A new verbal learning and memory test for English- and Spanish-speaking older people.

Word-list verbal learning and memory tests with appropriate normative data can be highly sensitive to cognitive decline, but there are significant limitations of such tests available for use with older Hispanic and non-Hispanic people living in the US. The purpose of this study was to (1) create a new word-list learning and memory test in both English and Spanish and, (2) validate it with respect to sensitivity to cognitive impairment, and (3) develop statistical corrections for the effects of significant demographic variables, including ethnicity, language of administration, age, education, and gender. A community dwelling sample of 801 English- and Spanish-speaking older people was employed. Recall on learning trials and the delayed recall trial of the word-list learning test were strongly related to the Mini-Mental State Examination (MMSE). moderately related to age, and weakly related to gender and education. The relationship of word-list variables and the MMSE did not significantly differ across ethnicity/language groups. Regression coefficients for demographic variables were used in a statistical correction formula to adjust raw word-list scores, and then to develop specific percentile cut-off values.     

Evaluation of a computerized test system to screen for mild cognitive impairment

Background: Mild cognitive impairment (MCI) refers to the clinical condition between normal aging and Alzheimer's disease (AD) and has a high probability of developing into AD. Early detection of MCI is important because early detection and appropriate follow‐up treatment can prevent the disease from progressing. Therefore, MCI is an important candidate for screening and possible intervention. Methods: We have developed a computerized screening test system to identify cognitive decline. This system consists of six tests (age and year‐of‐birth validity test, three‐word memory test, time orientation test, first modified delayed‐recall test, visual working memory test and second modified delayed‐recall test). The scores obtained from three groups (MCI patients, AD patients and healthy control subjects) were analyzed to evaluate the sensitivity and specificity required for the screening of MCI. Results: The system was well accepted by the patients. All of the test procedures were completed within 5 min. Significant group differences in all test results were found. The system has sensitivity and specificity values of 82% and 87%, respectively, when used as a screen for MCI. Conclusion: The system is useful for the screening of cognitive disorders.     

Serial position effects in mild cognitive impairment

Mild cognitive impairment (MCI) is often associated with the preclinical phase of Alzheimer's disease (AD). Special scoring of word-list recall data for serial position has been suggested to improve discrimination of normal aging from dementia. We examined serial position effects in word-list recall for MCI participants compared to Alzheimer patients and controls. Individuals with MCI, like Alzheimer patients, had a diminished primacy effect in recalling words from a list. No alternative scoring system was better than standard scoring of word-list recall in distinguishing MCI patients from controls. Retention weighted scoring improved the discrimination of MCI and AD groups.     

Semantic interference deficits and the detection of mild Alzheimer's disease and mild cognitive impairment without dementia.

Impairment in delayed recall has traditionally been considered a hallmark feature of Alzheimer's disease (AD). However, vulnerability to semantic interference may reflect early manifestations of the disorder. In this study, 26 mildly demented AD patients (mild AD), 53 patients with mild cognitive impairment without dementia (MCI), and 53 normal community-dwelling elders were first presented 10 common objects that were recalled over 3 learning trials. Subjects were then presented 10 new semantically related objects followed by recall for the original targets. After controlling for the degree of overall memory impairment, mild AD patients demonstrated greater proactive but equivalent retroactive interference relative to MCI patients. Normal elderly subjects exhibited the least amount of proactive and retroactive interference effects. Recall for targets susceptible to proactive interference correctly classified 81.3% of MCI patients and 81.3% of normal elderly subjects, outperforming measures of delayed recall and rate of forgetting. Adding recognition memory scores to the model enhanced both sensitivity (84.6%) and specificity (88.5%). A combination of proactive and retroactive interference measures yielded sensitivity of 84.6% and specificity of 96.2% in differentiating mild AD patients from normal older adults. Susceptibility to proactive semantic interference may be an early cognitive feature of MCI and AD patients presenting for clinical evaluation.     

