Chinese Version of the Baylor Profound Mental Status Examination: A Brief Staging Measure for Patients with Severe Alzheimer's Disease.

BACKGROUND: A specialized instrument for assessing the cognition of patients with severe Alzheimer's disease (AD) is needed in China. OBJECTIVES: To validate the Chinese version of the Baylor Profound Mental Status Examination (BPMSE-Ch). DESIGN: The BPMSE is a simplified scale which has proved to be a reliable and valid tool for evaluating patients with moderate to severe AD, it is worthwhile to extend the use of it to Chinese patients with AD. SETTING: Patients were assessed from the Memory Clinic Outpatient. PARTICIPANTS: All participants were diagnosed as having probable AD by assessment. MEASUREMENTS: The BPMSE was translated into Chinese and back translated. The BPMSE-Ch was administered to 102 AD patients with a Mini-Mental State Examination (MMSE) score below 17. We assessed the internal consistency, reliability, and construct validity between the BPMSE-Ch and MMSE, Severe Impairment Battery (SIB), Global Deterioration Scale (GDS-1), Geriatric Depression Scale(GDS-2), Instrumental Activities of Daily Living (IADL), Physical Self-Maintenance Scale (PSMS), Neuropsychiatric Inventory (NPI) and Clinical Dementia Rating (CDR). RESULTS: The BPMSE-Ch showed good internal consistency (α = 0.87); inter-rater and test-retest reliability were both excellent, ranging from 0.91 to 0.99. The construct validity of the measure was also supported by significant correlations with MMSE, SIB. Moreover, as expected, the BMPSE-Ch had a lower floor effect than the MMSE, but a ceiling effect existed for patients with MMSE scores above 11. CONCLUSIONS: The BPMSE-Ch is a reliable and valid tool for evaluating cognitive function in Chinese patients with severe AD.

Frontal-lobe mediated behavioral dysfunction in amyotrophic lateral sclerosis.

BACKGROUND: Cognitive impairment secondary to frontal lobe atrophy exists in 40-60% of Amyotrophic Lateral Sclerosis (ALS) cases. We aimed to determine the prevalence of frontal-lobe mediated behavioral impairment in (ALS) and to ascertain its relationship to cognitive impairment. METHODS: Two-hundred and twenty five patients diagnosed with sporadic ALS were evaluated for behavioral dysfunction using the Frontal Systems Behavior Scale (FrSBe), a validated measure used to examine frontal-lobe mediated behaviors, specifically apathy, executive dysfunction and disinhibition; a total behavior score is also provided. Additionally, a subset of patients also underwent a comprehensive neuropsychological evaluation. RESULTS: Changes in the total FrSBe scores were observed in 24.4% of the patients and 39.6% of the patients had impairment in at least one behavioral domain with symptoms of Apathy being the most common (31.1%). Cognitively impaired ALS patients had worse total (P = 0.05) and apathy scores (P < 0.01); however, behavioral dysfunction was also present in 16% of the cognitively intact patients. Half of the behaviorally intact patients exhibited cognitive impairment. Significant correlations were observed for performance on certain neuropsychological tests (Animal fluency, Block Design, Logical Memory I and Verbal Series Attention Test) and severity of behavioral dysfunction on certain FrSBe sub scores. CONCLUSIONS: Frontal-lobe mediated behavioral dysfunction appears to be common in ALS. Cognitively impaired ALS patients had greater behavioral dysfunction. Recognition of behavioral and cognitive dysfunction may assist health-care providers and care-givers recognize changes in decision-making capacity and treatment compliance of patients with ALS.

Influence of premorbid IQ and education on progression of Alzheimer's disease.

