阿尔茨海默病不同严重程度时的神经心理学研究

目的 研究阿尔茨海默病（ＡＤ）不同痴呆严重程度时的神经心理模式特点。方法 使用多种神经心理测验测试了符合国际公认的痴呆诊断标准（ＮＩＮＣＤＳ－ＡＤＲＤＡ）“很可能为ＡＤ”的患者,使用临床痴呆评定（ＣＤＲ）确定痴呆严重程度。结果 ＡＤ早期即出现视空间功能障碍,中、重度阶段均明显衰退。认知功能障碍也始于ＡＤ早期,中、重度阶段呈持续性显著衰退趋势,记忆功能在ＡＤ早期即出现大幅度衰退,,中期衰退幅度不大,     

Scenery Picture Memory Test: A new type of quick and effective screening test to detect early stage Alzheimer's disease patients

Aim: It is highly desirable to develop a neuropsychological screening test which is sensitive to the early stage of Alzheimer's disease (AD), and is easy to administer at the primary care physician's (PCP's) office. Methods: Participants were 128 AD patients and 54 healthy volunteers. Brief cognitive screening tests were administered to the participants including the Mini‐Mental State Examination (MMSE), Clock Drawing Test (CDT), Verbal Fluency Test (VFT), a Verbal Category Cued Memory test (CCMT) and the Scenery Picture Memory Test (SPMT). In the SPMT, a scenery picture of a living room containing 23 familiar objects was used. The administration of the SPMT comprised the first shallow memory session (Pict 1) and the second deep memory session (Pict 2). The area under the receiver–operator curve (AUC) was used to compare the efficacy of SPMT with other cognitive tests. Results: Pict 1, which requires less than 2 min to complete, had the same AUC as Pict 2, and showed significantly larger AUC than MMSE, CDT and VFT for all (MMSE 19–23) and very mild (MMSE ≥ 24) AD patients. When we conducted the similar analysis separately for those younger than 75 years and those aged 75 years or older, we obtained the same results as above among the older age group. Pict 1 showed larger AUC than CCMT in overall sample and also in the older age group, although the difference was not statistically significant. Conclusion: The SPMT could be useful for detection of mild and very mild AD in settings even where time is limited.     

早发和晚发遗忘型轻度认知损害与阿尔茨海默病的神经心理学比较研究

目的:比较早发性与晚发性阿尔茨海默病(AD)、早发性和晚发性遗忘型轻度认知损害(aMCI)的神经心理学表现。方法:记忆障碍门诊患者根据首诊年龄分组,70岁为晚发组。接受简明精神状态量表(MMSE)、听觉词语学习测验(AVMT)、逻辑记忆测验(LM)、斯特鲁普(Stroop)色词测验(CWT)、Rey-Osterrich复杂图形测验(CFT)、言语流畅性测验(VFT)、连线测验(TMT)、画钟测验(CDT)等。结果:共257例患者,分为4组,分别为早发AD34例,晚发AD78例,早发aMCI58例,晚发aMCI87例;早发、晚发AD间大部分神经心理学表现相似;早发aMCI患者在大部分测验上的表现优于晚发患者,听觉词语延迟回忆、言语流畅性、TMTB耗时等项目的差异最为显著(P<0.01)。晚发aMCI患者逻辑记忆即刻、延迟回忆更佳。结论:早发与晚发AD认知损害较为相似,晚发aMCI患者的认知损害较早发aMCI患者更为弥漫。     

Cognitive effects of treating obstructive sleep apnea in Alzheimer's disease: a randomized controlled study

OBJECTIVES: To examine whether treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients with Alzheimer's disease (AD) results in better cognitive function. DESIGN: Randomized double‐blind placebo‐controlled trial. Participants were randomized to therapeutic CPAP for 6 weeks or placebo CPAP for 3 weeks followed by therapeutic CPAP for 3 weeks. SETTING: General clinical research center. PARTICIPANTS: Fifty‐two men and women with mild to moderate AD and OSA. INTERVENTION: CPAP. MEASUREMENTS: A complete neuropsychological test battery was administered before treatment and at 3 and at 6 weeks. RESULTS: A comparison of subjects randomized to 3 weeks of therapeutic versus placebo CPAP suggested no significant improvements in cognition. A comparison of pre‐ and posttreatment neuropsychological test scores after 3 weeks of therapeutic CPAP in both groups showed a significant improvement in cognition. The study was underpowered to make definitive statements about improvements within specific cognitive constructs, although exploratory post hoc examination of change scores for individual tests suggested improvements in episodic verbal learning and memory and some aspects of executive functioning such as cognitive flexibility and mental processing speed. CONCLUSION: OSA may aggravate cognitive dysfunction in dementia and thus may be a reversible cause of cognitive loss in patients with AD. OSA treatment seems to improve some cognitive functioning. Clinicians who care for patients with AD should consider implementing CPAP treatment when OSA is present.     

