Behavioural Neurology - Volume 21, issue 1-2

Article Type: Other

DOI: 10.3233/BEN-2009-0242

Citation: Behavioural Neurology, vol. 21, no. 1-2, pp. 1-1, 2009

Authors: Fennema-Notestine, Christine | McEvoy, Linda K. | Hagler, Jr., Donald J. | Jacobson, Mark W. | Dale, Anders M. | the Alzheimer's Disease Neuroimaging Initiative,

Article Type: Research Article

Abstract: Current research supports the strong potential of structural MRI profiles, even within cross-sectional designs, as a promising method for the discrimination of Alzheimer's Disease (AD) from normal controls and for the prediction of Mild Cognitive Impairment (MCI) progression and conversion to AD. Findings suggest that measures of structural change in mesial and lateral temporal, cingulate, parietal and midfrontal areas may facilitate the assessment of a treatment's ability to halt the progressive structural loss …that accompanies clinical decline in MCI. The performance of prediction is likely to continue to improve with the incorporation of measures from other neuroimaging modalities, clinical assessments, and neuromedical biomarkers, as the regional profile of individuals at risk for progression is refined. Show more

Keywords: MRI, Alzheimer's disease, Mild Cognitive Impairment (MCI), morphometry, brain imaging

DOI: 10.3233/BEN-2009-0230

Citation: Behavioural Neurology, vol. 21, no. 1-2, pp. 3-12, 2009

Authors: Appel, Jason | Potter, Elizabeth | Shen, Qian | Pantol, Gustavo | Greig, Maria T. | Loewenstein, David | Duara, Ranjan

Article Type: Research Article

Abstract: Dementia is a debilitating and life-altering disease which leads to both memory impairment and decline of normal executive functioning. While causes of dementia are numerous and varied, the leading cause among patients 60 years and older is Alzheimer's disease. The gold standard for Alzheimer's diagnosis remains histological identification of amyloid plaques and neurofibrillary tangles within the medial temporal lobe, more specifically the entorhinal cortex and hippocampus. Although no definitive cure for Alzheimer's …disease currently exists, there are treatments targeted at preserving cognition and memory while delaying continued loss of function. Alzheimer's disease exists along a spectrum of cognitive decline and is often preceded by Mild Cognitive Impairment (MCI). Patients with MCI demonstrate memory loss and cognitive impairment while still continuing normal activities of daily living, and are considered to be at increased risk for developing Alzheimer's Dementia. Identifying patients with prodromal states of Alzheimer's dementia such as MCI may allow initiation of appropriate treatment planning and delay of cognitive decline. Therefore, the need for a non-invasive early biomarker for the detection of Alzheimer's disease has never been greater. Multiple neuroimaging methods utilizing visual rating scales, volumetric measurements, and automated methods have been developed to identify, quantify, and track anatomic sequelae of Alzheimer's Disease. Show more

DOI: 10.3233/BEN-2009-0225

Citation: Behavioural Neurology, vol. 21, no. 1-2, pp. 13-19, 2009

Authors: Brewer, J.B.

Article Type: Research Article

Abstract: Neurodegenerative disorders, such as Alzheimer's disease (AD), are associated with characteristic patterns of neuropathological spread in the brain. Disease progression is usually accompanied by regional atrophy that can be detected noninvasively using structural magnetic resonance imaging (MRI). A wealth of data has demonstrated the value of quantitative measurements of regional atrophy in AD, suggesting that volumetric MRI (vMRI) may be a useful clinical tool. vMRI provides biological evidence of neurodegenerative disease in …patients with cognitive impairment. However, several hurdles impede implementation of vMRI in clinical practice. These include a lack of standardized MRI acquisition protocols, spatial distortions in MRI data, labor-intensive vMRI methods susceptible to interoperator variability, a lack of normative ranges for volume measures, and difficulty integrating vMRI in clinical workflow. Advances in vMRI have resulted from multi-institutional studies of brain imaging, such as the Alzheimer's Disease Neuroimaging Initiative (ADNI), and help address these challenges. New, fully-automated measures of brain structure volumes coupled with large, multi-center studies using standardized MRI protocols now allow the development of age-adjusted normative ranges for vMRI. Such advances are critical for providing physicians a framework for assessing the pattern and degree of regional atrophy in a patient's brain and applying vMRI in clinical practice. Show more

Keywords: Alzheimer's disease, hippocampus, entorhinal, quantitative, neuroimaging, brain atrophy, temporal horn

