Biomedical subjects
Publications and source records attributed to E Koss.
Behavior modification principles are described as they relate to patients with Alzheimer disease and related disorders. Sample cases are used to illustrate application of the principles to both an inpatient setting and a home setting. Values and limitations along with recommendations are suggested.
This article discusses the usefulness of neuropsychological testing in AD, as an adjunct to the diagnosis, as a means of the evaluation of progression, and response to treatment. Clinical neuropsychological tests that have direct relevance to AD are reviewed, with particular emphasis on recently developed tests of memory function.
OBJECTIVES: To evaluate if caregivers are reliable informants concerning memory deficits in patients with Alzheimer's disease (AD). DESIGN: Responses of caregivers of patients with probable AD and responses of healthy control subjects on a standardized memory questionnaire were compared with objective measures of cognition (Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery) and with clinical estimates of activities of daily living, depression, and psychopathology (Consortium to Establish a Registry for Alzheimer's Disease [CERAD] clinical assessment battery) using the Self-report Memory Questionnaire. SETTING: A federally funded AD research center. SUBJECTS: The referred sample included 117 patients with probable AD, their informants, and 41 healthy control subjects age-matched to the patients. Patients and control subjects were between the ages of 58 and 85 years, had between 9 and 19 years of education, and were in good health. EXCLUSIONS: Patients who did not meet NINCDS-ADRDA criteria of probable AD. MAIN OUTCOME MEASURE: The optimal number of questionnaire items yielding the best combination of sensitivity and specificity. RESULTS: An abbreviated version of the scale, renamed the Short-Memory Questionnaire, had excellent specificity and sensitivity for identifying dementia. Positive and negative predictive values were 63.5% and near 100%, respectively. The Short-Memory Questionnaire showed good reliability, internal consistency, and external validity. Caregiver appraisals of memory deficits significantly correlated with objective measures of memory and also with generalized cognitive dysfunction. CONCLUSIONS: Caregivers of patients with AD are reliable informants of their relatives' deficits. The Short-Memory Questionnaire is an easily administered, informant-based scale that may be useful in clinical settings or epidemiologic studies to screen out persons with memory difficulties.
Reliable information on rate of progression of cognitive impairment in probable Alzheimer's disease (AD) is important for evaluating possible beneficial effects of therapeutic agents and in planning long-term care for patients with this chronic illness. However, wide variability exists in published rates of change for psychometric measures of the dementing process, and there is need for an accurate analysis of large numbers of persons with the disorder studied over long periods. Utilizing the large, well-characterized sample of the Consortium to Establish a Registry for Alzheimer's Disease and employing a least squares regression method to adjust for different levels of impairment and periods of observation, we report rates of change on the Short Blessed Test, Mini-Mental State Examination, Blessed Dementia Scale, Clinical Dementia Rating, and other cognitive measures in 430 patients with probable AD (mean age at entry = 70.9 +/- 8.0 SD years) studied for up to 4 years. We found that rate-of-change determinations are less reliable when the observation period is 1 year or less, that dementia progression may be nonlinear when described by certain measures, and that simple change scores do not accurately characterize the rate of decline. We also found that rate of progression in AD is determined by the severity of cognitive impairment: the less severe the dementia, the slower the rate of decline.
The drawings of Alzheimer's disease (AD) patients and elderly control subjects were rated on a number of specific performance scales, such as attention to configuration, attention to detail, and stimulus boundedness. AD patients showed significantly poorer performance than controls on most drawing scales, and the drawing measures were differentially affected by disease severity. Regional cerebral glucose metabolism (rCMRglc) was assessed via positron emission tomography (PET, with 18FDG) in a subgroup of the AD patients. Partial correlations of rCMRglc with drawing measures (age, sex, and education served as control variables) were conducted. Five out of eight of the drawing measures were significantly correlated (p less than .005) with rCMRglc in occipital and/or temporal-parietal regions, for both left and right hemispheres. Only one of the eight drawing measures, attention to detail, was significantly correlated with rCMRglc in both frontal and posterior regions of interest, again for both hemispheres. Overall dementia severity showed no significant correlations with rCMRglc in any of the regions. These findings are suggestive of a posterior-anterior differentiation, but no left-right hemisphere differentiation, in the relationship between drawing performance and cerebral metabolism in AD, which cannot be accounted for by overall dementia severity. Differences between the drawing performance of AD and unilateral brain damaged patients are discussed, and further applications of the rating scales (provided in the Appendix) are suggested.
