Oscar L. Lopez

Generalized Tensor-Based Morphometry of HIV/AIDS Using Multivariate Statistics on Deformation Tensors

This paper investigates the performance of a new multivariate method for tensor-based morphometry (TBM). Statistics on Riemannian manifolds are developed that exploit the full information in deformation tensor fields. In TBM, multiple brain images are warped to a common neuroanatomical template via 3-D nonlinear registration; the resulting deformation fields are analyzed statistically to identify group differences in anatomy. Rather than study the Jacobian determinant (volume expansion factor) of these deformations, as is common, we retain the full deformation tensors and apply a manifold version of Hotellings test to them, in a Log-Euclidean domain. In 2-D and 3-D magnetic resonance imaging (MRI) data from 26 HIV/AIDS patients and 14 matched healthy subjects, we compared multivariate tensor analysis versus univariate tests of simpler tensor-derived indices: the Jacobian determinant, the trace, geodesic anisotropy, and eigenvalues of the deformation tensor, and the angle of rotation of its eigenvectors. We detected consistent, but more extensive patterns of structural abnormalities, with multivariate tests on the full tensor manifold. Their improved power was established by analyzing cumulative-value plots using false discovery rate (FDR) methods, appropriately controlling for false positives. This increased detection sensitivity may empower drug trials and large-scale studies of disease that use tensor-based morphometry.

Chapter 2 Alzheimer's Disease

Publisher Summary The chapter outlines the history, epidemiology, genetics, and clinical features of Alzheimers disease. Alzheimers disease (AD) was originally described in 1907 by the German psychiatrist and neuropathologist Alois Alzheimer as a unique case of presenile dementia. With the age distinction removed, AD is now recognized as one of the most common diseases of the aging population and is now the fourth most common cause of death in the United States. Demographic factors increasing risk include the apolipoprotein E-4 allele (APOE-4), gender (women are perhaps more susceptible to AD than men), lower education, family history of AD, cerebrovascular disease, and significant prior head trauma. Midlife hypertension, elevated homocysteine, and elevated fat in the diet (the latter perhaps in combination with presence of an APOE-4 allele) also are reported risk factors. Diabetes mellitus is increasingly being recognized as a risk factor for AD, possibly through vascular mechanisms or because of interactions of insulin degrading enzyme with amyloid metabolism. In retrospective population or clinic studies, the use of nonsteroidal anti-inflammatory drugs (NSAIDs), antioxidants, and cholesterol-lowering agents may reduce the risk of AD. Similar observations were made for exercise, social activities, and cognitively stimulating activites.AD is a progressive neurodegenerative disease, with onset usually in late life, in which recent memory function, naming and language function, visuospatial abilities, and frontal/executive function decline. The chapter also discusses differential diagnosis, mild cognitive impairment the neurologic examination of AD, extrapyramidal symptoms, and dementia with Lewy bodies, and so on. Memantine is an N-methyl-D-aspartate (NMDA) receptor modulator that was approved for use in the United States in 2003. The mechanism by which memantine is hypothesized to work is based on allowing normal glutamatergic neurotransmission but blocking potential excitotoxic stimulation.

Neurobiology of Alzheimer’s Disease

Intended for readers new to the field, “Neurobiology of Alzheimer’s Disease” also covers an extensive range of themes for those with in-depth knowledge of Alzheimers disease. It will therefore act either as an introduction to the whole field of neurodegeneration or it will help experienced researchers to access the latest research in specialist topics. Each chapter is written by eminent scientists leading their fields in neuropathology, clinical practice and molecular neurobiology; appendices detail disease-associate proteins, their sequences, familial mutations and known structures.