Neuropsychological profile of prodromal Alzheimer's disease (Prd-AD) and their radiological correlates

This study describes the cognitive profile of Prd-AD, the neuropsychological tests that may predict progression to dementia, and to study their brain structural correlates. We enrolled 24 stable amnesics who did not develop dementia after two years follow-up; 27 patients were considered as Prd-AD, in the initial visit, since they fulfilled NINCDS-ADRDA criteria after two years; 31 Alzheimer's disease (AD) patients and 27 controls (CTR). Structural magnetic resonance imaging (MRI), as well as a neuropsychological battery was performed at the initial visit. The key findings were: Prd-AD patients were characterized by prominent episodic memory dysfunction and minimal semantic memory and executive dysfunction. Semantic fluency test (Sem-Flu), delayed text memory test (Del-text-mem) and memory alteration test (M@T) (including both episodic and semantic memory), together with trail making test A (TMT-A), resulted significant predictors for dementia development in this group of amnesic patients. This optimal predictive model obtained an estimated accuracy of 53% after two years follow-up. M@T and semantic Sem-Flu test performance presented high correlation with decreased gray matter density in the left lateral temporal lobe. We conclude that Prd-AD is characterized by prominent episodic memory dysfunction and minimal semantic memory and executive dysfunction which are related with left medial, inferior and lateral temporal density loss, predominantly in the left side.     

Donepezil provides greater benefits in mild compared to moderate Alzheimer's disease: Implications for early diagnosis and treatment

We assessed the cognitive and functional outcomes of donepezil treatment in mild versus moderate Alzheimer's disease (AD) patients. We performed a 6-month prospective, observational, multicenter study of the progression of cognitive and functionality abilities in a large sample patients with AD who initiated treatment with donepezil in monotherapy. According to baseline mini mental state examination (MMSE), patients were divided in two groups: mild AD (MMSE ≥ 21) and moderate AD (MMSE < 21). Patients were evaluated with the memory alteration test (M@T) and the Alzheimer's disease functional assessment and change scale (ADFACS) at baseline and at 6 months. A total of 403 patients finished the study (mild AD = 152; moderate AD = 251). The MMSE total score and M@T score remained stable at 6 months in the whole sample, with MMSE memory domain and M@T free and cued recall domains improving significantly from baseline. Total ADFACS, instrumental (IADL) and basic activities of daily living (BADL) got significantly worse, with the worsening being significantly greater in the moderate AD group. Significant differences between the groups favoring mild AD were observed for MMSE memory, orientation and language domains, M@T temporal orientation and semantic memory domains, and for IADL. We concluded that in AD patients on donepezil, cognition remains stable at 6 months. The beneficial effect of donepezil treatment, in terms of cognition and functionality, is greater for mild than for moderate AD.     

EC301数字加工和计算量表在早期识别阿尔茨海默病中的作用

目的分析EC301数字加工和计算量表中文修订版(EC301-CR)在早期识别阿尔茨海默病(AD)中的作用。方法正常老年人41例(正常组)、轻度认知功能损伤患者41例(MCI组)和轻度AD患者23例(轻度AD组)完成简易智能状态量表、逻辑记忆测验、听觉词语学习测验、韦氏成人智力测验-计算分测验和EC301-CR。EC301-CR包括数字与非数字次序、数字大小概念、数字的感知与表达、算术符号的感知与表达、数字转化、运算、数字相关记忆和说出相邻数字。结果MCI组患者的数字加工和计算能力介于正常组和AD组患者之间;AD组患者依然保持一般的数字大小和运算符号知识,但是,在心算、笔算、估算、珠算等所有计算方式、听写数字、数字转化和"说出相邻数字"方面有明显减退。对于识别AD最敏感的指标是"说出相邻数字"的能力,以其总分≤15分作为划界分,识别AD的敏感性是78%,特异性是87%。结论EC301-CR可用于AD早期诊断和严重度判断。     

