Monitoring Alzheimer's patients for acute changes in cognitive functioning.

To develop and evaluate the use of cognitive monitoring for detecting episodes of acute, excess cognitive decline in individual Alzheimer's disease (AD) patients, the authors conducted six repeated cognitive assessments over 11 weeks on 41 otherwise healthy people with mild-to-moderate AD. Patients demonstrated stable cognitive performance over 11 weeks on seven standard neuropsychological tests. Prediction intervals quantitatively defined the expected limits of cognitive decline. They indicated with 90% certainty that over the 11-week period, healthy mild-to-moderate AD patients should not decline more than 4 points on the Word List Recall test, 3 points on the Digit Span test, or 8 items on the Digit Symbol or Verbal Fluency tests. The cognitive stability of healthy AD patients indicates that it is possible to monitor them for acute, excess cognitive decline.     

Estrogen, cognitive function and negative symptoms in female schizophrenia

The aim of this study was to evaluate the relationship of serum reproductive hormone levels with cognitive function and negative symptoms in schizophrenic women during the follicular phase of the menstrual cycle. Thirty-five women with chronic schizophrenia who had minimal positive symptoms participated in this study. We evaluated the correlation of serum reproductive hormone levels with the Scale for the Assessment of Negative Symptoms (SANS) and cognitive function tests such as the Immediate Visual Recognition Scale, Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Tests A and B, and Digit Symbol Test. The patients were divided into two subgroups (low estradiol group and normal estradiol group) using the normal serum reference range for estradiol. Significant correlation between SANS subcategories, such as Alogia and Attention Impairment, and estradiol were found. Moreover, significant relationships between the estradiol level and the Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Test B and Digit Symbol Test were observed. In the low estradiol group, the SANS scores, except for Anhedonia-Asociality and Avolition-Apathy, were significantly higher than those in the normal estradiol group. Patients in the low estradiol group had a significantly lower performance in the cognitive function tests, except Visual Recognition Scale, when compared to patients in the normal estradiol group. These results suggest that for schizophrenic women of reproductive age, lower levels of estrogen are associated with more severe negative symptomatology as well as reduced performance in cognitive function, especially verbal performance and executive functioning.     

Magnetic resonance imaging predictors of cognition in mild cognitive impairment

OBJECTIVES: To describe magnetic resonance imaging characteristics in a large sample of subjects with mild cognitive impairment (MCI) and to investigate associations between these characteristics and cognition. DESIGN: Cohort study. SETTING: Baseline data of a randomized, double-blind, placebo-controlled clinical trial of galantamine in MCI. PATIENTS: Included in the study were 896 subjects with MCI (age [mean +/- SD], 70 +/- 9 years; 54% women) with available clinical and magnetic resonance imaging data. MAIN OUTCOME MEASURES: Neuropsychology: Alzheimer Disease Assessment Scale, cognitive subscale, MCI version, assessing global cognition; delayed recall on the New York University Paragraph Recall Test, assessing episodic memory; and Digit Symbol Substitution Test, assessing executive function. Neuroimaging: Medial Temporal Lobe Atrophy (MTA) Rating Scale (0-4) and Age-Related White Matter Changes Scale (0-30), assessing white matter hyperintensities (WMHs); and lacune counts. RESULTS: Median MTA score was 2 (range, 0-4), and mean (+/- SD) Age-Related White Matter Changes Scale score 6.0 (+/- 4.7). Lacunes were present in 33% of subjects. In unadjusted models, increasing MTA and WMHs were associated with poorer performance on all cognitive tests, and lacunes with poorer performance on the Alzheimer Disease Assessment Scale, cognitive subscale, MCI version, and the Digit Symbol Substitution Test. In multivariable models, including magnetic resonance imaging measures simultaneously, MTA remained a predictor of cognition, whereas WMH had no independent predictive value. There was an interaction between MTA and lacunes: the strength of the association with the Digit Symbol Substitution Test increased with decreasing MTA. CONCLUSIONS: Medial temporal lobe atrophy seems to be a more important predictor of cognition than small-vessel disease in MCI. Lacunes were associated with performance on the Digit Symbol Substitution Test, especially in subjects with milder MTA. Although WMHs were prevalent and associated with cognition in unadjusted analyses, there was no discernible association between WMHs and the cognitive measures in this study after adjustment for age.     

