The prediction of Alzheimer disease. The role of patient and informant perceptions of cognitive deficits.

OBJECTIVE: To determine whether the perceptions of patients' cognitive deficits by either the patient or an informant could predict who would develop Alzheimer disease (AD) in a group of 120 memory-impaired patients without dementia. METHODS: At entry into the study, patients were assessed by several measures that included neuropsychological tests and the Cambridge Mental Disorders of the Elderly Examination Interview Schedule. The latter schedule asks patients and their informants about their perceptions of cognitive deficits in the patients. After 2 years, patients underwent a diagnostic workup for AD: 29 had developed probable AD, whereas the other 91 did not develop dementia. We used logistic regression analyses to examine the predictive accuracy of patients' and informants' perceptions of deficits at entry into the study. RESULTS: Informants' perceptions, not patients' perceptions, contributed significantly to the prediction of AD. The best prediction of AD was obtained by the regression model that included both informants' perceptions and 2 neuropsychological tests. CONCLUSIONS: These results demonstrate the clinical use of including informant perceptions about patients' cognitive deficits in the diagnostic assessment of AD. They also indicate that patients' perceptions of their own deficits are not predictive of AD, but are related to depressive affect.

Domain specificity of the subtests of the Mini-Mental State Examination.

OBJECTIVE: To examine the convergent and, for the first time to our knowledge, the divergent validity of 4 of the subtests of the Mini-Mental State Examination (MMSE): attention, naming, memory, and copy. METHODS: Participants included 126 memory-impaired individuals (mean age, 74 years). Because the naming subtest showed no variability, we did not analyze it further. RESULTS: The convergent validity of the attention, memory, and copy subtests was confirmed with Spearman rank correlation coefficient. Each MMSE subtest was significantly related to a parallel neuropsychological test. We measured divergent validity by testing the difference between the MMSE subtest correlation with its parallel neuropsychological test and its nonparallel neuropsychological test. The MMSE subtests of attention and memory showed similar relationships with their parallel neuropsychological tests as they did with nonparallel neuropsychological tests of attention, memory, and naming. These 2 subtests, however, did show divergence from a neuropsychological test of copy, most likely indicating that these 2 MMSE subtests are measuring the verbal (and not the performance) domain. The MMSE subtest of copy showed the poorest convergent and divergent validity. CONCLUSIONS: The 3 subtests did not show sufficient divergent validity to warrant a conclusion of their domain specificity. Thus, when a more detailed diagnostic profile is required, a thorough neuropsychological evaluation will provide a more valid description of an individual's cognitive profile.

Psychometric differentiation of dementia. Replication and extension of the findings of Storandt and coworkers.

In a previous investigation by Storandt and coworkers, a brief battery of four neuropsychological tests was found to accurately distinguish a sample of patients with senile dementia of the Alzheimer type (SDAT) from normal elderly persons. The present study examined the value of these tests in the distinction between SDAT and dementias of other etiologies. Our results replicated those of Storandt and coworkers in that these tests did distinguish normal persons from patients with both SDAT and other dementias. These tests, however, did not accurately differentiate among the dementias. These results indicate that assessment batteries utilizing additional procedures to supplement cognitive testing are indicated to more accurately discriminate among the dementias.

Recognition memory and verbal fluency differentiate probable Alzheimer disease from subcortical ischemic vascular dementia.

BACKGROUND: Alzheimer disease (AD) and vascular dementia are among the most frequently occurring causes of dementia in the world, and their accurate differentiation is important because different pharmaceutical strategies may modify the course of each disease. OBJECTIVE: To determine which of 10 neuropsychological test scores can accurately differentiate patients with probable AD from those with subcortical ischemic vascular dementia (SIVD) for use in evidence-based clinical practice. DESIGN: Patients with suspected dementia were referred to the study by family physicians, geriatricians, and neurologists. All participants received a thorough assessment according to standard diagnostic guidelines. Diagnoses of probable AD (n = 31) and probable SIVD (n = 31) were made according to consensus criteria. The diagnosticians were blind to the results of the 10 neuropsychological test scores. RESULTS: There were no significant differences between the groups in age or Mini-Mental State Examination scores. Logistic regression analyses identified 2 neuropsychological tests that best distinguished the groups (sensitivity = 81%; specificity = 84%; positive likelihood ratio = 5.1). These were the recognition memory subtest of the Rey Auditory Verbal Learning Test and the Controlled Oral Word Association Test. The AD group performed better on the oral association test, whereas the SIVD group did better on the recognition memory test. CONCLUSION: Patients with probable AD and probable SIVD can be distinguished with a high degree of accuracy using these 2 neuropsychological tests.