BACKGROUND: Lower education is associated with a higher risk of developing Alzheimer's disease (AD). Years of education and measures of general intellectual function (IQ) are highly correlated. It is important to determine whether there is a relationship between education and AD outcomes that is independent of IQ. OBJECTIVE: To test the hypothesis that premorbid IQ is a stronger predictor of cognitive decline, global progression, and overall survival, than education in patients with AD. METHODS: The study included 478 probable AD patients (322 women and 156 men, mean age 74.5 years) followed in a large AD referral center for a mean of 3.2 years. Eligible participants had a baseline estimate of premorbid IQ using the American version of the Nelson Adult Reading Test (AMNART) and at least one follow-up visit with complete neuropsychological assessment. We used random effects linear regression analysis, and Cox proportional hazards analysis to determine whether or not education and/or premorbid IQ were independently associated with cognitive decline, global progression of AD, and survival. RESULTS: When the baseline AMNART score was included in regression models along with education and other demographic variables, AMNART score, but not education, was associated with a higher baseline score and slower rate of decline in MMSE and ADAS-Cog scores, and the Clinical Dementia Rating sum of boxes score. Neither higher premorbid IQ nor higher education was associated with longer survival. CONCLUSIONS: We conclude that a baseline AMNART score is a better predictor of cognitive change in AD than education, but neither variable is associated with survival after diagnosis.

Cognitive intervention in Alzheimer disease: a randomized placebo-controlled study.

The efficacy of a cognitive intervention consisting of training in face-name associations, spaced retrieval, and cognitive stimulation was tested in a sample of 37 patients (16 men, 21 women) with probable Alzheimer disease (AD). Patients with AD were randomly assigned to receive either the cognitive intervention or a mock (placebo) intervention for 5 weeks. The placebo group then crossed over to receive the intervention. During the intervention, AD patients showed significant improvement in recall of personal information, face-name recall, and performance on the Verbal Series Attention Test. Improvement did not generalize to additional neuropsychologic measures of dementia severity, verbal memory, visual memory, word generation, or motor speed, or to caregiver-assessed patient quality of life. Results suggest that although face-name training, spaced retrieval, and cognitive stimulation may produce small gains in learning personal information and on a measure of attention, improvement does not generalize to overall neuropsychologic functioning or patient quality of life.

Card sorting performance and ADHD symptomatology in children and adolescents with tourette syndrome.

Children and adolescents with Tourette Syndrome (TS) do not have a characteristic neuropsychological profile. Performance on complex cognitive tasks, particularly those associated with executive functioning (EF), has been variable and sometimes contradictory. The high rate of comorbidity of TS with disorders, especially Attention Deficit Hyperactivity Disorder (ADHD), may account for such variability. A group of 57 individuals with TS, aged 8 - 16, was examined on a component of executive functioning in relation to comorbid symptomatology of ADHD. Each participant was evaluated using two EF measures, the Wisconsin Card Sorting Test (WCST) and the California Card Sorting Test (CCST). Using factor analytic procedures for purposes of data reduction, WCST and CCST measures loaded on different factors. Individuals with TS who had a high rate of ADHD symptomatology did not differ from those with a lower rate of ADHD symptomatology on any measure of card sorting performance.

The influence of handedness on the clinical presentation and neuropsychology of Alzheimer disease.

BACKGROUND: Research on the influence of handedness on the clinical presentation and neuropsychology of Alzheimer disease (AD) is scarce. OBJECTIVE: To compare clinical presentation and neuropsychological test performance of right- and left-handed patients with AD. DESIGN: We hypothesized that left-handedness would be associated with younger onset, more rapid progression, and possibly cognitive hemispheric asymmetry. After determining handedness with the Edinburgh Inventory for Handedness for 922 patients with AD, 18 left-handed patients were compared with 18 right-handed patients matched individually on Mini-Mental State Examination scores, education, and age. We compared clinical characteristics (eg, age of onset), estimated rate of initial cognitive decline, language and visuospatial test performances, and patterns of cognitive and motor asymmetries for the 2 groups. SETTING: Alzheimer's Disease Research Center at Baylor College of Medicine, Houston, Tex. MAIN OUTCOME MEASURES: Results of the Wechsler Adult Intelligence Scale-Revised verbal and performance IQ tests, the Western Aphasia Battery sequential commands subtest, the Boston Naming Test, the Halstead-Reitan Finger-Tapping Test, and the calculated Rate of Initial Progression. RESULTS: We found that left-handed patients had younger ages of onset but unexpectedly lower estimated rates of initial cognitive decline, and their results on language tests did not differ from those of right-handed patients. Regarding asymmetry, left-handed patients were more likely than right-handers to obtain lower verbal IQ than performance IQ scores and to exhibit faster finger-tapping speeds with their nondominant hand, but group differences did not attain statistical significance. There were disproportionately few left-handed patients with AD compared with population norms. CONCLUSIONS: Left-handed patients with AD do not differ from right-handed patients in the severity or pattern of neuropsychological deficits. Left-handedness or some factor associated with it may contribute to the early appearance of cognitive deficits during the development of Alzheimer disease, but may temper the subsequent rate of progression of deficits.