Relationship of neuropsychological performance to functional status in nursing home residents and community-dwelling older adults.

OBJECTIVES: The authors examined the association between neuropsychological tests of executive functioning and episodic memory and functional disability in nursing home residents versus community-dwelling older adults. METHODS: The neuropsychological performance of 96 residents from the Jewish Home and Hospital, Bronx, NY and 192 gender- and age-matched older adults from residential communities in the New York metropolitan area was assessed in eight tasks (Word List Recall, Delayed Recall, Recognition, Boston Naming, Verbal Fluency, Trailmaking A and B, and Digit Symbol Substitution). Functional status was derived from the Clinical Dementia Rating scale (CDR) extended activities of daily living scores. Regression analyses were performed to test for differences in cross-sectional age-gradients for cognitive and functional status between nursing home residents and community-dwellers. Furthermore, regression analyses, controlling for age, gender, dementia status, and education, were performed to determine the association between neuropsychological performance and functional status, comparing domains of executive functioning and memory. RESULTS: Community-dwelling older adults showed age-related deficits both in overall cognitive status and functional disability, which were larger in nursing home residents. Executive functioning was associated with functional disability beyond the effects of age, gender, education, dementia status, residential status, overall cognitive status, memory, and cognitive speed. CONCLUSION: Executive functioning is associated with functional deficits in both community-dwelling older adults and nursing home residents. Measures of executive functioning may prove useful in intervention studies aimed at delaying institutionalization.     

The association between depression, anxiety, and cognitive function in the elderly general population--the Hordaland Health Study

OBJECTIVES: To examine the association between depression and/or anxiety and cognitive function in the elderly general population. SUBJECTS: Non-demented participants from the general population (n = 1,930) aged 72-74 years. METHODS: Symptoms and caseness of depression and anxiety disorder were assessed using the Hospital Anxiety and Depression Scale (HADS). Cognitive function was assessed by the Digit Symbol Test (modified version), the Kendrick Object Learning Test, and the 'S'-task from the Controlled Oral Word Association Test. RESULTS: There was a significant association between depression and reduced cognitive function. The inverse association between anxiety and reduced cognitive performance was explained by adjustment for co-morbid depression. The inverse association between depressive symptoms and cognitive function was found to be close to linear, and was also present in the sub-clinical symptom range. Males were more affected cognitively by depressive symptoms than females. CONCLUSION: The inverse association between depression and cognitive function is not only a finding restricted to severely ill patient samples, but it can also be found in the elderly general population.     

The brief repeatable battery of neuropsychological tests: normative values allow application in multiple sclerosis clinical practice

The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) is a sensitive measure of cognitive impairment in multiple sclerosis (MS) patients. It consists of the Selective Reminding Test, the 10/36 Spatial Recall Test, the Symbol Digit Modalities Test, the Paced Auditory Serial Addition Test and the Word List Generation Test. We administered one of two parallel versions of the test battery to 140 healthy subjects to produce normative values for both versions. As expected, test scores were influenced by certain variables like age, gender and education. Although constructed as two equivalent versions, for some tests the two versions showed significant differences in test scores, which could not be explained by differences in these variables.     

White matter hyperintensities at critical crossroads for executive function and verbal abilities in small vessel disease

The presence of white matter lesions in patients with cerebral small vessel disease (SVD) is among the main causes of cognitive decline. We investigated the relation between white matter hyperintensity (WMH) locations and executive and language abilities in 442 SVD patients without dementia with varying burden of WMH. We used Stroop Word Reading, Stroop Color Naming, Stroop Color‐Word Naming, and Category Fluency as language measures with varying degrees of executive demands. The Symbol Digit Modalities Test (SDMT) was used as a control task, as it measures processing speed without requiring language use or verbal output. A voxel‐based lesion–symptom mapping (VLSM) approach was used, corrected for age, sex, education, and lesion volume. VLSM analyses revealed statistically significant clusters for tests requiring language use, but not for SDMT. Worse scores on all tests were associated with WMH in forceps minor, thalamic radiations and caudate nuclei. In conclusion, an association was found between WMH in a core frontostriatal network and executive‐verbal abilities in SVD, independent of lesion volume and processing speed. This circuitry underlying executive‐language functioning might be of potential clinical importance for elderly with SVD. More detailed language testing is required in future research to elucidate the nature of language production difficulties in SVD.     