Regional cerebral metabolic rates for glucose (rCMRglc), as measured with positron emission tomography, and neuropsychological function were studied longitudinally (range, 15 to 48 months) in 11 mildly impaired patients with dementia of the Alzheimer type (DAT) and compared with results from patients with moderate and severe DAT and from controls. At initial evaluation, association cortex metabolic asymmetries were greater in patients with DAT than in controls for all dementia severities and correlated significantly with neuropsychological discrepancies between visuospatial and language abilities in patients with moderate dementia. In mildly impaired patients, right-left metabolic asymmetries in the association cortices were directionally stable and became more pronounced over time. At initial evaluation, these patients had significant impairment, relative to controls, on tests of memory and attention to complex tasks but not on tests of language and visuospatial function. Memory, attention, language, and visuospatial impairments, however, all worsened significantly over time. In mildly impaired patients, correlations between right-left metabolic asymmetries and neuropsychological discrepancies were insignificant initially but were significant at last evaluation. These results demonstrate that heterogeneous nonmemory language and visuospatial impairments in early DAT are related to and predicted by the earlier-appearing distribution of metabolic reductions in the association neocortex.
Abnormalities in calcium homeostasis have been reported in Alzheimer's disease (AD) and in the neurofibrillary tangle disorders of amyotrophic lateral sclerosis and parkinsonism-dementia occurring in the Pacific. In order to more fully evaluate calcium physiology in AD, we analyzed the size of pineal and choroid plexus calcifications, using X-ray computed tomography, in 23 patients with probable AD and 18 healthy age-matched control subjects. The area occupied by calcification was measured from hard copies of the data by two independent observers who were blind to the diagnosis. There were no differences in the areas occupied by pineal or choroid plexus calcifications between the two groups. These data suggest that AD is not accompanied by alternations in intracranial calcium deposition in pineal gland or choroid plexus.
We performed dynamic positron emission tomographic (PET) studies of glucose utilization, using (18F) 2-fluoro-2-deoxy-D-glucose (FDG), in patients with probable Alzheimer's disease (AD) and healthy age-matched controls, to evaluate blood-brain-barrier glucose transport and glucose utilization rates in the disease. We found no significant differences in rate constants for glucose transport (k1 and k2) and phosphorylation (k3), nor for the vascular fraction (fv), between the 2 groups, although k3 and fv were relatively depressed in temporal cortex in AD. Absolute rates of glucose use were depressed in temporal and parietal cortex, and relative rCMRglc rates were lower in frontal, temporal, parietal, and occipital cortices. These data suggest that in AD bidirectional glucose transport is intact, and that temporal-parietal hypometabolism is present upon a background of widespread cortical metabolic impairment.
The clinical and biological features of Alzheimer disease are not uniform in their expression; heterogeneity is evident in the disease's clinical, anatomic, and physiologic characteristics. The presence of considerable intersubject and intrasubject heterogeneity suggests that subtypes of the disease exist. We define subtypes of Alzheimer disease in regard to the behavioral features (for example, predominant right or left hemisphere, or symmetrical impairment), inheritance (familial or sporadic), dosage of chromosome 21 (presence of the Down syndrome), time course of progression, age of onset (presenile or senile), and presence or absence of motor deficit (myoclonus or signs of an extrapyramidal syndrome). Studies of regional cerebral glucose metabolism with positron emission tomography and [18-fluorine] fluorodeoxyglucose show focal alterations in glucose use, with cerebral metabolic asymmetries in patients with Alzheimer disease that are related to the nature of the cognitive deficit. Serial roentgenographic computed tomographic studies show heterogeneous rates of lateral ventricle enlargement in the disease that are related to rates of cognitive decline. Similar anatomic and physiologic abnormalities are also found in persons 45 years of age or older who have the Down syndrome. Furthermore, patients with Alzheimer disease who have extrapyramidal dysfunction or myoclonus are a distinct subgroup, with specific abnormalities of central monoamine markers of dopamine metabolism, serotonin metabolism, and the hydroxylation cofactor, biopterin. The concept of subtypes in Alzheimer disease serves as a model with which the interactions of genetic influences with environmental factors can be examined.
