The Behavioural Assessment of the Dysexecutive Syndrome as a Tool to Assess Executive Functions in Schizophrenia

The present investigation examined the validity of the revised Hopkins Verbal Learning Test (HVLT-R). In a principal components analysis with varimax rotation, measures of new learning and delayed recall loaded on a single factor distinguishable from measures related to general cognitive function and visual memory. The HVLT-R also correlated most strongly with other tests of verbal memory and relatively weakly with a test of general intelligence. Group comparisons showed that normal controls performed better than age- and education-matched patients with probable Alzheimer's disease (AD) or vascular dementia (VaD). Discriminant function analyses and Bayesian statistics revealed high classification accuracies for dementia patients versus controls. When scores on the HVLT-R and other neuropsychological tests were subjected to discriminant function analyses, performance on the HVLT-R delayed recognition task was found to be the most useful in discriminating patients with AD from those with VaD. We conclude that the HVLT-R is a valid test of verbal learning and memory that is best suited for use with elderly patients suspected of dementia.     

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.     

The St. George's dementia bed investigation study: cardiovascular,neurological and neuropsychological correlates

The results of the cardiovascular, neurological and neuropsychological examination of a series of patients admitted to the St. George's dementia investigation bed and who later came to postmortem are compared in relation to their pathological diagnosis. Individual clinical signs were not found to differentiate between cases of dementia with vascular versus those with Alzheimer's disease pathology, although multivariate analysis suggested that there was a pattern of signs associated with cerebrovascular disease. A vascularity index was constructed from these signs; it achieved a useful level of discrimination between vascular and nonvascular causes of dementia.     

DIFFERENTIAL PERFORMANCE OF ALZHEIMER'S AND VASCULAR DEMENTIA PATIENTS ON A BRIEF BATTERY OF NEUROPSYCHOLOGICAL TESTS

The purpose of this article was to examine the differences in neuropsychological test performance between groups with Alzheimer's and vascular dementia. Patients included in this study were those diagnosed with Alzheimer's Disease (AD) or Vascular Dementia (VAD) through a series of neuroradiological tests that included at a minimum a CT or MRI scan and a SPECT scan. Of the 113 AD patients, the average age was 80.08 (SD = 5.91) years and average education was 12.85 (SD = 2.88). Of the 109 VAD patients, average age was 78.67 (SD = 5.35) and average education was 13.10 (SD = 2.65). Tests included selected subtests of the WAIS-R, Word Fluency, Rey Figure, Boston Naming Test, Math, Reading, and subtests from the WMS-R. Five tests showed significant differences in favor of the VAD group: Information, Similarities, Picture Completion, WRAT Mathematics, and the Boston Naming Test. Both groups did well on Reading, while both did poorly on the Rey and Word Fluency. Although both groups did poorly on memory measures, the VAD patients showed better performance. Overall, the two groups did not differ significantly on the more complex tests, but did differ on more basic tests and all the memory tests. This pattern of similar score on complex tests and different scores on basic tests demonstrates the theory that both types of dementia affected higher, more complex skills. Differences between the groups were only apparent when basic skills were compared and were not reflected in more complex and neuropsychologically “sensitive” tests.     

Cognitive Decline in Patients with Familial Alzheimer's Disease Associated with E280a Presenilin-1 Mutation: A Longitudinal Study

Few longitudinal studies have been carried out to investigate the cognitive decline in early onset of familial Alzheimer's disease (FAD). In this study 12 patients with FAD (M age = 49.61 years, SD = 4.99), 10 patients with sporadic Alzheimer's disease (SAD) (M age = 71.40, SD =10.00), and 15 matched normal controls (M age = 45.01, SD = 7.24) were selected. A comprehensive neuropsychological battery was administered three times over a period of 18 months. Individuals designated as FAD met the criteria for dementia and were positive for the E280A presenilin 1 mutation. Participants with SAD met the criteria for dementia and were negative for the E280A presenilin 1 mutation. Normal control participants were the FAD patients' relatives, who were negative for the mutation. Two groups of neuropsychological instruments were administered: (1) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological test battery, and (2) additional neuropsychological tests of ion and constructional abilities. Patients with FAD were significantly impaired on all measures at the first examination except for reading of words. While the performance of the normal controls remained unchanged over the 18 months for most neuropsychological tests, the patients with FAD displayed a decline in verbal memory, language, constructional and abstraction tests. The greatest decline was observed on the Mini-Mental State Exam scores. Patients with SAD demonstrated a similar pattern of cognitive decline, but the decline was faster in FAD than in SAD participants.     

