI suggest fundamental differences in the brain perfusion between AD patients and cognitively healthy subjects and could contribution to the diagnoses of AD-related dementia.

Alzheimer-related differences in basal functional brain networks are likely be related to the regional distribution of neuropathology. To explore this relationship, we have scanned the same population of AD patients and age-matched controls both with fMRI in resting state condition and PET, employing two different amyloid-b tracers: 11C-PIB reveals the distribution of neurofibrillary tangles and 18F-FDDNP binds predominantly to amyloid plaques. The functional networks affected in AD, and the distribution of neuropathology largely overlaps. We will demonstrate the specific relationship between either type of amyloid pathology and particular functional networks.

Problem: PASL was used to study cerebral perfusion changes in patients with MCI and AD. Methods: Resting CBF maps were obtained from 16 young (30±10a) and 15 elderly (65±5a) cognitively normal controls, 13 patients with MCI (69±9a) and 7 patients with mild dementia in AD (70.9±11.2a). Results: Hypoperfusion was detected in parietal cortex and right angular gyrus when patients were compared to controls. A significant perfusion decrease in parietal cortex and left caudate was also detected in elderly compared to young controls. Conclusion: This suggests that PASL is capable to investigate the transition from normal ageing to dementia.

Precise and accurate quantification of the volume, and longitudinal change in volume, of the lateral ventricles (LV) based on MRI data is an important goal in understanding the natural progression of neurodegenerative disorders such as Alzheimer’s disease (AD) and multiple sclerosis. In the present study, we provide evidence from 270 AD patients for the accuracy of a novel, fully-automated, MRI-based technique for LV segmentation. Furthermore, we provide preliminary evidence (from a subset of 33 of these patients) for the validity and precision of two novel, fully-automated, MRI-based techniques for the estimation of longitudinal change in LV volume.

APOE and vascular dysfunction are associated with increased risk of AD. Changes in perfusion have been identified in APOE carriers verse non-carriers. The application of DSC perfusion with intravenous gadolinium contrast injection to investigate perfusion changes in AD has the ability to provide CBF, CBV, and MTT perfusion maps. We investigated the ability of DSC MRI to measure CBV, CBF, and MTT changes in non-demented children with increased risk for AD due to one or more risk factors: APOE and/or family history.

We tested a hypothesis that the integrity and organization patterns of specific modules (HIP-TP) responsible for memory processing are altered in Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD) subjects, in comparison with cognitively normal (CN) subjects. HIP-TP in CN is very well organized and has highly directed connected bilateral symmetric regions, but the MCI and AD HIP-TP module have fewer directed left and right connections, and the modules are hardly symmetric and organized. There is a potential that patterns of the HIP-TP modules could be employed to distinguish MCI subjects from CN subjects.

A quantitative Granger causality analysis, which can measure the causal strength among different time series, was employed to identify and quantify the directional hippocampus and default model network in cognitively normal subjects, and detect the changes in the directional network in AD patients. Interestingly in AD subjects, the functional afferents of parahippocampal gyrus is significantly decreased but the efferents of that are increased. And the abnormal network are correlated with abnormal behaviors.

We used DTI to investigate inferior fronto-occipital fasciculus (IFO) alterations in patients with Alzheimer’s disease and Mild Cognitive Impairment (MCI). Within each group, we compared DTI parameters between the two hemispheres in IFO. We found no differences in DTI parameters between the two patients groups. Our results reveal that the longitudinal and radial diffusivities, fractional anisotropy and apparent diffusion coefficient were significantly higher on the right lobe than on the left lobe in AD group. While, Within the MCI group, only FA and radial diffusivity were higher on the right lobe than on the left lobe.

White matter hyperintensities (WMH) provide an additive effect is considered to be a risk factor of Alzheimer¡¯s disease (AD). We investigated which DTI indices: fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (DR) and axial diffusivity (DX) values were more sensitive to differentiate AD from normal control and how different levels of WMH may contribute to AD in specific areas of the white matter. FA and DR were helpful to discriminate AD with different grade of WMH. Different level WMH contributed AD in different regions and extent. The increased DR may provide measurement of demyelination of AD in pathology.

Amyloid plaque deposition in the brain is one of the key pathological hallmarks of Alzheimer’s disease. Recently, CSF amyloid beta42 peptide levels and PET scans using C-11 Pittsburgh Compound B (PIB) have been established as potential biomarkers for dementia of the Alzheimer’s type (DAT). Using DTI, we evaluated white matter microstructure in subjects with and without established DAT and identified differences in both the corpus callosum and precuneus. The same white matter findings were identified in non-demented subjects with positive CSF and PIB-PET, suggesting that microstructural abnormalities in white matter integrity may precede cognitive changes in DAT.

