Alzheimer's DiseaseNeurology Solutions for more diagnostic confidence

Imaging and Lab Tests support Alzheimer’s disease Evaluation
At the moment, there are no stand-alone tests for a definitive diagnosis of Alzheimer’s disease (AD) other than histopathological confirmation at autopsy. Complete work up of AD includes a thorough medical history, mental status testing, physical and neurological exam, brain imaging and laboratory tests.

Moving towards earlier detection
In the future, new imaging technologies and disease biomarkers may be helpful to take the clinical evaluation of AD forward from simply ruling out the disease to supporting the identification of patients who have the strong likelihood of developing AD, by identifying characteristic patterns of functional and structural cerebral alterations.
The actual guidelines for the Mild Cognitive Impairment (MCI) stage are largely for research, but they may be applied in specialized clinical settings. They supplement standard clinical tests to help determine possible causes of MCI symptoms.¹ Currently, imaging is being used in research to help establish correlations between pathophysiologic manifestations, clinical status and their relation to other biomarkers, and their prognosis as well as therapeutic trials. Going forward, imaging could be valuable to identify which MCI patients might progress to a clinical diagnosis of AD and support the identification of proper disease modifying therapies.²
Combining diagnostic imaging and laboratory capabilities, Siemens is your partner in the evaluation of AD and in pushing diagnostic boundaries going forward.

Screening

There are a variety of types of dementia and cognitive impairment, which can have various underlying causes, ranging from Alzheimer’s disease (AD) to vascular dementia to name but a few, requiring different therapeutical approaches. Hence various risk factors need to be assessed. While imaging and laboratory tests have traditionally been used independently on a diagnostic basis to rule out other causes of dementia, they may in the future help to assess multiple different aspects of AD pathology and have immediate prognostic importance. Siemens provides technology and laboratory equipment to help effectively differentiate AD from other dementias and venture forward in AD research.

Genetic Testing

The ɛ4 allele of the apolipoprotein E (APOE) gene has been identified as a major genetic risk factor for AD. It encodes a protein that plays a key role in cholesterol metabolism and has been found to increase the risk of developing AD. APOE-ɛ4 contributes to AD pathogenesis seems to act primarily as a risk factor in brain beta-amyloid deposition.²Hence, screening for APOE gene mutations and micro RNA pattern indicating a risk profile will become important screening tools in the future.

Laboratory testing

In patients with suspected AD, the clinical evaluation essentially includes lab tests for a number of mimicking diseases such as hypo- and hyperthyroidism, vitamin deficiencies, and infections of the central nervous system (Creutzfeldt-Jakob disease, AIDS dementia, neurosyphilis). As your partner in thyroid testing, Siemens solutions help labs keep pace with the evolving standards in thyroid disease diagnostics.

Morphological Evaluation

Brain scans are used to rule out other possible causes of dementia, including brain tumors, stroke, subdural hematomas, normal-pressure hydrocephalus, and other conditions. Non-contrast and contrast-enhanced CT imaging is a highly efficient neuro-imaging technique that provides differential and cause-related information on possible causes of dementia. The unmatched soft tissue contrast of MRI and additional information gained from dedicated sequences enables to reliably rule out differential diagnoses. With state-of-theart CT and MR scanners together with software for all your clinical and research related data handling, Siemens is the ideal partner in AD image based evaluation.

Functional Evaluation

The simultaneous acquisition of MR imaging (MRI)/ CT imaging and positron emission tomography (PET) data provides exceptional insights into brain anatomy, functions, and metabolism. Biograph mMR and Biograph mCT/Biograph mCT Flow have the ability to precisely visualize areas of decreased or increased glucose metabolism in the brain. This supports differentiation between AD, frontoemporal dementia and other dementias. It also allows a determination of the extent and progression of the disease. In AD, a characteristic pattern of decreased uptake can be seen in the posterior temporo parietal association cortex.² PET imaging is utilized to estimate beta-amyloid neuritic plaque density in adult patients with cognitive impairment who are being evaluated for AD and other causes of cognitive decline.³ Through the combination of CT or MR with PET in one modality, Siemens technology enables shorter acquisition times and optimizes accuracy with motion compensation in agitated patients. Siemens’ exceptional molecular PET/MR and PET/CT technology promises unprecedented insights into AD pathology, more comprehensive brain imaging, and improved functional analysis.

