Faculty Bibliography

Objective: The purpose of the study was to develop a standardized instrument, the Behavior Rating Scale for Dementia, for rating psychopathology in patients with probable Alzheimer's disease and to conduct a multicenter pilot study of this instrument. Method: The rating scale was developed collaboratively on the basis of clinical experience and existing instruments. Items were scaled according to frequency of psychopathology and were administered to an informant who was familiar with the subject. The scale was administered in a standardized manner by trained examiners who had met predetermined certification standards. The study group consisted of 303 subjects with probable Alzheimer's disease who had undergone standardized clinical evaluations by the Consortium to Establish a Registry for Alzheimer's Disease. Results: Subjects had an average of 15 problems rated as present in the preceding month. Wide variability in the nature of disturbances was found, with a number of items rated as present since the illness began but not in the east month. Interrater agreement was high. Factor analysis suggested eight preliminary factors that mapped onto clinically relevant domains: depressive features, psychotic features, defective self-regulation, irritability/agitation, vegetative features, apathy, aggression, and affective lability. Conclusions: The Behavior Rating Scale for Dementia provides a standardized, reliable measure that can be administered to caregivers of demented subjects. On the basis of the present study, the scale has been revised slightly. After additional studies in progress, the Behavior Rating Scale for Dementia will be available for general use in assessing a wide range of psychopathology in dementia.

Measurements of hippocampal formation atrophy using MRI have been useful in distinguishing demented patients with a diagnosis of probable Alzheimer's disease from cognitively normal controls. To determine whether there is a similar relationship between hippocampal size and dementia in elderly patients suspected of normal pressure hydrocephalus (NPH), the authors obtained mini-mental status examination (MMSE) scores and MRI measurements of hippocampal size and CSF volume on 16 elderly patients whose severe ventriculomegaly and unexplained gait impairment made NPH a probable diagnosis. Hippocampal size correlated strongly with MMSE score (r = 0.75, p < 0.001); no significant MMSE correlation was found for ventricular CSF volume or extra-ventricular/ventricular CSF ratio. It was concluded that hippocampal atrophy is associated with severe cognitive dysfunction in many elderly patients with a diagnosis of NPH. As a hypothesis for further investigation, the detection of such atrophy may help identify cases where the presence of a pathology of Alzheimer's disease complicates the diagnosis of NPH

Although mild progressive memory impairment is commonly associated with normal human aging, it is unclear whether this phenomenon can be explained by specific structural brain changes. In a research sample of 54 medically healthy and cognitively normal elderly persons (ages 55-87, x = 69.0 +/- 7.9), magnetic resonance imaging (MRI) was used to derive head-size-adjusted measurements of the hippocampal formation (HF) (dentate gyrus, hippocampus proper, alveus, fimbria, subiculum), the superior temporal gyrus (STG), and the subarachnoid cerebrospinal fluid (CSF) (to estimate generalized cerebral atrophy). Subjects were administered tests of primary memory (digit span) and tests of secondary memory with immediate and delayed recall components (paragraph, paired associate, list recall; facial recognition). Separate composite scores for the immediate and delayed components were created by combining, with equal weighting, the subtests of each category. The WAIS vocabulary subtest was used as a control measure for language and intelligence. A highly significant correlation (P < 0.001), independent of age, gender, and generalized cerebral atrophy was found between HF size and delayed memory performance. No significant correlations were found between HF size and primary or immediate memory performance. STG size was not significantly correlated with any of the composite memory variables. These results suggest that HF atrophy may play an important independent role in contributing to the memory loss experienced by many aging adults

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

OBJECTIVE--To estimate the prevalence of radiographically detectable hippocampal atrophy (HA) in a normal aging sample and to test whether such atrophy is associated with memory dysfunction. DESIGN--One hundred fifty-four medically healthy and cognitively normal elderly persons (aged 55 to 88 years) received magnetic resonance imaging and/or computed tomographic scans designed to identify HA. One hundred forty-five of these subjects also underwent psychometric tests of memory function. Multivariate analyses of variance were used to evaluate differences in memory performance between subjects with and without HA. SETTING--This study was conducted at a research clinic for the investigation of age-associated neuropsychological and neuroradiologic changes. PARTICIPANTS--Based on the following criteria, 154 subjects were consecutively selected from a larger group of elderly research volunteers participating in a study of normal aging: age of 55 years or greater; Global Deterioration Scale score of 2 or less; and Mini-Mental State examination score of 28 or greater. Subjects with evidence for significant medical, psychiatric, or neurologic disease were excluded. MAIN OUTCOME MEASURES--Outcome measurements included individual psychometric test scores and computed tomographic-magnetic resonance imaging hippocampal atrophy ratings. RESULTS--Nearly 33% of the subjects had radiographic evidence for HA. The prevalence of HA increased significantly with age and was more common in male than female subjects. After controlling for age, level of education, and vocabulary, subjects with HA were found to perform more poorly on tests of recent (secondary) verbal memory when compared with subjects without HA (P < .01). No significant differences were found for tests of immediate (primary) memory. CONCLUSION--We conclude that HA is a common accompaniment of normal aging and is associated with mild memory impairment. Additional research is needed to determine whether HA constitutes a significant risk for future dementia