A series of animal experiments that demonstrated the possibility of removal of plaques by immunization against amyloid has led to human studies with a similar vaccination. One trial was stopped because of the occurrence of an immune encephalitis in a small number of patients, but in autopsy material there were indications that this approach may have had the desired effect of reducing amyloid deposition (Orgogozo et al). Revised vaccines are being formulated for further testing of this approach.
Given the state of therapeutics for Alzheimer disease, always important is the general management of the demented patient, which should proceed along the lines outlined in Chap. 20, keeping in mind that the physician’s counsel is often the family’s main resource for important medical and social decisions. As pointed out in a monograph that summarized the deliberations of a commission on the state of dementia care in Europe (Winblad et al), the care of affected patients “does not fit easily into typical health care delivery systems.” It is clear that community, family, and medical resources are difficult to coordinate and that end of life and competency decisions are fragmented. Considering the magnitude of the problem, this is a serious societal fault.
As indicated earlier, the histologic changes of Alzheimer disease have a number of interesting associations. Amyloid plaques and tangle deposition are far more common in the brains of patients with Parkinson disease (20 to 30 percent) than in the brains of age-matched controls (Hakim and Mathieson). These findings partly explain the high incidence of dementia in patients with Parkinson disease (see further on). As also mentioned, with the advance of Alzheimer disease, extrapyramidal features may emerge. In such cases, Burns and colleagues found changes in the substantia nigra including accumulation of synuclein and tau representative of Lewy bodies. Another association between the 2 diseases is apparent in the Guamanian Parkinson–dementia complex, which is also discussed below. In this entity, the symptoms of dementia and parkinsonism are related to neurofibrillary changes in the cerebral cortex and substantia nigra, respectively; senile plaques and Lewy bodies are unusual findings. What can be deduced from the crossover syndromes is that multiple degenerative changes can occur in these diseases and give rise to heterogeneity in clinical presentation.
The finding of neurofibrillary tangles (and to a lesser extent of plaques) in boxers (“punch-drunk” syndrome, or dementia pugilistica) and in the similar condition, chronic traumatic encephalopathy, is another interesting ramification of the Alzheimer disease process in that trauma appears to be able to elicit one of the core features of the disease as discussed in Chap. 34. Some cases of primary progressive aphasia (see further on) have Alzheimer change and amyloid plaque deposition as the primary pathologic change. There are other unusual and meaningful associations, such as dementia with motor neuron disease or the cases of familial dementia with spastic paraplegia reported by Worster-Drought and by van Bogaert and their associates (see later in this chapter). Here, neurofibrillary change is the most prominent feature whereas amyloid plaques are negligible in number or absent.
Another provocative connection is the already mentioned interrelationship between cerebrovascular disease and Alzheimer disease. This is a complex area that at one time, considered the 2 processes to be intimately related and later, was rejected, only to now be resurrected with clearer focus, as discussed Chap 33.
Lobar Atrophies (Frontotemporal Degeneration [FTD], Primary Progressive Aphasia, Posterior Cortical Atrophy)