María Valles-Salgado

Evaluation of the new consensus criteria for the diagnosis of primary progressive aphasia using fluorodeoxyglucose positron emission tomography.

Background: New consensus criteria have been proposed to classify primary progressive aphasia (PPA) into three variants: agrammatic, semantic, and logopenic. Some studies have subsequently addressed the usefulness of these criteria, with controversial results. We aimed to determine the correlation between the clinical diagnosis according to the new criteria and brain topography in 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). Methods: Patients meeting the PPA criteria were prospectively recruited in a single center during a period of 18 months. They were clinically classified according to the new criteria and underwent FDG-PET. The cerebral metabolism of each patient was compared to a healthy control group using statistical parametric mapping. The expected variant according to the analysis of PET imaging was compared with the clinical diagnosis using the consensus criteria. Results: 32 patients were included. 90% of them fulfilled the consensus criteria and could be classified into one of the three clinical variants. The correlation with the cerebral metabolism was high: the kappa index was 0.91 in the agrammatic variant, 0.71 in the semantic variant, and 0.74 in the logopenic variant. Conclusions: A high correlation with the diagnosis obtained using FDG-PET was found. However, an overdiagnosis of the logopenic variant was observed. These results support the use of the new criteria, but some modifications or complementary studies may still be necessary.

Normative Data for the Spanish Version of the Addenbrooke's Cognitive Examination III

Background: Addenbrookes Cognitive Examination III (ACE-III) is a cognitive test that has been validated for the diagnosis of cognitive disorders. The aim of this study was to provide normative data for the ACE-III for age, education and gender. Methods: The Spanish version of the ACE-III was administered to a group of 273 healthy subjects in a multicenter study in Spain. Correlation and determination coefficients for age, education and gender were estimated. The overlapping interval strategy and linear regression analyses were used to provide adjusted norms for demographic factors and to explore the potential influence of these factors in the performance of the test. Results: Age and education correlated significantly with the total score and with all the domains. Gender correlated only with the domains of attention and visuospatial skills. Norms for the total score and for cognitive domains (attention, memory, fluency, language, and visuospatial skills) are provided. Conclusion: This study confirms the influence of demographic factors (especially age and education) on the performance in the ACE-III and provides normative data for the Spanish version of the ACE-III.

The Hayling Test: Development and Normalization of the Spanish Version

OBJECTIVE The Hayling Sentence Completion Test evaluates the ability to inhibit an automatic response. It has also been suggested for the assessment of orbitofrontal cortex function. The aim of the study was to develop a Spanish version of the Hayling test and to obtain normative data. METHOD Responses to 60 sentences from 50 healthy controls were used to develop the task. Additionally, 185 healthy controls aged between 18 and 99 years were examined with the test in order to obtain normative data. The overlapping interval strategy was used to maximize the sample size. Age- and education-adjusted scores were obtained using linear regression analysis. RESULTS Age and educational level had a significant effect on the different scores. Good internal reliability and inter-rater variability were observed. CONCLUSIONS We provide normative data adjusted for age and education. Our results enable the use of this test for clinical and research purposes in the field of neuropsychological assessment.

Different apathy clinical profile and neural correlates in behavioral variant frontotemporal dementia and Alzheimer's disease

Apathy is one of the most common and disabling syndromes of dementia. Clinical apathy expression and neuroanatomical basis of apathy seem to differ between behavioral variant frontotemporal dementia (bvFTD) and Alzheimers disease (AD), although evidence is scarce and poorly understood. Our main purposes were to compare the clinical apathy profile from patients with bvFTD and AD and analyze the relationship between apathy and brain metabolism measured using positron emission tomography imaging with 18F fluorodeoxyglucose (FDG‐PET).

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.

Addenbrooke's cognitive examination III: diagnostic utility for mild cognitive impairment and dementia and correlation with standardized neuropsychological tests.

BACKGROUND Addenbrookes Cognitive Examination III (ACE-III) is a screening test that was recently validated for diagnosing dementia. Since it assesses attention, language, memory, fluency, and visuospatial function separately, it may also be useful for general neuropsychological assessments. The aim of this study was to analyze the tools ability to detect early stages of Alzheimers disease and to examine the correlation between ACE-III scores and scores on standardized neuropsychological tests. METHODS Our study included 200 participants categorized as follows: 25 healthy controls, 48 individuals with subjective memory complaints, 47 patients with amnestic mild cognitive impairment and 47 mild Alzheimers disease, and 33 patients with other neurodegenerative diseases. RESULTS The ACE-III memory and language domains were highly correlated with the neuropsychological tests specific to those domains (Pearson correlation coefficient of 0.806 for total delayed recall on the Free and Cued Selective Reminding Test vs. 0.744 on the Boston Naming Test). ACE-III scores discriminated between controls and patients with amnestic mild cognitive impairment (AUC: 0.906), and between controls and patients with mild Alzheimers disease (AUC: 0.978). CONCLUSION Our results suggest that ACE-III is a useful neuropsychological test for assessing the cognitive domains of attention, language, memory, and visuospatial function. It also enables detection of Alzheimers disease in early stages.