遗忘型轻度认知障碍和轻度阿尔茨海默病的认知损害特征研究

目的明确遗忘型轻度认知障碍（amnesia-mild cognitive impairment,a-MCI）患者和轻度阿尔茨海默病（alzheimer＇s disease,AD）患者的认知损害特征。方法对13例a-MCI患者、22例轻度AD患者和37例正常对照进行全面的认知测查,除简易精神状态检查（mini-mental state examination,MMSE）外,测验可覆盖4个认知域：记忆力、信息处理速度、执行功能、视空间结构能力,进行组间比较。结果 3组患者在年龄、受教育程度及性别组成上匹配。轻度AD组的所有认知测验成绩都差于正常对照组,而且多数测验较a-MCI组也有减退。a-MCI组的MMSE、记忆相关测验以及多个执行功能相关测验结果都差于正常对照组,信息处理速度和视空间结构能力相关测验与对照组间无统计学差异。结论轻度AD患者表现为全面的认知功能减退。a-MCI患者除存在显著的记忆障碍外,还存在执行功能的异常,信息处理速度和视空间结构能力尚正常。     

Correlations Between Cerebral Glucose Metabolism and Neuropsychological Test Performance in Nonalcoholic Cirrhotics

Many cirrhotics have abnormal neuropsychological test scores. To define the anatomical–physiological basis for encephalopathy in nonalcoholic cirrhotics, we performed resting-state fluorodeoxyglucose positron emission tomographic scans and administered a neuropsychological test battery to 18 patients and 10 controls. Statistical parametric mapping correlated changes in regional glucose metabolism with performance on the individual tests and a composite battery score. In patients without overt encephalopathy, poor performance correlated with reductions in metabolism in the anterior cingulate. In all patients, poor performance on the battery was positively correlated (p < 0.001) with glucose metabolism in bifrontal and biparietal regions of the cerebral cortex and negatively correlated with metabolism in hippocampal, lingual, and fusiform gyri and the posterior putamen. Similar patterns of abnormal metabolism were found when comparing the patients to 10 controls. Metabolic abnormalities in the anterior attention system and association cortices mediating executive and integrative function form the pathophysiological basis for mild hepatic encephalopathy.     

The effect of a digital health coaching and health education protocol on cognition in adults at-risk for Alzheimer’s

Several modifiable lifestyle factors have been linked to cognitive ability and the risk of developing Alzheimer’s disease and related dementias (ADRD). Health coaching (HC) is an intervention that addresses lifestyle factors associated with cognition. The effectiveness of an HC protocol was evaluated and compared with a health education (HE) intervention, representing the current standard of care, in a sample of 216 adults between the ages of 45 and 75 years who were at-risk for developing ADRD. Outcomes examined were global cognition, neuropsychological cognition, and Alzheimer’s risk. HC participants received personalized coaching from a health coach focusing on nutrition, physical activity, sleep, stress, social engagement, and cognitive activity. HE participants received biweekly education materials focusing on the same modifiable lifestyle factors addressed by HC. Participants were assessed at baseline and again 4 months later. Self-reported global cognition scores improved only in the HC group (16.18 to 15.52, p?=?.03) and neuropsychological cognitive ability improved in the HE group (104.48 to 108.76, p?<?.001). When non-adherence in the HC group was accounted for, however, the mean change in neuropsychological score was similar between groups (p?>?.05), self-reported global cognition demonstrated an even larger mean improvement in the HC group (16.20 to 15.41, p?=?.01), and the HC group saw an improvement in ADRD protective risk score (??10.39 to???11.45, p?=?.007). These results indicate that HC and HE can both improve cognition, but HC may be more effective and may yield increased protection against ADRD risk.