Baylor profound mental status examination: a brief staging measure for profoundly demented Alzheimer disease patients.

There is no brief patient-derived rating scale for staging and following profoundly demented Alzheimer disease (AD) patients. We developed the Baylor Profound Mental Status Examination (BPMSE) modeled after the Mini-Mental State Examination (MMSE) to meet this need. The BPMSE consists of 25 cognitive questions that assess orientation, language, attention, and motor functioning; 10 examiner ratings of presence or absence of problem behaviors; and 2 qualitative observations of language and social interaction. Two hundred eight probable or possible AD patients (MMSE scores of 20 or less) received the BPMSE. Some were also rated on the clinical dementia rating (CDR) and Lawton activities of daily living (ADL). A ceiling effect occurred at MMSE scores above 11. BPMSE cognitive scores and MMSE scores correlated significantly (r = 0.76, p < 0.0001). Subareas of the BPMSE also intercorrelated significantly. The BPMSE correlated with both CDR and ADL scores (p < 0.001). Internal consistency, interrater reliability, and test-retest stability were excellent. There was no floor effect, and BPMSE scores continued to decline after the MMSE reached 0. The BPMSE is a quick and easy staging tool with excellent validity and test-retest stability that measures cognitive function successfully in patients with MMSE scores below 12. The scale is sensitive to longitudinal change and continues to assess decline when performance has reached the lowest levels on conventional measures.

Prevalence and correlates of category versus letter fluency discrepancies in Alzheimer's disease.

Alzheimer's disease (AD) patients typically exhibit greater category than letter fluency impairment, but the prevalence of this discrepancy has not been studied in a large group of patients. In the present study of 217 AD patients, we found that 145 subjects (66.8 %) demonstrated the expected pattern of better letter fluency (FAS test, i.e, generating as many words as possible in 1 minute beginning with "F", "A," and "S") than category fluency (animal generation). However, an unexpectedly large group of patients exhibited the opposite pattern of category fluency equal to or better than letter fluency (n = 72, 33.2%). Paired t-tests between groups revealed no significant differences on demographic variables such as age, gender, education level, or duration of illness. However, the smaller group exhibiting the unexpected fluency pattern exhibited significantly higher Mini-Mental State Examination (MMSE; Folstein, Folstein, & McHugh, 1975) scores compared to the larger group. Comparisons were made between group performance on other neuropsychological tasks, using MMSE performance as a covariate, but no significant differences were found. Therefore, the present results do not offer strong support for the neuropsychological (and possibly neuroanatomical) distinctiveness of the two fluency subgroups.

Cognitive consequences of subcortical magnetic resonance imaging changes in Alzheimer's disease: comparison to small vessel ischemic vascular dementia.