图片学习测验在识别老年人轻微认知功能损害中的作用

目的　分析图片学习测验在识别老年人轻微认知功能损害 (MCI)中的作用。方法　选择符合MCI诊断标准的老年人 4 8例与正常对照组 5 6名完成图片学习测验、简易智能状态检查、听觉词语学习测验及多种非记忆测验。结果　图片学习测验的 3个记忆指标 (图片短时记忆、延迟记忆和学习记忆 )在MCI与正常对照组之间有非常显著的差异。已经给出这三个图片记忆指标区分MCI与正常老年人的划界分、敏感性和特异性。结论　图片记忆操作简便、信度和效度好 ,可以作为临床医师筛选MCI的有效工具     

CERAD test performances in amnestic mild cognitive impairment and Alzheimer's disease

OBJECTIVES: The aim of the study was to examine the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test performances cross-sectionally in patients suffering from amnestic mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Moreover, we wanted to determine the sensitivity to amnestic MCI and mild AD, as well as the specificity of different CERAD subtests in our study groups. MATERIAL AND METHODS: Fifteen healthy elderly individuals, 15 amnestic MCI patients and 15 probable AD patients suffering from mild dementia were tested with the CERAD neurocognitive dementia screening test. RESULTS: Significant differences were found in all CERAD tests except Constructional praxis (copy) and Clock drawing between the controls and the AD group. The MCI group was differentiated from the controls only in the Wordlist learning test. In the language tests the sensitivity to MCI and AD was quite low and the specificity very high. In the savings scores the sensitivity to AD was high, but the specificity rather low. The Wordlist recognition test screened no false positives using the current cut-off score and the sensitivity to AD was 0.6, but only one MCI patient was detected using the current cut-off score. Raising the cut-off score also raised the sensitivity to MCI without dramatic loss of specificity. Cut-off scores for the Wordlist learning test and Wordlist delayed recall, which have been found to differentiate normal aging from dementia, are lacking in the Finnish CERAD. The current data indicates that the Wordlist learning test might be relatively sensitive to MCI. CONCLUSIONS: The results indicate that the Finnish CERAD test battery with its current cut-off scores has low sensitivity to MCI, and using it as a sole cognitive screening instrument for MCI and preclinical dementia might result in false negatives.     

The impact of self-reported depressive symptoms on memory function in neurological outpatients

OBJECTIVES: To examine the effect of self-reported depressive symptoms on memory function in a non-psychiatric, non-litigation outpatient sample and to identify which memory tests may be most susceptible for depression-related decline. METHODS: Self-reported depressive symptoms were measured by the Beck Depression Inventory (BDI-II) and memory function was assessed using a wide range of neuropsychological memory tests (digit span, word-list learning, visuospatial learning, incidental memory, story recall). Patients who visited the neurological outpatients clinic and were referred for a neuropsychological examination were included (N=50). RESULTS: Correlation analyses showed that the BDI-II was significantly correlated with immediate story recall, delayed verbal recognition and the digit span. Furthermore, patients with mild or moderate-to-severe depressive symptoms performed worse than non-depressed patients on immediate story recall, but not on any of the other memory tests. DISCUSSION: Memory performance is only minimally disrupted in neurological outpatients with depressive symptoms compared to non-depressed outpatients. These results are discussed in relation to limited mental effort and weak encoding in patients with self-reported depressive symptoms.     

Learning potential: a new method for assessing cognitive impairment

BACKGROUND: In recent years, it has been claimed that learning potential (also called cognitive plasticity or rehabilitation potential) may be a good predictor of the course of cognitive impairment and the process of dementia. The basic objective of this research program is to test the extent to which the "Battery of Learning Potential for Assessing Dementia" (BEPAD) discriminates healthy people from those diagnosed with Mild Cognitive Impairment (MCI) and with Alzheimer's Disease (AD). METHODS: Two hundred people: 100 healthy elders (51 women, 49 men, mean age: 73.13), 50 diagnosed with MCI (30 women, 20 men, mean age: 74.89), and 50 diagnosed with mild AD (36 women, 14 men, mean age: 75.07). Learning potential was assessed through dynamic assessment (or testing-the-limits), using experimental test-training-post-test, a form of evaluation closely related to functional or stress testing in medicine. In several previous studies the BEPAD was developed, with four tasks: visuo-spatial, verbal recall (including delayed verbal recall), executive control and verbal fluency. For all of these tasks, training procedures were developed, converting them into learning potential tests. RESULTS and CONCLUSIONS: All "dynamic" or learning scores (post-test) discriminate better healthy, MCI and AD subjects than all static or pre-test scores. A total of 89% of cases are correctly classified by the BEPAD: 95.7% of the healthy subjects, 90.6% of AD patients, and 71.1% of the MCI individuals were correctly classified.     

