Norms for the Triana Test: A Story Recall Test Based on Emotional Material.

Background: The "Triana Test" is a novel story recall test based on emotional material with demonstrated accuracy in diagnosing mild cognitive impairment patients. Objective: This study aims to obtain normative data for the "Triana Test". Methods: A normative study was conducted at a university hospital in Spain. Partners of patients were systematically recruited if eligible (age ≥50, no memory complaints, and a total TMA-93 score at or above the 10th percentile). The "Triana Test" was administered and scored. For developing the normative data, a regression-based method was followed. Results: The final sample included 362 participants (median age = 66, range = 50-88; 64.9% females). A model including age and educational level better predicted the total scores. Combinations of these variables resulted in different 10th percentile scores. Conclusions: Norms for using the "Triana Test" are now available. The provided cutoffs for the 10th percentile will aid in the diagnosis of prodromal Alzheimer's disease.

Using Cognitive Reserve to Create Norms for the TMA-93 (Relational Binding of Images).

BACKGROUND: TMA-93 examines relational binding using images. Biomarker validation has demonstrated that it is discriminative for diagnosing early AD. The effect of cognitive reserve on TMA-93 performance remains unexplored and could improve the interpretative framework for using the test. OBJECTIVE: To study the effect of cognitive reserve on TMA-93 performance and to provide new norms for the test that include its measurement. METHODS: Cognitively unimpaired people aged 55 and over were systematically recruited for this cross-sectional normative study in southern Spain. Age, sex, and scores on the Cognitive Reserve Questionnaire (CRQ; maximum score: 25 points) were collected, and the TMA-93 was administered (maximum score: 30 points). Percentile-based reference data that captured combinations of socio-demographics variables with significant effect on TMA-93 performance were calculated. RESULTS: 902 participants (62.5% female; age: median = 68, IQR = 61-75, range = 55-90) were included. CRQ total scores were globally low (median = 8, IQR = 5-13, range = 0-24). Cognitive reserve, including modifiable items as reading activity and intellectual gaming activity, and age mainly supported the TMA-93 total score variance. Sex seemed to have some influence in the elderly. TMA-93 total scores medians began to drop from 70-75 years old. Higher total score on the CRQ and, possibly, female sex determined a gentler slope. New norms based on these variables showed wide variations in scores for the 5th and 10th percentiles. CONCLUSION: Visual relational binding ability depends on cognitive reserve, including modifiable items. The age-related binding deficit is buffered by higher cognitive reserve and, at older ages, by female sex.

Lessons learned from a sporadic FUSopathy in a young man: a case report.

BACKGROUND: In frontotemporal dementia (FTD) spectrum, younger patients may correspond to fusopathy cases, and cognitive decline could be rapidly progressive. We present a clinical and neuropathological description of a patient. CASE PRESENTATION: A 37-year-old man, without a family history of neurodegenerative diseases, was brought by his family to consult for dysarthria and behavioural change. Initial exploration showed spastic dysarthria and disinhibition. He progressively worsened with a pseudobulbar syndrome, right-lateralized pyramidal signs, left hemispheric corticobasal syndrome and, finally, lower motor neuron signs in his right arm. He died four years after the initiation of the syndrome from bronchopneumonia. Laboratory tests (including blood and cerebrospinal fluid (CSF)) were normal. Magnetic resonance imaging (MRI) and fluorodeoxyglucose-containing positron emission tomography (PET-18F-FDG) showed left fronto-insular atrophy and hypometabolism. Subsequently, 123I-ioflupane (DaT-SCAN®) single-photon emission computed tomography (SPECT) was pathologic, manifesting bilaterally decreased activity with greater affection on the left side. Only a third electromyogram (EMG) detected denervation in the last year of evolution. No mutations were found in genes such as Tau, progranulin, C9orf72, FUS, TDP-43, CHMP2B, or VCP. In necropsy, severe frontotemporal atrophy with basophilic neuronal cytoplasmic and intranuclear inclusions, negative for tau and TAR DNA binding protein 43 (TDP-43), but positive for fused in sarcoma (FUS) consistent with specifically basophilic inclusions body disease (BIBD) type was found. CONCLUSIONS: In patients affected by FTD, particularly the youngest, with rapidly progressive decline and early motor affection, fusopathy must be suspected. These cases can include motor signs described in the FTD spectrum. Lower motor neuron affection in EMG could be detected late.