OBJECTIVE: The objective of this study was to compare psychometric profiles of Alzheimer's disease (AD) patients with subcortical magnetic resonance imaging (MRI) signal abnormalities to those of AD patients without such MRI findings (normal subcortical MRI) and to those of patients with ischemic vascular dementia (IVD) associated with small and primarily subcortical ischemic changes. BACKGROUND: The cognitive significance of MRI white matter and other subcortical abnormalities in AD is unknown. Prior studies comparing AD patients with white matter changes on MRI have not included IVD patients with comparable MRI findings. If white matter/subcortical changes in AD reflect vascular abnormalities, they might be associated with cognitive profiles similar to those seen in subcortical IVD. METHOD: We studied 15 AD patients with normal subcortical MRIs, 22 AD patients with subcortical MRI hyperintensities, and 18 IVD (NINCDS-ADRDA and NINDS-AIREN criteria) at the Alzheimer's Disease Research Center of the Baylor College of Medicine. IVD patients had predominantly small and subcortical signal abnormalities, and none had large cortical infarcts. AD patients had only nonspecific subcortical signal abnormalities with or without atrophy (atrophy was not analyzed). We compared the AD group with abnormal MRIs to the AD group with normal subcortical MRIs and the AD group to the IVD group using ANCOVA planned comparisons (dementia severity and education covaried). RESULTS: AD patients with abnormal MRIs did not differ significantly from AD patients with normal subcortical MRIs on any of the neuropsychological measures. AD patients exhibited significantly better attention/concentration, visuospatial/visuoconstructional performance, letter fluency, motor programming, and simple motor speed than IVD patients as well as significantly worse delayed verbal recognition memory. Because MRI changes were generally more extensive in IVD, a subset of AD patients with abnormal subcortical MRIs was compared to a subset of IVD patients matched for degree of MRI signal abnormalities. These subsets of AD and IVD patients still showed distinctive neuropsychological profiles. CONCLUSIONS: AD patients with or without MRI subcortical signal abnormalities have similar neuropsychological profiles, and they differ from IVD patients with comparable MRI changes. Although MRI signal abnormalities in AD patients who have no history or examination findings of cerebrovascular disease overlap with those seen in IVD patients, they do not seem to have the same cognitive significance. Periventricular hyperintensities (PVHs) and deep signal hyperintensities, especially those of a mild to moderate degree, may reflect a different pathophysiologic process in AD than in IVD and do not necessarily have cognitive consequences in AD patients.

Neuropsychological asymmetry in Alzheimer's disease: verbal versus visuoconstructional deficits across stages of dementia.

The incidence of clinically apparent asymmetric profiles of neuropsychological deficits in Alzheimer's disease (AD) patients similar to those reported in the PET literature is currently unclear. This study investigated lateral neuropsychological asymmetry using principal component factor analysis in a sample of 153 patients diagnosed with probable AD. Using factor scores, patients were classified into groups exhibiting asymmetric or symmetric profiles of neuropsychological deficits. In the analysis of lateral asymmetry, 27.5% of patients were classified as asymmetric (10% verbally and 17% visuospatially). Consistent with reports of continued asymmetry beyond the mild dementia stage, asymmetry was exhibited in the mild, moderate, and severely demented groups. These findings of neuropsychological asymmetry across stages of dementia are consistent with the picture of significant neuropsychological heterogeneity in AD that has been emerging in the decade.

Prevalence and correlates of neuropsychological deficits in amyotrophic lateral sclerosis.

OBJECTIVE: To determine the prevalence and correlates of neuropsychological impairment in a large cohort (n = 146) of patients with typical, sporadic (non-familial) amyotrophic lateral sclerosis. METHODS: A battery of neuropsychological tests was administered to patients with amyotrophic lateral sclerosis who were attending a monthly outpatient clinic or who were in hospital undergoing diagnostic tests. RESULTS: Comparing individual patient's scores with relevant normative data, 35.6% of the patients displayed evidence of clinically significant impairment, performing at or below the 5th percentile on at least two of the eight neuropsychological measures. Deficits were most common in the areas of problem solving, attention/mental control, continuous visual recognition memory, word generation, and verbal free recall. Impairment was most prevalent in patients with dysarthria (48.5%), but 27.4% of non-dysarthric patients were also impaired. Impaired patients had more severe or widespread symptoms of amyotrophic lateral sclerosis than non-impaired patients, and had fewer years of education. CONCLUSION: Neither the conventional wisdom that cognition is intact in nearly all patients with amyotrophic lateral sclerosis, nor more recent suggestions that cognition is often at least mildly impaired seems to be correct. A minority of patients with amyotrophic lateral sclerosis displayed evidence of significant impairment. Dysarthria, low education, and greater severity of motor symptoms were risk factors for impairment.

Neuropsychological functioning in cortical-basal ganglionic degeneration: Differentiation from Alzheimer's disease.

