Topics and Speakers Lawrence S. Honig, MD, PhD
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Synopsis
What causes dementia, how does it develop, and how do different dementias vary from each other? These are the key questions Dr Lawrence S. Honig explores in this lecture on the pathophysiology of dementing disorders. In introducing this talk, Dr Honig begins by challenging the commonly held belief that dementia must involve memory loss. Rather, he defines dementia more broadly, as a state of deterioration in cognitive functions.
Neurodegenerative disorders are disorders in which the nervous system degenerates without a clear vascular, inflammatory, infectious, neoplastic, or physical cause. Of the many neurodegenerative disorders, Alzheimer's disease in the elderly is by far the most common of the dementing disorders, representing 65 to 85% of dementing disorders in those over 65. Other prevalent dementing disorders include dementia with Lewy bodies, frontotemporal dementia, and vascular dementia.
Given the prominence of Alzheimer's disease, Dr Honig dedicates most of his lecture to discussing this important disorder. The four main symptoms complexes are memory loss, language loss, higher order motor, and sensory perceptual difficulties. In later stages of Alzheimer's, the patient may exhibit difficulties apathy toward his or her appearance, sloppy dressing, difficulty with hygiene and gait trouble. The final stages are characterized by incontinence, and a loss of self-awareness (e.g. forgetting to dress) and a bedridden state.
After discussing these signs and symptoms of Alzheimer's, Dr Honig examines the structural and functional changes in the brain that gives rise to the symptoms. There is profound atrophy and shrinkage that occurs primarily in the temporal structures, more than in structures such as the sensory motor cortex or occipital lobes. Brain scans detect decreased function in language and memory areas. The neuropathologies of Alzheimer's disease include synaptic loss, nerve cell loss, and development of plaques and tangles. The plaques form when beta-amyloid protein aggregates extracellularly. The neurofibrillary tangles are twisted filaments of a polymeric form of hyperphosphorylated Tau protein. Although Tau protein is normal intracellular proteins, in Alzheimer's disease they grow into enormous depositions that represent neuronal injury. There is also decreased cholinergic function in Alzheimer's disease. Four genes are known to be involved in the disease at this point. In concluding his discussion of Alzheimer's disease, Honig describes several treatment options including new therapies that prevent beta-amyloid deposition.
In the remaining half of the lecture, Dr Honig describes other dementing disorders. The core features of Lewy bodies dementia are fluctuations in cognition, particularly attention, visual hallucinations, and Parkinsonism. Frontotemporal dementia can be divided into three basic varieties: behavioral dysfunction, dysfunction of expressive speech, and dysfunction of semantic processing. As its name suggest, frontotemporal dementia involvesdegeneration of the front part of the brain which spares the rear part of the brain. Honig then discusses other less common dementing disorders, such as corticobasal degeneration and Wilson's disease.
While Alzheimer's disease with cerebrovascular disease is extremely common, pure vascular dementia due to strokes is not as common. Several types of vascular disease can contribute to vascular dementia, such as strokes and hydrocephalus.
Dr Honig concludes the lecture with a discussion of Creutzfeldt-Jakob(CJD) disease, which includes both ordinary CJD and bovarian CJD, otherwise known as mad cow disease. Ordinary CJD appears most commonly in the elderly. Early signs are subtle mental decline. Although it is a familial disorder, the vast majority of cases are sporadic. Bovarian CJD exhibits a different symptom complex than ordinary CJD and often includes a psychiatric component. Most cases occur in young people. Despite the widespread fear of mad cow disease, Honig ends his lecture by reassuring the audience of the small risk of mad cow disease in the United States.
