Rosie E. Curiel

Test anxiety in relation to measures of cognitive and intellectual functioning.

The potential impact of test anxiety on cognitive testing was examined in a sample of 300 predominantly male veteran referrals who were administered a comprehensive neuropsychological test battery. Exclusionary criteria included failure on effort testing (n= 14). Level of test anxiety was significantly related to performance on the WAIS-III Working Memory Index (r = -.343, p < .001) but not to scores on the Processing Speed, Perceptual Organization, or Verbal Comprehension indexes. Test anxiety was not related to a global index of neuropsychological performance on the HRNES-R (Average Impairment Scale). Level of education had a collinear relationship with test anxiety in predicting cognitive test performance. Regression analyses revealed a more prominent role for education, indicating the possibility that test anxiety may be a reaction to, more than a cause of, deficient working memory performance. These results suggest that clinicians who use these particular tests should be reluctant to attribute poor test performance to anxiety that occurs during the testing process.

The utility of age-specific cut-offs for visual rating of medial temporal atrophy in classifying Alzheimer's disease, MCI and cognitively normal elderly subjects

Background: New research criteria for diagnosing Alzheimers disease (AD) in the mild cognitive impairment stage (MCI-AD) incorporate biomarkers to assign a level of certainty to the diagnosis. Structural MRI is widely available but greatly under-utilized for assessing atrophy of structures affected in early AD, such as the hippocampus (HP), because the quantification of HP volumes (HP-v) requires special expertise, and normative values have not been established. Methods: Elderly subjects (n =273) from the Florida ADRC were classified as having no cognitive impairment (cognitively normal, CN), amnestic mild cognitive impairment (aMCI) or AD. Volumes for the hippocampus (HP-v) were measured on structural MRI scans. A validated visual rating system for measuring medial temporal atrophy (VRS-MTA), including hippocampal, entorhinal cortex and perirhinal cortex atrophy was employed. The participants were subdivided into younger (less than or equal to 75 years of age) and older (greater than 75 years of age) subgroups. Results: Volumetric and VRS-MTA measures were equivalent in predicting classification of CN vs. aMCI for older (area under the receiver operator curves [aROC]: 0.652 vs. 0.723) and younger subjects (aROC: 0.764 vs. 0.736). However, for younger AD subjects, aROC values were significantly higher for VRS-MTA measures (0.920) than for volumetric measures (0.847). Relative to HP-v, VRS-MTA score was significantly more correlated to impairment on a range of memory tests and was more associated with progression of aMCI to AD than HP-v. Conclusion: Structural MRI with VRS-MTA assessment can serve as a biomarker for supporting the diagnosis of MCI-AD. Age-adjusted VRS-MTA scores are at least as effective as HP-v for distinguishing aMCI and AD from CN and for predicting progression from aMCI to AD. VRS-MTA is convenient for use in the clinic as well as for clinical trials and can readily be incorporated into a standardized radiological report.

A New Scale for the Evaluation of Proactive and Retroactive Interference in Mild Cognitive Impairment and Early Alzheimer’s Disease

Objective: The authors evaluated the psychometric properties and clinical utility of the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), in patients with amnestic Mild Cognitive Impairment (aMCI) and early Alzheimer’s disease (AD). Methods: Subjects were administered Target List A and instructed to remember 15 common words belonging to a specific semantic category, using multi-modal, active encoding procedures. After free recall and cued recall trials of the target list, a second learning trial was offered, followed by a cued recall trial, to facilitate the initial acquisition of targets. Thereafter, the subject was exposed to a semantically-related List B, which was administered in the same manner as Target List A. Test-retest reliability, concurrent and discriminative validity were assessed. LASSI-L measures were then correlated with Magnetic Resonance Imaging (MRI) measurements of medial temporal lobe atrophy (MTA). Results: High test-retest, concurrent and discriminative validity was obtained for LASSI-L subscales, and MTA atrophy scores were highly and negatively correlated with LASSI-L indices. Conclusion: Subtests of the LASSI-L demonstrate high reliability and validity, and are strongly associated with MRI biomarkers of early neurodegenerative disease. It is concluded that the LASSI-L is a highly promising test for the assessment of mild cognitive impairment and early AD among the elderly.