老年轻度认知障碍记忆损害特点的研究

目的探讨老年轻度认知障碍患者的记忆损害特点,比较不同神经心理学测验对诊断和发现轻度认知障碍的敏感性,筛选临床实用的简捷敏感的神经心理学测验工具。方法轻度认知障碍患者20例,轻度阿尔茨海默病患者26例,健康老年人30名。应用词语回忆测验、图片回忆测验、数字广度测验、本顿视觉保持测验C式A法及D式D法进行测试。结果轻度认知障碍组在图片回忆分、视觉保持测验D式D法正确分及持续错误分上的成绩较正常对照组差(P<0．05);轻度认知障碍组视觉保持测验D法成绩明显差于A法(P<0．01)。结论轻度认知障碍患者对具体视觉形象的记忆能力及对无意义图形的视觉记忆能力受损,存在即刻记忆和延迟记忆障碍,且延迟回忆较即刻回忆损害明显,短时记忆更新的可塑性差;图片回忆测试、本顿视觉保持测验的延迟回忆测试或与即刻回忆联合测试有助于轻度认知障碍的早期发现。     

Greater memory impairment in dementing females than males relative to sex-matched healthy controls

Previously we demonstrated sex differences in episodic memory in healthy elderly and suggested that normative data be separated by sex. The present study extended the exploration of sex differences on memory measures into two clinical populations, mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Seventy-six subjects with MCI and 101 subjects with AD diagnosed by a multidisciplinary team were included. These two groups were also compared to a group of 177 healthy elderly control participants. Sex differences on the Rey Auditory Verbal Learning Test (RAVLT; total and delayed recall) raw scores and Brief Visuospatial Memory Test–Revised (BVMT–R) were demonstrated within the healthy but not the MCI or AD groups. Calculating z scores by sex for both dementing groups based on the healthy controls suggested a larger performance gap between healthy and dementing women than between healthy and dementing men. MCI females were on average 0.48 standard deviations lower for total verbal learning compared to healthy female controls than were MCI males when compared to healthy male controls. For verbal delayed recall the gap was even larger (SD = 1.09). Similarly, on the BVMT–R, a measure of visual memory, the difference was 0.60 standard deviations for total visual learning and 0.99 standard deviations for delayed recall. This same sex difference, with females showing greater impairment compared to the controls group than did the males, was also present within the AD group. The greater memory impairment in dementing females rather than males when compared to sex-matched healthy controls was unlikely to be due to more severe illness since females performed equivalently to males on the Clinical Dementia Rating Scale, Mini-Mental Status Examination, and Dementia Rating Scale, and were also similar for age, education, and apolipoprotein status. The present study suggested relatively greater memory impairment in females with MCI or AD than in controls.     

轻度认知功能障碍患者的神经心理学研究

目的 探讨轻度认知功能障碍(MCI)患者神经心理学的特点. 方法 对42例MCI患者和55例健康对照者进行多项神经心理学检查,包括简易精神状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)、临床痴呆评定量表(CDR)、语言流畅性测验(RVR)、韦氏智力测验(WAIS-RC)[包括数字广度测验(DS)、积木测验(BD)、相似性测验]、韦氏记忆测验(WMS-R)(包括逻辑记忆、联想学习、视觉再认、图片回忆)、日常生活能力量表(ADL),比较2组患者上述量表评分和MMSE、MoCA量表各亚项评分的差异.结果 与对照者比较,MCI患者MMSE、MoCA总分和RVR、WAIS-RC、WMS-R分测验,MoCA量表各亚项(地点定向力除外),MMSE量表中计算与注意、延迟回忆两亚项评分较低,差异均有统计学意义(P<0.05).结论 MCI患者不仅记忆受损,其计算与注意力、命名、视空间结构能力、执行功能也可受损,尤以延迟回忆、计算与注意力受损明显.MoCA涵盖了重要的认知领域,能较全面评估MCI患者的认知功能,值的临床推广应用.     

Routine clinical diagnosis of primary progressive non-fluent aphasia

It may be difficult to distinguish between a primary progressive aphasia at a very mild stage from the beginning of Alzheimer's disease (AD). However, this may be achieved by carrying out simple neuro-psychological tests. Nine non-fluent PPA (NFPPA) and 76 AD patients with comparable MMSE as well as 58 control subjects were evaluated using simple tests: MMSE, fluency, apraxia, naming, digital span, story memory, 5 words memory test. NFPPA patients had significantly impaired functions during the semantic category fluency and naming tests as compared to AD patients, whereas they showed a better delayed recall of the 5 words and story memory tests. As compared to AD, MMSE of NFPPA patients was also better in the time orientation and word recall sub-tests, although inferior in words repetition and language items. Thus, with comparable MMSE, NFPPA patients have more lexico-semantic difficulties, but a better delayed verbal memory than AD patients. These simple tests easily confirm the language impairment of NFPPA patients as opposed to the mnestic difficulties of AD, even at very early stages of these pathologies.     

