Journal of Alzheimer's Disease - Volume 31, issue s3

Authors: Yamasaki, Takao | Horie, Shizuka | Muranaka, Hiroyuki | Kaseda, Yumiko | Mimori, Yasuyo | Tobimatsu, Shozo

Article Type: Review Article

Abstract: Visuospatial dysfunction including defects in motion perception in Alzheimer's disease (AD) and mild cognitive impairment (MCI) are clues to search for potential in vivo biomarkers. In this review, we focus on the clinical relevance of non-invasive neurophysiological findings in event-related potentials (ERPs) and functional magnetic resonance imaging (fMRI) to assess visual dysfunction in AD and MCI. We first summarize the current concept of the parallel visual pathways in primates and humans. Next, we outline the results of previous electrophysiological and fMRI studies on visual function in AD and MCI. Finally, we present the recent findings of our systematic ERP and …fMRI approach to visual perception in AD and MCI. Our overview strongly indicates that visual impairments in patients with AD and MCI are mainly caused by dysfunction in higher-level parallel visual pathways. In particular, a deficit in ventro-dorsal stream function related to optic flow perception is responsible for the earliest and most prominent visual symptoms in MCI. Therefore, we conclude that ERP and fMRI measurements for visual perception can be used as in vivo biomarkers for early functional brain changes in MCI and AD patients. Show more

Keywords: Alzheimer's disease, dorsal and ventral streams, event-related potentials, functional magnetic resonance imaging, mild cognitive impairment, visual perception

DOI: 10.3233/JAD-2012-112093

Citation: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S137-S154, 2012

Authors: Chhatwal, Jasmeer P. | Sperling, Reisa A.

Article Type: Review Article

Abstract: Functional magnetic resonance imaging (fMRI) is a non-invasive technique that has come into common use to examine neural network function in normal and impaired cognitive states. Using this promising type of analysis, researchers have identified the presence of anatomically distributed regions operating as large-scale neural networks, which are observed both during the performance of associative memory tasks and in the resting state. The assembly of these anatomically distinct regions into functional ensembles and their choreographed activation and deactivation sets the stage for complex behaviors such as the formation and retrieval of associative memories. We review progress in the use of …task-related and task-free MRI to elucidate the changes in neural activity in normal older individuals, patients with mild cognitive impairment, and those with Alzheimer's disease, focusing on the altered activity of the default mode network and medial temporal lobe. We place task-free fMRI studies into the larger context of more traditional, task-based fMRI studies of human memory, which have firmly established the critical role of the medial temporal lobe in associative encoding. Lastly, we discuss the data from our group and others that suggests task-free MRI and task-based fMRI may prove useful as non-invasive biomarkers in studying the progression of memory failure over the course of Alzheimer's disease. Show more

Keywords: Aging, Alzheimer's disease, default mode network, dementia, functional connectivity, functional magnetic resonance imaging, memory

DOI: 10.3233/JAD-2012-120730

Citation: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S155-S167, 2012

Authors: Mandal, Pravat K. | Mahajan, Rashima | Dinov, Ivo D.

Article Type: Review Article

Abstract: Structural magnetic resonance imaging (MRI) provides anatomical information about the brain in healthy as well as in diseased conditions. On the other hand, functional MRI (fMRI) provides information on the brain activity during performance of a specific task. Analysis of fMRI data requires the registration of the data to a reference brain template in order to identify the activated brain regions. Brain templates also find application in other neuroimaging modalities, such as diffusion tensor imaging and multi-voxel spectroscopy. Further, there are certain differences (e.g., brain shape and size) in the brains of populations of different origin and during diseased conditions …like in Alzheimer's disease (AD), population and disease-specific brain templates may be considered crucial for accurate registration and subsequent analysis of fMRI as well as other neuroimaging data. This manuscript provides a comprehensive review of the history, construction and application of brain atlases. A chronological outline of the development of brain template design, starting from the Talairach and Tournoux atlas to the Chinese brain template (to date), along with their respective detailed construction protocols provides the backdrop to this manuscript. The manuscript also provides the automated workflow-based protocol for designing a population-specific brain atlas from structural MRI data using LONI Pipeline graphical workflow environment. We conclude by discussing the scope of brain templates as a research tool and their application in various neuroimaging modalities. Show more

Keywords: Alzheimer's disease, brain atlas, method for brain template design, MRI, population specific brain template

DOI: 10.3233/JAD-2012-120412

Citation: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S169-S188, 2012

Authors: Abdi, Hervé | Williams, Lynne J. | Beaton, Derek | Posamentier, Mette T. | Harris, Thomas S. | Krishnan, Anjali | Devous Sr, Michael D.