DOI: 10.3233/BEN-2009-0226

Citation: Behavioural Neurology, vol. 21, no. 1-2, pp. 21-28, 2009

Authors: Jacobson, Mark W. | McEvoy, Linda K. | Dale, Anders | Fennema-Notestine, Christine

Article Type: Research Article

Abstract: Identifying a preclinical phase of Alzheimer's Disease (PCAD) that is distinct from cognitive changes in healthy aging continues to be a major research focus. Combining neuropsychological and neuroimaging methodologies should improve our ability to differentiate healthy from pathological aging, although studies that utilize both methods often result in equivocal findings, possibly due to variability in cognitive test performance that may be capturing distinct phenotypes. One method of capturing this cognitive variability is to …utilize contrasting neuropsychological tests to identify subgroups representative of distinct cognitive phenotypes, and determine whether differences in brain morphometry support these classifications. We review several approaches to defining cognitive subgroups, and we consider the possibility that cognitive asymmetry might provide one means of identifying both functional and structural changes associated with aging and dementia. Show more

Keywords: MRI, Alzheimer's disease, cognition, morphometry, asymmetry

DOI: 10.3233/BEN-2009-0229

Citation: Behavioural Neurology, vol. 21, no. 1-2, pp. 29-37, 2009

Authors: Stebbins, G.T. | Murphy, C.M.

Article Type: Research Article

Abstract: Structural magnetic resonance imaging (MRI) studies of Alzheimer's disease and mild cognitive impairment (MCI) have focused on the hippocampus and entorhinal cortex; gray matter structures in the medial temporal lobe. Few studies have investigated the integrity of white matter in patients with AD or MCI. Diffusion tensor imaging (DTI) is a MRI technique that allows for the interrogation of the microstructural integrity of white matter. Based on increases in translational diffusion (mean diffusivity: MD) and decreases …directional diffusion (fractional anisotropy: FA) damage to white matter can be assessed. Studies have identified regions of increased MD and decreased FA in patients with AD and MCI in all lobes of the brain, as well as medial temporal lobe structures including the hippocampus, entorhinal cortex and parahippocampal white matter. The pattern of white matter integrity disruption tends to follow an anterior to posterior gradient with greater damage noted in posterior regions in AD and MCI. Recent studies have exploited inter-voxel directional similarities to develop models of white matter pathways, and have used these models to assess the integrity of inter-cerebral connections. Particular focus has been applied to the parahippocampal white matter (including the perforant path) and the posterior cingulum. Although many studies have found DTI indicators of impaired white matter in AD and MCI, other studies have failed to detect any differences in MD or FA between the groups, demonstrating the need for large replicative studies. DTI is an evolving technique and advances in its application ought to provide new insights into AD and MCI. Show more

Keywords: Dementia, fractional anisotropy, mean diffusivity, perforant path, tractography, entorhinal cortex, magnetic resonance imaging, hippocampus, memory, medial temporal lobe

DOI: 10.3233/BEN-2009-0234

Citation: Behavioural Neurology, vol. 21, no. 1-2, pp. 39-49, 2009

Authors: Rogalski, E.J. | Murphy, C.M. | deToledo-Morrell, L. | Shah, R.C. | Moseley, M.E. | Bammer, R. | Stebbins, G.T.

Article Type: Research Article

Abstract: In the present study, changes in the parahippocampal white matter (PWM), in the region that includes the perforant path, were investigated, in vivo, in 14 individuals with amnestic mild cognitive impairment (aMCI) compared to 14 elderly controls with no cognitive impairment (NCI). For this purpose, (1) volumetry; (2) diffusion tensor imaging (DTI) derived measures of mean diffusivity (MD) and fractional anisotropy (FA); and (3) tractography were used. In addition, regression models were utilized to examine …the association of PWM measurements with memory decline. The results from this study confirm previous findings in our laboratory and others, showing that compared to controls, individuals with aMCI have PWM volume loss. In addition to volume reduction, participants with aMCI demonstrated a significant increase in MD, but no difference in FA, both in the PWM region and in fibers modeled to pass through the PWM region. Further, the DTI metric of MD was associated with declarative memory performance, suggesting it may be a sensitive marker for memory dysfunction. These results indicate that there is general tissue loss and degradation (decreased volume; increased MD) in individuals with aMCI compared to older people with normal cognitive function. However, the microstructural organization of remaining fibers, as determined by measures of anisotropic diffusion, is not significantly different from that of controls. Show more

Keywords: MRI, dementia, perforant path, tractography, entorhinal cortex, magnetic resonance imaging, hippocampus, memory, mesial temporal lobe, volumetry

DOI: 10.3233/BEN-2009-0235

Citation: Behavioural Neurology, vol. 21, no. 1-2, pp. 51-61, 2009

Authors: Dickerson, Bradford C. | Sperling, Reisa A.