     

Boundary extension as a tool for detection of cognitive change among individuals with mild cognitive impairment: A preliminary study

ObjectivesRecent neuropathological research suggests that recognition memory supported by familiarity rather than recollection may be the earliest cognitive change in course of Alzheimer's disease (AD). Nonetheless, the findings on the issue of familiarity capacity in the prodromal AD remain inconsistent. Boundary extension (BE), in which the view recollected by the subject covers a wider angle than was actually observed, is a form of false memory. Given that BE occurs implicitly and automatically, it may be a candidate for assessing familiarity functioning in cases of AD. This was the issue explored in the current study.Methods: One-hundred and six participants comprising a younger adult group (YA, n = 40), a healthy older adult group (OA, n = 40), and a group of patients with mild cognitive impairment (MCI, n = 26) underwent testing for BE and neuropsychological functions. Parts of OA and MCI underwent analysis for plasma tau levels. Receiver-operating characteristic analysis was used to assess memory associated with familiarity and recollection among participants.Results: The OA and MCI groups could be differentiated by the degree of familiarity associated with BE, wherein the latter group displayed minimal familiarity. Among OAs, familiarity was positively associated with education level. We observed a correlation between plasma tau levels and various neuropsychological functions. Most of the associations between plasma tau levels and neuropsychological functions were mediated by education level.Conclusions: Our findings indicate that BE could detect early decline in familiarity and assess preserved cognitive functions in aging     

Apolipoprotein E (APOE) genotype has dissociable effects on memory and attentional–executive network function in Alzheimer’s disease

The ε4 allele of the apolipoprotein E (APOE) gene is the major genetic risk factor for Alzheimer’s disease (AD), but limited work has suggested that APOE genotype may modulate disease phenotype. Carriers of the ε4 allele have been reported to have greater medial temporal lobe (MTL) pathology and poorer memory than noncarriers. Less attention has focused on whether there are domains of cognition and neuroanatomical regions more affected in noncarriers. Further, a major potential confound of prior in vivo studies is the possibility of different rates of clinical misdiagnosis for carriers vs. noncarriers. We compared phenotypic differences in cognition and topography of regional cortical atrophy of ε4 carriers (n = 67) vs. noncarriers (n = 24) with mild AD from the Alzheimer’s Disease Neuroimaging Initiative, restricted to those with a cerebrospinal fluid (CSF) molecular profile consistent with AD. Between-group comparisons were made for psychometric tests and morphometric measures of cortical thickness and hippocampal volume. Carriers displayed significantly greater impairment on measures of memory retention, whereas noncarriers were more impaired on tests of working memory, executive control, and lexical access. Consistent with this cognitive dissociation, carriers exhibited greater MTL atrophy, whereas noncarriers had greater frontoparietal atrophy. Performance deficits in particular cognitive domains were associated with disproportionate regional brain atrophy within nodes of cortical networks thought to subserve these cognitive processes. These convergent cognitive and neuroanatomic findings in individuals with a CSF molecular profile consistent with AD support the hypothesis that APOE genotype modulates the clinical phenotype of AD through influence on specific large-scale brain networks.     

Spatial versus verbal memory impairments in patients with fibromyalgia

Mounting evidence suggests that individuals with fibromyalgia (FM) have impairments in general cognitive functions. However, few studies have explored the possibility of dissociation between verbal and visuospatial memory impairments in FM. Therefore, the purpose of this study was to investigate the asymmetrical impairment of cognitive functions between verbal and visuospatial memory and between short-term and long-term memory. Neuropsychological assessments were carried out on 23 female patients with FM and 24 healthy female controls. Verbal memory abilities were assessed using the Korean version of the Rey auditory verbal learning test (KAVLT) and digit span task, and visuospatial memory abilities were assessed using the Korean version of the Rey complex figure test (KCFT) and spatial span task. The analysis of covariance was used to assess group differences in performance on cognitive tests after controlling for depression. The two groups did not significantly differ in terms of age, years of education, or in their estimated verbal and performance IQ, but FM patients reported more severe depressive symptoms than did controls on the Beck depression inventory. Significant group differences were found in immediate and delayed recall on the KCFT (F _1,44 = 6.49, p = 0.014 and F _1,44 = 6.96, p = 0.011, respectively), whereas no difference was found in immediate and delayed recall on the KAVLT. In terms of short-term memory, neither the digit span task nor spatial span task showed any difference between groups, regardless of whether repetition was forward or backward. These findings suggest that spatial memory abilities may be more impaired than verbal memory abilities in patients with FM.     