Patients with cortical-basal ganglionic degeneration (CBGD) display prominent rigidity and apraxia, exhibit an asymmetric onset of symptoms, and may show other symptoms including abnormal saccadic eye movements, the "alien limb" sign, limb dystonia, and myoclonus. We compared the neuropsychological test performances of 21 CBGD patients with 21 Alzheimer's disease (AD) patients displaying no extrapyramidal symptoms and with 12 ADA patients who did show such symptoms. Groups were matched for age, educational level, and overall severity of dementia. Since the cognitive deficit was mild in most CBGD patients, most AD patients included in this study were also only mildly demented. The CBGD patients performed significantly better than the AD patients on test of immediate and delayed recall of verbal material; whereas the AD patients (with or without extrapyramidal symptoms) performed better on tests of praxis, finger tapping speed, and motor programming. The CBGD and AD groups all displayed prominent deficits on tests of sustained attention/mental control and verbal fluency, and exhibited mild deficits on confrontation naming. The CBGD patients endorsed significantly more depressive symptoms on the Geriatric Depression Scale.

Hemispheric asymmetry in Alzheimer's disease is apparent in motor functioning.

We examined the prevalence and correlates of anomalous motor speed asymmetry in 104 right-handed patients with a diagnosis of probable Alzheimer's disease (AD). On the Halstead-Reitan Finger Tapping Test, over 60% of the AD patients exhibited notable departures from expected finger tapping asymmetry; 26% displayed an exaggerated right hand tapping advantage (ASYM RIGHT patients) and 37% showed a reversal of expected asymmetry (left hand speed equal to or greater than right hand speed, ASYM LEFT patients). ASYM-RIGHT patients had significantly more years of education than the ASYM-LEFT patients, suggesting that these patients had higher premorbid verbal abilities and possibly had a left hemisphere that was relatively resilient to the effects of AD. Motor speed asymmetry was correlated significantly with cognitive asymmetries (e.g., Verbal IQ vs. Performance IQ, naming vs. figure copying). Finally, ASYM-RIGHT patients exhibited a lower incidence of hallucinations and apathy than ASYM-LEFT patients or patients with normal motor asymmetry.

A quantitative review of the diagnostic utility of the WAIS-R Fuld profile.

The prevalence of Fuld's WAIS "cholinergic deficit" profile has been examined in 18 studies, in which the profiles of over 3700 subjects have been evaluated. When these data were pooled, it was found that the profile's sensitivity to dementia of the Alzheimer type (DAT) was only 24.1%; 77 of 319 DAT patients evaluated across seven studies displayed the Fuld profile. The profile's specificity was considerably better than its sensitivity; 93.3% (2256/2418) of normals had "negative" profiles, as did 88.5% (1058/1198) of non-DAT patients (e.g., patients with multi-infarct dementia). With its poor sensitivity, the profile's diagnostic utility under different base rate conditions was unimpressive. Memory indices possess far greater sensitivity to DAT, and have been shown to reliably differentiate DAT from many other causes of cognitive dysfunction. It was recommended that future diagnostic studies of DAT should evaluate whether additional neuropsychological measures, such as WAIS-R indices, enhance the diagnostic accuracy achieved by memory measures.

Directed and divided attention in Alzheimer's disease: impairment in shifting of attention to global and local stimuli.

This study investigated the relative performance of Alzheimer's disease (AD) patients and normal controls on directed and divided attention reaction time (RT) tasks that involved the use of global-local stimuli (e.g., a large '1' made from small '2s'). Relative to normals, AD patients displayed disproportionately greater impairment on the divided attention task compared to the directed attention task. On the divided attention task, when the target remained at the same global-local level across consecutive trials, the AD patients displayed a greater facilitation effect than did the controls when responding to the second stimulus. However, when the target changed levels across consecutive trials (i.e., from the global to the local, or vice versa) the AD patients' RTs to the second stimulus were disproportionately slower than were the controls' RTs. These results demonstrated that AD patients are impaired in disengaging and shifting attention across levels of perceptual organization within the same stimulus.

The subcortical dysfunction hypothesis of memory deficits in depression: neuropsychological validation in a subgroup of patients.

