The familial occurrence of Alzheimer disease has been well established. In less than 1 percent of such cases there is a dominant inheritance pattern with a high degree of penetrance and appearance of disease at a younger age (Nee et al; Goudsmit et al; see further). Reports of substantial familial aggregations of dementia without a specific pattern of inheritance also suggest the operation of more than 1 genetic factor. Many studies have documented an increase in the risk of ostensibly sporadic Alzheimer disease among first-degree relatives of patients with this disorder. This risk is disproportionately greater in females, adding to the evidence that women in general are at slightly higher risk for Alzheimer disease (Silverman et al). Li and coworkers (1995) have provided evidence that patients with an earlier age of onset of Alzheimer disease (before age 70 years) are more likely to have relatives with the disease than are patients with later onset. Genetic studies are difficult to carry out because the disease does not appear at the same age in a given proband. Even in identical twins, the disease may develop at the age of 60 years in one of the pair and at 80 years in the other. Death from other causes may prevent its detection. The dominantly inherited type, which is prevalent in certain countries, is being used as a model to understand both the genetic aspects and therapeutic measures for the disease. The other genetic contributions to the occurrence of Alzheimer disease are discussed further on.
Clinical Features (See Also Chap. 20)
The onset of mental changes is usually so insidious that neither the family nor the patient can date the time of its beginning and most patients come to attention months or years after the decline began. Occasionally, however, the process becomes manifest by an unusual degree of confusion in relation to a febrile illness, an operation, mild head injury, or the institution of a new medication. Other patients have as their initial complaints dizziness, mental fogginess, nondescript headaches, or other vaguely expressed and changeable somatic symptoms.
The gradual development of forgetfulness is the major symptom. Small day-to-day happenings are not remembered. Seldom-used names become particularly elusive. Little-used words from an earlier period of life also tend to be lost. Appointments are forgotten and possessions misplaced. Questions are repeated again and again, the patient having forgotten what was just discussed. It is said that remote memories are preserved and recent ones lost (one of Ribot’s laws of memory), but this is only relatively true and it is difficult to check the accuracy of distant personal memories. For example, Albert and associates, who tested Alzheimer patients’ recognition of dated political events and pictures of prominent people past and present, found that some degree of memory loss extends to all previous decades of the person’s life (neuropsychologic testing is discussed further on).
Once the memory disorder has become pronounced in the prototypic disorder, other failures in cerebral function become increasingly apparent. The patient’s speech is halting because of failure to access the needed word. The same difficulty interrupts writing. Vocabulary becomes restricted, and expressive language becomes stereotyped and inflexible. Comprehension of spoken words seems at first to be preserved, until it is observed that the patient does not carry out a complicated request; even then it is uncertain whether the request was not understood because of inattention or because it was forgotten. Almost imperceptible at first, these disturbances of language become increasingly apparent as the disease progresses. The range of vocabulary and the accuracy of spelling are reduced. Finally, after many years of illness, there is a failure to speak in full sentences; the finding of words requires a continuous search; and little that is said or written is fully comprehended. There is a tendency to repeat a question and later, there may be a rather dramatic repetition of every spoken phrase (echolalia). The deterioration of verbal skills has by then progressed beyond a groping for names and common nouns to an obvious anomic aphasia. Other elements of receptive and executive aphasia are later added, but discrete aphasias of the Broca or Wernicke type are characteristically lacking. In general, there is a paucity of speech and a quantitative reduction in mentation.