Heterogeneity in executive impairment in patients with very mild Alzheimer's disease

BACKGROUND/AIMS: The presence of executive impairment in mild Alzheimer's disease (AD) has primarily been demonstrated by means of group comparison. Whether executive dysfunction is a common feature of mild AD or only present in a subgroup of patients remains unclear. The aim of this study was to describe the frequency of impairment on a set of internationally well-known executive tests in patients with very mild AD. METHODS: Thirty-six patients with very mild AD (MMSE scores above 23) and 32 healthy control subjects were administered a battery of 7 executive tests: Trail Making part B, Stroop Interference Test, modified Wisconsin Card Sorting Test (WCST), category- and letter-based verbal fluency, a design fluency task and the Similarities subtest from WAIS. Impairment was defined as a score of 2 SD or more below control means. RESULTS: Executive impairment on at least 1 measure was seen in 76% of the patients, and 50% were impaired on 2 or more tests. Trail Making B and Stroop Interference Test were impaired in more than 40%, whereas only few patients were impaired on Similarities, WCST and design fluency. A wide variation of executive test profiles was seen among the patients. CONCLUSION: Executive impairments are common in early AD and not just a feature characteristic of a subgroup of patients. Complex attentional skills are more frequently affected than other executive functions. There is, however, considerable heterogeneity among AD patients in the pattern of executive dysfunction.     

Anosognosia in Alzheimer's disease: association with patient characteristics, psychiatric symptoms and cognitive deficits

Anosognosia is one of the major problems in the treatment and care of Alzheimer's disease (AD) patients. The aim of the study was to determine the patient characteristics, psychiatric symptoms, and cognitive deficits associated with anosognosia, because these are currently poorly understood. Eighty-four patients who met the National Institute of Neurological and Communicative Disease and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable AD were examined for anosognosia based on the difference between questionnaire scores of the patient and their caregiver. The relationship of anosognosia with patient characteristics (age, age at onset, duration of illness, education, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Hyogo Activities of Daily Living Scale (HADLS)), psychiatric symptoms (Neuropsychiatric Inventory (NPI), Geriatric Depression Scale (GDS)), and cognitive function (Digit Span, Word Fluency Test, Trail Making Test, Stroop Test, Raven's Coloured Progressive Matrices Test) were studied. Anosognosia showed positive correlations with age, age at onset, duration of illness, CDR, HADLS, and NPI disinhibition, and negative correlations with MMSE and GDS. Regarding cognitive function, only Part III of the Stroop Test was a predictor of anosognosia. The severity of anosognosia increased with disease progression and with a later age at onset. Subjective complaints of depression requiring self-monitoring of mood tended to decrease and, in contrast, inhibition of socially unsuitable behavior became more difficult as anosognosia worsened. Regarding cognitive function, anosognosia appeared to be associated with response inhibition impairment. Both disinhibition, as a psychiatric symptom, and response inhibition impairment are known to be correlated with disturbance of orbitofrontal function, which therefore may be associated with anosognosia.     

Single Neuropsychological Test Scores Associated With Rate of Cognitive Decline in Early Alzheimer Disease

Alzheimer disease (AD) characteristically begins with episodic memory impairment followed by other cognitive deficits; however, the course of illness varies, with substantial differences in the rate of cognitive decline. For research and clinical purposes it would be useful to distinguish between persons who will progress slowly from persons who will progress at an average or faster rate. Our objective was to use neurocognitive performance features and disease-specific and health information to determine a predictive model for the rate of cognitive decline in participants with mild AD. We reviewed the records of a series of 96 consecutive participants with mild AD from 1995 to 2011 who had been administered selected neurocognitive tests and clinical measures. Based on Clinical Dementia Rating (CDR) of functional and cognitive decline over 2 years, participants were classified as Faster (n = 45) or Slower (n = 51) Progressors. Stepwise logistic regression analyses using neurocognitive performance features, disease-specific, health, and demographic variables were performed. Neuropsychological scores that distinguished Faster from Slower Progressors included Trail Making Test - A, Digit Symbol, and California Verbal Learning Test (CVLT) Total Learned and Primacy Recall. No disease-specific, health, or demographic variable predicted rate of progression; however, history of heart disease showed a trend. Among the neuropsychological variables, Trail Making Test - A best distinguished Faster from Slower Progressors, with an overall accuracy of 68%. In an omnibus model including neuropsychological, disease-specific, health, and demographic variables, only Trail Making Test - A distinguished between groups. Several neuropsychological performance features were associated with the rate of cognitive decline in mild AD, with baseline Trail Making Test - A performance best separating those who declined at an average or faster rate from those who showed slower progression.     