Comparative Diagnostic Accuracy of the ACE-III, MIS, MMSE, MoCA, and RUDAS for Screening of Alzheimer Disease

Background: Our aim was to evaluate and compare the diagnostic properties of 5 screening tests for the diagnosis of mild Alzheimer disease (AD). Methods: We conducted a prospective and cross-sectional study of 92 patients with mild AD and of 68 healthy controls from our Department of Neurology. The diagnostic properties of the following tests were compared: Mini-Mental State Examination (MMSE), Addenbrookes Cognitive Examination III (ACE-III), Memory Impairment Screen (MIS), Montreal Cognitive Assessment (MoCA), and Rowland Universal Dementia Assessment Scale (RUDAS). Results: All tests yielded high diagnostic accuracy, with the ACE-III achieving the best diagnostic properties. The area under the curve was 0.897 for the ACE-III, 0.889 for the RUDAS, 0.874 for the MMSE, 0.866 for the MIS, and 0.856 for the MoCA. The Mini-ACE score from the ACE-III showed the highest diagnostic capacity (area under the curve 0.939). Memory scores of the ACE-III and of the RUDAS showed a better diagnostic accuracy than those of the MMSE and of the MoCA. All tests, especially the ACE-III, conveyed a higher diagnostic accuracy in patients with full primary education than in the less educated group. Implementing normative data improved the diagnostic accuracy of the ACE-III but not that of the other tests. Conclusions: The ACE-III achieved the highest diagnostic accuracy. This better discrimination was more evident in the more educated group.

Neural Basis of Cognitive Assessment in Alzheimer Disease, Amnestic Mild Cognitive Impairment, and Subjective Memory Complaints

INTRODUCTION Interpreting cognitive tests is often challenging. The same test frequently examines multiple cognitive functions, and the functional and anatomical basis underlying test performance is unknown in many cases. This study analyses the correlation of different neuropsychological test results with brain metabolism in a series of patients evaluated for suspected Alzheimer disease. METHODS 20 healthy controls and 80 patients consulting for memory loss were included, in which cognitive study and 18F-fluorodeoxyglucose PET were performed. Patients were categorized according to Reisbergs Global Deterioration Scale. Voxel-based analysis was used to determine correlations between brain metabolism and performance on the following tests: Free and Cued Selective Reminding Test (FCSRT), Boston Naming Test (BNT), Trail Making Test, Rey-Osterrieth Complex Figure test, Visual Object and Space Perception Battery (VOSP), and Tower of London (ToL) test. RESULTS Mean age in the patient group was 73.9 ± 10.6 years, and 47 patients were women (58.7%). FCSRT findings were positively correlated with metabolism in the medial and anterior temporal region bilaterally, the left precuneus, and posterior cingulate. BNT results were correlated with metabolism in the middle temporal, superior, fusiform, and frontal medial gyri bilaterally. VOSP results were related to the occipital and parietotemporal regions bilaterally. ToL scores were correlated to metabolism in the right temporoparietal and frontal regions. CONCLUSIONS These results suggest that different areas of the brain are involved in the processes required to complete different cognitive tests. Ascertaining the functional basis underlying these tests may prove helpful for understanding and interpreting them.

Validation of the Lille's Apathy Rating Scale in Very Mild to Moderate Dementia.

OBJECTIVE Apathy is one of the most common and disabling syndromes of dementia and presents at all stages of the disease. Comprehensive and structured methods to assess apathy in dementia are still needed. Lilles Apathy Rating Scale (LARS) has shown good psychometric properties for apathy evaluation in Parkinson disease but has not been validated in dementia. The aim of this study was to validate the LARS in a cohort of patients with very mild to moderate dementia. METHODS 101 patients with cognitive impairment (Clinical Dementia Rating ≤ 2) and 50 healthy subjects were recruited. Patient diagnoses included 43 individuals with Alzheimer disease, 41 frontotemporal dementia, and 17 primary progressive aphasia. In addition to LARS, the following assessments were administered: Clinical Dementia Rating, Interview for Deterioration in Daily Living Activities in Dementia, Functional Activities Questionnaire, Frontal Behavioral Inventory, Neuropsychiatric Inventory (NPI), and Hamilton Depression Rating Scale. RESULTS Internal consistency for LARS (Cronbachs alpha) was 0.940. Test-retest intraclass correlation coefficient (ICC) was 0.940 and inter-rater ICC was 0.987. The correlation among LARS and NPI apathy scores (concurrent validity) was 0.834. Receiver operating characteristic analysis estimated an area under the curve of 0.987. The optimal cutoff point was -10. Although total LARS score was influenced by the presence of depression, this disorder was independent with respect to apathy. CONCLUSION LARS is reliable and valid for detecting and quantifying apathy in patients with dementia, even in very early stages of the disease.

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.