Article Type: Research Article

Abstract: Functional MRI (fMRI) studies of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have begun to reveal abnormalities in large-scale memory and cognitive brain networks. Since the medial temporal lobe (MTL) memory system is a site of very early pathology in AD, a number of studies have focused on this region of the brain. Yet it is clear that other regions of the large-scale episodic memory network are affected early in the disease as well, and …fMRI has begun to illuminate functional abnormalities in frontal, temporal, and parietal cortices as well in MCI and AD. Besides predictable hypoactivation of brain regions as they accrue pathology and undergo atrophy, there are also areas of hyperactivation in brain memory and cognitive circuits, possibly representing attempted compensatory activity. Recent fMRI data in MCI and AD are beginning to reveal relationships between abnormalities of functional activity in the MTL memory system and in functionally connected brain regions, such as the precuneus. Additional work with "resting state" fMRI data is illuminating functional-anatomic brain circuits and their disruption by disease. As this work continues to mature, it will likely contribute to our understanding of fundamental memory processes in the human brain and how these are perturbed in memory disorders. We hope these insights will translate into the incorporation of measures of task-related brain function into diagnostic assessment or therapeutic monitoring, which will hopefully one day be useful for demonstrating beneficial effects of treatments being tested in clinical trials. Show more

Keywords: Alzheimer's disease, mild cognitive impairment, functional magnetic resonance imaging, hippocampus, parietal cortex

DOI: 10.3233/BEN-2009-0227

Citation: Behavioural Neurology, vol. 21, no. 1-2, pp. 63-75, 2009

Authors: Pihlajamäki, Maija | Sperling, Reisa A.

Article Type: Research Article

Abstract: Alzheimer's disease (AD) is the most common form of dementia in old age, and is characterized by prominent impairment of episodic memory. Recent functional imaging studies in AD have demonstrated alterations in a distributed network of brain regions supporting memory function, including regions of the default mode network. Previous positron emission tomography studies of older individuals at risk for AD have revealed hypometabolism of association cortical regions similar to the metabolic abnormalities seen in AD patients. …In recent functional magnetic resonance imaging (fMRI) studies of AD, corresponding brain default mode regions have also been found to demonstrate an abnormal fMRI task-induced deactivation response pattern. That is, the relative decreases in fMRI signal normally observed in the default mode regions in healthy subjects performing a cognitive task are not seen in AD patients, or may even be reversed to a paradoxical activation response. Our recent studies have revealed alterations in the pattern of deactivation also in elderly individuals at risk for AD by virtue of their APOE e4 genotype, or evidence of mild cognitive impairment (MCI). In agreement with recent reports from other groups, these studies demonstrate that the pattern of fMRI task-induced deactivation is progressively disrupted along the continuum from normal aging to MCI and to clinical AD and more impaired in e4 carriers compared to non-carriers. These findings will be discussed in the context of current literature regarding functional imaging of the default network in AD and at-risk populations. Show more

Keywords: Aging, Alzheimer's disease (AD), apolipoprotein E, default mode network, functional magnetic resonance imaging (fMRI), memory, mild cognitive impairment (MCI), posterior cingulate cortex, precuneus, task-induced deactivation

DOI: 10.3233/BEN-2009-0231

Citation: Behavioural Neurology, vol. 21, no. 1-2, pp. 77-91, 2009

Authors: Brickman, Adam M. | Small, Scott A. | Fleisher, Adam

Article Type: Research Article

Abstract: During its earliest stage, before cell loss and independent of amyloid plaques and neurofibrillary tangles, Alzheimer's disease (AD) causes synaptic loss affecting the basal functional properties of neurons. In principle, synaptic loss can be detected by measuring AD-induced changes in basal function, or by measuring stimulus-evoked responses on top of basal changes. Functional magnetic resonance imaging (fMRI) is sensitive to both basal changes and evoked-responses, and there are therefore two experimental approaches …in which fMRI can be used to pinpoint synaptic loss in AD. In this review, we will compare and contrast both approaches for pinpointing when and where synaptic loss in AD begins and for monitoring therapeutic efficacy. Show more

DOI: 10.3233/BEN-2009-0240

Citation: Behavioural Neurology, vol. 21, no. 1-2, pp. 93-100, 2009