Utility of behavioral versus cognitive measures in differentiating between subtypes of frontotemporal lobar degeneration and Alzheimer's disease

We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), along with a few cognitive tests, would be clinically useful in distinguishing between clinically defined Alzheimer's disease (AD) and subtypes of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the basis of a comprehensive neuropsychological battery, imaging, neurological examination, and history. We found significant between-group differences on the FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning and delayed recall), and the Trail Making Test Part B (one measure of 'executive functioning'). AD was characterized by relatively severe impairment in verbal learning, delayed recall, and executive functioning, with relatively normal scores on the FBI-mod. Frontotemporal dementia was characterized by relatively severe impairment on the FBI-mod and executive functioning in the absence of severe impairment in verbal learning and recall. Progressive nonfluent aphasia was characterized by severe impairment in executive functioning with relatively normal scores on verbal learning and recall and FBI-mod. Finally, semantic dementia was characterized by relatively severe deficits in delayed recall, but relatively normal performance on new learning, executive functioning, and on FBI-mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B categorized the majority of patients as subtypes of FTLD or AD in the same way as a full neuropsychological battery, neurological examination, complete history, and imaging. These tests may be useful for efficient clinical diagnosis, although progressive nonfluent aphasia and semantic dementia are likely to be best distinguished by language tests not included in standard neuropsychological test batteries.     

Impairments of executive/attentional functions in schizophrenia with primary and secondary negative symptoms

Frontal cognitive inabilities have been amply described in schizophrenic patients with negative symptoms, but findings are controversial. These discrepancies could be due to the fact that negative symptoms are heterogeneous, composed of primary and secondary negative symptoms. The hypothesis tested was that executive/attentional dysfunctions would be significantly more impaired in patients with primary than in patients with secondary negative symptoms independently of IQ, the severity of negative or positive symptoms, treatments and side effects. Fifty-six DSM-IV schizophrenic patients characterized either by primary or secondary negative symptoms and 56 controls matched on age, sex and level of education were assessed with executive/attentional cognitive tests. The categories score of the Modified Card Sorting Test (MCST) and the Verbal Fluency Test, which reflect solving and organizing skills, were significantly more impaired in the primary negative subtype than in the secondary negative subtype. In contrast, scores on the MCST (perseveration), the Trail Making Test and the Stroop Color Word Test, which test the ability to inhibit an automatic response, did not differ between the two subtypes. In conclusion, this study supports the view that primary and secondary negative symptoms could be associated with different levels of executive/attentional dysfunctions.     

Behavioral Dyscontrol Scale deficits among traumatic brain injury patients, part II: Comparison to other measures of executive functioning

The clinical utility of the Behavioral Dyscontrol Scale (BDS) was compared to that of verbal fluency, the Trail Making Test, and the Stroop Color-Word Test, as well as measures of processing speed/cognitive efficiency and manual dexterity. The ability of these measures to classify 49 TBI patients into frontal versus nonfrontal and mild to moderate versus severe groups was examined. The results showed that the Fluid Intelligence Factor of the BDS improved classifications above and beyond traditional executive measures, but was particularly successful at classifying patients who sustained mild injuries. In contrast, traditional executive instruments were successful at lesion location classifications only among the patients with severe injuries. Severity classifications were successful both for traditional measures of processing speed/cognitive efficiency and for the Motor Programming Factor of the BDS, but only among patients with nonfrontal injuries. These results demonstrate that severity of injury may be an important moderator of tests' sensitivity to frontal lobe involvement.     