Validation of the Spanish Version of the LASSI-L for Diagnosing Mild Cognitive Impairment and Alzheimer’s Disease

BACKGROUND The Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L) is a novel cognitive test that measures recovery from proactive semantic interference, which may be an early cognitive marker of Alzheimers disease (AD). OBJECTIVE To generate normative data for a Spaniard population and to validate the LASSI-L for the diagnosis of amnestic mild cognitive impairment (aMCI) and mild AD. METHODS We performed a cross-sectional study in which 97 healthy participants, 34 with aMCI, and 33 with mild AD were studied with LASSI-L and a comprehensive neuropsychological protocol. The overlapping strategy analysis was used to maximize the sample size and to provide age- and education-adjusted normative data using a logistic regression analysis. RESULTS Internal consistency was 0.932. Convergent validity with the Free and Cued Selective Reminding Test was moderate. LASSI-L raw scores were correlated with age and years of education, but not gender. The area under the curve for discriminating between healthy controls and aMCI was 0.909, and between healthy controls and mild AD was 0.986. LASSI-L sub-scores representing maximum storage capacity, recovery from proactive interference, and delayed recall yielded the highest diagnostic accuracy. CONCLUSIONS The LASSI-L is a reliable and valid test for the diagnosis of aMCI and mild AD. The age and education influences on the performance of the test and normative data are provided. LASSI-L merits further studies to evaluate its ability to detect preclinical AD and predict progression to aMCI and early dementia.

Proactive Semantic Interference is Associated with Total and Regional Abnormal Amyloid Load in Non-Demented Community-Dwelling Elders: A Preliminary Study

OBJECTIVE To evaluate the relationship between susceptibility to proactive semantic interference (PSI) and retroactive semantic interference (RSI) and brain amyloid load in non-demented elders. METHODS 27 participants (11 cognitively normal [CN] with subjective memory complaints, 8 CN without memory complaints, and 8 with mild cognitive impairment [MCI]) underwent complete neurological and neuropsychological evaluations. Participants also received the Semantic Interference Test (SIT) and AV-45 amyloid PET imaging. RESULTS High levels of association were present between total amyloid load, regional amyloid levels, and the PSI measure (in the entire sample and a subsample excluding MCI subjects). RSI and other memory measures showed much weaker associations or no associations with total and regional amyloid load. No associations between amyloid levels and non-memory performance were observed. CONCLUSIONS In non-demented individuals, vulnerability to PSI was highly associated with total and regional beta-amyloid load and may be an early cognitive marker of brain pathology.

Novel Cognitive Paradigms for the Detection of Memory Impairment in Preclinical Alzheimer’s Disease:

In spite of advances in neuroimaging and other brain biomarkers to assess preclinical Alzheimer’s disease (AD), cognitive assessment has relied on traditional memory paradigms developed well over six decades ago. This has led to a growing concern about their effectiveness in the early diagnosis of AD which is essential to develop preventive and early targeted interventions before the occurrence of multisystem brain degeneration. We describe the development of novel tests that are more cognitively challenging, minimize variability in learning strategies, enhance initial acquisition and retrieval using cues, and exploit vulnerabilities in persons with incipient AD such as the susceptibility to proactive semantic interference, and failure to recover from proactive semantic interference. The advantages of various novel memory assessment paradigms are examined as well as how they compare with traditional neuropsychological assessments of memory. Finally, future directions for the development of more effective assessment paradigms are suggested.

Evaluating Different Aspects of Prospective Memory in Amnestic and Nonamnestic Mild Cognitive Impairment

Prospective memory, the inability to remember an intended action, is a common complaint, but not formally assessed in most clinical and research studies of mild cognitive impairment (MCI). In this study, patients with amnestic mild cognitive impairment (aMCI), non-amnestic cognitive impairment (naMCI), and cognitively normal (CN) elders were assessed using the Miami Prospective Memory Test (MPMT). A unique aspect of the paradigm was that participants were scored for intention to perform, accuracy in recollection for specific elements of the task, and the need for reminder cues. Excellent test-retest stability was obtained for MPMT Event-Related (ER), combined Time-Related (TR) subscales, and total MPMT score for aMCI subjects. MPMT impairments were observed in 48.6% of aMCI, 29.4% of naMCI, and 10.0% of normal elderly participants. Prospective memory deficits were common in participants with aMCI, and occurred in almost a third of naMCI participants. Intention to perform and need for reminder cues were significantly more impaired than retrospective memory for specific details of the task. It is concluded that assessment of different elements of prospective memory is important in MCI research and that inability to remember intended actions is a significant feature in those as risk for Alzheimers disease.

