The symptomatic course of this illness is quite variable but usually extends over a period of 5 or more years, but judging from pathology studies, the pathologic course has a much longer asymptomatic duration. This concept of a preclinical stage is supported by the detailed studies of Linn and colleagues, who found that a lengthy period (7 years or more) of stepwise decline in memory and attention span preceded the clinical diagnosis. In the dominantly inherited forms of disease, careful studies of biomarkers in the spinal fluid and by imaging show that changes occur 15 years or longer before the clinical manifestations are apparent (Bateman et al). Throughout this period, corticospinal and corticosensory functions, visual acuity, ocular movements, and visual fields remain intact. If there is hemiplegia, homonymous hemianopia, and the like, either the diagnosis of Alzheimer disease is incorrect or the disease has been complicated by a stroke, tumor, or subdural hematoma. Exceptions to this statement are rare. The tendon reflexes are little altered and the plantar reflexes almost always remain flexor. There is no sensory or cerebellar ataxia. Convulsions are rare until late in the illness, when up to 5 percent of patients reportedly have infrequent seizures. Occasionally, widespread myoclonic jerks or mild choreoathetotic movements are observed late in the illness. Eventually, with the patient in a bedfast state, an intercurrent infection such as aspiration pneumonia or some other disease mercifully terminates life.
The sequence of neurologic disabilities may not follow this described order and one or another deficit may take precedence, presumably because the disease process, after becoming manifest in the memory cortex of the temporal lobes, affects a particular part of the associative cortex earlier or more severely in one patient than in another. This allows a relatively restricted deficit to become the source of early medical complaint, long before the full syndrome of dementia has declared itself.
There are at least 5 limited deficits that may represent the opening features of Alzheimer disease but each of which alone may be mild enough to qualify as mild cognitive impairment (MCI). According to Petersen and colleagues, who developed this concept, the MCI syndrome is defined by the presence of cognitive difficulties in one or all spheres that are not severe enough to interfere with daily life. The early presentation of Alzheimer disease may manifest mainly as one of the following syndromes with the first, memory dysfunction being the most common and, even as other aspects of the disease advance, it tends to remain the most prominent.
1. Amnesia The early stages of Alzheimer disease are usually dominated by a disproportionate failure of episodic (autobiographical) memory, with integrity of other cognitive abilities. This may be the sole difficulty for many years. In such patients, immediate memory (essentially a measure of attention), tested by the capacity to repeat a series of numbers or words, is intact; it is the shortand long-term (retentive) memory that fails. Memory may become impaired but as a business executive, for example, the individual may continue to make acceptable decisions if the work uses long-established habit patterns and practices.