Longitudinal PET evaluation of cerebral glucose metabolism in rivastigmine treated patients with mild Alzheimer’s disease

Summary. In this study 11 patients with mild Alzheimer’s disease (AD) were treated with the cholinesterase inhibitor rivastigmine (mean dose 8.6 ± 1.3’mg) for 12 months and underwent positron emission tomography (PET) studies of cerebral glucose metabolism (CMRglc) and neuropsychological testing at baseline and after 12 months. An untreated group of 10 AD patients served as control group. While the untreated AD patients showed a significant decline of CMRglc in the temporo-parietal and frontal cortical regions after 12 months follow-up the rivastigmine-treated patients showed no decline in CMRglc in corresponding cortical brain regions. Furthermore, a significant dose-related increase in CMRglc was recorded in the right frontal association region after 12 months rivastigmine treatment. A positive correlation was observed between changes in CMRglc and several cognitive tests in patients receiving higher doses (10.5–12’mg) of rivastigmine. These results suggest a stabilization effect of rivastigmine on CMRglc in mild AD patients receiving long-term rivastigmine treatment.     

Greater impairment of ability in the divided attention task is seen in Alzheimer's disease patients with depression than in those without depression

BACKGROUND: Recent studies have emphasized specific deficits of attention and executive functions, such as those of cognitive flexibility, divided attention, in geriatric patients with depression. In Alzheimer's disease (AD), depressive symptoms are known to occur even from an early stage of the disease. However, the nature of the impairment of executive functions in depression associated with AD remains unclear, because of the frequent occurrence of the apathy syndrome as a major confounding factor. METHOD: In this study, we conducted a comprehensive comparative neuropsychological assessment in AD patients with (n=21) and without (n=21) depression. The diagnosis of depression was based on provisional criteria proposed by Olin's group. RESULTS: In terms of apathy symptoms, both groups had a similar degree of deficits, which were mild as assessed according to Neuropsychiatric Inventory criteria. While no significant differences were observed in regard to the scores in general intellectual functioning, episodic memory and some attention and executive tasks between the two groups, AD patients with depression showed significantly lower scores in several attention and executive function tasks, such as the dual-task performance task administered to assess the capacity for divided attention, and the cognitive flexibility (Trail Making Test; Part B), than AD patients without depression. CONCLUSIONS: Our results suggest that depressive symptoms in AD patients increase the deficits of cognitive flexibility and divided attention. This is the first study to report a correlation between depressions, diagnosed based on the provisional criteria for depression in AD by Olin's group, and an impaired capacity for divided attention in AD patients.     

Executive/attentional cognitive functions in schizophrenic patients and their parents: a preliminary study.

The aim of this study was to determine whether executive/attentional cognitive performances could be considered as markers of vulnerability to schizophrenia.The Stroop Color Word and fluency tests were significantly impaired in schizophrenic patients and their parents compared to controls matched on age and sex while performances on Nelson's Modified Card Sorting Test and the Trail Making Test did not differ.The impairments on the Stroop and fluency could be considered as endophenotypic markers of schizophrenia.     