Medical help-seeking intentions among patients with early Alzheimer's disease.

Background: Limited information is available on the active process of seeking medical help in patients with Alzheimer's disease (AD) at early stages. The aim of this study was to assess the phenomenon of medical help-seeking in early AD and to identify associated factors. Methods: A multicenter, non-interventional study was conducted including patients of 50-90 years of age with prodromal or mild AD (National Institute on Aging/Alzheimer's Association criteria), a Mini-Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5-1.0. A multivariate logistic regression analysis was conducted. Results: A total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years, 50.3% were female, and 87.2% had a CDR-GS score of 0.5. Mean disease duration was 1.4 (1.8) years. Ninety-four (63.1%) patients sought medical help, mostly from neurologists. Patients with help-seeking intentions were mostly female (60.6%) with a CDR-GS score of 0.5 (91.5%) and had a greater awareness of diagnosis, poorer quality of life, more depressive symptoms, and a more severe perception of their condition than their counterparts. Lack of help-seeking intentions was associated with male sex (p = 0.003), fewer years of education (p = 0.005), a low awareness of diagnosis (p = 0.005), and a low emotional consequence of the condition (p = 0.016). Conclusion: Understanding the phenomenon of active medical help-seeking may facilitate the design of specific strategies to improve the detection of cognitive impairment, especially in patients with a lower level of educational attainment and poor awareness of their condition.

Quality of Life and the Experience of Living with Early-Stage Alzheimer's Disease.

BACKGROUND: There is a need to better understand the experience of patients living with Alzheimer's disease (AD) in the early stages. OBJECTIVE: The aim of the study was to evaluate the perception of quality of life in patients with early-stage AD. METHODS: A multicenter, non-interventional study was conducted including patients of 50-90 years of age with prodromal or mild AD, a Mini-Mental State Examination (MMSE) score ≥22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5.-1.0. The Quality of Life in Alzheimer 's Disease (QoL-AD) questionnaire was used to assess health-related quality of life. A battery of self-report instruments was used to evaluate different psychological and behavioral domains. Associations between the QoL-AD and other outcome measures were analyzed using Spearman's rank correlations. RESULTS: A total of 149 patients were included. Mean age (SD) was 72.3 (7.0) years and mean disease duration was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1). The mean QoL-AD score was 37.9 (4.5). Eighty-three percent (n = 124) of patients had moderate-to-severe hopelessness, 22.1% (n = 33) had depressive symptoms, and 36.9% (n = 55) felt stigmatized. The quality of life showed a significant positive correlation with self-efficacy and negative correlations with depression, emotional and practical consequences, stigma, and hopelessness. CONCLUSION: Stigma, depressive symptoms, and hopelessness are frequent scenarios in AD negatively impacting quality of life, even in a population with short disease duration and minimal cognitive impairment.

Awareness of Diagnosis in Persons with Early-Stage Alzheimer's Disease: An Observational Study in Spain.

