Brain Imaging in Alzheimer Disease

Departments of Radiology and Neurology, Massachusetts General Hospital, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02114.
Cold Spring Harbor Perspectives in Medicine (Impact Factor: 9.47). 04/2012; 2(4):a006213. DOI: 10.1101/cshperspect.a006213
Source: PubMed


Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-d-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process. No one imaging modality can serve all purposes as each have unique strengths and weaknesses. These modalities and their particular utilities are discussed in this article. The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies.

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    • "Such subjects would be correspondingly re-classified as having 1 or 2 points, although another study that compared xMAP AlzBio3 A 1-42 to another vendor's A 42/40 ratio showed no improvement by the latter on the former [27]. On the other hand, the percent of the CSF-negative subjects having converted to AD in this study roughly corresponds to the ratio of MCI subjects without evidence of A pathology on positron emission tomography who convert to AD within 1–3 years (7%, reviewed in [28]). "
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    ABSTRACT: Background: In previous studies, a dichotomous stratification of subjects into "cerebrospinal fluid (CSF) normal" and "CSF pathologic" was used to investigate the role of biomarkers in the prediction of progression to dementia in pre-dementia/mild cognitive impairment subjects. With the previously published Erlangen Score Algorithm, we suggested a division of CSF patterns into five groups, covering all possible CSF result combinations based on the presence of pathologic tau and/or amyloid-β CSF values. Objective: This study aimed to validate the Erlangen Score diagnostic algorithm based on the results of biomarkers analyses obtained in different patients cohorts, with different pre-analytical protocols, and with different laboratory analytical platforms. Methods: We evaluated the algorithm in two cohorts of pre-dementia subjects: the US-Alzheimer's Disease Neuroimaging Initiative and the German Dementia Competence Network. Results: In both cohorts, the Erlangen scores were strongly associated with progression to Alzheimer's disease. Neither the scores of the progressors nor the scores of the non-progressors differed significantly between the two projects, in spite of significant differences in the cohorts, laboratory methods, and the samples treatment. Conclusions: Our findings confirm the utility of the Erlangen Score algorithm as a useful tool in the early neurochemical diagnosis of Alzheimer's disease.
    Journal of Alzheimer's disease: JAD 09/2015; 48(2):433-441. DOI:10.3233/JAD-150342 · 4.15 Impact Factor
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    • "In terms of pathological relevance , amyloid-β deposition is thought to be an initiating event of AD that then drives further pathological changes eventually resulting in neuronal dysfunction [10]. The above PET tracers adhere to this time course with amyloid PET representing an early disease biomarker that outperforms [ 18 F]-FDG in identifying prodromal AD subtypes [3] [11] [12] [13]. "
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    ABSTRACT: Positron emission tomography studies of cerebral glucose utilization and amyloid-β deposition with fluoro-deoxy-D-glucose ([18F]-FDG) and amyloid tracers have shown characteristic pathological changes in Alzheimer's Disease that can be used for disease diagnosis and monitoring. Application of this technology to preclinical research with transgenic animal models would greatly facilitate drug discovery and further understanding of disease processes. The results from preclinical studies with these imaging biomarkers have however been highly inconsistent, causing doubts over whether animal models can truly replicate an AD-like phenotype. In this study we performed in vivo imaging with [18F]-FDG and [18F]-AV45 in double transgenic TASTPM mice, a transgenic model that been previously demonstrated high levels of fibrillar amyloid-β and decreases in cerebral glucose utilization with ex vivo techniques. Our results show widespread and significant retention of [18F]-AV45 (p < 0.0001) in aged TASTPM mice in addition to significantregional decreases in [18F]-FDG uptake (p < 0.05). In vivo quantification of amyloid-β showed a strong (Pearson's r = 0.7078), but not significant (p = 0.1156), positive correlation with ex vivo measures suggesting some limitations on tracer sensitivity. In the case of [18F]-FDG, voxelwise analysis greatly enhanced detection of hypometabolic regions. We further evidenced modest neuronal loss (thalamus p = 0.0318) that could underlie the observed hypometabolism. This research was performed in conjunction with the European Community's Seventh Framework Program (FP7/2007-2013) for the Innovative Medicine Initiative under the PharmaCog Grant Agreement n°115009.
    Current Alzheimer research 07/2015; 12(7). DOI:10.2174/1567205012666150710104713 · 3.89 Impact Factor
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    • "This pattern of atrophy then extends to the temporal neocortex, followed by all neocortical association areas, usually in a rather symmetrical manner. This sequence of progression of atrophy on magnetic resonance imaging (MRI) most closely fits histopathological studies that have derived stages for the spread of neurofibrillary tangles (Johnson et al., 2012). Cerebrospinal fluid (CSF) concentrations of Ab42 as well as total and phosphorylated tau (p-tau181p) have been shown to serve as in vivo proxy measures of the central neuropathological hallmarks of AD (Braak et al., 2013). "
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    ABSTRACT: The progression of Alzheimer's disease (AD) is characterized by complex trajectories of cerebral atrophy that are affected by interactions with age and apolipoprotein E allele ε4 (APOE4) status. In this article, we report the nonlinear volumetric changes in gray matter across the full biological spectrum of the disease, represented by the AD-cerebrospinal fluid (CSF) index. This index reflects the subject's level of pathology and position along the AD continuum. We also evaluated the associated impact of the APOE4 genotype. The atrophy pattern associated with the AD-CSF index was highly symmetrical and corresponded with the typical AD signature. Medial temporal structures showed different atrophy dynamics along the progression of the disease. The bilateral parahippocampal cortices and a parietotemporal region extending from the middle temporal to the supramarginal gyrus presented an initial increase in volume which later reverted. Similarly, a portion of the precuneus presented a rather linear inverse association with the AD-CSF index whereas some other clusters did not show significant atrophy until index values corresponded to positive CSF tau values. APOE4 carriers showed steeper hippocampal volume reductions with AD progression. Overall, the reported atrophy patterns are in close agreement with those mentioned in previous findings. However, the detected nonlinearities suggest that there may be different pathological processes taking place at specific moments during AD progression and reveal the impact of the APOE4 allele. Copyright © 2015 Elsevier Inc. All rights reserved.
    Neurobiology of aging 07/2015; 36(10). DOI:10.1016/j.neurobiolaging.2015.06.027 · 5.01 Impact Factor
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