Heterogeneity Of Alzheimer S Disease

The term "Alzheimer's disease" is currently used to refer to senile and also presenile dementia, but the heterogeneity of this disorder is demonstrated in many of its aspects. This is of great theoretical interest, and with the appearance of new therapeutic interventions, it may well also start to have very significant practical importance. To shed some light on the debate, the Fondation Ipsen organized an international symposium which took place on April 6, 1992. This volume contains the proceedings of this meeting, which was attended by researchers in epidemiology, clinical neurology and geriatrics, neuropsychology, neuropathology, molecular biology, and genetics.

Published in 1996: Alzheimer's disease is characterized by memory disturbances and changes in personality and is associated with aging, although it can occur in people under 65. It is a progressive disease, painful to witness as the patient's health declines. Alzheimer's Disease: Cause(s), Diagnosis, and Care, with its complete and authoritative discussions, will help you understand all facets of this complex disease. This book addresses a broad spectrum of topics ranging from diagnosis, causes, treatment, epidemiology, genetics, risk factors, and care and management. Alzheimer's Disease: Cause(s), Diagnosis, and Care is intended for a diverse audience, including practitioners and students, family members, and everyone who is concerned about this disease.

Alzheimer"s disease, the commonest neurodegenerative condition, is characterised by accumulation of amyloid plaques and neurofibrillary tangles, neuronal loss, brain atrophy and cognitive impairment. Sporadic young onset Alzheimer"s disease shows marked clinical heterogeneity, with non-memory presentations including the syndromes of posterior cortical atrophy, logopenic aphasia and frontal Alzheimer"s disease, seen in around a third of individuals. This variability presents challenges for diagnosis and may confound clinical trial outcomes, but provides an opportunity to explore factors influencing differential selective vulnerability within neural networks which in turn may provide important clues to Alzheimer"s disease pathogenesis. This thesis describes the recruitment of a cohort of a deeply phenotyped patients with sporadic young onset Alzheimer"s disease (n=45) and healthy controls (n=24), and a series of genetic, clinical, neuropsychological, and structural, diffusion and functional magnetic resonance imaging experiments to explore disease heterogeneity and its associations. There are a number of key findings. APOE IÌ‚Î1⁄44 genotype contributes to, but does not fully explain clinical heterogeneity, with the youngest ages of onset and most atypical presentations seen in IÌ‚Î1⁄44-ve individuals. Heterozygosity of the rare TREM2 genetic variant for late-onset Alzheimer"s disease, p.R47H, is shown to confer risk for young onset Alzheimer"s disease, driving younger age of onset rather than clinical phenotype. Regional brain atrophy profiles in APOE IÌ‚Î1⁄44 genotypes are shown to broadly align with the associated neuropsychological deficits. Microstructural damage studied using diffusion tensor imaging, and "†applied for the first time to Alzheimer"s disease "†Neurite Orientation Dispersion and Density Imaging "†provides a fine-grained profile of white matter network breakdown, revealing regional differences based on APOE IÌ‚Î1⁄44 genotype, and correlations with focal neuropsychological deficits. Finally, activation fMRI using a music paradigm to probe relationships between cognitive performance and brain function is shown to delineate different patterns of brain activation during memory tasks in different Alzheimer"s disease phenotypes.

This up-to-date, superbly illustrated book is a practical guide to the effective use of neuroimaging in the patient with cognitive decline. It sets out the key clinical and imaging features of the various causes of dementia and directs the reader from clinical presentation to neuroimaging and on to an accurate diagnosis whenever possible. After an introductory chapter on the clinical background, the available "toolbox" of structural and functional neuroimaging techniques is reviewed in detail, including CT, MRI and advanced MR techniques, SPECT and PET, and image analysis methods. The imaging findings in normal ageing are then discussed, followed by a series of chapters that carefully present and analyze the key findings in patients with dementias. Throughout, a practical approach is adopted, geared specifically to the needs of clinicians (neurologists, radiologists, psychiatrists, geriatricians) working in the field of dementia, for whom this book will prove an invaluable resource.

The management of Alzheimer's Disease and the related dementias is one of the major challenges to health care professionals and American society-at-large for the coming decade and the coming millennium. The rapid growth of the over-eighty-five population, the group which, as recent studies have confirmed and as many of us clinicians have long suspected, has an even higher prevalence than previously quoted of dementing disorders, is the major cause of this. We are thus challenged by, as Bernard Issacs used to call it, "the survival of the unfittest," as well as the oPtimistic approach of "bringing life to years," as John F. Kennedy said. The fact is that we, as a society, tend to confuse "treatment" and "cure" (and "prevention"). As the proceedings of the conference which this book represents emphasize, there is considerable work going on about the potential prevention of, or at least the reduction of, symptomatology in these illnesses by interventions genetically, chemIcally, and so forth. However, the more we find out, the more complicated it becomes, and the more heterogeneous Alzheimer's and the related disorders appear to be, not only in their manifestations (as clinicians have long recognized) but also in the individual initiating and underlying processes. For these reasons, absolute preventive techniques or the likelihood of an intervention which will reverse the process in a high proportion of patients, do not appear to be just around the corner.