Prediction of recovery of continuous memory after traumatic brain injury.

OBJECTIVE: To evaluate the ability of measures of initial severity, tests of attention, and demographic characteristics to predict recovery of continuous memory for words over a 24-hour period in patients with acute traumatic brain injury. METHODS: Recovery of continuous memory was assessed prospectively in 94 patients with nonpenetrating traumatic brain injury. A classification and regression tree analysis identified a hierarchical subset of variables that may be used as a simple guideline for predicting recovery of continuous memory. Weibull regression models evaluated and compared the predictive ability of multiple variables. RESULTS: Four groups of patients were identified based on measures of severity of injury and demographic characteristics. These four groups had recovery profiles that were more precise than could be obtained by using the Glasgow Coma Scale alone: mild, about 1 week to recovery of continuous memory; moderate, 1 to 4 weeks; severe, 2 to 6 weeks; and extremely severe, 4 to 8 weeks. Regression analysis confirmed that measures of capacity (inherent resources such as indicated by age) and compromise (general functional brain state measured neuropsychologically) improved prediction over models based only on injury severity measures, such as the Glasgow Coma Scale. CONCLUSIONS: Approaches to predicting recovery of continuous memory in the acute period after traumatic brain injury that take into account multiple measures provide a more sensitive predictive index.

A prospective study of the clinical utility of ApoE genotype in the prediction of outcome in patients with memory impairment.

Given the relationship between the presence of ApoE epsilon 4 and Alzheimer's disease (AD), were studied whether knowledge of epsilon 4 status would predict which memory-impaired patients would develop AD over time. One hundred seven patients who presented with memory impairment but not dementia were referred to the study by their family physicians. These patients were followed prospectively over a 2-year period. Twenty-nine patients developed AD, while 78 did not develop dementia. We found that ApoE genotype was a reliable prognostic indicator of who developed AD in this group only when memory test performance was included in the predictive model. These findings indicate that limitations of ApoE genotyping in isolation as a prognostic indicator of AD. Because this study included prospectively selected patients who were followed longitudinally, our findings are likely to have more relevance in the clinical setting than those obtained from currently available retrospective studies.

Prediction of probable Alzheimer's disease in memory-impaired patients: A prospective longitudinal study.

We determined whether a battery of neuropsychological tests could predict who would develop Alzheimer's disease (AD) in a group of 123 memory-impaired nondemented patients. Patients were followed longitudinally for 2 years with a research battery of neuropsychological tests. After 2 years, 29 developed probable AD, and 94 did not develop dementia. We used logistic regression analyses to examine the classification accuracy of subjects' performance at entry to the study on the research battery. The logistic regression model was significant with an accuracy of 89%, sensitivity of 76%, and specificity of 94%. Two tests contributed significantly to this model: the delayed recall from the Rey Auditory Verbal Learning Test and the Mental Control subtest of the Wechsler Memory Scale. These two tests alone produced the same accuracy, sensitivity, and specificity as the larger model. These results demonstrate that probable AD can be predicted with a high degree of accuracy and with a relatively brief battery of neuropsychological tests.

The NINCDS-ADRDA Work Group criteria for the clinical diagnosis of probable Alzheimer's disease: a clinicopathologic study of 57 cases.

Neuropathologic confirmation is required to validate the NINCDS-ADRDA Work Group criteria for the clinical diagnosis of Alzheimer's disease (AD). Neuropathologic inclusion and exclusion criteria for AD, however, are not uniform. The purpose of this investigation was to examine the confirmation rate for the Work Group criteria against differing neuropathologic criteria for AD. The sample consisted of 57 cases, 22 of which had received a clinical diagnosis of AD. Nine neuropathologic criteria for AD were applied in a blind fashion to each of the 57 cases. Our results indicated that, depending on the neuropathologic criteria applied, the clinicopathologic agreement ranged from 64% to 86%. These findings demonstrate the need for universally accepted neuropathologic and clinical criteria for AD.

On the clinical value of the London Psychogeriatric Rating Scale.

The London Psychogeriatric Rating Scale (LPRS) was administered to 76 probable Alzheimer's patients, 59 patients with dementia unrelated to Alzheimer's, 102 neurologically normal subjects, and 27 patients with symptoms of both Alzheimer's and dementia of other etiologies. By examining the relationships among the four subscales of the LPRS and conducting factor analyses, it was demonstrated that the four subscales were not measuring different phenomena. The internal consistency of the full 36-item scale was high (Cronbach's Alpha = 0.96) indicating the total LPRS score provided a reliable global index of behavioral function. The total LPRS scores correlated with the independently administered Goldfarb Mental Status Examination scores (r = -0.79). The LPRS differentiated between the normals and the combined demented groups and between inpatients and outpatients. The LPRS continues to have clinical value for functional assessments in a non-intrusive manner. The LPRS may be particularly useful in situations where direct assessment of mental status is not practical.