抑郁对帕金森病患者执行功能的影响

目的 探讨抑郁对帕金森病(PD)患者执行功能的影响。方法 对41例PD患者及20例对照组进行整体认知功能、执行功能及抑郁状况的评定。整体认知功能评定使用简易智力状态量表(MMSE); 执行功能评定包括言语流畅性测验(VFT),连线测验(TMT),Stroop字色干扰测验(SCWT),画钟测验(CDT),数字符号替换测试(DSST)及数字广度测试(DST)等; 使用贝克抑郁自评量表(BDI)评估抑郁状态。结果 抑郁组SFT, PFT, DST, DSST, CDT, TMA,TMB, Stroop-B, Stroop-C,SIE评分均差于对照组(P<0.05); 非抑郁组PFT, DST, DSST,TMA,TMB, Stroop-C,SIE评分差于对照组(P<0.05); 与非抑郁组比较,抑郁组SFT, PFT, DST, DSST, TMA, TMB, Stroop-B, Stroop-C, SIE评分较差(P<0.05)。结论 PD患者存在明显的执行功能障碍,抑郁可以明显加重PD患者的执行功能障碍。     

Executive dysfunction and periventricular diffusion tensor changes in amnesic mild cognitive impairment and early Alzheimer's disease

Our aim in this study was to explore the neural substrates of executive function in frontal and nonfrontal white matter using diffusion tensor imaging (DTI). We studied the relationship between executive dysfunction and DTI measurements on 13 subjects with amnesic mild cognitive impairment (aMCI), 11 subjects with early Alzheimer's disease (AD), and 16 control subjects. All participants underwent an examination of their intelligence, memory, and executive function and were subjected to DTI. Both aMCI and early AD subjects showed executive function impairment with differential performance in frontal‐related behaviors. Both aMCI and early AD subjects showed increased mean diffusivity in the genu of the corpus callosum and left frontal periventricular white matter (PVWM), whereas subjects with early AD showed an additional decrease in the fractional anisotropy of bilateral frontal PVWM and in the genu of the corpus callosum. The frontal PVWM was associated with performance on the Verbal Fluency Test, the Wisconsin Card Sorting Test (WCST), and Part B of the Trail Making Test. The parietal PVWM was associated with perseverative errors on the WCST and Part A of the Trail Making Test. In summary, executive function was impaired in subjects with aMCI and early AD and was associated with frontal and parietal PVWM changes. These changes may be due to early AD degeneration of the lateral cholinergic projections or to early change of the superior longitudinal fasciculus. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

轻度颅脑损伤患者执行功能障碍研究

目的探讨轻度颅脑损伤(mild traumatic brain injury,m TBI)患者伤后执行功能(executive function,EF)的动态变化特点。方法对63例m TBI患者(研究组)在伤后1周、1个月、3个月和6个月进行执行功能测查,并与60例健康受试者(对照组)比较。测查工具采用连线测验(trail making test,TMTA)、霍普金斯词语学习测验修订版(Hopkins verbal learning test-revised,HVLT-R)、简易视觉记忆测验—修订版(brief visuospatial memory test-revised,BVMT-R)、Stroop色词测验、持续操作测验(continuous performance test,CPT)。结果伤后1周与对照组比较,TMTA、HVLT-R、BVMT-R、Stroop和CPT-IP分值差异有统计学意义(P0.05);与伤后1周相比,伤后1个月、3个月和6个月时的TMTA分值下降,HVLT-R、BVMT-R、Stroop和CPT-IP分值增加(P0.05)。组内两两比较,伤后1个月与伤后1周比较,TMTA分值下降,BVMT-R、Stroop分值增加(P0.05);伤后3个月与伤后1个月比较,Stroop、BVMT-R和CPT-IP分值增加(P0.05);伤后6个月与伤后3个月比较,Stroop和CPTIP分值增加(P0.05)。结论m TBI患者在注意能力/警觉性、学习与工作记忆、信息处理速度及执行功能上都可能存在一定的损害,伤后不同时间点恢复速度并不一致。     

Tone duration mismatch negativity deficits predict impairment of executive function in schizophrenia

Impairment in mismatch negativity (MMN) potentials is a robust finding in schizophrenia. There are few studies which examined the correlation between MMN deficits and neuropsychological performances. The purpose of this study was to investigate the relationship between deficits of tone duration MMN and various neuropsychological measures in schizophrenic patients (n=23). The results demonstrated a significant correlation between low MMN amplitude and poor performances of executive function in Wisconsin Card Sorting Test, Stroop Test and Trail Making Test. Our finding suggests MMN deficits in schizophrenia predict deficits of executive function and might reflect ongoing functional abnormality of fronto-temporal interaction.     