To assess the occurrence and related features of motor vehicle crashes in patients with dementia of the Alzheimer type (DAT) we studied 30 patients who had been followed longitudinally and 20 healthy age-matched control subjects. Data were gathered from first-degree relatives who had lived with the subjects for the previous 5 years or more. Forty-seven percent of the DAT patients incurred at least one crash while they were driving, whereas only 10% of the control subjects had had a crash in the previous 5 years. The odds ratio for crashes in the DAT group was 7.9 (p less than 0.01). Moreover, in 77% of DAT patients, a deterioration in driving performance was noted, and 63% of the patients had stopped driving. However, only 42% of the DAT patients who stopped driving did so before a crash occurred. Mean illness duration was 4.0 (+/- 1.8) years, and the mean Mini-Mental Status Examination score was 19.9 (+/- 6.3) at the time of the first crash in the DAT group. The occurrence of crashes was not significantly correlated with dementia severity or with disease duration. These data suggest that the occurrence of driving crashes in patients with DAT is an important public health problem.
Explore the source record for details and available documents.
The parietal-frontal distribution of reductions of regional cerebral metabolic rates for glucose (rCMRglc) was studied in 32 patients with mild to severe dementia of the Alzheimer type (DAT), using positron emission tomography and fluorodeoxyglucose, and was related to patterns of neuropsychological impairment. In moderate and severe DAT patients, one frontal association region, the premotor cortex, demonstrated significant metabolic reductions equivalent to reductions in the parietal association cortex, and the ratio of parietal to premotor rCMRglc had significantly greater variance than in controls. In moderately demented patients, parietal-premotor and parietal-prefrontal metabolic ratios correlated significantly with neuropsychological impairments. Disproportionate parietal hypometabolism was associated with more impairment of verbal comprehension, calculations, visuospatial construction, and immediate visuospatial memory span. Disproportionate frontal hypometabolism was associated with more impaired verbal fluency and attention. Longitudinal follow-up of 20 of the patients showed that parietal/frontal metabolic ratios and their correlated neuropsychological patterns were stable over time, as dementia severity worsened. These results indicate that in moderate to severe DAT patients, metabolic reductions in the premotor cortex are as severe as the reductions in the parietal association cortex. Moreover, the parietal-premotor distribution of metabolic reductions is variable and related to variable patterns of cognitive impairment.
Measurement of cerebral glucose metabolism in six patients with Alzheimer's disease using positron emission tomography demonstrated that hypometabolism remained relatively more severe in parietal cortex than in frontal cortex over time. Lateral metabolic asymmetries were preserved in less severely involved brain regions, but were less stable in parietal cortex.
Ten carefully screened men with very mild symptoms of Alzheimer's disease (AD) and ten healthy controls of similar age were compared on multiple chemosensory tasks: odor detection and identification, and taste detection. The patients scored significantly worse than controls on identification of odors and of a subset of airborne stimuli providing trigeminal stimulation. In contrast, the patients' olfactory detection thresholds as well as taste detection thresholds were not impaired relative to those of controls. The patients' scores on neuropsychological tests and the results 18F-2 deoxy-D-glucose PET studies did not correlate with any of the chemosensory measures. The isolated odor identification deficit suggests that the initial chemosensory impairment in AD is central rather than peripheral.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Retrieval from semantic memory, measured by tasks requiring subjects to name items from a given category, was studied in mild Alzheimer-type dementia (Mild-ATD) subjects, moderate-to-severe Alzheimer-type dementia (MS-ATD) subjects, and normal controls. Semantic retrieval performance was shown to be highly sensitive to both the presence and the severity of ATD. Retrieval from both semantic categories and letter categories showed differences in the rate of production of correct responses between subject groups. These rate differences were not due to differences in accessibility of low-dominance semantic category members or low-frequency letter category members. An increase in errors as well as a decrease in correct responses contributed to the performance deficits of the ATD subjects. Furthermore, the pattern of errors changed from Mild- to MS-ATD. Qualitative as well as quantitative differences were also observed in the performance of Mild- versus MS-ATD groups on a third type of semantic retrieval task--the supermarket task. As performance of the ATD subjects declined on these semantic retrieval tasks, so did their performance on other tasks assessing primarily attention, language, and memory. The findings are discussed in terms of the progressive breakdown in both attentional and semantic memory functions which are associated with ATD.
We performed dynamic positron emission tomographic studies with [18F]fluorodeoxyglucose in 17 subjects with presumed Alzheimer's disease (AD) and 7 healthy aged subjects. Glucose metabolism was depressed by 27% in temporal-parietal cortex of the AD group, as compared to healthy aged controls. This focal impairment in temporal-parietal glucose use was found in all AD subjects. In addition, the AD group showed a striking lateral asymmetry of cortical metabolism not favoring either hemisphere, which has not been previously reported. Relationships between these focal changes and behavioral features of the illness were demonstrated. These results have important implications for the diagnosis and perhaps the etiology of Alzheimer's disease.