Wechsler intelligence scale profiles in Alzheimer type dementia and healthy ageing

Meta-analytic techniques were used to integrate the Wechsler Adult Intelligence (WAIS) scores of healthy elderly subjects and Alzheimer type dementia patients from 21 studies. Although age-scaled scores for demented subjects were lower than those of healthy elderly subjects for all subtests, the profiles for both groups were essentially parallel, with no subtest having significantly poorer scores than the others for the dementia patients. The pattern confirms other findings that verbal tests do not ‘hold’ to a greater degree than performance tests in dementia.     

Discriminant analysis of WAIS results in different types of dementia and depressed patients

A Multivariate Analysis of Covariance and Discriminant Analysis were carried out on complete WAIS profiles obtained from three groups of demented patients: Multi-Infarct Dementia patients, Senile Dementia of Alzheimer Type patients, and Alcoholic Dementia patients. A group of middle-aged Depressed patients was also included. WAIS did not differentiate among dementias, but Picture Completion and Block Design subtests proved to be effective in differentiating dementia from depression.     

Test profile of cholinergic dysfunction and of Alzheimer-Type dementia

Abstract

A characteristic profile of subtest scores from the Wechsler Adult Intelligence Scale (WAIS) similar to that seen in clinically tested dementia patients was found in 10 of 19 normal young adult subjects with a drug-induced cholinergic deficiency of mental functioning but in only 4 of 22 control subjects. The same subtest profile was then found in test data from two groups of consecutive dementia patients (61 and 77 patients, respectively) with research diagnoses of Alzheimer-type dementia (DAT, senile and presenile), multi-infarct, and other dementias.

The profile identified 44% of testable patients with AD and was 96% specific to DAT (only two false positives). A Verbal-Performance IQ discrepancy of 15 or more points was associated with cholinergic dysfunction in the normal drug subjects, but this IQ-score discrepancy did not differentiate AD from multi-infarct dementia patients. It was concluded that the subtest profile could contribute to the differentiation of DAT from other dementias. The association of this profile with drug-induced cholinergic deficiency suggested that the cholinergic deficiency of DAT might be responsible for the intellectual changes seen in this disease.     

Clock drawing in dementia: its reliability and relation to the neuropsychological measures]

To examine the reliability and validity of clock drawing (CD) for evaluating dementia patients in Japan, we investigated the CD performance and its relation to several neuropsychological tests in 150 demented patients including 105 patients with Alzheimer disease and 30 age- and education-matched non-demented subjects (16 patients with mild cognitive impairment and 14 normals). Patients were also evaluated using the Mini-mental State Exam (MMSE), Wechsler Memory Scale (WMS), Kohs Block Design, and word fluency. CD was scored using the Shulman method. CD scores showed a high interrater reliability (r = 0.97). CD by non-demented subjects was essentially normal. As a screening test for Alzheimer disease (AD, mean MMSE = 18.0), CD had a sensitivity of 57.1% and a specificity of 96.7%. However, four of eight AD patients who showed normal MMSE score (> or = 24) drew abnormal clocks. CD scores in dementia were significantly correlated with performance on the Block Design (r = 0.68), MMSE (r = 0.56), and the Mental Control subtest in the WMS (r = 0.58). Stepwise regression analysis revealed that performance on the MMSE and the Block Design explain 53.8% of the variance in the CD scores. These findings indicate that low CD score by the Shulman method may be reflective of a constructional disability and general severity of dementia. CD is not so sensitive as the result of the original report when the patient group includes milder cases of AD. CD is, however, an efficient screening test for detecting and following the patients with dementia, especially combined with the MMSE.     

Alzheimer Disease Assessment Scale: a subtest analysis.