Case study: a patient with agenesis of the corpus callosum with minimal associated neuropsychological impairment.

This is a case study of an 88-year-old man who presented with agenesis of the corpus callosum and colpocephaly. Symptomatically, he reported a sudden onset of mild, intermittent left hand apraxia, but denied any previous manifestations consistent with this type of brain malformation. The patient underwent neuroimaging, evaluation by neurology, and comprehensive neuropsychological testing to determine the nature of any other associated impairments. Test results indicated that he was, with a few exceptions, neuropsychologically normal. He performed well on tests that are highly sensitive to acquired brain dysfunction. His most notable deficit was failed performance in the simultaneous and coordinated use of both hands in using tactile and proprioceptive feedback on the Tactual Performance Test. This case is discussed in terms of plasticity of the developing brain, including compensatory mechanisms, highlighting the variability in clinical outcome in the context of congenital brain malformation. This case study illustrates the strong influence of cerebral plasticity as well as a possible circumscribed manifestation of interhemispheric disconnection.

Comparison between FCSRT and LASSI-L to Detect Early Stage Alzheimer's Disease

BACKGROUND The Free and Cued Selective Reminding Test (FCSRT) is the most accurate test for the diagnosis of prodromal Alzheimers disease (AD). Recently, a novel cognitive test, the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), has been developed in order to provide an early diagnosis. OBJECTIVE To compare the diagnostic accuracy of the FCSRT and the LASSI-L for the diagnosis of AD in its preclinical and prodromal stages using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a reference. METHODS Fifty patients consulting for subjective memory complaints without functional impairment and at risk for AD were enrolled and evaluated using FCSRT, LASSI-L, and FDG-PET. Participants were evaluated using a comprehensive neurological and neuropsychological protocol and were assessed with the FCSRT and LASSI-L. FDG-PET was acquired concomitantly and used for classification of patients as AD or non-AD according to brain metabolism using both visual and semi-quantitative methods. RESULTS LASSI-L scores allowed a better classification of patients as AD/non-AD in comparison to FCSRT. Logistic regression analysis showed delayed recall and failure to recovery from proactive semantic interference from LASSI-L as independent statistically significant predictors, obtaining an area under the curve of 0.894. This area under the curve provided a better discrimination than the best FCSRT score (total delayed recall, area under the curve 0.708, p = 0.029). CONCLUSIONS The LASSI-L, a cognitive stress test, was superior to FCSRT in the prediction of AD features on FDG-PET. This emphasizes the possibility to advance toward an earlier diagnosis of AD from a clinical perspective.

A novel cognitive assessment paradigm to detect Pre-mild cognitive impairment (PreMCI) and the relationship to biological markers of Alzheimer's disease

OBJECTIVE A number of older adults obtain normal scores on formal cognitive tests, but present clinical concerns that raise suspicion of cognitive decline. Despite not meeting full criteria for Mild Cognitive Impairment (MCI), these PreMCI states confer risk for progression to Alzheimers disease (AD). This investigation addressed a pressing need to identify cognitive measures that are sensitive to PreMCI and are associated with brain biomarkers of neurodegeneration. METHOD Participants included 49 older adults with a clinical history suggestive of cognitive decline but normal scores on an array of neuropsychological measures, thus not meeting formal criteria for MCI. The performance of these PreMCI participants were compared to 117 cognitively normal (CN) elders on the LASSI-L, a cognitive stress test that uniquely assesses the failure to recover from proactive semantic interference effects (frPSI). Finally, a subset of these individuals had volumetric analyses based on MRI scans. RESULTS PreMCI participants evidenced greater LASSI- L deficits, particularly with regards to frPSI and delayed recall, relative to the CN group. No differences on MRI measures were observed. Controlling for false discovery rate (FDR), frPSI was uniquely related to increased dilatation of the inferior lateral ventricle and decreased MRI volumes in the hippocampus, precuneus, superior parietal region, and other AD prone areas. In contrast, other LASSI-L indices and standard memory tests were not related to volumetric findings. CONCLUSIONS Despite equivalent performance on traditional memory measures, the frPSI distinguished between PreMCI and CN elders and was associated with reductions in brain volume in numerous AD-relevant brain regions.