The subcortical dysfunction hypothesis of verbal learning and memory deficits in depression was evaluated by comparing the memory test profiles of unipolar depressives (n = 40) and bipolar depressives (n = 9) with those of patients with a prototypical subcortical dementia (Huntington's disease, HD), patients with a prototypical cortical dementia (Alzheimer's disease, AD), and normal controls. In a discriminant function analysis that well-differentiated the HD, AD, and normal subjects, it was found that 28.6% of the depressed patients were classified as HD patients (DEP-HD subjects), 49.0% were classified as normals (DEP-N subjects), none were classified as AD patients, and 22.4% were not well-classified. The DEP-HD group closely resembled the HD group on additional indices of verbal learning and memory, and differed from the DEP-N group, which strongly resembled the normal control group. DEP-N patients also performed significantly better than DEP-HD patients on a number of other neuropsychological tests (e.g., WAIS-R Digit Symbol, category fluency, Trail Making Test Part B). The findings provide support for the subcortical dysfunction hypothesis, but only for a subgroup of depressed patients. Implications for differentiating depressive "pseudodementia" from AD are discussed.

Spatial cognition in Alzheimer's disease: subtypes of global-local impairment.

This study investigated whether subgroups of AD patients exhibit different patterns of impairment in analyzing global (configural) and local (detail) features of complex visual stimuli. A High Spatial AD subgroup (i.e., patients with better block constructions than naming) and a High Verbal AD subgroup (i.e., patients with better naming than block constructions) were impaired in analyzing both global and local forms. As predicted, however, the High Spatial AD patients exhibited greater impairment in analyzing the local forms than the High Verbal AD patients and normal controls. In contrast, the High Verbal AD patients exhibited greater impairment in analyzing the global forms than the High Spatial AD patients and normal controls. There was a striking separation of the subgroups: Using the local-global difference score, the hit rate for classifying these patients into the two subgroups was 91%. Robust correlations were found between the AD patients' ability to construct global and local forms and their scores on traditional visuospatial and verbal tests, respectively. The findings suggest that it may be misleading to subdivide AD patients using a verbal/spatial dichotomy, because even those AD patients who appear to have relative strengths on traditional visuospatial tests are likely to exhibit a primary impairment in analyzing local features of complex visual stimuli. The results underscore the importance of a process (qualitative) approach to neuropsychological assessment for a more valid understanding of the behavioral subtypes of Alzheimer's disease.

Are all subcortical dementias alike? Verbal learning and memory in Parkinson's and Huntington's disease patients.

The utility of the concept of 'subcortical dementia' was investigated by comparing the verbal learning and memory abilities of Parkinson's disease (PD) patients with those of Huntington's disease (HD) patients. Many similarities between the PD and HD groups emerged, including impaired immediate memory spans, inconsistency of recall across learning trials, deficient use of a semantic clustering learning strategy, elevated intrusion rates on delayed recall, impaired recognition memory performance, normal retention of information over delay periods, normal vulnerability to proactive or retroactive interference, and normal types of intrusion errors. The HD subjects, however, displayed inferior free recall, deficient improvement across learning trials, abnormal serial position recall effects, higher perseveration rates, and supranormal improvement on recognition testing compared with free recall. Implications of these results for characterizing memory deficits associated with subcortical system dysfunction are discussed.

The mediating effect of age on the relationship between Child Behavior Checklist hyperactivity scores and neuropsychological test performance.

The relationship between hyperactivity and neuropsychological test performance at different age levels was examined. It was found that for young children (6 to 8 years of age, n = 90), there was no significant association between hyperactivity/attentional problems (as measured by the Hyperactivity scale of the Child Behavior Checklist) and performance on neuropsychological tasks thought to contain an attentional component (WISC-R Coding, Arithmetic, and Digit Span; WRAT Arithmetic; and the Benton Visual Retention Test). However, for older children (9 to 12 years of age, n = 92), there were significant and large negative correlations between CBC Hyperactivity scores and Coding, WRAT Arithmetic, and Benton VRT scores. Multiple regression analyses supported the above results (for Coding and WRAT Arithmetic), indicating that hyperactivity/inattention has a particularly deleterious effect on test performance (relative to same-age peers) as age increases.

Handedness and dementia.

Some researchers have speculated that left-hand dominance is more prevalent among patients suffering from dementia of the Alzheimer's type which began prior to age 65 yr. and that, in those patients, the disease runs a more rapid course. In the present study, seven left-handed dementia patients were matched with seven right-handed dementia patients on the basis of age and years of education and were compared with regard to neuropsychological compromise. While the left-handed group was somewhat more impaired than the right-handed subjects, the difference between the two groups was not statistically significant.