The Alzheimer Disease Assessment Scale (ADAS) was administered to 61 Alzheimer patients, 52 elderly controls, and 80 controls between age 7 and 54 years. The Alzheimer group was categorized into different severity levels of dementia based on MMSE scores: very mild (> or = 24), mild (> or = 20), moderate (10-19), and severe (0-9). All 11 ADAS Cognitive subtest scores for the mild, moderate, and severe dementia groups were statistically worse than the elderly control group. This was also the case for the very mild group, except for Naming, Commands, Constructional Praxis, and Ideational Praxis. In terms of magnitude of effect, memory and spontaneous language items were the earliest indicators on the ADAS, while praxis, commands, and naming items were only sensitive later in the course of the disorder. The best single indicators of progression throughout the severity continuum of dementia (i.e., from normal to severe) were the Orientation subtest, the ADAS Cognitive score, and the ADAS Total score. The ADAS Noncognitive subtests generally did not show the progression with increasing dementia that was evident on the ADAS Cognitive subtest. Differences in educational level had no statistically significant effects on any of the ADAS subtest scores, and age differences were few and small in magnitude. The differential rate of decline of the various ADAS subtests appears to reflect both the changing pattern of cognitive impairments as a function of severity of DAT and also to some extent the psychometric limitations of some of the subtests.     

The short test of mental status. Correlations with standardized psychometric testing

The Short Test of Mental Status can be administered to patients in inpatient and outpatient settings in approximately 5 minutes, and it contains items that test orientation, attention, immediate recall, arithmetic, abstraction, construction, information, and delayed (approximately 3 minutes) recall. The test was administered to a group of demented community patients and their age- and sex-matched control subjects. Using an age-adjusted approach, sensitivity of the test to identifying dementia is 86.4, with a specificity of 93.5. The test was compared with standardized tests of cognitive function such as the Wechsler Adult Intelligence Scale, Mattis Dementia Scale, and the Auditory Verbal Learning Test, and showed a high degree of correlation. Group means and standard deviations for subtest items and total score are presented for control subjects (n = 138), demented patients (n = 130), and patients with memory impairment only (n = 20). Percentile scores for subtest items in control subjects are also provided.     

The relative frequency of "dementia of unknown etiology" increases with age and is nearly 50% in nonagenarians

CONTEXT: With the recent change in pathological criteria for Alzheimer disease (AD), a group of patients has emerged who do not meet pathological criteria for any well-characterized degenerative dementias. Whether these unclassified patients have vascular dementia or some other form of dementia is not known. OBJECTIVE: To determine the clinical characteristics, pathological substrate, and relative frequency of dementia not caused by well-characterized degenerative dementias. DESIGN/SETTING: Clinicopathological study of a prospectively observed sample of elderly nondemented and demented subjects recruited from our urban community. METHODS: In our series of 128 subjects with prospective neuropsychological evaluations as well as neuropathology, we identified 35 clinically nondemented subjects and 20 demented patients who did not meet pathological criteria for well-characterized degenerative dementias such as AD or dementia with Lewy bodies. The 20 demented patients were grouped together under the term dementia of unknown etiology (DUE). We compared clinical, genetic, neuropsychological, pathological, and neurochemical characteristics of the nondemented group, patients with DUE, and 28 patients with AD and no other pathological abnormality. RESULTS: Mean age at death for patients with DUE was 89.1 +/- 5.8 years compared with 79.9 +/- 11.4 years for AD (P<.001). Patients with AD and DUE did not differ in sex, risk factors, apolipoprotein E genotype, neuropsychological features, or neurological features. Hippocampal sclerosis (in 11 patients with dementia and no controls) and leukoencephalopathy (in 7 patients with dementia and 1 control) were associated with cognitive impairment; other vascular markers were not. Dementia of unknown etiology accounted for 5% of all cases of dementia among patients dying in their 70s, 21% for patients dying in their 80s, and 48% for patients dying in their 90s. CONCLUSIONS: A significant percentage of demented patients older than 80 years do not meet pathological criteria for AD or dementia with Lewy bodies. Hippocampal sclerosis and leukoencephalopathy are common in these patients but rare in clinically nondemented subjects.     

Cause of death in demented and non-demented elderly inpatients; an autopsy study of 308 cases

Few studies evaluated cause of death (COD) in elderly demented and non-demented people, the majority based on death certificates alone. The present study is based on autopsy reports with neuropathological examination of 308 inpatients (58.1% female) over age 60 years (mean: 83.5, SD: +/-8.6). CODs were classified into seven groups. The most common were bronchopneumonia (n=117; 38%) and cardiovascular disease (n=116, 37.7%). In 176 patients (57.1%) neuropathology was indicative for dementia: 76.7% Alzheimer disease (AD), 4.5% vascular dementia, 4.0% mixed type dementia (AD + vascular dementia), and 14.8% other dementias. Main COD significantly differed in demented and non-demented patients: bronchopneumonia (45.5% in demented versus 28.0% in non-demented), cardiovascular disease (46.2% in non-demented versus 31.3% in demented). Whereas there were significant differences in COD between AD patients and non-demented ones (bronchopneumonia versus cardiovascular disease), no differences were seen between the latter and patients with other types of dementia than AD. Our data emphasize the high incidence of bronchopneumonia as a COD in patients suffering from AD.     