The purpose of this study is to find an effective white matter biomarker of Alzheimer’s disease (AD) which may indicate disease severity and progression. In this study, DTI and T1 weighted images were acquired from 38 subjects (20 AD, 18 controls). We surveyed all white matter tracts by labeling of the ICBM-DTI-81 digital atlas and correlated FA values of individual white matter tracts with cognitive testing score and cortical atrophy map respectively. The correlation analyses show that tracts in the limbic system, namely fornix and cingulum, are the most sensitive tract to cognitive testing scores and cortical atrophy.

Longitudinal water proton (¹H₂O) relaxation time constants (T₁) are strongly associated with macromolecular volume fraction. Here, we report that ¹H₂O T₁ values are increased in the thalamus of subjects with early AD compared to age-matched, cognitively normal controls. Further, we find that the increased ¹H₂O T₁ values in early AD reflect, at least in part, neurodegenerative (macromolecular loss) processes and that contributions to the increased ¹H₂O T₁ values from altered blood water content (via dilation or increased vessel density) are small.

We present a novel, unsupervised method, sparse canonical correlation analysis for neuroimaging (SCCAN), that automatically locates correlated sets of voxels in complementary imaging modalities. The method reveals significant and syndrome-specific cortical thickness-diffusion tensor imaging networks in two neurodegenerative diseases, AD and FTD. Subject diagnosis was confirmed by autopsy or CSF-biomarker ratios. The SCCAN summary correlates, in AD, with MMSE reduction and, in FTD, with reduced verbal fluency. Thus, SCCAN identifies disease-specific networks of effects in white matter and cortical thickness that appear in anatomy suspected to be involved in these diseases and that relate specifically to impaired cognitive processes.

Resting-state fMRI was used to investigate changes of functional connectivity (FC) within specific resting-state networks (RSNs) in the presence of Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB) as compared to normal aging. Using ICA analysis, we identified 10 RSNs across subjects. AD patients revealed reduced FC in the posterior cingulate, within the default-mode-network. Conversely, DLB patients showed reduced FC in occipital areas, within the visual network. These findings respectively account for brain disconnection between medial temporal lobes and other association cortexes in the development of AD symptoms, and for occipital abnormalities potentially responsible for visual hallucinations in DLB.

Accurate and repeatable mI measurements may offer a simple means for diagnosing or monitoring treatment in mild cognitive impairment (MCI) patients. Unfortunately, such repeatable measurements are difficult to obtain in vivo. The current report investigates the capability of CPRESS to better separate MCI subjects from normal controls (NC’s). With only 12 subjects in each of the MCI and NC categories, p-values separating the two classes decrease from 0.03 to 0.002 when using CPRESS instead of a short TE PRESS sequence. The impact of more repeatable mI concentration measurements in diagnosing or monitoring MCI evolution or treatment is discussed.

There has been great interest in developing objective biologically based markers that can be used to predict risk, diagnose, stage, or track the course and treatment of dementia and other neurodegenerative diseases. Alzheimer disease (AD) is the most common form of dementia. Mild cognitive impairment (MCI) is a transitional state between normal aging and dementia, and is often considered a risk factor for AD. In this study, we employed resting-state MRI connectivity methods and the large-scale network analyses to discriminate between AD, MCI and healthy control subjects.

Rotating frame relaxation (T1rho and T2rho) were measured under a variety of RF pulses (namely continuous-wave, and frequency swept pulses in the adiabatic and subadiabatic regime) on twenty one Parkinson's disease (PD) subjects at 4T. Results demonstrate that different RF pulses significantly modulate the rotating frame relaxations in the substantia nigra (SN), providing the opportunity to extract fundamental parameters of the system based on theoretical modeling of the relaxation channels. The greatest sensitivity to identify sub-regions of the SN was achieved by the so-called RAFF pulse, which combines T1rho and T2rho relaxation mechanisms. Measurements from ferritin samples were additionally performed.

T2* weighted MR image is influenced by iron deposition, so that SN shows up iron-related MRI contrast for all that SN is gray matter. Therefore T2* MR imaging shows great potential in PD study using ultra high field (UHF) 7.0T. And 3D T2* Gradient Echo (GE) sequence makes it possible to study a volumetric analysis and a structural morphometry for SN. This method is validated, despite the reduced SNR associated with fast imaging techniques. And 3D model of the SN shows quite well structural changes in PD case.

Pseudo-continuous ASL was used to investigate cerebral blood flow in 44 Parkinson’s disease (PD) patients and 26 controls. Principal component analysis produced a set of covariance patterns which were used to form a perfusion network that successfully distinguished PD from control. The PD-related network was characterized by decreased perfusion in PD versus controls in bilateral posterior parietal-occipital regions, posterior medial cortices, precentral and bilateral middle frontal gyri, and left caudate. Preserved perfusion occurred in bilateral globus pallidus. This ASL-derived PD network provides a marker to objectively gauge disease severity and serves as a potential method to longitudinally track disease progression.