INTRODUCTION: Limited information is available on people's experiences of living with Alzheimer's disease (AD) at earlier stages. This study assessed awareness of diagnosis among people with early-stage AD and its impact on different person-centered outcome measures. METHODS: We conducted an observational, cross-sectional study in 21 memory clinics in Spain. Persons aged 50-90 years, diagnosed with prodromal or mild AD (NIA/AA criteria), a Mini Mental State Examination (MMSE) score ≥ 22, and a Clinical Dementia Rating-Global score (CDR-GS) of 0.5 or 1.0 were recruited. The Representations and Adjustment to Dementia Index (RADIX) was used to assess participants' beliefs about their condition and its consequences. RESULTS: A total of 149 persons with early-stage AD were studied. Mean (SD) age was 72.3 (7.0) years and 50.3% were female. Mean duration of AD was 1.4 (1.8) years. Mean MMSE score was 24.6 (2.1) and 87.2% had a CDR-GS score of 0.5. Most participants (n = 84, 57.5%) used a descriptive term related to specific AD symptoms (e.g., memory difficulties) when asked what they called their condition. Participants aware of their diagnosis using the term AD (n = 66, 45.2%) were younger, had more depressive symptoms, and poorer life satisfaction and quality of life compared to those without awareness of their specific diagnosis. Practical and emotional consequences RADIX scores showed a significant negative correlation with Quality of Life in Alzheimer's Disease score (rho = - 0.389 and - 0.413, respectively; p < 0.0001). Years of education was the only predictor of awareness of AD diagnosis [OR = 1.04 (95% CI 1.00-1.08); p = 0.029]. CONCLUSIONS: Awareness of diagnosis was a common phenomenon in persons with early-stage AD negatively impacting their quality of life. Understanding illness representations in earlier stages may facilitate implementing optimized care that supports improved quality of life and well-being.

Testing Visual Binding by the TMA-93 in People Aged 75 and Over.

BACKGROUND: TMA-93 examines relational binding using images. The test has been proven to be discriminative for diagnosing early Alzheimer's disease by biomarkers. Norms for this test are available, but the elderly, at high risk for Alzheimer's disease, have not yet been widely represented. OBJECTIVE: To extend normative data on the TMA-93 for people aged 75 and over. METHODS: An extension of the Spanish TMA-93 normative study was undertaken. Only cognitively unimpaired people aged 75 and over were included. Age, gender, and educational attainment were registered as socio-demographic variables. Using histograms analysis, median comparisons, and linear regression analysis, we selected variables that demonstrated influence on TMA-93 total scores and provided percentile-base reference data according to combinations of those variables. RESULTS: We included 431 new participants, resulting in a total sample of 657 individuals (median age = 78, interquartile range = 76-81, range = 75-93). Percentile-base reference data stratified by a combination of age ranges (75-79, n = 428; and ≥80 years, n = 229), and educational attainment (< first grade, n = 253; first grade, n = 209; > first grade, n = 195) revealed that participants achieved a minimum TMA-93 total score of 26/30 at the 50th-percentile regardless of stratum. At the 10th-percentile, a maximum of 24/30 was achieved in the more educated stratum contrasting with a minimum of 19/30 in the less educated stratum. CONCLUSION: Although mitigated by lower levels of education, performance on the TMA-93 is widely preserved in cognitively unimpaired people aged 75 and over. The test could facilitate the screening of elderly patients with memory complaints.

Evaluation of aquaporins in the cerebrospinal fluid in patients with idiopathic normal pressure hydrocephalus.

Brain aquaporin 1 (AQP1) and AQP4 are involved in cerebrospinal fluid (CSF) homeostasis and might participate in the origin of hydrocephalus. Studies have shown alterations of perivascular AQP4 expression in idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD). Due to the overlapping of clinical signs between iNPH and certain neurological conditions, mainly AD, specific biomarkers might improve the diagnostic accuracy for iNPH. The goal of the present study was to analyze and quantify the presence of AQP1 and AQP4 in the CSF of patients with iNPH and AD to determine whether these proteins can be used as biomarkers of iNPH. We examined AQP1 and AQP4 protein levels in the CSF of 179 participants (88 women) classified into 5 groups: possible iNPH (81 participants), hydrocephalus associated with other neurological disorders (13 participants), AD (41 participants), non-AD dementia (32 participants) and healthy controls (12 participants). We recorded each participant's demographic and clinical variables and indicated, when available in the clinical history, the record of cardiovascular and respiratory complications. An ELISA showed virtually no AQP content in the CSF. Information on the vascular risk factors (available for 61 patients) confirmed some type of vascular risk factor in 86% of the patients with possible iNPH and 58% of the patients with AD. In conclusion, the ELISA analysis showed insufficient sensitivity to detect the presence of AQP1 and AQP4 in CSF, ruling out the possible use of these proteins as biomarkers for diagnosing iNPH.

