Alzheimer Disease: New Concepts on Its Neurobiology and the Clinical Role Imaging Will Play

Department of Radiology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Radiology (Impact Factor: 6.87). 05/2012; 263(2):344-61. DOI: 10.1148/radiol.12110433
Source: PubMed


Alzheimer disease (AD) is one of, if not the most, feared diseases associated with aging. The prevalence of AD increases exponentially with age after 60 years. Increasing life expectancy coupled with the absence of any approved disease-modifying therapies at present position AD as a dominant public health problem. Major advances have occurred in the development of disease biomarkers for AD in the past 2 decades. At present, the most well-developed AD biomarkers are the cerebrospinal fluid analytes amyloid-β 42 and tau and the brain imaging measures amyloid positron emission tomography (PET), fluorodeoxyglucose PET, and magnetic resonance imaging. CSF and imaging biomarkers are incorporated into revised diagnostic guidelines for AD, which have recently been updated for the first time since their original formulation in 1984. Results of recent studies suggest the possibility of an ordered evolution of AD biomarker abnormalities that can be used to stage the typical 20-30-year course of the disease. When compared with biomarkers in other areas of medicine, however, the absence of standardized quantitative metrics for AD imaging biomarkers constitutes a major deficiency. Failure to move toward a standardized system of quantitative metrics has substantially limited potential diagnostic usefulness of imaging in AD. This presents an important opportunity that, if widely embraced, could greatly expand the application of imaging to improve clinical diagnosis and the quality and efficiency of clinical trials.

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    • "Additionally, brain atrophy within the medial temporal lobes (MTL) has been associated with objective learning and memory deficits in MCI [3] [4]. The current report addresses a knowledge gap about self-and informantreport of memory complaints and their relationship with objective memory performance and MTL volumes. "
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    ABSTRACT: The current study examined the relationship between subjective memory complaints (both self- and informant-report), objective memory performance, and medial temporal lobe (MTL) volume. MCI patients (n=58) and their informants (n=51) completed the Memory Assessment Clinics Self (MAC-S) and Family (MAC-F) rating scales as a measure of subjective memory. RBANS Immediate and Delayed Memory indices were used as objective measures of memory and a subset of MCI participants also underwent MRI, which was used to measure MTL volume. Patients reported greater difficulty with semantically based information (e.g., word and name recall) relative to informant report. However, the severity of these self-reports was unrelated to objective memory performance and only a single MAC-S scale was related to amygdalar volume. Conversely, several MAC-F indices were related to the RBANS Delayed Memory index as well as to amygdalar and hippocampal volumes. Measures of executive functioning were associated with MAC-S Frequency scales but not any MAC-F scale. The results of the current study suggest that, in those who are cognitively symptomatic, the frequency of self-reported subjective memory difficulty may reflect executive dysfunction but holds little value for verifying memory impairment. Conversely, informant report provides meaningful information about actual memory deficits in those with MCI.
    Full-text · Article · May 2015
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    • "In recent decades there has been a remarkable improvement in several imaging techniques for clinical diagnosis and therapy and one of these advances has been the improvement of brain imaging techniques such as diffusion-weighted magnetic resonance imaging (DWI and DTI). Many studies in neuroscience has been made with this promising diffusion techniques, which makes it possible to improve the diagnosis of various neuropathologies such as Alzheimer disease, Parkinson disease, Multiple Sclerosis and others [1]–[4]. However, these imaging techniques are still noisy and data processing is needed in order to have a precise diagnosis. "
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    ABSTRACT: Diffusion weighted imaging (DWI) and dif-fusion tensor imaging (DTI) are noisy submodalities images in magnetic resonance imaging (MRI) and usu-ally have long acquisition time due to repetitions needed to improve the signal noise ratio (SNR). Here we pro-pose and evaluate anisotropic anomalous diffusion (AAD) filter on DTI and DWI to enhance SNR and reduce the need for repetitions. Anisotropic anomalous diffusion filter is an iterative parametric diffusion filter based on anomalous diffusion. Fractional anisotropy (FA) and mean diffusivity (MD) maps were acquired with different repetitions times and processed using AAD filter to investigate optimum q parameter. SNR, RMSE and Full Width at Half Maximum (FWHM) measures were evaluated as image quality metrics. The results show that filtering based on AAD approach can improve DWI and DTI image quality and preserving relevant aspects in images. We conclude that when the AAD is applied on DWI and DTI images maps we can use images with lower acquisition repetitions time and maintain the image quality comparable to higher acqui-sition images.
    Full-text · Conference Paper · Oct 2014
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    • "In the imaging domain most research has focused on three measures: hippocampal volume measured on T1-weighted structural MRI, glucose metabolism measured with fluorodeoxyglucose positron emission tomography (FDG PET), and amyloid plaque burden measured with Pittsburgh compound B (PIB) PET or one of the F-18 amyloid agents such as florbetapir (AV45 PET) (Jack 2012). Resting-state functional MRI (fMRI) is a fourth candidate biomarker, which is also gaining some traction in the field and has recently been added to the Alzheimer's Disease Neuroimaging Initiative (ADNI, discussed below) (Greicius et al. 2004; Jack et al. 2010). "
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    ABSTRACT: Alzheimer’s disease (AD) is an increasingly prevalent, fatal neurodegenerative disease that has proven resistant, thus far, to all attempts to prevent it, forestall it, or slow its progression. The ε4 allele of the Apolipoprotein E gene (APOE4) is a potent genetic risk factor for sporadic and late-onset familial AD. While the link between APOE4 and AD is strong, many expected effects, like increasing the risk of conversion from MCI to AD, have not been widely replicable. One critical, and commonly overlooked, feature of the APOE4 link to AD is that several lines of evidence suggest it is far more pronounced in women than in men. Here we review previous literature on the APOE4 by gender interaction with a particular focus on imaging-related studies.
    Full-text · Article · Jun 2014 · Brain Imaging and Behavior
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