Idiopathic REM sleep behavior disorder in the transition to degenerative disease

Idiopathic REM sleep behavior disorder (RBD) predicts Parkinson's disease (PD) and dementia. However, the nature of the disease that emerges from RBD has not been fully characterized. Since 2004, we have been conducting a prospective study of idiopathic RBD patients, providing an opportunity to directly observe patients as they transitioned to a defined neurodegenerative syndrome. Patients with idiopathic RBD underwent an extensive annual evaluation of motor function, olfaction, color vision, autonomic function, cognition and psychiatric symptoms. Neurodegenerative disease was defined according to standard criteria. We compared these measures in patients who had developed PD to those with dementia, all within the first year of developing disease. Of 67 patients, 6 developed PD and eleven developed dementia. Except for cognitive functioning, all tests of olfaction, color vision, autonomic function, depression, and quantitative measures of motor speed were similar in patients with PD and dementia. Of dementia patients, seven met criteria for probable Lewy body dementia (LBD) and four for Alzheimer's disease (or, possible LBD). In all probable LBD cases, the diagnosis was made because of parkinsonism, with no patient experiencing hallucinations or fluctuations. Patients with “Alzheimer's disease” seemed to have LBD, as they demonstrated typical LBD cognitive profiles on neuropsychological testing and were indistinguishable from LBD patients in ancillary measures. Therefore, among RBD patients with new‐onset LBD, hallucinations or fluctuations are absent, suggesting that RBD is a reliable early sign of LBD. The indistinguishability of dementia and PD in all ancillary measures suggests a single unitary “RBD‐then‐neurodegeneration” process, the clinical presentation of which depends upon selective neuronal vulnerability. © 2009 Movement Disorder Society     

Memory failure in binswanger's disease and alzheimer's disease

The heterogeneity within vascular dementia has made neuropsychological research in this area difficult to interpret. We studied a subtype of vascular dementia, Binswanger's disease (BD), diagnosed according to recently specified clinical and radiological criteria. Measures of episodic and semantic memory were administered to BD patients, patients with Alzheimer's disease (AD) comparable to the BD sample in dementia severity, age, and education, and normal controls. Episodic memory was more defective in AD than in BD; these patient groups were equally impaired on measures of semantic memory. The findings suggest that assessment of episodic memory may be useful in differentiating AD from BD.     

Mental calculation in mild Alzheimer's disease: A pilot study

The purpose of this study was to determine whether dyscalculia is present in the early stages of Alzheimer's disease (AD) and if it is associated with a characteristic neuropsychological pattern. We examined 28 probable AD patients with scores of 18 or greater on the Mini-Mental State Examination (MMS) and with an educational level of 12 or more years. The ability to perform mental calculation was assessed by two tests: the Stamp Test (ST) and the Serial Seven Subtraction Test (SSST). The other cognitive domains were evaluated with an extensive neuropsychological battery. We found significant differences in performances on the calculation tests between patients and controls. The ST was correlated with attention and visuospatial skills, whereas the SSST was correlated with both receptive language and the MMS; both test were similarly correlated with productive language. This study suggests that impairment in mental calculation can be an early sign of AD. The ST seems to represent a more complex task dependent on attentional resources, whereas the SSST would be a purer measure of anarithmetia.     