Phenotype properties and status of corticosteroid resistance among patients with uncontrolled asthma

BackgroundControl cannot be achieved in some asthmatics although optimal monitoring and treatment is administered. Glucocorticoid (GC) resistance is one of the reasons of poor asthma control. We aimed to investigate GC resistance by lymphocyte proliferation suppression test (LPST) in uncontrolled asthmatics.MethodsAfter assessing asthma control level of 77 asthmatics their treatment was adjusted upon GINA guidelines. They were followed-up for three to six months and the patients who remained uncontrolled were accepted as uncontrolled patients. Steroid resistance test (SRT) was applied to them (7–14 days oral prednisolone) and the patients who were still uncontrolled and/or had a FEV1 increase <15% after SRT were assessed as the “case group” while the remaining composed the “control group”. Optimal treatment was adjusted and at the end of a follow-up period LPST was performed to both groups.ResultsFourteen of the case (n = 22) and four (n = 8) of the control groups could be evaluated by LPST. Proliferated lymphocytes were observed to be significantly suppressed in all dexamethasone concentrations in the control group (p = 0.001). However, in the case group LPST was positive only at 10^?6 and 10^?4 concentrations although statistically not significant (p = 0.147). There was no significant relationship between clinically GC resistance and LPST positivity (p = 0.405).ConclusionWe determined that in vitro responses to the GCs were significantly declined in the uncontrolled asthma cases. An SRT alone does not seem to be very sensitive for evaluating GC sensitivity, LPST may be performed for demonstrating GC responsiveness in asthmatic patients in addition to SRT.     

The Development and Validation of a Neuropsychological Assessment for Mild Cognitive Impairment of Filipino Older Adults

Mild Cognitive impairment (MCI) has become increasingly recognized and studied because of its, greater opportunity for taking preventive measures to preserve cognition for as long as possible. So far, there are only two published neuropsychological tests for MCI developed abroad. These tests are automated. Only those who are computer literate can avail these tests. This study was an attempt to provide a reliable and valid neuropsychological tool to detect Mild Cognitive Impairment in Filipino older adults. Two weeks interval test-retest reliability correlations were all significant (r?=?.911 to r?=?1.000). Construct and Criterion validity correlations were significant (p?<?0.01). t-Test for equality of means showed significant differences: between Normal and with MCI (associated risk for the development of dementia or Alzheimer’s disease, a degenerative disease of the brain from which there is no recovery. This disease attacks nerve cells in all parts of the cortex of the brain, as well as some surrounding structures, thereby impairing a person’s abilities to govern emotions, recognize errors and patterns, coordinate movement, and remember. In the final stages, an afflicted person may lose all memory and mental functioning. Early diagnosis of MCI can provide?= ?99.479, p?<?.05); and between MCI & Mild AD (t?= ?36.254, p?<?.05). Confirmatory factor analysis indicated that tests measured the intended dimensions of memory, cognitive functions, and language. Initial and Final construct validation analyses indicated that the Neuropsychological Assessment for Mild cognitive Impairment (NAMCI) showed indications of being a reliable and valid screening instrument in determining mild cognitive impairment in Filipino Older Adults.     

Characteristics of cognitive function in early and late stages of amnestic mild cognitive impairment

Aim: The detection of the early stages in amnesic mild cognitive impairment (aMCI) is considered important in diagnosing progression to Alzheimer's disease. The current study sought to investigate differences in cognitive function between control subjects with no memory loss (control), and subjects in the early stage of aMCI (EMCI) and late stage of aMCI (LMCI). Methods: A total of 100 community‐dwelling older adults aged 65 years and over were recruited from 1543 potential subjects. Subjects were classified into three groups based on the degree of objective memory impairment; control (n = 29), EMCI (n = 34) and LMCI (n = 37). Multiple neuropsychological tests were carried out to examine cognitive function. Results: The EMCI individuals showed lower cognitive function relative to controls; not only in logical memory, but also in letter fluency (P < 0.05). There were no significant differences in neuropsychological scores between the EMCI and LMCI groups, except for category fluency and logical memory. In addition, the EMCI subjects' logical memory score showed a significant relationship with letter fluency, category fluency and digit span backward test performance (P < 0.05). Conclusions: These results suggest that the application of multiple neuropsychological tests might be useful in diagnosing older adults with EMCI and LMCI. Geriatr Gerontol Int 2013; 13: 83–89 .     