Event-related potentials and neuropsychological tests in obsessive-compulsive disorder

OBJECTIVE: Previous studies have provided evidence from event-related potentials (ERPs) and neuropsychological testing of abnormal cognitive processing in obsessive-compulsive disorder (OCD). The aim of this study was to further characterize the cognitive functions of the patients with OCD by utilizing ERPs and neuropsychological tests. METHODS: ERPs were recorded in a group of 31 drug-free OCD patients without depression and 30 normal controls following verbal auditory stimuli using an oddball paradigm. The specific neuropsychological tests administered to assess cognitive functions in all participants were the Stroop Test, Trail Making Test, Design Fluency Test, Controlled Word Association Test (Verbal Fluency test). RESULTS: The patient group showed shorter P300 duration compared to normal controls. In neuropsychological tests, no significant differences were found between the two groups. Negative correlations between Stroop duration and P300 amplitudes in occipital, parietal, and temporal anterior regions were observed. CONCLUSION: Shorter P300 duration may indicate an acceleration in the P300 process, and speeding of cognitive processing, dysfunction of cortico-subcortical circuits, or some combination of all of the above.     

Ecological validity of executive function tests in moderate traumatic brain injury in Ghana

Abstract

Objective: While executive functioning (EF) tests are frequently administered in several Sub-Saharan African countries, studies examining their predictive relationships with real-world behaviors (i.e. ecological validity) are nonexistent. The present study investigated the predictive relationship between the Stroop Test, Controlled Oral Word Association Test, and Trail Making Test (TMT), a general cognitive screening test, Revised Quick Cognitive Screening Test (RQCST), and measures of activities of daily living, quality of life, and cognitive failures in Ghana. Method: A total of 50 literate urban dwellers who were diagnosed with moderate traumatic brain injury (TBI) were administered the neuropsychological tests and the self-report measures stated above. The informant version of the Cognitive failure questionnaire (CFQ) was completed by 50 ‘significant other’ who knew the patients very well. Results: There was no statistically significant difference between the self and informant versions of the CFQ. Some EF test scores, specifically the Stroop Test, TMT and EF composite scores, correlated significantly with the outcome measures, with correlations ranging from .29 to .55. The RQCST explained 40–49% variance in the outcome measures, while the addition of the EF composite score not only resulted in 57–62% variance accounted for but also added incremental validity to the RQCST in predicting the behavioral measures, with the exception of cognitive failures. Conclusion: This study has shown that although EF test scores, specifically the Stroop Test, TMT and EF composite scores, can be used to predict real-world behavior after moderate TBI in Ghana, such predictions are likely to be limited. The general implication for cross-cultural neuropsychology is that the (limited) ecological validity of EF tests may not necessarily be affected by whether the tests were administered in settings where they have not been standardized. This argument is, however, tenable granted that the test taker’s backgrounds are similar to those on which the tests have been standardized.     

Cognitive correlates of brain MRI subcortical signal hyperintensities in non-demented elderly

OBJECTIVE: To investigate the relationship between magnetic resonance imaging (MRI) subcortical gray and capsular (SGCH) and white matter hyperintensities (WMH) and cognitive functions in non-demented community dwelling elderly. METHODS: The severity of SGCH and WMH on proton density and T2 MR images in 16 subjects was scored using the semi-quantitative rating scale of Scheltens et al. (1993). A limited series of cognitive tests selected a priori were then correlated with severity of SGCH and WMH. RESULTS: Analysis demonstrated that severity of SGCH was inversely related to performance on the Digit Span (R = -0.64, p < 0.01) and the Stroop Color Word Tests (R = -0.64, p < 0.01). Severity of WMH was related to worsening performance on the Trail Making Test (R = 0.67, p < 0.005). CONCLUSIONS: These findings indicate that severity of WMH is negatively related to more pure executive cognitive functions, specifically set shifting, while severity of SGCH is inversely related to more basic functions of attention and working memory.     

