Alzheimer's disease is a leading cause of morbidity and mortality among the elderly. Several families have been described in which Alzheimer's disease is caused by an autosomal dominant gene defect. The chromosomal location of this defective gene has been discovered by using genetic linkage to DNA markers on chromosome 21. The localization on chromosome 21 provides an explanation for the occurrence of Alzheimer's disease-like pathology in Down syndrome. Isolation and characterization of the gene at this locus may yield new insights into the nature of the defect causing familial Alzheimer's disease and possibly, into the etiology of all forms of Alzheimer's disease.

http://science.sciencemag.org/content/sci/235/4791/885.full.pdf

The genetic defect causing familial Alzheimer's disease maps on chromosome 21

We reviewed records of 121 consecutive patients with dementia of the Alzheimer type. Patients with myoclonus or extrapyramidal signs had greater intellectual decline and functional impairment in daily activities. Among patients studied over 4 years, there were four groups: benign —little to no progression; myoclonic —severe intellectual decline and frequent mutism after younger onset; extrapyramidal —severe intellectual and functional decline and frequent psychotic symptoms; typical —a gradual progression of intellectual and functional decline, but without other distinguishing features. Except for the group with myoclonus, no subgroup was segregated by age at onset or other demographic variables. This study suggests that dementia of the Alzheimer type is heterogeneous, and that certain clinical manifestations may be useful in predicting outcome.

Heterogeneity in dementia of the Alzheimer type Evidence of subgroups

Speech and language assessment in 30 patients with dementia of the Alzheimer type and in 70 normal controls revealed that all Alzheimer patients were aphasic. Throughout most of the course, the language disorder resembled transcortical sensory aphasia, and increasing language impairment correlated with increasing severity of dementia. Aphasia was present regardless of age of onset or family history of dementia. Aphasia is an important diagnostic criterion of dementia of the Alzheimer type.

Aphasia in dementia of the Alzheimer type

Eight patients with early Alzheimer disease were treated with gradually increasing multiple daily doses of oral physostigmine and supplemental lecithin. Six individuals showed improvement in total recall and retrieval from long-term storage (LTR), with a decrease in intrusions (a measure of inaccurate recall). The optimal individual dose was either 2.0 or 2.5 mg of physostigmine for each responding patient. Results of this open trial were subsequently replicated during a double-blind crossover trial comparing physostigmine treatment to placebo. All six patients again demonstrated improvement in total recall and LTR, with a decrease in intrusions. The decrease in intrusions was strongly correlated with increasing inhibition of cholinesterase activity in cerebrospinal fluid, suggesting that the degree of improvement in the patient's memory was related to the amount of physostigmine that reached the brain. Other neurotransmitters and metabolites in cerebrospinal fluid were unaffected by the physostigmine therapy, suggesting a specific effect of physostigmine on the cholinergic system. The results suggest that small oral doses of physostigmine combined with lecithin ingestion have therapeutic benefit for some patients with Alzheimer disease.

Oral physostigmine and lecithin improve memory in Alzheimer disease.

Clinical investigations of senile dementia of the Alzheimer type require establishment of explicit clinical diagnostic criteria before histological confirmation is possible. Criteria for selection of mildly impaired subjects with senile dementia of Alzheimer type, free of other major disease, are proposed. Problems of recruitment of this select population for a longitudinal study are discussed. A study population with matched healthy control subjects has been enrolled and described. Short term follow-up has provided preliminary support for the diagnostic criteria.

https://jnnp.bmj.com/content/jnnp/45/11/962.full.pdf

Mild senile dementia of Alzheimer type: research diagnostic criteria, recruitment, and description of a study population.

The diagnosis of patients presenting with memory or attentional deficits characteristic of dementia is a growing problem. Dementia may be symptomatic of a range of reversible medical and psychiatric conditions which appear to be indistinguishable from primary neuronal degeneration of the Alzheimer's type. While Alzheimer's disease is a neuropathological diagnosis, the importance of establishing a presumptive diagnosis which can be employed for investigational as well as clinical use is underscored. This paper proposes a diagnostic schema which reflects the current understanding of this disorder. There must be evidence of gradual progressive mental deterioration in attention, learning, memory, cognitive style, motivation, and higher order thinking. A comprehensive medical and psychiatric evaluation is obligatory to eliminate reversible physical illness, psychiatric disorder, or cerebrovascular condition as underlying causes of cognitive dysfunction.

Diagnostic criteria for primary neuronal degeneration of the Alzheimer's type.

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Diagnostic criteria for primary neuronal degeneration of the Alzheimer's type.