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.     

Neuropsychological features of mild cognitive impairment and preclinical Alzheimer's disease

Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). MCI patients experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. An issue currently under investigation is whether MCI represents the preclinical stages of AD or a distinct and static cognitive aetiology. In an attempt to address this issue, the present investigations are adopting a convergent approach to the detection of preclinical AD, where multiple risk factors are considered when making a diagnosis. Currently, one of the most important tools when assessing early cognitive changes is neuropsychological evaluation. MCI subjects typically record neuropsychological performance between that of healthy older individuals and demented patients. Tests assessing new learning, delayed recall and attention/executive function seem to provide valuable information for screening and diagnosis of MCI and early AD if interpreted properly. Recommendations concerning methodological issues and the early management of neuropsychological MCI studies were made.     

Patterns of verbal memory performance in mild cognitive impairment, Alzheimer disease, and normal aging.

OBJECTIVE: Individuals with mild cognitive impairment (MCI) typically demonstrate memory loss that falls between normal aging (NA) and Alzheimer disease (AD), but little is known about the pattern of memory dysfunction in MCI. METHOD: To explore this issue, California Verbal Learning Test (CVLT) performance was examined across groups of MCI, AD, and NA. RESULTS: MCI subjects displayed a pattern of deficits closely resembling that of AD, characterized by reduced learning, rapid forgetting, increased recency recall, elevated intrusion errors, and poor recognition discriminability with increased false-positives. MCI performance was significantly worse than that of controls and better than that of AD patients across memory indices. Although qualitative analysis of CVLT profiles may be useful in individual cases, discriminant function analysis revealed that delayed recall and total learning were the best aspects of learning/memory on the CVLT in differentiating MCI, AD, and NA. CONCLUSIONS: These findings support the position that amnestic MCI represents an early point of decline on the continuum of AD that is different from normal aging.     

Diagnostic and screening power of neuropsychological testing in detecting mild cognitive impairment in Parkinson’s disease

Prevalence of mild cognitive impairment (MCI) in Parkinson’s disease (PD) is variable likely due to methodological differences in classification criteria and lack of consensus about neuropsychological tests used for cognitive profiling. The main objective of our study was to identify the most suitable neuropsychological tests and determine their screening and diagnostic cutoff scores for PD-MCI. A series of 104 consecutive PD patients performed an extensive neuropsychological evaluation. Individual test values were converted into Z-scores using relative published normative data. According to published criteria, PD patients were categorized as PD-CNT (PD without cognitive impairment), PD-MCI (patients performing ?1.5 SDs below the mean score in at least one cognitive domain), and PDD. We used receiver operating characteristic (ROC) curves and K-means clustering analyses to calculate the best discriminating power of each neuropsychological tests in detecting PD-MCI. PD patients were categorized as follows: 55 PD-CNT (53 %), 34 PD-MCI (33 %), and 15 PDD (14 %). PD-MCI had lower education, longer disease duration and greater frequency of hallucinations than PD-CNT. We found that only the Trail Making test, Rey-Osterrieth Complex Figure Test (ROCF) copy, Frontal Assessment Battery (FAB), Digit Span Backward, and Rey’s word auditory verbal learning test (RVLT) immediate recall reached significant screening and diagnostic validity in predicting PD-MCI (AUC 0.705–0.795) with cutoff scores calculated by ROC analyses lying within normal range for normative data. Specific neuropsychological tests covering verbal memory, attention/set-shifting, and visual-spatial deficits are the best predictors of MCI in PD if valid cutoff scores are used. These results have consequences for cognitive diagnosis and potentially in establishing the rate of PD cognitive decline.     

Mild cognitive impairment and Alzheimer's disease: an investigation of the CERAD-NP test battery

To investigate the psychometric properties of the German version of the CERAD-NP, neuropsychological deficits were compared between 49 patients with mild cognitive impairment (MCI), 80 patients with Alzheimer's disease (AD), 36 with major depression (MD), and 26 elderly controls. All participants were outpatients of the memory clinic of the Section of Geriatric Psychiatry, Heidelberg University. Diagnoses were established based on clinical examination, laboratory testing, neuroimaging, and routine neuropsychological testing according to the criteria of aging-associated cognitive decline (AACD) for MCI, NINCDS-ADRDA for AD, and DSM-IV for MD, respectively. All CERAD-NP subtests discriminated between controls and AD patients with the latter showing significantly (p< or = 0.05) lower test scores. The subtests verbal fluency and constructive apraxia differed significantly between mildly and moderately AD, while the subtests assessing declarative (epsisodic) memory performance showed only minor, non-significant differences between the respective groups. The LKB patients took an intermediate position between controls and AD patients with significantly lower scores in verbal fluency and declarative memory performance than the controls. When compared with the AD patients, MCI patients were significantly impaired in all subtests except constructive apraxia. Relative to the controls, the patients with MD showed a decreased episodic memory performance but no evidence suggesting an impairment in other neuropsychological domains. Our results indicate that the CERAD-NP is a psychometric instrument which allows a sensitive discrimination between mild and moderate AD, MCI, MD and healthy controls. However, sensitivity of discrimination between different stages of dementia varies with respect to the different subtest. While the subtest for episodic memory showed floor effects already for mild dementia, subtests for verbal fluency and constructive apraxia were able to discriminate even between more advanced stages of the disease.     