Cardiopulmonary bypass, rewarming, and central nervous system dysfunction.

BACKGROUND: During cardiopulmonary bypass a nasopharyngeal temperature greater than 38 degrees C at the end of rewarming may indicate cerebral hyperthermia. This could exacerbate an ischemic brain injury incurred during cardiopulmonary bypass. METHODS: In a cohort of 150 aortocoronary bypass patients neuropsychologic test scores of 66 patients whose rewarming temperature exceeded 38 degrees C were compared with those who did not. There were no differences between groups with respect to demographic and intraoperative variables. RESULTS: A trend was seen for hyperthermic patients to do worse on all neuropsychologic tests in the early postoperative period but not at 3-month follow-up. By analysis of covariance hyperthermic patients did worse on the visual reproduction subtest of the Weschler memory scale at 3 months (p = 0.02), but this difference was not found by linear regression (p = 0.10). CONCLUSIONS: We were unable to demonstrate any significant deterioration in patients rewarmed to greater than 38 degrees C in the early postoperative period. The poorer performance in the visual reproduction subtest of the Wechsler memory scale at 3 months in the group rewarmed to more than 38 degrees C is interesting but far from conclusive. Caution with rewarming is still advised pending more in-depth study of this issue.

Quality of life in patients 2 to 4 years after closed head injury.

This study evaluated quality of life in 78 patients with closed head injury (CHI) 2 to 4 years postinjury. Using both interview data and mean data from the Sickness Impact Profile questionnaire, impaired quality of life was observed in the areas of psychosocial functioning, social role functioning, leisure activities, and, to a lesser extent, physical functioning, during chronic phases of recovery. Relatives and close friends reported by means of the Katz Adjustment Scale that the CHI patients showed a series of negative behavioral symptoms 2 to 4 years postinjury. These data suggest that CHI patients may experience impaired quality of life in a number of domains well beyond the acute postinjury phases. An attempt was also made to compare patients' and relatives' reports of patient quality of life. Preliminary analyses indicated modest correspondence between relatives' and patients' ratings of some areas of postinjury dysfunction, including cognitive and behavioral slowing and social withdrawal.

The acute period of recovery from traumatic brain injury: posttraumatic amnesia or posttraumatic confusional state?

OBJECT: The goal of this study was to characterize more fully the cognitive changes that occur during the period of acute recovery after traumatic brain injury (TBI). METHODS: The pattern of performance recovery on attention and memory tests was compared with the results of the Galveston Orientation and Amnesia Test (GOAT). Tests of memory and attention were administered serially to a hospitalized group of patients with TBI of varying severity. The tests differed in their level of complexity and/or requirement for more effortful or strategic processing. The authors found a regular pattern to recovery. As expected, ability to perform on simpler tests was recovered before performance on more effortful ones. The ability to recall three words freely after a 24-hour delay (the operational definition in this study of return to continuous memory) was recovered last, later than normal performance on the GOAT. Ability to perform simple attentional tasks was recovered before the less demanding memory task (recognition); ability to perform more complex attentional tasks was recovered before the free recall of three words after a 24-hour delay. This recovery of attention before memory was most notable and distinct in the group with mild TBI. CONCLUSIONS: The period of recovery after TBI, which is currently termed posttraumatic amnesia, appears to be primarily a confusional state and should be labeled as such. The authors propose a new definition for this acute recovery period and argue that the term posttraumatic confusional state should be used, because it more appropriately and completely characterizes the early period of recovery after TBI.

Psychological, topographic EEG, and CT scan correlates of frontal lobe function in schizophrenia.

This study examined frontal lobe function in a group of 20 patients with schizophrenia, on and off medication, compared to 20 normals matched for age, sex, handedness, intelligence, and educational level. Schizophrenic patients generally did not perform as well as normals on the Wisconsin Card Sorting Test (WCST). Patients off medication performed less well on this test than those on medication. Those on medication did not perform as well as those off medication on the design and word fluency tests, which suggested that medications may affect various aspects of frontal lobe function differently. During the WCST, normal subjects demonstrated an increase in beta mean frequency of the electroencephalogram in frontal and centrotemporal regions which was not statistically significant in either schizophrenic group. This shift in beta mean frequency was found to correlate positively with performance on the WCST in normals, but not in patients. Patients with more negative symptoms tended to show a smaller increase in beta mean frequency during the WCST. Performance on the WCST was correlated negatively with ventricle-brain ratio in all subjects, suggesting that frontal lobe function might be related to computed tomographic measures in the normal population as well as in schizophrenic patients. There was no correlation with performance on the WCST and length of illness.

