The purpose of this pilot study was to evaluate the usefulness of the Assessment of Motor and Process Skills (AMPS) as an outcome measure of instrumental activities of daily living (IADL) in pharmacologic studies of people with Alzheimer's disease. The AMPS simultaneously measures motor and process skills and their effect on the ability of the person to perform familiar IADL tasks. We administered the AMPS to 11 Alzheimer inpatients in a 31/2-month, double-blind, placebo-controlled, crossover study of fluoxetine and selegiline administered as single agents and in combination with physostigmine. Results indicated that there was a significant difference in IADL ability among study conditions for process skills, but not for motor skills, thereby suggesting that the AMPS is useful as a sensitive outcome measure of IADL ability in drug trials with this population.

The identification of cholinergic contributions to the dysfunction in patients with Alzheimer's disease (AD) appears straightforward at first. However, complicating questions arose more than a decade ago. For example, why, if AD patients indeed experienced cholinergic damage, was the number of cholinergic receptors similar in both AD patients and normal controls at autopsy? Researchers speculated about the possibility of an upregulation of cholinergic receptors in response to the loss of functional receptors subsequent to presynaptic cholinergic neuronal loss. This led to research on the consequences of administering a cholinergic antagonist rather than an agonist in AD patients as a pharmacologic challenge test in an attempt to test the functional sensitivity of the remaining cholinergic receptors.

The behavioral symptoms seen in patients with dementia are diverse, ranging from agitation to hallucinations and paranoid delusions. Many patients with dementia have affective disturbances, including depressed mood. To provide a means of assessing the severity of depression and mood changes in demented patients, the authors and colleagues at the National Institute of Mental Health developed the Dementia Mood Assessment Scale.

Patients with Alzheimer's disease (AD) have been reported to have a rate of nonsuppression on the dexamethasone suppression test (DST) comparable to that of patients with major depression. With symptoms of depression being increasingly recognized in patients with AD, studying their DST response may provide clues to the etiology of the abnormal response in both diagnostic groups. A correlation between dementia severity and post-dexamethasone cortisol was found within the group of male, but not female AD patients. Within the group of elderly depressives, a correlation between post-dexamethasone cortisol and ratings of depression was found. Serum dexamethasone levels were not significantly lower in the nonsuppressors as compared with suppressors in either diagnostic group.

Although the central cholinergic deficits are still considered to be of primary importance in Alzheimer's disease, there is great need for an expansion of the pharmacological approach in this illness beyond the simple cholinergic replacement hypothesis. This report focuses on the concept of “combination chemotherapy” in Alzheimer's disease as the next generation of therapeutic strategies. Based on earlier positive findings in Alzheimer patients with the monoamine oxidase B inhibitor, 1-deprenyl, the authors speculate that a combination of physostigmine, the short-acting cholinesterase inhibitor, and 1-deprenyl might be more beneficial than either agent alone. The authors outline a sample paradigm for such combination studies, report preliminary data on the first 16 Alzheimer subjects to have received an initial combination of physostigmine and deprenyl, and point to other possible “combination chemotherapy” strategies for future study.

The aim of the study was to determine whether the ε4 allele of the apolipoprotein E (ApoE) gene was associated primarily with context-specific memory among individuals at genetic risk for developing Alzheimer's disease. The effect of ApoE status on comprehensive neuropsychological results was examined in 176 healthy adults during baseline cognitive testing in the NIMH Prospective Study of Biomarkers for Older Controls at Risk for Alzheimer's Disease (NIMH Prospective BIOCARD Study). The presence of the ε4 allele was associated with significantly lower total scores on the Logical Memory II subtest of the Wechsler Memory Scale–Revised and percent of information retained after delay. Further analysis indicated the prose recall and retention effect was partially explained by a small subgroup of ε4 homozygotes, suggesting a gradually progressive process that may be presaged with specific cognitive measures. The current results may represent an ε4-associated breakdown between gist-related information and context-bound veridical recall. This relative disconnection may be understood in light of putative ε4-related preclinical accumulation of Alzheimer pathology (tangles and plaques) in the entorhinal cortex (EC) and among frontal networks, as well as the possibility of less-efficient compensatory strategies. (JINS, 2004, 10, 362–370.)

Two patients with moderately severe AD, when asked directly, could identify their own images in a mirror, but also consistently misidentified their own reflections as that of another person. Both patients were paranoid and mildy depressed at times, but had no evidence of other concurrent psychotic symptoms. It appeared that mood substantially modified the nature of the symptom and the patients' reaction to it over time. These cases illustrate the ability of an organic symptom to be modified by a concurrent affective state, indicating the importance of the interaction between biological and psychological factors in the expression of such symptoms.