Canadian Study of Health and Aging (CaSHA)

A Canada-wide study of the epidemiology of dementias was initiated in the summer of 1990 with the support of Health and Welfare Canada. The four objectives are to estimate the prevalence of dementias among elderly Canadian citizens, to determine the risk factors for dementia of the Alzheimer type, to describe the current pattern of caring for demented patients and assess the burden on informal caregivers, and to establish a uniform database for future incidence and longitudinal studies of dementias. Trained interviewers will screen a representative sample of senior citizens in the community. The screening is followed by a standardized clinical assessment for putative cases of dementia, for institutionalized patients and for a number of controls. Diagnosis will follow DSM-III-R criteria for dementia, the NINCDS-ADRDA criteria for dementia of the Alzheimer type and the ICD-10 criteria for other dementias. A sample of cases and controls will then enter the caregiver and risk factor sub-studies.     

Differential diagnosis of Alzheimer disease with cerebrospinal fluid levels of tau protein phosphorylated at threonine 231

BACKGROUND: Phosphorylation of tau protein at threonine 231 (using full-length tau, 441 amino acids, for the numbering scheme) (p-tau(231)) occurs specifically in postmortem brain tissue of patients with Alzheimer disease (AD) and can be sensitively detected in cerebrospinal fluid (CSF). OBJECTIVES: To determine to what extent CSF levels of p-tau(231) distinguish patients with AD from control subjects and from patients with other dementias, and to investigate whether p-tau(231) levels are a better diagnostic marker than levels of total tau protein (t-tau) in CSF. DESIGN AND SETTING: Cross-sectional, multicenter, memory clinic-based studies. PARTICIPANTS: One hundred ninety-two patients with a clinical diagnosis of AD, frontotemporal dementia (FTD), vascular dementia, Lewy body dementia, or other neurological disorder and healthy controls. MAIN OUTCOME MEASURES: Levels of CSF tau proteins as measured with enzyme-linked immunosorbent assays. RESULTS: Mean CSF levels of p-tau(231) were significantly elevated in the AD group compared with all other groups. Levels of p-tau(231) did not correlate with dementia severity in AD, and discriminated with a sensitivity of 90.2% and a specificity of 80.0% between AD and all non-AD disorders. Moreover, p-tau(231) levels improved diagnostic accuracy compared with t-tau levels when patients with AD were compared with healthy controls (P =.03) and demented subjects (P<.001), particularly those with FTD (P<.001), but not those with vascular and Lewy body dementias. Sensitivity levels between AD and FTD were raised by p-tau(231) compared with t-tau levels from 57.7% to 90.2% at a specificity level of 92.3% for both markers. CONCLUSION: Increased levels of CSF p-tau(231) may be a useful, clinically applicable biological marker for the differential diagnosis of AD, particularly for distinguishing AD from FTD.     

Lexical, semantic, and action verbal fluency in Parkinson's disease with and without dementia.

Previous research suggests that lexical and semantic verbal fluency are differentially sensitive to the effects of cortical and subcortical dementias, but little is known about action fluency performance in dementias. The present study compared lexical, semantic, and action fluency in groups of patients with Parkinson's disease (PD) with and without dementia and an elderly control group. Findings revealed an interaction between fluency type and subject group. Although the demented PD (PDD) group performed significantly more poorly than their non-demented counterparts and normal controls on all three fluency tasks, a disproportionate disparity in scores was noted on the action fluency task. The findings suggest that action fluency may be particularly sensitive to PD-associated dementia and may be an early indicator of the conversion from PD to PDD. As reported elsewhere, PD without dementia was not associated with significant impairment on any of the fluency tasks.     

Clinical factors associated with dementia in ischaemic stroke.