Neuropsychological Characteristics of the Dementia Syndrome of Depression: Onset,Resolution, and Three-Year Follow-Up

In this prospective double-blind study 13 hospitalized older adults with dementia syndrome of depression (DSD) were compared to 14 with Alzheimer's dementia with a concurrent major depression on a battery of neuropsychological tests. On admission to hospital (onset), patients with DSD differed from those with Alzheimer's dementia and depression only in that the former had stronger short-term verbal memory. Resolution of depression in patients with DSD resulted in a return to normal levels in most measures of verbal functioning, but nonverbal abilities remained impaired. Three years later those with DSD continued to cognitively outperform those with Alzheimer's dementia, indicating that treating depression in DSD appears to “buy back” up to 3 years of above-baseline cognitive functioning.     

Quantitative Evidence for Neuroanatomic and Neuropsychological Markers in Dementia of the Alzheimer's Type

Meta-analytic methods were used to determine the sensitivity of neuropsychological, structural, and physiological measures to temporal-hippocampal system function in dementia of the Alzheimer's type. Effect sizes are reported for the California Verbal Learning Test, the Wechsler Memory Scale-Revised, structural (i.e., magnetic resonance imaging [MRI]), and functional (i.e., positron emission tomography [PET], single photon emission computed tomography [SPECT]) neuroimaging methods. Overall, effect sizes from MRI studies are larger than those obtained from SPECT and PET, respectively, but not as large as those obtained from the neuropsychological measures. On the basis of this finding, the neuropsychological and gross pathologic similarities between Alzheimer's disease, other dementing conditions, and mixed dementias, warrants the coupling of neuropsychological evaluation for its sensitivity with neuroimaging visualization for its specificity in improving diagnostic and differential accuracy.     

Cognitive test scores in community-based older adults with and without dementia

In an epidemiological survey of a rural, largely blue-collar, community, 1,363 randomly selected adults, aged 65 years, were administered a cognitive screening battery (including in part the CERAD neuropsychological tests): Mini-Mental State Examination; Word List Learning, Recall, and Recognition; Story, Immediate and Delayed Recall; Boston Naming Test; Verbal Fluency; Temporal Orientation; Constructional Praxis; Draw a Clock; and Trailmaking. Cognitively impaired subjects and cognitively intact controls underwent independent standardized diagnostic assessments and were rated on Clinical Dementia Rating (CDR) scale. Overall, subjects at higher CDR levels (more severe dementia) had worse scores on all tests; showing that standard neuropsychological tests are valid for characterizing the cognitive impairments seen in dementia, even in community settings. However, non-demented scores on the CERAD tests in this community-based sample were lower than reported from CERAD's pooled healthy controls from Alzheimer's Disease Centers (ADCs) nationwide. Thus, 'normal' scores from specialty dementia clinics, where there may be a selection bias, may differ from normative scores from rural and/or less-educated populations. Patients from such populations may be functionally intact despite low test scores. Community-based studies are required to complement specialty clinic-based studies of dementia and cognitive functioning.     

Do depressive symptoms in memory-impaired elders predict probable Alzheimer's disease?

Our purpose was to determine whether performance on the Geriatric Depression Scale (GDS) predicted the development of probable Alzheimer's disease (AD) in memory-impaired non-demented participants. Participants were followed for two years, after which they underwent a diagnostic assessment: 27 developed probable AD, 98 remained cognitively impaired but not demented, and 18 developed other neurological conditions.The GDS did not contribute significantly to the prediction of probable AD, it was not related to scores on selected neuropsychological tests, but it was related to complaints of memory on a self-report scale. These findings highlight the need to consider patient characteristics and the method of assessing depression when examining the role of depression in dementia.     