健康成人事件相关电位与神经心理学测验的相关性研究

目的 探讨事件相关电位P300的四个主要成分是否反映特定的认知功能。方法 将120名正常受试者按年龄分为三组，即20～34岁组、35～54岁组和55～70岁组，对所有受试者采用全套韦氏成人智力测验(WAIS-RC)等多项神经心理学测验以及P300进行测评，将神经心理学测验结果与P瑚结果进行Spearman等级相关分析。结果 三个年龄组中的N2潜伏期、P2波幅、N2波幅均与反映注意、短时记忆的神经心理学测验存在以下相关：在20～34岁组中，N2潜伏期与即刻视觉再生呈负相关(r=-0．352)，P2波幅与即刻视觉再生呈正相关(r=0．339)，N2波幅与即刻视觉再生呈正相关(r=0．331)。在35～54岁组中，N2潜伏期与数字广度、数字符号、词汇流畅均呈负相关(r分别=-0．357、-0．385、-0．316)；P2波幅与延线测验B呈负相关(r=-0．427)；Nl波幅与即刻逻辑记忆呈正相关(r=0．343)。在55～70岁组中，N2潜伏期与数字符号、词汇流畅呈负相关(r分别=-0．488和-0．321)，与延线测验B呈正相关(r=0．366)；P2波幅与数字符号呈正相关(r=0．314)；N2波幅与词汇流畅呈正相关(r=0．437)。在不同的年龄组中，P300的其他指标与神经心理学测验相关性不一致。结论 P300的四个主要成分可反映一定的认知功能，但不具有特异性，部分P300指标所反映的认知功能受年龄的影响。     

Motor dysfunction influence on executive functioning in manifest and premanifest Huntington's disease

Motor disturbances can be present in both manifest and premanifest Huntington's disease (HD). We aimed to investigate the role of motor functioning on executive functioning to better understand the progression of cognitive dysfunction in HD. Forty patients with manifest HD, 21 patients with premanifest HD, and a group of 28 controls were tested twice with a 1‐year interval. For the Symbol Digit Modalities Test and the Figure Fluency Test, extra conditions were designed to measure motor involvement. Subtraction of this motor score from the original test score resulted in isolation of the cognitive component. Groups were compared on motor, cognitive, and original test scores using multilevel regression analysis. Manifest patients had lower baseline scores of 0.53 standard deviations (SD) on the original Symbol Digit Modalities Test (P = 0.03) and 0.71 SD on the motor isolation part (P = 0.006), and they showed a deterioration of 0.47 SD over 1 year of follow‐up on the original Symbol Digit Modalities Test (P = 0.001) compared with controls. Premanifest patients had lower baseline scores of 0.67 SD on the Symbol Digit Modalities motor part (P = 0.008) and deterioration of 0.48 SD on the original (P = 0.001) and cognitive isolation (P = 0.02) parts. Secondary analyses revealed that the premanifest deterioration resulted from the close‐to‐predicted‐onset group. Motor disturbances have a negative influence on performance on the Symbol Digit Modalities Test. Isolation of the cognitive component of this test revealed cognitive deterioration in the premanifest group only, caused by deteriorating scores for patients who were close to their predicted clinical disease onset. The Figure Fluency Test did not prove sensitive to cognitive change. © 2014 International Parkinson and Movement Disorder Society     

Association of lung function with cognitive decline and dementia: the Atherosclerosis Risk in Communities (ARIC) Study