The differential diagnosis of Alzheimer's disease: conceptual and methodological issues.

The study of Alzheimer's disease is hampered by insufficient knowledge of its cause. It can best be described as a syndrome whose clinical and pathological features, and their associations over time, need to be more carefully examined. Issues which impede our understanding of this syndrome include the lack of: a singular "gold standard" for its identification; longitudinal studies with appropriate comparison groups and neuropathological follow-up; and standardized multifaceted clinical assessment procedures. Our awareness of the significance of these issues has led us to undertake a large-scale prospective, longitudinal investigation of 399 dementing and normal individuals at Sunnybrook Medical Centre. As a result of problems identified, it is proposed that research efforts across various Canadian centres be coordinated to best utilize available resources and expertise.

The course of post-traumatic amnesia: three little words.

OBJECTIVE: To provide a simple means of "real time" recognition of emergence from post-traumatic amnesia (PTA). METHODS: Ninety-one patients with traumatic brain injury (PBI); 53 minor (GCS 13-15), 19 moderate (GCS 9-12), 18 severe (GCS 3-8). Twenty-seven control subjects treated at two regional trauma units for their acute phase and followed in a hospital-based research institute were studied prospectively. Subjects were examined repeatedly following injury with the Galveston Orientation and Amnesia Test (GOAT) and tests of their ability to learn and retain new information. Word triplets balanced for concreteness and frequency were presented. Immediate and 24-hour recall were tested. If 24-hour recall was imperfect, recognition was tested by presenting the 3 target words and 6 distracters. The target words were then re-presented and recall was tested the next day. The time intervals to first perfect recognition and first free perfect recall were compared with the patients' first GOAT score of 75 or greater on 2 successive days. Simple line drawings of common objects were also presented to the subjects using an identical paradigm. The outcome measures were GOAT, 3-word recognition and recall, 3 picture recognition and recall. RESULTS: For all categories of head injury severity, the median interval to perfect free recall of words followed the achievement GOAT criterion by a significant interval. The mean GOAT scores for perfect 3-word recall and recognition corresponding to minor, moderate and severe injuries were 97, 90 and 88, and 97, 76 and 68 respectively. The recognition and recall of pictures preceded the recognition and recall of words by approximately 1 day. CONCLUSIONS: The orientation measures of the GOAT that contain material that the patient knew prior to injury obscure the determination of recovery of continuous memory and should be tested separately. Three-word recall which is simpler to administer than the GOAT is a more reliable measure of emergence from PTA. For patients who are dysphasic or who do not share a common language with the examiner, 3-picture recognition and recall may substitute for word recognition and recall.

Are the Rey and Taylor figures equivalent?

We examined the comparability of the Rey-Osterrieth Complex Figure Test (ROCFT) and the Taylor Complex Figure Test (TCFT) as measures of constructional praxis and visual recall in a sample of 38 patients who were administered the two figures in counterbalanced order. Copy scores did not differ for the two figures. There was some evidence that percent recall scores, but not absolute recall scores, were higher for the TCFT and more susceptible to proactive interference than those for the ROCFT. These results suggest that the two figures yield comparable results when copy or absolute recall scores are used, but that the TCFT may be easier to recall than the ROCFT when percent recall scores are used.

The place of cooperation in the examination of neuropsychological impairment.

We examined the relationship between ratings of patient cooperation and neuropsychological test performance in a sample (N = 333) of dementing patients and normal controls. We also examined the stability of the relationship in a subset of this same sample (N = 299) who were retested a year later. All the correlation coefficients in both years were significant, with a median Pearson of.64 in year one and.725 in year two. The test-retest reliability for ratings of cooperativeness over the one-year time period (rated by different examiners) was also significant,r =.64 (p <.0001). This analysis indicates that cooperation plays a significant role in neuropsychological test performance and that ratings of cooperativeness are relatively stable over periods of up to a year in length.

Reduced accuracy of classification with a short form of the Speech Sounds Perception Test.

This study attempts to cross-validate the accuracy in classification of Golden and Anderson's (1977) abbreviated version of the Halstead Speech Sounds Perception Test. A relatively high correlation was obtained between their short form and the standard long form for a sample of 150 patients, aged 15 to 70 yr. However, the long form was more accurate in discriminating between 31 brain-damaged and 31 nonbrain-damaged patients. These results suggest that the use of the short form of this test may reduce accuracy of classification.