Preliminary Validation of the Triana Test: A New Story Recall Test Based on Emotional Material.

OBJECTIVE: To first validate the diagnostic accuracy of the "Triana Test," a new story recall test based on emotional material. METHOD: A phase I study of validation. We included 55 patients with amnestic Mild Cognitive Impairment and 69 healthy controls, diagnosed according to the "Memory Associative Test of the district of Seine-Saint-Denis" (TMA-93), and matched by age, gender, and educational level. The Triana Test's diagnostic accuracy was calculated by ROC curve analysis and Spearman correlations estimated its convergent validity with a hippocampal memory test, the Free and Cued Selective Reminding Test with Immediate Recall (FCSRT+IR). RESULTS: The "Triana Test" immediate and delayed recalls showed adequate diagnostic accuracy (AUC ≥ 0,74). The delayed free recall showed the highest diagnostic accuracy (AUC = 0.86). Correlations with the FCSRT+IR were moderate to strong. CONCLUSIONS: The "Triana Test" demonstrated accuracy for discriminating amnestic Mild Cognitive Impairment patients from healthy controls and convergent validity with the FCSRT+IR.

TMA-93 Validation by Alzheimer's Disease Biomarkers: A Comparison with the Free and Cued Selective Reminding Test on a Biobank Sample.

BACKGROUND: The Memory Associative Test TMA-93 examines visual relational binding, characteristically affected in early-AD stages. OBJECTIVE: We aim to validate the TMA-93 by biomarkers determination and compare its diagnostic characteristics with the Free and Cued Selective Reminding Test (FCSRT). METHODS: Retrospective analysis of a Biobank database. Patients' records initially consulted for memory complaints, scored MMSE≥22, had TMA-93 and FCSRT tested, and AD biomarker determination (Amyloid-PET or CSF), either positive or negative, were selected. As cutoffs, we considered the 10-percentile for TMA-93 (P10/TMA-93), and "total free recall" (TFR) 21/22, total recall (TR) 43/44, and Cued Index < 0.77 for FCSRT from previous Spanish validation and normative studies. Diagnostic utilities were calculated using ROC curves and compared by the DeLong method. We studied if one test improved the other test's prediction, following a forward stepwise logistic regression model. RESULTS: We selected 105 records: 64 "positive" and 41 "negative" biomarkers. TMA-93 total score diagnostic utility (AUC = 0.72; 95%CI:0.62-0.82) was higher than those of the FCSRT: TFR (AUC = 0.70; 95%CI: 0.60-0.80), TR (AUC = 0.63; 95%CI:0.53-0.74), and Cued Index (AUC = 0.62; 95%CI:0.52-0.73). The P10/TMA-93 cutoff showed 86%sensitivity, similar to that of the most sensitive FCSRT cutoff (TFR21/22, 89%) and 29%specificity, lower than that of the most specific FCSRT cutoff (Cued Index < 0.77, 57%). 32.8%of the positive-biomarker group scored above CI/0.77 but below p10TMA-93. The addition of TMA-93 total score to FCSRT variables improved significantly the biomarkers results' prediction. CONCLUSION: TMA-93 demonstrated "reasonable" diagnostic utility, similar to FCSRT, for discriminating AD biomarker groups. TMA-93 total score improved the AD biomarker result prediction when added to FCSRT variables.

Reliability and Feasibility of the Memory Associative Test TMA-93.