Delirium in dementia

Delirium is a common mental disorder in the elderly with old age being a major risk factor for delirium. Another major risk factor is dementia. The aim of the present study was to identify differences in occurrence of episodes of delirium between the most common dementia diagnoses and the possible importance of age, gender, severity and duration of dementia for the development of delirium. Included in the study were 175 consecutive patients with probable Alzheimer's disease, vascular dementia (VAD) or frontotemporal dementia (FTD) who were admitted to a neuropsychiatric diagnostic unit. There were no significant differences in sex distribution or duration of dementia between the delirious and non delirious patients. The rate of delirium was higher in late onset Alzheimer's disease (LAD) than in early onset Alzheimer's disease (EAD) and FTD. It was also higher in VAD than in EAD. The differences in occurrence of delirium between the diagnostic groups in this sample could not be explained by differences in age. It seems that delirium is more common in brain disorders such as LAD and VAD in which the damage to the brain is more widespread. In the two brain disorders that are predominantly cortical, EAD and FTD, the occurrence of delirium was comparatively low. © 1998 John Wiley & Sons, Ltd.     

Emotional processing in bipolar disorder: Behavioural and neuroimaging findings

Mild cognitive impairment (MCI) was previously defined as a transitional state that can precede dementia, but the condition and the rates of conversion remain controversial. MCI is now the focus of natural history studies, along with Alzheimer's disease (AD) prevention. The objective of our review will be to consider the question of whether MCI is a well enough established entity that it can be a diagnosis in medical practice and a valid target of Alzheimer's prevention therapy. MCI was originally defined by Petersen et al. () as progressive memory loss, prodrome of Alzheimer's disease. More recently MCI has been expanded to other cognitive domains with other potential causes like normal aging, fronto-temporal dementia, and vascular dementia. Despite many consensus conferences, experts cannot agree on critical aspects of the MCI, particularly with respect to its clinical utility. Based on neuropsychological studies, a hippocampal memory profile has been proposed for MCI as prodromal AD. Further research is needed to advance these criteria. We have no doubt, however, that in the future, the diagnosis of AD as disease (not only a dementia syndrome) will be made in the early pre-dementia stage and will be drawn from a combination of neuropsychological, neuro-imaging and CSF biomarkers.     

Characterization of a temporoparietal junction subtype of Alzheimer's disease

Alzheimer's disease (AD) subtypes have been described according to genetics, neuropsychology, neuropathology, and neuroimaging. Thirty‐one patients with clinically probable AD were selected based on perisylvian metabolic decrease on FDG‐PET. They were compared to 25 patients with a typical pattern of decreased posterior metabolism. Tree‐based machine learning was used on those 56 images to create a classifier that was subsequently applied to 207 Alzheimer's Disease Neuroimaging Initiative (ADNI) patients with AD. Machine learning was also used to discriminate between the two ADNI groups based on neuropsychological scores. Compared to AD patients with a typical precuneus metabolic decrease, the new subtype showed stronger hypometabolism in the temporoparietal junction. The classifier was able to distinguish the two groups in the ADNI population. Both groups could only be distinguished cognitively by Trail Making Test‐A scores. This study further confirms that there is more than a typical metabolic pattern in probable AD with amnestic presentation.     

Metabolic reduction in the posterior cingulate cortex in very early Alzheimer's disease

This study investigated cerebral glucose metabolism in very early Alzheimer's disease, before a clinical diagnosis of probable Alzheimer's disease is possible, using [¹⁸F]fluorodeoxyglucose positron emission tomography. First, 66 patients with probable Alzheimer's disease with a spectrum of dementia severity (Mini-Mental State Examination score, 0–23) were recruited and studied. Cortical metabolic activity was analyzed topographically using three-dimensional stereotactic surface projections. Regression analysis was performed for each brain pixel to predict metabolic patterns of very early disease. Predictions were tested prospectively in a group of 8 patients who complained only of memory impairment without general cognitive decline (Mini-Mental State Examination score, 25 · 1) at the time of scanning but whose condition later progressed to probable Alzheimer's disease. Both results were compared to cerebral metabolic activity in 22 age-similar normal control subjects. Prediction and analysis of actual patients consistently indicated marked metabolic reduction (21–22%) in the posterior cingulate cortex and cinguloparietal transitional area in patients with very early Alzheimer's disease. Mean metabolic reduction in the posterior cingulate cortex was significantly greater than that in the lateral neocortices or parahippocampal cortex. The result suggests a functional importance for the posterior cingulate cortex in impairment of learning and memory, which is a feature of very early Alzheimer's disease.     