Morphometry

By the time a typical Alzheimer’s disease (AD) patient comes to diagnosis, atrophy is normally well established. Even in patients with mild clinical symptoms, entorhinal volumes are already reduced by around 20–30 % and hippocampal volumes by about 15–25 %.⁴ In particular, the assessment of medial temporal atrophy with MRI has been shown to have a predictive value for AD. Consequently, medial temporal lobe atrophy is now included as one of the biomarkers of AD in proposed criteria for diagnosing (prodromal) AD at a pre-dementia stage.

3T MRI Scanners

Structural MRI in AD can assess atrophy and changes in tissue characteristics. Also, progressive cerebral atrophy can be visualized in patients, in particular, with T1-weighted volumetric sequences. MRI offers a range of different sequences that can probe different tissue characteristics, providing multiple clinical and research measures in a single session. MRI measures of atrophy reflect cumulative neuronal damage, which in turn is directly responsible for the clinical state.

MAGNETOM family

Biograph mMR

The benefits of single modality MR and PET in the study of neurological diseases such as AD are well known. Combining these modalities brings the potential for a more complete imaging picture and better understanding of AD pathologies. In addition, the current research and development of new tracers offers great promise. Biograph mMR fully integrates state-of-the-art 3T MRI and cutting-edge molecular imaging. Simultaneous acquisition of the morphology, function, and metabolism of the brain are now possible. You can obtain a comprehensive diagnostic picture with just one scan, which shows MR and PET data in virtually seamless spatial alignment. In addition, the MR acquisition can be used to correct motion-related effects in PET, greatly improving image quality.

Biograph mMR

Function

Functional MRI (fMRI) is being increasingly used to investigate the functional integrity of brain networks in AD. In combination with other tests, the information gained from fMRI will help differentiate the diseases and determine the status of progression. Synaptic activity is measured either by the visualization of glucose metabolism of brain cells using PET or the visualization of signal changes due to changes in blood volume, blood flow, and the blood oxyhemoglobin/ deoxyhemoglobin ratio using BOLD MRI. Many fMRI studies in MCI and AD focus on the pattern of fMRI activation in the hippocampus and related structures in the medial temporal lobe. In patients with clinically diagnosed AD, the results have been quite consistent, showing decreased hippocampal activity during theencoding of new information. Furthermore, several studies report increased prefrontal cortical activity in AD patients. These results suggest that other networks may increase activity as an attempted compensatory mechanism during hippocampal failure.⁴ Other MRI techniques such as diffusion tensor imaging (DTI), arterial spin labeling measures of cerebral blood flow and PET tracers targeted at the cholinergic system, microglial activation and other tracers in development will also be contributing to our understanding of AD pathology in the future.

Inline BOLD Imaging

Automatic real-time calculation of z-score (t-test) maps with inline technology for variable paradigms
Compatible with single-shot EPI with high susceptibility contrast for fast multi-slice imaging
ART (Advanced Retrospective Technique) for fully automatic 3D retrospective motion correction for 6 degrees of freedom (3 translations and 3 rotations)
Mosaic images for efficient storage and transfer of large data sets
Inline calculation of t-statistics (t-maps) based on a general linear model (GLM), including the hemodynamic response function and correction for slow drifts (GLM not available for MAGNETOM ESSENZA)
Overlay of statistical results calculated inline onto EPI images.

syngo DTI Tractography

Multiple parameters can be derived from the diffusion tensor, including the trace, ADC (Apparent Diffusion Coefficient), relative anisotropy, and fractional anisotropy. These secondary parameters are independent of the frame of reference and are very sensitive to white matter pathology.
syngo DTI (Diffusion Tensor Imaging) Tractography uses diffusion tensor data and allows 3D visualization of specific white matter tracts.
syngo DTI and syngo DTI Evaluation will help you to identify anatomical substructures, and with fiber direction maps and fiber tracts (tractography) you will be able to assess the microstructural aspects of the brain lesions.
The Siemens Multidirectional DTI with 256 directions allows a finer and more precise visualisation of fiber tracks and direction.

syngo DTI Tractography

Clifford R. J.et al. Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011; 7(3) 257-262

Clifford R. J. Alzheimer disease: New Concepts on Its Neurobiology and the Clinical Role Imaging Will Play. Radiology 2012;263 (2): 344-361

Adam S. Fleisher et al: “Using Positron Emission Tomography and Florbetapir F 18 to Image Cortical Amyloid in Patients With Mild Cognitive Impairment or Dementia Due to Alzheimer Disease”, Archives of Neurology, July 12, 2011

Johnson KA et al. Brain Imaging in Alzheimer Disease. Cold Spring Harb Perspect Med 2012;2:a006213