Basic Principles Neurological Perspective

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The neurologic chapters in this handbook stress three general principles of neurology as applied to dementia. These principles are not unique to neurology, but are routinely used by neuroscientists and clinical neurologists. These chapters and approaches emphasize the biomedical model of disease causation and treatment and demonstrate that their application can result in more accurate diagnosis and more appropriate and effective treatments.

Principle 1: Biomedical Research Can Lead to a Better Understanding of the Pathophysiology of Dementing Diseases and the Development of Disease-Modifying Treatments

Each of the neurology chapters summarizes scientific advances in our understanding of the pathophysiology of the most common causes of dementia and progress in the development of safe and effective disease-altering treatments. An example from Alzheimer's disease (AD) biomedical research demonstrates the multidisciplinary nature of this type of research and shows how discoveries can move from patients to the laboratory and back to patients again. For example, genetic researchers identified families with early-onset autosomal dominant AD. Blood samples taken from these families were used to identify specific genetic mutations in three genes that can produce this type of AD. Transgenic animal models of AD were developed using these genes. These animal models have been used to develop drugs and treatments that are effective in delaying or stopping the development of AD pathology. Promising drugs are then moved into clinical trials for testing in patients with AD. Additionally, the development of genetic tests for specific mutations that cause early-onset, autosomal dominant AD allows their clinical use for at-risk patients who desire presymp-tomatic genetic testing. Similar multidisciplinary research is occurring that focuses on the other major causes of dementia also, with the ultimate goal of developing safe and effective disease-altering treatments for each of the major causes of dementia. The successes achieved so far toward this goal are outlined in each of the neurology chapters.

Principle 2: A Careful History and Neurologic Examination, Supplemented by Knowledge of Dementing Diseases and Selected Ancillary Tests, Can Result in an Accurate Diagnosis for Patients Suffering from Dementia

Traditionally, neurology has emphasized the importance of an accurate diagnosis in the care of patients with neurologic disease. The specialty of neurology uses a systematic approach to the evaluation of patients with neurologic complaints described by some as neurologic problem solving. The principles of neurologic problem solving are at the foundation of diagnostic evaluations of patients with dementia. In neurologic problem solving, the clinician uses the history to gain information about the time course of the disease (e.g., acute, subacute, chronic) and to understand other coexisting factors that may be causing or influencing the patient's symptoms and signs. The neurologic examination is used to identify signs of neurologic dysfunction. This information is used along with knowledge of neuroanatomy and brain-behavior relationships to localize the area in the nervous system where there are signs of dysfunction. Information about the time course of disease and location within the nervous system is combined with knowledge of diseases of the nervous system to generate a differential diagnosis. This differential diagnosis helps dictate which diagnostic tests are ordered. The results of the diagnostic tests are used to refine or confirm the diagnosis or diagnoses.

In the evaluation of dementia, each of these aspects of neurologic problem solving is important. For example, a detailed understanding of the time course of a dementing illness is important for differentiating potential causes (e.g., AD vs. vascular dementia). The history may also provide clues as to other factors (e.g., medications, comorbid diseases, depression) that may be contributing to the patient's symptoms of cognitive impairment. The neurologic examination then tests cognitive functioning in multiple cognitive domains to determine what brain regions are involved. The pattern of brain involvement helps distinguish the major causes of dementia, especially early in their course. The neurologic examination also provides information about whether there are signs of parkinsonism, cerebrovascular disease, mass lesions, or hydrocephalus. Clinicians then use their knowledge of the typical presentation and natural history of the major causes of dementia to generate differential diagnoses and to help decide what additional testing is needed. Useful ancillary tests include neuropsychological testing, laboratory tests, and brain imaging. Finally, information from the history, the exam, and the ancillary testing are combined to reach a conclusion as to the cause or causes of a patient's dementia. The neurology chapters in this handbook provide summaries of the common presentations, natural histories, and current approaches to the diagnosis of the major causes of dementia.

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