BACKGROUND: Memory tests focused on binding may be more sensitive to diagnose Alzheimer's disease (AD) at an early phase. TMA-93 examines relational binding by images. OBJECTIVE: Evaluate the reliability (internal consistency and inter-rater and test-retest reliability) and feasibility of the TMA-93 in a clinic setting with low-educated individuals and limited face-to-face time per patient. METHODS: The study was undertaken in a neurology outpatient clinic of a hospital in Southern Spain. The internal consistency of the TMA-93 was estimated in 35 patients with amnestic mild cognitive impairment (aMCI) and 40 healthy controls (HCs). The inter-rater reliability (by two raters) and feasibility (by recording the percentage of participants who completed the test, and by timing the administration time) were evaluated in HCs (n = 16), aMCI patients (n = 18), and mild dementia patients (n = 15). The test-retest reliability for the TMA-93 total score was studied in 51 HCs tested by the same examiner 2-4 months apart. The internal consistency was estimated by Cronbach's alpha. The inter-rater and test-retest reliability was quantified by the intraclass correlation coefficient (ICC). The administration time was compared by diagnosis. RESULTS: The internal consistency was "optimal" (Cronbach's alpha = 0.936). The test-retest reliability was "good" [ICC = 0.802 (CI 95%  = 0.653-0.887)]. The inter-rater reliability was "optimal" [ICC = 0.999, (CI 95%  = 0.999-1)]. All participants completed the test. The administration time ranged from less than 3 min in HCs to 6 min in aMCI patients, and 7 min in mild dementia patients. CONCLUSION: Good feasibility and reliability support using the TMA-93 for examining visual relational binding, particularly in the context of low-educational attainment and limited time per patient.

Norms for Testing Visual Binding Using the Memory Associative Test (TMA-93) in Older Educationally-Diverse Adults.

BACKGROUND: TMA-93 examines binding by images, a potential advantage for less-educated individuals. OBJECTIVE: To obtain norms from older Spanish adults for TMA-93. METHODS: A cross-sectional normative study was undertaken in a general neurology outpatient clinic of a university hospital in the Southern Spanish region of Andalusia. Partners of patients who attended the clinic were systematically recruited when eligible: aged 50 and over, no memory complaints, and a total score equal or above percentile 10 on Phototest. Age, gender, and educational attainment were considered as sociodemographic variables. TMA-93 was administered and the total score was registered. RESULTS: The final sample contained 1,131 participants (mean age = 65.7, SD = 9.2), including 305 individuals (27%) who did not completed primary studies. The total score on TMA-93 showed a non-normal, left asymmetric, and leptokurtic distribution (median = 29, interquartile range = 27-30, range = 16-30) mitigated by lower education and older age. Stratified analysis by age and education showed wide variations of the scores for the 5-percentile. CONCLUSION: TMA-93 runs with a ceiling effect in non-cognitively impaired older Spanish adults. The score for the 5-percentile depends on age and education. The test is feasible for low-educated individuals.

TMA-93 for Diagnosing Amnestic Mild Cognitive Impairment: A Comparison With the Free and Cued Selective Reminding Test.

BACKGROUND: TMA-93 examines binding by images, an advantage for the less educated individuals. AIM: To compare the discriminative validity of TMA-93 against the picture version of Free and Cued Selective Reminding Test (FCSRT) to distinguish patients with amnestic mild cognitive impairment (aMCI) from normal controls (NCs) without excluding less educated individuals. DESIGN: Phase I diagnostic evaluation study. PARTICIPANTS: A total of 30 patients with aMCI and 30 NCs matched for sociodemographics variables. STATISTICAL ANALYSIS: The diagnostic accuracy for each test was calculated by conducting receiver operating characteristic curve analysis. Hanley and McNeil method was used to compare diagnostic accuracy of different tests on the same sample. RESULTS: Up to 41.7% of the sample had less than a first grade of education. Both tests showed excellent diagnostic accuracy. The comparisons did not show significant differences. CONCLUSIONS: TMA-93 is so accurate as FCSRT to differentiate aMCI from controls including less educated individuals. The test could be considered as a choice in this sociodemographic context.