Article Type: Research Article

Abstract: We present a generalization of mean-centered partial least squares correlation called multiblock barycentric discriminant analysis (MUBADA) that integrates multiple regions of interest (ROIs) to analyze functional brain images of cerebral blood flow or metabolism obtained with SPECT or PET. To illustrate MUBADA we analyzed data from 104 participants comprising Alzheimer's disease (AD) patients, frontotemporal dementia (FTD) patients, and elderly normal controls. Brain images were analyzed via 28 ROIs (59,845 voxels) selected for clinical relevance. This is a discriminant analysis (DA) question with several blocks (one per ROI) and with more variables than observations, a configuration that precludes using DA. MUBADA …revealed two factors explaining 74% and 26% of the total variance: Factor 1 isolated FTD, and Factor 2 isolated AD. A random effects model correctly classified 64% (chance = 33%) of “new” participants (p < 0.0001). MUBADA identified ROIs that best discriminated groups: ROIs separating FTD were bilateral inferior, middle frontal, left inferior, and middle temporal gyri, while ROIs separating AD were bilateral thalamus, inferior parietal gyrus, inferior temporal gyrus, left precuneus, middle frontal, and middle temporal gyri. MUBADA classified participants at levels comparable to standard methods (i.e., SVM, PCA-LDA, and PLS-DA) but provided information (e.g., discriminative ROIs and voxels) not easily accessible to these methods. Show more

Keywords: BADA, dementia, discriminant analysis, MUBADA, multiblock analysis, neuroimaging, partial least squares correlation, PET, PLS methods, SPECT

DOI: 10.3233/JAD-2012-112111

Citation: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S189-S201, 2012

Authors: Richard, Edo | Schmand, Ben | Eikelenboom, Piet | Westendorp, Rudi G. | Van Gool, Willem A.

Article Type: Research Article

Abstract: The focus of most of the research on Alzheimer's disease in the last decades has been on senile plaques and neurofibrillary tangles. The vast majority of patients with Alzheimer's disease are over 75 years of age, whereas most of the research focuses on younger subjects. To consider old-age dementia as a homogenous well-defined condition ignores the complexity of this condition and limits the development of new diagnostic methods, preventive strategies, or treatment strategies that could be widely applicable in daily practice in the majority of the older patients. The current research on biomarkers focuses on correlates of plaques and tangles, …which are poor markers in older dementia subjects. Acknowledging that dementia in old age is an essentially different condition from dementia at relatively younger age is needed and should lead to new approaches in dementia research. Show more

Keywords: Age, biomarkers, cerebrospinal fluid, magnetic resonance imaging, neuroimaging, old-age dementia, prevention

DOI: 10.3233/JAD-2012-112216

Citation: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S203-S209, 2012

Authors: Liberati, Giulia | da Rocha, Josué Luiz Dalboni | van der Heiden, Linda | Raffone, Antonino | Birbaumer, Niels | Olivetti Belardinelli, Marta | Sitaram, Ranganatha

Article Type: Research Article

Abstract: Brain-computer interfaces (BCIs) provide alternative methods for communicating and acting on the world, since messages or commands are conveyed from the brain to an external device without using the normal output pathways of peripheral nerves and muscles. Alzheimer's disease (AD) patients in the most advanced stages, who have lost the ability to communicate verbally, could benefit from a BCI that may allow them to convey basic thoughts (e.g., “yes” and “no”) and emotions. There is currently no report of such research, mostly because the cognitive deficits in AD patients pose serious limitations to the use of traditional BCIs, which are …normally based on instrumental learning and require users to self-regulate their brain activation. Recent studies suggest that not only self-regulated brain signals, but also involuntary signals, for instance related to emotional states, may provide useful information about the user, opening up the path for so-called “affective BCIs”. These interfaces do not necessarily require users to actively perform a cognitive task, and may therefore be used with patients who are cognitively challenged. In the present hypothesis paper, we propose a paradigm shift from instrumental learning to classical conditioning, with the aim of discriminating “yes” and “no” thoughts after associating them to positive and negative emotional stimuli respectively. This would represent a first step in the development of a BCI that could be used by AD patients, lending a new direction not only for communication, but also for rehabilitation and diagnosis. Show more

Keywords: Alzheimer's disease, dementia, emotions, fMRI, machine learning, user computer interface

DOI: 10.3233/JAD-2012-112129

Citation: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S211-S220, 2012

Authors: Zaidel, Liam | Allen, Greg | Cullum, C. Munro | Briggs, Richard W. | Hynan, Linda S. | Weiner, Myron F. | McColl, Roderick | Gopinath, Kaundinya S. | McDonald, Elizabeth | Rubin, Craig D.

Article Type: Research Article

Abstract: We used functional connectivity magnetic resonance imaging (fcMRI) to investigate changes in interhemispheric brain connectivity in 11 patients with mild Alzheimer's disease (AD) following eight weeks of treatment with the cholinesterase inhibitor donepezil. We examined functional connectivity between four homologous temporal, frontal, and occipital regions. These regions were selected to represent sites of AD neuropathology, sites of donepezil-related brain activation change in prior studies, and sites that are minimally affected by the pathologic changes of AD. Based on previous findings of selective, localized frontal responses to donepezil, we predicted that frontal connectivity would be most strongly impacted by treatment. Of …the areas examined, we found that treatment had a significant effect only on functional connectivity between right and left dorsolateral prefrontal cortices. Implications for understanding the impact of donepezil treatment on brain functioning and behavior in patients with AD are discussed. This preliminary report suggests that fcMRI may provide a useful index of treatment outcome in diseases affecting brain connectivity. Future research should investigate these treatment-related changes in larger samples of patients and age-matched controls. Show more

Keywords: Alzheimer's disease, donepezil, dorsolateral prefrontal cortex, functional connectivity, hippocampus, magnetic resonance imaging

DOI: 10.3233/JAD-2012-120709

Citation: Journal of Alzheimer's Disease, vol. 31, no. s3, pp. S221-S226, 2012