71 patients with an ischaemic stroke were studied. The patients were separated into two groups on the basis of the results of clinical investigation, computed tomography and psychological testing (WAIS). 40 patients showed an early dementia and 31 were without mental impairment. The mean age was 57 years in the demented group and 54 years in the non-demented group. The mean duration of the history of cerebrovascular disease was also not statistically different in both groups. The frequency of strokes was identical since 50% of the patients in both groups had more than one stroke. The history of neurological symptoms together with the neurological deficits seen on admission were distributed evenly. The dominant hemisphere was more often diseased in the demented group. Bilateral symptoms were also more common in the demented stroke patients. The WAIS showed a similar IQ in both groups but the deterioration index was significantly altered in the demented group. Hypertension was the only risk factor which differed between both groups. Cardiac disease, diabetes, viscosity and fibrinogen did not differ in both groups. The CT showed more normal scans in the non-demented group, the distribution of atrophy on its own and infarction in the left or right hemisphere were both inconclusive, whilst patients with bilateral infarcts were more common in the dementia group. Also, generalised atrophy in combination with an infarct was found more often in the demented patients.     

Lexical,Semantic, and Action Verbal Fluency in Parkinson's Disease with and without Dementia

Previous research suggests that lexical and semantic verbal fluency are differentially sensitive to the effects of cortical and subcortical dementias, but little is known about action fluency performance in dementias. The present study compared lexical, semantic, and action fluency in groups of patients with Parkinson's disease (PD) with and without dementia and an elderly control group. Findings revealed an interaction between fluency type and subject group. Although the demented PD (PDD) group performed significantly more poorly than their non-demented counterparts and normal controls on all three fluency tasks, a disproportionate disparity in scores was noted on the action fluency task. The findings suggest that action fluency may be particularly sensitive to PD-associated dementia and may be an early indicator of the conversion from PD to PDD. As reported elsewhere, PD without dementia was not associated with significant impairment on any of the fluency tasks.     

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.     

Analysis of intellectual and cognitive performance in patients with multi-infarct dementia, vertebrobasilar insufficiency with dementia, and Alzheimer's disease.

A prominent feature in dementia is intellectual deterioration. Review of the clinical literature indicates a lack of suitably quantitated studies of specific intellectual defects in dementia. The present study investigated the performance of patients with multi-infarct dementia (MID), dementia due to Alzheimer's disease (AD), and vertebrobasilar insufficiency (VBI) with dementia using the Wechsler Adult Intelligence Scale (WAIS). Forty-two patients ranging in age from 45 to 85 years (x 66) were included. Significant differences in cognitive and intellectual performance were found between patients with dementia due to VBI and MID versus neuronal atrophy of the Alzheimer's type. The group with AD performed significantly and consistently lower on all measures. There were no significant differences between the two cerebrovascular disease groups, even though the MID group performed consistently more poorly than the VBI group. A discriminant function analysis classified 74% of the patients correctly based on the individual WAIS scores. The diagnosis was more easily made when tasks measuring visual motor coordination and abstract reasoning were included in the analysis.     

Cinguloparietal atrophy distinguishes Alzheimer disease from semantic dementia

BACKGROUND: Progressive brain atrophy is associated with Alzheimer disease (AD) and other dementias. Regional differences in brain atrophy may reflect clinical features of disease. OBJECTIVE: To identify regions of cerebral atrophy that are associated with AD vs other dementias. SETTING: University hospital dementia clinic. PARTICIPANTS: Eleven patients with AD and 11 with semantic dementia (SD), matched for age, sex, education, and degree of overall cognitive impairment and 15 normal controls. METHODS: Voxel-based morphometry was used to compare patterns of gray matter loss, measured on T1-weighted magnetic resonance images, between patients with AD or SD, a subtype of frontotemporal lobar degeneration, and controls. Statistically significant differences in regional gray matter concentration, after multiple-comparisons correction, between groups of subjects were identified. RESULTS: Patients with AD were more impaired than those with SD on tests of visuospatial function and on simple calculations. Consistent with these neuropsychological deficits, the most significant area of atrophy in the AD group was the left parietal cortex vs controls (z = 5.0; P =.04). Compared with SD, AD was associated with more atrophy in the left parietal lobe (z = 5.6; P =.04) and bilaterally in the posterior cingulate/precuneus (z = 5.1; P =.04). A discriminant function analysis demonstrated that the degree of atrophy of right posterior cingulate, left parietal lobe, right amygdala, and right anterior temporal lobe structures correctly classified 96% of the patients. CONCLUSION: Alzheimer disease is associated with a specific pattern of cortical atrophy compared with SD.     

