Faculty Bibliography

OBJECTIVE: To assess change in cognitive function in elderly individuals with subjective memory loss over a follow-up interval of more than 3 years. DESIGN: Prospective cohort study. SETTING: An outpatient research clinic in aging and dementia at a university hospital. PARTICIPANTS: A convenience sample of 59 healthy, elderly individuals (mean age 68.7 years) with memory complaints but no clinically apparent cognitive dysfunction. MEASUREMENTS: Participants were given a full diagnostic evaluation and were administered a neuropsychological test battery at baseline and follow-up. The cognitive assessment battery included 12 tests of recent memory, immediate memory, language function, visuospatial praxis, and psychomotor speed. Most of the tests had been established to be sensitive to cross-sectional age differences. RESULTS: Of 59 subjects, 54 (91.5%) were successfully followed up an average of 3.4 years later. Between baseline and follow-up, two tests exhibited significant improvement, two tests exhibited significant decline, and the other eight were unaffected. CONCLUSION: Elderly individuals with subjective perceptions of cognitive decrements who fail to provide clear evidence of cognitive impairment upon clinical interview are not at high risk for progressive cognitive deterioration over the subsequent 3- to 4-year interval

OBJECTIVE--To assess the possible association between functional decline and noncognitive neurologic signs in the severe stages of Alzheimer's disease (AD). DESIGN--Case series. SETTING--Subjects from a dementia research referral center, longitudinally followed, when necessary, into residential home and nursing home settings. PATIENTS--A consecutive sample of 56 patients (16 men, 40 women; mean age, 74.6 years) with a clinical diagnosis of probable AD in the moderately severe and severe stages. MAIN OUTCOME MEASURE--For global dementia severity, the Global Deterioration Scale and Mini-Mental State examination; for functional assessment, the Functional Assessment Staging Scale; and for assessment of neurologic function, nine release signs (primitive reflexes), 10 measures of extrapyramidal function, and five measures of pyramidal function, including deep-tendon reflexes and plantar signs. Changes in activity or presence of neurologic signs were rated on a seven-point scale. Results were analyzed in terms of prevalence and magnitude of change in relation to functional impairment. RESULTS--Prevalence and mean scores of certain release signs, certain extrapyramidal measures commonly referred to as bradykinesia, and certain pyramidal signs showed significant associations with the magnitude of functional impairment. Other neurologic measures, for example, the palmomental reflex, and certain extrapyramidal measures commonly seen in Parkinson's disease, including the glabellar blink reflex, cogwheeling, tremor, shuffling gait, and festination, did not show significant increments with continuing functional decline in AD. CONCLUSIONS--Functional decline in the advanced stages of AD appears to be associated with a particular combination of progressive cortical, extrapyramidal, and pyramidal system dysfunction. The characteristics of this neurologic syndrome of the severe stages of AD differ from those of other neurologic disorders. For example, the pattern of extrapyramidal system disease is different from that seen in Parkinson's disease. The neurologic syndrome of the severe stages of AD is amenable to description and deserves further investigation

A group of 136 elderly subjects were administered a comprehensive neuropsychological test battery, which was readministered 2 years later. Among the 136 elderly subjects, 86 were assigned a diagnosis of probable Alzheimer's disease. An additional 33 young subjects were administered the assessment battery at baseline only. The normal elderly group exhibited no decline in cognitive test performance over the 2-year follow-up interval. Subjects with mild cognitive impairment, however, were as likely to deteriorate between baseline and follow-up as the more severely impaired subjects. The tests that exhibited longitudinal decline in the Alzheimer's disease patients constituted a subset of the tests that revealed cross-sectional deficits relative to the normal elderly. Differences in baseline cognitive test performance and in rate of cognitive deterioration were examined in relatively young versus relatively old Alzheimer's disease patients. Potential psychometric predictors of cognitive decline in the normal elderly were identified