Bilateral subthalamic or pallidal stimulation for Parkinson's disease affects neither memory nor executive functions: a consecutive series of 62 patients.

There is a renewal of interest in surgical approaches including lesions and deep brain stimulation directed at motor subcorticofrontal loops. Bilateral lesioning presents a far greater risk of adverse effects, especially cognitive impairment. Furthermore, the main advantages of the stimulation procedure over lesioning are adaptability and reversibility of effects. The aim of this study was to assess the influence of bilateral stimulation of the subthalamic nucleus or internal globus pallidus on memory and executive functions in Parkinson's disease. Sixty-two patients were assessed before and after 3 to 6 months of chronic bilateral stimulation of the subthalamic nucleus (n = 49) or internal globus pallidus (n = 13). The neuropsychological tests used were the Mattis Dementia Rating Scale, the Grober and Buschke Verbal Learning Test, the Wisconsin Card Sorting Test, category and literal fluency, graphic and motor series, the Stroop Test, and the Trail Making Test. Mood was evaluated by the Beck Depression Inventory. Only 4 of 25 cognitive variables were affected by deep brain stimulation. Under stimulation, performance improved for Parts A and B of the Trail Making Test, but there was a deterioration in literal and total lexical fluency. There was also a mild but significant improvement in mood. It may therefore be concluded that stimulation of the subthalamic nucleus or internal globus pallidus does not change the overall cognitive performance in Parkinson's disease and does not greatly affect the functioning of subcorticofrontal loops involved in cognition in humans. This relative absence of cognitive impairment in bilateral deep brain stimulation is likely because of the accurate positioning of the electrodes, allowing the effects of stimulation to be confined to sensorimotor circuits.     

Interpreting the trail making test following traumatic brain injury: comparison of traditional time scores and derived indices

The purpose of this study was to examine the clinical application of traditional time scores and various derived indices from the Trail Making Test (TMT) in a sample of 571 patients with acute traumatic brain injury (TBI). Participants were classified into four injury severity groups. A clear linear relation between injury severity and TMT performance was demonstrated, with the more severely brain injured patients performing more poorly on most measures. Hierarchical logistic regression analysis of TMT time scores across binary extreme groups based on injury severity resulted in high classification rates for patients with very mild TBI (93.0% correctly classified) and low classification rates for patients with moderate to severe TBI (50.0% correctly classified). However, TMT derived indices did not provide a unique contribution to test interpretation beyond what is already available from Part A and B separately.     

Caudate atrophy and impaired frontostriatal connections are linked to executive dysfunction in temporal lobe epilepsy

This study tested the hypothesis that executive dysfunction, common in temporal lobe epilepsy (TLE), is associated with an abnormal frontostriatal network. Structural and diffusion tensor MR scans, the Wisconsin Card Sorting Test (WCST) targeting cognitive flexibility, and the Trail Making Test B examining parallel sequencing were obtained from 9 patients with left TLE and 17 healthy controls. The five major findings were: (1) Caudate volume is reduced on the left side in TLE. (2) The atrophy involves the dorsal and ventral head of the caudate. (3) These atrophic caudate regions have a corresponding high probability of connections to dorsal prefrontal, anterior cingulate, and orbitofrontal cortex. (4) Smaller caudate volumes are linked to greater numbers of WCST perseverative errors. (5) Reduced connections between caudate and dorsal prefrontal cortex correlated with poorer scores on the Trail Making Test B. The results suggest that atrophy in the dorsal head of the caudate might disrupt frontostriatal networks that are critical for executive functioning in TLE.