Predictive features in mild senile dementia of the Alzheimer type

Forty-three subjects with mild senile dementia of the Alzheimer type, diagnosed and staged by clinical research criteria, were studied with clinical, psychometric, EEG, visual evoked potential, and CT measures. During the 12 months following entry into the study, 21 subjects progressed to moderate or severe dementia, 21 remained mild, and one was lost to follow-up. Many of the clinical and psychometric measures of impairment were predictive of the progression to moderate or severe dementia. Electrophysiologic and CT measures were not. In a discriminant function analysis, the scores on two measures (the digit symbol subtest of the Wechsler Adult Intelligence Scale and an Aphasia Battery) correctly predicted the stage of dementia 1 year later in 95% of the subjects.     

Small vascular and Alzheimer disease-related pathologic determinants of dementia in the oldest-old

The relative contributions of Alzheimer disease (AD) and vascular lesion burden to the occurrence of cognitive decline are more difficult to define in the oldest-old than they are in younger cohorts. To address this issue, we examined 93 prospectively documented autopsy cases from 90 to 103 years with various degrees of AD lesions, lacunes, and microvascular pathology. Cognitive assessment was performed prospectively using the Clinical Dementia Rating scale. Neuropathologic evaluation included the Braak neurofibrillary tangle (NFT) and β-amyloid (Aβ) protein deposition staging and bilateral semiquantitative assessment of vascular lesions. Statistics included regression models and receiver operating characteristic analyses. Braak NFTs, Aβ deposition, and cortical microinfarcts (CMIs) predicted 30% of Clinical Dementia Rating variability and 49% of the presence of dementia. Braak NFT and CMI thresholds yielded 0.82 sensitivity, 0.91 specificity, and 0.84 correct classification rates for dementia. Using these threshold values, we could distinguish 3 groups of demented cases and propose criteria for neuropathologic definition of mixed dementia, pure vascular dementia, and AD in very old age. Braak NFT staging and severity of CMI allow for defining most of demented cases in the oldest-old. Most importantly, single cutoff scores for these variables that could be used in the future to formulate neuropathologic criteria for mixed dementia in this age group were identified.     

Arithmetic skills in patients with unilateral cerebral lesions

In this paper we describe the construction of a Graded Difficulty Arithmetic test (GDA) consisting of 12 additions and 12 subtractions which are orally presented. The test was administered to a control group of 100 volunteer subjects with extra-cerebral neurological disorders and to two experimental groups of patients with unilateral cerebral lesions of the left and right hemisphere. In the control group performance on the GDA was found to correlate highly with other measures of verbal intelligence, namely the National Adult Reading Test, the WAIS Arithmetic subtest and the WAIS Digit Span subtest. Between group analysis showed a significant groups effect on the GDA, the left hemisphere lesion group showing greater impairment compared to the right hemisphere lesion group and the controls. Using "cut-off" scores the left hemisphere lesion group's performance was shown to be significantly worse than that of the right hemisphere lesion group, who in turn were not significantly worse than the control group.     

SPECT Perfusion Imaging in the Diagnosis of Dementia

Single-photon emission computed tomography (SPECT) imaging has provided the practicing clinician with a method of studying brain function in patients with dementia. A large and growing number of papers report the experiences of a number of laboratories in the use of this technique in the evaluation of demented patients. Studies from several laboratories comparing patients with Alzheimer's disease to control subjects report sensitivity and specificity of SPECT perfusion imaging to be in the 80% vicinity. In addit1on, a number of studies suggest that the dementias that show the greatest similarities in perfusion patterns to Alzheimer's disease are multi-Infarct dementia and dementia associated with ParkinSon's d1sease. Although considerable data exist to guide the physician, a rigorous scientific approach to studying patients in a prospective, unselected clinical sample, with autopsy confirmation of the diagnosis, is needed to define clearly the utility of the technique in diagnosing dementias.