Positron emission tomographic studies of cerebral glucose metabolism have shown high diagnostic specificity in distinguishing among the degenerative dementias and differentiating between Alzheimer's disease (AD) and normal aging. The current investigation was undertaken to characterize the regional glucose metabolic deficits in AD, using cross-sectional and longitudinal study designs. All subjects met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for AD (n = 45) or were normal (n = 20), and the AD subjects were subdivided into incipient and mild AD and moderate plus moderately severe subgroups based on the Global Deterioration Scale. The subjects underwent a non-contrast computed tomographic scan and a positron emission tomographic (PETT VI) scan. The AD subjects (n = 14) and normal control subjects (n = 15) received evaluations 2 to 3 years after baseline study. The brain regions that show glucose metabolic deficits cross-sectionally (temporal and parietal association areas, with lesser degrees of deficit in subcortical gray matter structures), over the stages of AD, also show further deficits longitudinally within the same AD subjects. The reduction in glucose metabolism is greater than would be expected from the degree of brain atrophy. The glucose metabolic deficits are discussed in the context of neuropathologic findings and neurotransmitter deficits in AD

OBJECTIVE: Milacemide, a MAO-B inhibitor that is also a prodrug for glycine, was tested as a treatment for senile dementia of the Alzheimer type (SDAT) because of its potential for enhancing cognition in animal models of impaired learning and memory. DESIGN: Double-blind, placebo-controlled, randomized clinical trial. SETTING: Sixteen study sites, both university-affiliated and private. PATIENTS: A total of 228 outpatients (116 men and 112 women) with SDAT, ranging in age from 49-93 years. INTERVENTION: 1200 mg/day milacemide treatment for 1 month (113 patients received milacemide, and 115 patients received placebo). MAIN OUTCOME MEASURES: Alzheimer's Disease Assessment Scale and the Mini-Mental State Examination. RESULTS: Milacemide-treated SDAT patients did not show significant improvement in any of the outcome measures used. Significant elevations in liver enzymes in four subjects were of sufficient magnitude to necessitate withdrawal from the study. CONCLUSIONS: Milacemide does not appear to be an effective treatment in enhancing cognition in SDAT patients

Research on the nature of clinical symptomatology in AD indicates that two fundamentally different types of symptoms are identifiable. Symptoms within each of these two domains have common characteristics. The first symptomatic domain has been termed the 'cognitive domain' and the second the 'noncognitive behavioral domain.' Symptoms and losses in the cognitive domain occur invariably and progressively with the advance of AD over time. Symptoms in the behavioral domain do not invariably occur in AD and do not progress monotonically with the advance in AD over time. However, characteristic behavioral domain symptoms can be described over the course of AD. The two symptomatic domains are likely to differ not only in nature and progression in AD, but also in underlying pathophysiology and in terms of possible treatment modalities. They also pose fundamentally different issues of assessment in AD. These distinct factors necessitate the separate assessment of the two symptomatic domains in AD treatment trials. Judgments of efficacy and utility in remediating either symptomatic domain in AD should take into consideration the effects of treatment on both cognitive domain and behavioral domain symptoms separately and interactively. Appropriate assessment procedures are discussed

Evaluation of changes in functional performance and activities of daily living skills is an essential aspect of the assessment of elderly individuals with chronic illness. Although functional decrement is a central aspect of Alzheimer's disease (AD), many measures currently utilized to assess these changes have limitations. Empirical and systematic examination of the functional changes occurring in patients with AD has resulted in the development of an assessment measure termed Functional Assessment Staging (FAST) that allows for the specific evaluation of these changes throughout the entire course of AD. In this paper the results of three separate investigations regarding the reliability, validity, and progressive ordinality of FAST are described. The results indicate that FAST is a reliable and valid assessment technique for evaluating functional deterioration in AD patients throughout the entire course of the illness. Moreover, the results suggest that the FAST elucidates a characteristic pattern of progressive, ordinal, and functional decline in AD. Because the elements of functional capacity incorporated in FAST are relatively universal and readily ascertainable, as well as characteristic of the course of AD, FAST can serve as a strong diagnostic and differential diagnostic aid for clinicians. The sensitivity of FAST to the entire course of AD, even in its most severe stages, may be indicative of the potential value of this instrument for further investigation of the temporal longitudinal course of AD, and of the relationships between clinical pathology and neuropathology throughout the entire longitudinal course of AD

Assessment and treatment of behavior problems in patients with Alzheimer disease and related disorders is a seriously neglected area of study. Despite the fact that such problems are integral to the disorder, little is known about effective management. This article summarizes the current thinking on five areas of prime importance to patients, care providers, and health care professionals: agitation, assault/aggression, screaming, wandering, and depression/apathy/withdrawal. Methodological guidelines for studying these disorders are provided. Emphasis is on recognizing that behavior problems are important areas of study in their own right as well as in conjunction with studies of cognition