The Prodromal Phase

The insidious onset of Alzheimer's disease (AD) means that there is a significant prodromal phase of varying length, with research indicating a length of up to 20

Encyclopedia of the Human Brain Volume 1

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years. During this period, there is an accumulation of neuropathological alterations accompanied by subtle cognitive changes, but not yet detected as AD. The nature of these changes has been investigated by following up a random sample of individuals without dementia in a prospective fashion and determining the characteristics of those who develop AD. Such studies indicate that poor performance on tests of episodic memory are highly predictive of AD. There are also individuals who develop isolated substantial memory impairment in the absence of a diagnosis of dementia who then develop AD. This prodromal phase may last many years. Studies suggest that subsequent AD in individuals with isolated memory impairment can be predicted on the basis of short batteries of neuropsy-chological tests of episodic memory and mental control. Allied to this is the finding that atrophy of the hippocampus is predictive of subsequent conversion to AD. So too are decreased cerebral perfusion rates in the posterior and anterior cingulate, the hippocampal-amygdala complex, and the anterior thalamus, which are structures comprising the network that is thought to support episodic memory function. The prodromal phase has been studied in individuals at greater risk for developing AD, specifically those who are at risk for autosomal-dominance familial AD. This research indicates that the onset of AD is preceded by measurable decline approximately 2 or 3 years before symptoms are observable and 4 or 5 years before the individual fits the criteria for AD. Again, memory dysfunction is the best predictor of subsequent AD.

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