Automated Neuropsychological Test Battery (CANTAB) in mild cognitive impairment and in Alzheimer's disease

Neuropsychological deficits, such as poor episodic memory, are consistent features of mild cognitive impairment and also that of early stage of dementia. The aim of the present study was to detect cognitive dysfunction among patients with Alzheimer's disease or with mild cognitive impairment (MCI), which refers to a transitional state between the cognition of normal aeging and mild dementia regarded as a high-risk condition for the development of clinically probable Alzheimer's disease (AD). Computerized tests of memory, attention and executive functions were studied in groups of AD subjects (n=15) and MCI subjects (n=25). On all measures, the performance of the AD group was significantly weaker compared to healthy individuals or to the MCI group. The performance of both the AD and MCI patients in the Paired Associate Learning test was significantly impaired, which may suggest that MCI patients are already in the early stages of the disease.     

Different deficit patterns on word lists and short stories predict conversion to Alzheimer’s disease in patients with amnestic mild cognitive impairment

Episodic memory impairment is the most common and initial cognitive symptom of AD related to the early involvement of the medial temporal lobe (MTL). In this study, we compared performance on tasks routinely used in the neuropsychological assessment of episodic memory to evaluate which test is more sensitive in predicting subsequent progression to AD in patients with amnestic mild cognitive impairment (a-MCI). For this purpose, we conducted a longitudinal study in 61 patients diagnosed as a-MCI at baseline and followed for 3 years. Baseline memory performance on the word list and short story tests was analyzed to determine the diagnostic ability of the tests to predict subsequent conversion to AD. Results showed that stable a-MCI patients performed worse on word list than on story recall, whereas patients who later converted to AD tended to have similar poor memory performance on both tasks. Furthermore, a pronounced memory decay passing from immediate to delayed recall on the short story test was significantly associated with both higher risk and faster mean time of conversion to AD. We hypothesized that this pattern of results is a consequence of the early involvement in converter a-MCI of MTL areas which are fundamental in the consolidation of new memory traces.     

Cerebrospinal fluid biomarkers and memory present distinct associations along the continuum from healthy subjects to AD patients

The objective was to study the association between cerebrospinal fluid (CSF) levels of amyloid-β (Aβ)(1-42), t-tau, and p-tau and cognitive performance along the Alzheimer's disease (AD) continuum from healthy subjects to AD patients and, specifically, among patients in the pre-dementia stage of the disease. A total of 101 subjects were studied: 19 healthy controls (CTR), 17 subjects with subjective memory complaints (SMC), 47 with mild cognitive impairment (MCI), and 18 AD patients. Only memory performance significantly correlated with CSF levels of Aβ(1-42), t-tau, and p-tau along the AD continuum. Subgroup analyses revealed that in SMC patients Aβ(1-42) levels positively correlated with the total recall score of the Free and Cued Selective Reminding Test (FCRST) (r = 0.666; p < 0.005), Digit Span (r = 0.752; p < 0.005), and CERAD world list learning (r = 0.697; p < 0.005). In MCI patients, a significant inverse correlation was found between the word list recall score from the CERAD and t-tau (r = -0.483; p < 0.005) and p-tau levels (r = -0.495; p < 0.005), as well as between the total recall subtest score from the FCRST and both t-tau (r = -0.420; p < 0.005) and p-tau levels (r = -0.422; p < 0.005). No significant correlations were found between other aspects of cognition and CSF levels in CTR or AD patients. These results indicate that memory performance is related to Aβ(1-42) levels in SMC, while it is associated with tau in the prodromal stage of the disease. This suggests that in the continuum from healthy aging to AD, memory performance is first related with Aβ(1-42) levels and then with t-tau or p-tau, before becoming independent of biomarker levels in the dementia stage.