Altered plasma antioxidant status in subjects with Alzheimer's disease and vascular dementia

Objectives. Oxygen-free radicals and lipid hydroperoxides may have an aetiological role in the development of lesions in the central nervous system in patients with Alzheimer's disease and in those with vascular dementia. This study aimed to make a cross-sectional comparison of blood markers of oxidative stress in two groups of patients with these disorders and a control group. Design. Cross-sectional comparative study. Setting. Established memory clinics in Cardiff organized by a University Department of Geriatric Medicine within an acute care NHS Trust. Methods. Following a dietary assessment, postprandial venous blood samples were obtained from the following: 25 subjects with probable Alzheimer's disease (AD) (mean age 74.3; 10 F, 15 M); 17 subjects with probable vascular dementia (VD) (mean age 75.5; 5 F, 12 M); and 41 controls (mean age 73.4; 24 F, 17 M) for measurement of circulating lipid peroxides (LP), total antioxidant capacity (TAC), vitamin C (VitC), vitamin E (VitE) and beta-carotene (BC). Results. Plasma levels of VitC were significantly lower in subjects with vascular dementia compared with controls (VD, 6.5 (4.8, 8.2); controls, 10.0 (8.38, 11.6); VD vs controls, p=0.015), but no significant difference was seen between controls and patients with Alzheimer's disease (AD, mean 8.3 (6.2, 10.4)). VitE levels were significantly lower in subjects with AD compared with controls (31.1 (28.2, 34.0) vs 36.0 (32.8, 39.2), p=0.035). BC levels were similar in subjects with AD and controls, but significantly elevated in those with VD (AD, 0.28 (0.2, 0.34); VD, 0.40, (0.27, 0.53); controls, 0.28 (0.22, 0.34); VD vs controls, p=0.046). There were no significant differences in LP or TAC between the three groups. Conclusions. Subjects with dementia attributed to Alzheimer's disease or to vascular disease have a degree of disturbance in antioxidant balance which may predispose to increased oxidative stress. This may be a potential therapeutic area for antioxidant supplementation. Copyright © 1998 John Wiley & Sons, Ltd.     

Crise suicidaire et maladie d’Alzheimer débutante : intérêt d’une analyse neuropsychologique détaillée

IntroductionThe role of Alzheimer's disease as a risk factor for suicide is unclear. The aim of this study was to understand neuropsychological component of the suicidal crisis in Alzheimer's disease.MethodUsing an extensive neuropsychological battery, different aspects of cognitive inhibition were particularly examined: Access to relevant information (using the Reading with distraction task), suppression of no longer relevant information (Trail Making Test, Rule Shift Cards), and restraint of cognitive resources to relevant information (Stroop test, Hayling Sentence Completion test, Go/No-Go). One female Alzheimer depressed case was assessed before and after a suicide attempt.ResultsTen days after the patient's suicide attempt, dementia was still moderate with a MMSE score at 21/30 but with a worsening of executive functions (FAB at 8/18) in the context of depression and suicide. The Hamilton-Depression Rating Scale was at 24 (maximal score at 52), and the Cornell Scale for Depression was at 21 (maximal score at 38). Suicidal intent was moderate with a score of 9 on the Beck Suicide Intent Scale (maximal score at 25). The patient did not present a delirium, psychotic symptoms, or anosognosia. Her episodic memory was altered as shown by her semantic performance on verbal fluency (naming 12 animals in 120 seconds) and on lexical fluency (naming 8 words beginning with the letter P). Initially preserved, executive function declined during a suicidal crisis in a context of depression in Alzheimer's disease case. Neuropsychological testing confirmed a dysexecutive syndrome (FAS at 8/18), with an impairment in her conceptualization capacity (MCST) and a deficit in cognitive inhibition and its access (reading task in the presence of distractors), deletion (TMT) and restraint (Stroop, Go/No-Go, Hayling) functions. Computed tomography has shown no signs of intracranial expansive process.ConclusionAssessing predictors of suicide and means of completion in patients with dementia may help the development of interventions to reduce risk of suicide among the growing population of individuals with dementia. Because of Alzheimer's-related cognitive inhibition impairment, identification and intervention addressing the complex issues of depression, executive dysfunction and dementia may help clinicians to mitigate the risk of suicide in patients with Alzheimer's disease.     