Background: Previous studies reported a higher risk of cognitive decline and dementia amongst individuals with impaired lung function. However, many did not adjust for important confounders or did not include women and non‐whites. Methods: We studied 10 975 men and women aged 47–70 years (23% African‐Americans) enrolled in the Atherosclerosis Risk in Communities Study. Pulmonary function tests and a cognitive assessment, including the Delayed Word Recall, the Digit Symbol Substitution, and the World Fluency Tests, were carried out in 1990–1992. Repeated cognitive assessments were performed in 1996–1998 for the entire cohort, and in 1993–1995, and 2004–2006 in 904 eligible individuals. Dementia hospitalization was ascertained through 2005. Results: In analysis adjusted for lifestyles, APOE genotype, and cardiovascular risk factors, impaired lung function was associated with worse cognitive function at baseline. No association was found between lung function and cognitive decline over time. Impaired lung function at baseline was associated with higher risk of dementia hospitalization during follow‐up, particularly amongst younger individuals. The hazard ratios (95% confidence intervals) of dementia hospitalization were 1.6 (0.9, 2.8) and 2.1 (1.2, 3.7) comparing the lowest with the highest quartile of forced expiratory volume in 1 s and forced vital capacity, respectively. Presence of a restrictive ventilatory pattern, but not of an obstructive pattern, was associated with reduced cognitive scores and higher dementia risk. Conclusion: Reduced lung function was associated with worse performance in cognitive assessments and with an increased risk of dementia hospitalization. Future research should determine whether maintaining optimal pulmonary health might prevent cognitive impairment and dementia.     

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。     

癫(癎)患者认知功能特点的研究

目的:研究癫(EP)患者认知功能的特点及其影响因素。方法:采用听觉词语测验、逻辑记忆测验、数字符号转换测验、Stoop字色干扰测验、连线测验、言语流畅性测验、Rey-Osterrieth复杂图片测验及Boston命名测验对166例EP患者进行认知评定。结果:EP患者存在广泛的认知损害,包括言语记忆、情景记忆、视觉空间结构记忆、词语学习能力、注意力、抗干扰能力、精神运动速度及言语命名功能等方面,以词语延迟回忆、注意力及精神运动速度损害最为明显。而未经药物干预的新诊断EP患者已存在除视觉空间记忆、注意力及抗干扰能力外的上述认知功能的损害,以词语延迟回忆最为明显。随访病例与新诊断病例的区别在于,前者在抗干扰能力及精神运动速度方面损害更明显。结论:新诊断EP组以及随访EP组病例在多项神经心理学测验中得分均低于正常对照组,两组之间差异有统计学意义。     

Normative Data on Neuropsychological Tests for Very Old Adults Living in Retirement Villages and Hostels

Normative data on neuropsychological tests for very old adults living in retirement villages and hostels are under-represented in the literature. This study reports normative data on the Mini-Mental State Examination, Digit Span Forwards, Digit Span Backwards, the Digit Symbol Substitution Test, the Controlled Oral Word Association Test, the Stroop Neuropsychological Screening Test and the National Adult Reading Test. Age and education showed moderate correlations with neuropsychological test performance. For all tests except the Stroop, differences between residents of retirement villages and hostels were explained by age and education. Men performed better on the NART than women, but this difference was eliminated when education was controlled for statistically.     

Normative data on neuropsychological tests for very old adults living in retirement villages and hostels

Normative data on neuropsychological tests for very old adults living in retirement villages and hostels are under-represented in the literature. This study reports normative data on the Mini-Mental State Examination, Digit Span Forwards, Digit Span Backwards, the Digit Symbol Substitution Test, the Controlled Oral Word Association Test, the Stroop Neuropsychological Screening Test and the National Adult Reading Test. Age and education showed moderate correlations with neuropsychological test performance. For all tests except the Stroop, differences between residents of retirement villages and hostels were explained by age and education. Men performed better on the NART than women, but this difference was eliminated when education was controlled for statistically.     

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.     

Mild head injury and speed of information processing: A prospective study of professional rugby league players

Abstract

The sensitivity of several short tests of speed of information processing to the effects of mild head injury in rugby league football was investigated. The measures used were the Symbol Digit Modalities Test, the Digit Symbol Substitution Test, and the Speed of Comprehension Test. Two studies were conducted, the first to examine the effect of practice, the second to determine sensitivity to cognitive impairment immediately following injury. The first study established alternate form equivalence and demonstrated that performance on the Speed of Comprehension and Digit Symbol Substitution tests improved with practice, whereas the Symbol Digit Modalities test remained stable. A second study of 10 players who subsequently sustained mild head injuries showed that measures of speed of information processing were sensitive to impairment in the postacute phase, whereas an untimed task of word recognition (Spot-the-Word) was not. Speed of Comprehension was more sensitive to postinjury impairment than either the Digit Symbol Substitution or Symbol Digit Modalities tests. A repeated baseline assessment before injury using the higher score to reflect a player's potential, allowed measurement of impaired performance on sensitive tests.     