Development of a three‐factor neuropsychological approach for detecting minimal hepatic encephalopathy

Background: Minimal hepatic encephalopathy (HE) has profoundly negative effects on daily functioning ad quality of life. However, standard psychometric procedures have not been widely incorporated into efforts to develop a neuropsychological battery for this condition. Aims: To establish the construct and diagnostic validity of a neuropsychological approach for the recognition of minimal HE in patients with cirrhosis. Methods: A comprehensive battery of neuropsychological tests was administered to cirrhotic patients with at most grade 1 HE, recruited from the liver transplant and advanced liver disease clinics. An inflammatory bowel disease comparison group was similarly evaluated, thus controlling for the secondary effects of chronic illness on cognition. Testing results for the cirrhosis group were subjected to principal component analysis to establish the relevant cognitive constructs and associated measures. Factor analysis was applied to the neuropsychological battery of 20 tests to determine the cognitive factors to be used. Age‐adjusted standardized neuropsychological factor scores were then compared for the two groups. Results: Factor analysis revealed that our battery of 20 tests was measuring three cognitive factors. Based on the pattern of factor loadings, we labeled these important cognitive factors: global cognitive function; psychomotor speed; and learning and memory. Logistic regression revealed that only impaired psychomotor speed distinguished cirrhotics with no more than grade 1 HE from medically ill controls. Conclusions: The cirrhosis group was characterized by a pattern of preserved global cognitive functioning, mild memory impairment, and moderate psychomotor speed impairment. Discussion: This distinctive pattern of focal psychomotor speed deficits is suggestive of subcortical pathway involvement in minimal HE.     

Early experience using salvage radiotherapy for relapsed/refractory non-Hodgkin lymphomas after CD19 chimeric antigen receptor (CAR) T cell therapy

Radiotherapy is potentially an important salvage strategy post-chimeric antigen receptor T cell therapy (CART), but limited data exist. We reviewed 14 patients treated with salvage radiation post-CART progression (SRT). Most received SRT for first post-CART relapse (71%) to sites previously PET-avid pre-CART (79%). Median overall survival (OS) post-SRT was 10 months. Post-SRT, six localized relapses achieved 100% response (3 = complete, 3 = partial), with improved freedom from subsequent relapse (P = 0·001) and OS (P = 0·004) compared to advanced stage relapses. Three were bridged to allogeneic transplantation; at analysis, all were alive/NED. SRT has diverse utility and can integrate with novel agents or transplantation to attempt durable remissions.     

The association between blood pressure components and cognitive functions and cognitive reserve

Objective: Hypertension exerts a subtle impact on the brain that is revealed by diminished cognitive function. This study aimed at evaluating the association between blood pressure components and cognitive functions and cognitive reserve. Methods: In this cross-sectional study, 500 subjects from general population were evaluated. All neuropsychological tests were negatively associated with age; memory and executive function were also positively related with education. Results: The hypertensives (HT) were less efficient than the normotensives (NT) in the test of memory with interference at 10?s (MI-10) (?32%, p?=?0.043), clock drawing test (CLOX) (?26%, p?<?0.001), and mini-mental state examination (MMSE) (?7.4%, p?=?0.02). Lower MMSE, MI-10, and CLOX were predicted by higher systolic (OR, 0.94, p?=?0.032; OR 0.96, p?<?0.001; OR 0.94, p?<?0.001) and higher pulse pressure (BP) (OR 0.95, p?=?0.04; OR 0.97, p?<?0.001; and OR 0.92, p?<?0.001). The cognitive reserve index (CRI) was 8% lower in the HT (p?=?0.04) and was predicted by higher pulse BP (OR 0.86, p?<?0.001). The BP vectors of lower MMSE, MI-10, and CLOX were directed towards higher values of systolic and diastolic BP, that of low CRI towards higher systolic and lower diastolic. Conclusion: This study contributes to the belief that a link exists between BP and cognition, higher values of systolic BP being associated to impaired cognitive function.