Cognitive Assessment and Reference Diagnosis System: development of a neuropsychological and clinical examination for clinic and population use

Background: Recent therapeutic advances to delay the progression of dementia have renewed calls to improve the early detection and management of individuals with dementia. A new computerized neuropsychological interview and clinical examination, the Cognitive Assessment and Reference Diagnosis System (CARDS) was developed to incorporate in a single instrument all the information required to make an accurate clinical diagnosis of dementia (its subtype, depression and delirium), to present reference diagnoses following the completion of tests and to detect early dementia. This study aims to verify the validity and reliability of CARDS. Methods: The CARDS was administered to 70 dementia patients (51 Alzheimer's disease, 19 vascular dementia) and 34 healthy (control) subjects. Three aspects of reliability (internal consistency reliability, inter‐rater and test–retest reliability) were tested. Correlations with the Alzheimer's Disease Assessment Scale, Korean version (ADAS‐K), the Cambridge Cognitive Examination, Korean version (CAMCOG‐K) and the Mini‐Mental State Examination, Korean version (MMSE‐K) were used to estimate the concurrent validity of CARDS. To evaluate the sensitivity of CARDS, mean scores from CARDS, ADAS‐K, CAMCOG‐K and MMSE‐K were compared between dementia patients and control subjects. Results: The CARDS demonstrated high levels of reliability. Mean CARDS scores for dementia patients were significantly different from the control group (P < 0.001). Furthermore, CARDS was significantly correlated with other tests and scales (P < 0.01). Conclusion: We demonstrated that CARDS is a reliable and valid instrument not only for dementia diagnosis, but also for the evaluation of impaired cognitive domains. A regression equation, derived from nationwide population surveys for norm data from CARDS, will be applied for individualized cutoff scores of five domains of dementia to eliminate the influence of age, sex and educational attainment on test scores.     

A clinical role for 99mTc-HMPAO SPECT in the investigation of dementia?

OBJECTIVES—To provide the clinician with a guide to the clinical utility of ^99mTc-HMPAO single photon emission computed tomography (SPECT) and to the interpretation of specific test results in the differential diagnosis of dementia.
METHODS—Three hundred and sixty three patients with dementia were studied prospectively for a median three (range 1-6) years and classified into disease groups on the basis of established clinical criteria. The degree to which different patterns of cerebral blood flow (CBF) abnormality found on ^99mTc-HMPAO SPECT imaging at the time of initial patient presentation modified clinical diagnoses was determined by calculating the likelihood ratios for pairwise disease group comparisons. The optimal clinical usage of ^99mTc-HMPAO SPECT was determined by calculating the percentage of significant test results for each pairwise disease group comparison.
RESULTS—Bilateral posterior CBF abnormality was found to significantly increase the odds of a patient having Alzheimer''s disease as opposed to vascular dementia or frontotemporal dementia. Bilateral anterior CBF abnormality significantly increased the odds of a patient having frontotemporal dementia as opposed to Alzheimer''s disease, vascular dementia, or Lewy body disease. "Patchy" CBF changes significantly increased the odds of a patient having vascular dementia as opposed to Alzheimer''s disease. Unilateral anterior, unilateral anterior plus unilateral posterior, and generalised CBF abnormality failed to contribute to the differentiation of any of these forms of dementia.
CONCLUSIONS—^99mTc-HMPAO SPECT was found to be most useful in distinguishing Alzheimer''s disease from vascular dementia and fronto temporal dementia, and least useful in differentiating between Alzheimer''s disease and Lewy body disease, and between vascular dementia, frontotemporal dementia, and progressive aphasia. It is suggested that CBF SPECT should be used selectively and as an adjunct to clinical evaluation and CT.