Personality dimensions and neuropsychological performance in first-degree relatives of patients with schizophrenia and affective psychosis

Recent evidence suggests that schizophrenia patients taking atypical antipsychotic medications may perform better on some tests of cognitive function than those treated with older antipsychotics. The current study compared the effects of quetiapine and haloperidol on measures of executive function, memory and attention. Subjects were 58 stable outpatients with schizophrenia (DSM III-R) who received a battery of cognitive tests as part of a randomized, double-blind, multi-site clinical efficacy study conducted by AstraZeneca Pharmaceuticals. Cognitive assessments were conducted prior to randomization when patients were receiving < or =30 mg haloperidol or equivalent (mean: 9.2mg/day haloperidol equivalents), and again after 24 weeks of fixed-dose treatment with either quetiapine 600 or 300 mg/day or haloperidol 12 mg/day. Analyses of covariance with planned comparisons were used to compare scores on cognitive measures at the end of 24 weeks by treatment group with baseline cognitive function scores used as covariates. Patients receiving quetiapine 600 mg/day improved to a greater extent than patients receiving haloperidol on overall cognitive function (p<0.02). Specific differences were found for executive function (Verbal Fluency Test, p<0.04), attention (Stroop Color Word Test, p<.03) and verbal memory (Paragraph Recall Test, p<0.02). Treatment group differences were not solely due to benztropine use, medication side effects, or changes in symptomatology. Treatment with quetiapine at higher doses (600 mg/day) relative to haloperidol appears to have a positive impact on important domains of cognitive performance that have been found to predict role function and community outcomes in patients with schizophrenia.     

Fourteen-year longitudinal study of vascular risk factors,APOE genotype,and cognition: The ARIC MRI Study

BackgroundStrokes, vascular risk factors, and apolipoprotein E (APOE) genotype are associated with cognitive decline in the elderly, but definitive evidence that these affect cognition as early as middle age is limited.ObjectiveWe describe the relationships of APOE genotype, stroke, and vascular risk factors with cognitive change over a 14-year follow-up in the Atherosclerosis Risk in Communities (ARIC) Study cohort recruited while in middle age.MethodsParticipants included a subset of the ARIC Study who underwent assessments of cognitive function and vascular risk factors. Four cognitive assessments were performed between 1990–1992 and 2004–2006. Cognitive assessments included the Delayed Word Recall (DWR) Test, the Digit Symbol Substitution (DSS) Test, and the Word Fluency (WF) Test. Vascular risk factors were assessed during the baseline visit in 1990–1992. Incident stroke was recorded over the 14 years of follow-up.ResultsThere were 1130 participants (mean age, 59 ± 4.3 [SD] years; 62% women; 52% African-American) with longitudinal data. In multivariate, random-effects linear models adjusted for age, education, gender, and race, the risk factors diabetes and APOE ?4 genotype were independently associated with a decline in performance on the DSS test (both P < .005), whereas hypertension and stroke were not. For DWR, stroke and APOE ?4 genotype were independent predictors of decline (both P < .001). For the WF test, metabolic syndrome, hypertension, and stroke were independently associated with decline (all P < .005). No evidence of differential effects of risk factors on cognitive decline by race, gender, or interactions between risk factors was found.ConclusionsThe vascular risk factors diabetes and hypertension, a history of stroke itself, and APOE ?4 genotype independently contribute to cognitive decline in late middle age and early elderly years.     

Anti-inflammatory agents and cognitive decline in a bi-racial population

In a prospective study among 4,409 subjects aged 65+ years, we assessed the relation of nonsteroidal anti-inflammatory agents (NSAIDs) to cognition. The main outcome was decline in global cognitive function, determined by average performance across four cognitive tests, over up to four interviews. We found similar rates of cognitive decline among recent users of aspirin and of other NSAIDs (largely ibuprofen) compared to those who did not use these NSAIDs. For lifetime duration of aspirin use, we failed to find an association with cognitive decline. However, for other NSAIDs, increasing duration of lifetime use was related to slower rates of cognitive decline, relative to no use of other NSAIDs (5+ years vs. no use: mean difference = 0.12; p trend = 0.03). Overall, we found no relation between regular aspirin use and cognitive decline, but long-term use of ibuprofen may be related to decreased rates of cognitive decline in older persons.