Regression-Based Normative Data for Independent and Cognitively Active Spanish Older Adults: Free and Cued Selective Reminding Test, Rey–Osterrieth Complex Figure Test and Judgement of Line Orientation

The aim of this work was to develop normative data for neuropsychological tests for the assessment of independent and cognitively active Spanish older adults over 55 years of age. Methods: regression-based normative data were calculated from a sample of 103 nondepressed independent community-dwelling adults aged 55 or older (66% women). The raw data for the Free and Cued Selective Reminding Test (FCSRT), the Rey–Osterrieth Complex Figure Test (ROCF) and the Judgement of Line Orientation Test (JLO) were regressed on age, sex and education. The model predicting the FCSRT delayed-recall (FCSRT-Del) scores also included the FCSRT immediate-recall (FCSRT-Imm) scores. The model predicting the ROCF immediate-recall (ROCF-Imm) scores included the ROCF copy-trial (ROCF-C) scores, and the model predicting the ROCF delayed-recall (ROCF-Del) scores included both the ROCF-C and the ROCF-Imm scores. In order to identify low scores, z-scores were used to determine the discrepancy between the observed and the predicted scores. The base rates of the low scores for both the SABIEX normative data and the published normative data obtained from the general population were compared. Results: the effects of the different sociodemographic variables (age, sex and education) varied throughout the neuropsychological measures. Despite finding similar proportions of low scores between the normative data sets, the agreement was irrelevant or only fair-to-good. Conclusions: the normative data obtained from the general population might not be sensitive enough to identify low scores in cognitively active older adults, incorrectly classifying them as cognitively normal compared to the less active population.

Enhancing the Sensitivity of Memory Tests: Reference Data for the Free and Cued Selective Reminding Test and the Logical Memory Task from Cognitively Healthy Subjects with Normal Alzheimer’s Disease Cerebrospinal Fluid Biomarker Levels

Background: Cognitive performance of a given individual should be interpreted in the context of reference standards obtained in cognitively healthy populations. Recent evidence has shown that removing asymptomatic individuals with biomarker evidence of Alzheimer’s disease (AD) pathology from normative samples increases the sensitivity of norms to detect memory impairments. These kind of norms may be useful for defining subtle cognitive decline, the transitional cognitive decline between normal cognition and mild cognitive impairment. Objective: The present study aims to provide norms for the Free and Cued Selective Reminding Test (FCSRT) and the Logical Memory subtest of the Wechsler Memory Scale-IV in a sample of individuals aged 50–70 years with normal levels of amyloid (A) and tau (T) cerebrospinal fluid (CSF) biomarkers. Methods: The sample was composed of 248 individuals from the ALFA+ study with negative amyloid-β and tau CSF biomarker levels. Regression-based norms were developed, including adjustments for age, education, and sex when applicable. Results: We found that education was associated with the performance in all the variables of both tests while age had a marginal effect only in the delayed free recall of the FCSRT. Sex was also related to the performance in the FCSRT, with women outperforming men. Equations to calculate z-scores and normative percentile tables were created. As compared with previously published norms the reference data presented were more sensitive but less specific, as expected. Conclusion: The use of the norms provided in this work, in combination with the already published conventional norms, may contribute to detecting subtle memory impairment.

A-17 Examining Cognitive Trajectories in SuperAgers within the LonGenity Study

Objective Rogalski and colleagues (2013) use the term SuperAgers to indicate individuals aged 80 and older who have exceptional memory with the goal of clarifying factors that impact successful aging. Using a modified definition, we explored cognitive trajectories of SuperAgers within our longitudinal study of the genetic factors associated with exceptional longevity (OPEL) in individuals of Ashkenazi Jewish descent. Method LonGenity Study participants complete annual physical and cognitive assessments which include the Free and Cued Selective Reminding Test (FCSRT) and WMS-R Logical Memory (LMI). All participants who completed a visit at age 80 were included in the analysis (N = 230; 56.5% female; mean education 17.57 ± 2.74 years; 46.5% OPEL; median follow-up 4 years). Twenty-one participants met modified SuperAger criteria (FCSRT: >38 and LMI: >25; no other cognitive impairment). Descriptive statistics, t-tests, and linear mixed effects models of cognitive trajectories were used to examine the differences between SuperAgers and non-SuperAgers. Results Although there were no differences in demographics or familial history of exceptional longevity, SuperAgers were less likely to have a history of cardiac problems (p = 0.02). Overall cognitive functioning remained stable with age in the SuperAgers, whereas non-SuperAgers demonstrated declining overall cognition with age (β = −0.029, CI: −0.036—0.022). Memory task performances demonstrated a similar discrepancy in trajectories. Conclusion(s) In our unique and high functioning population, SuperAgers as defined at age 80 do not demonstrate the typical cognitive declines thought to be associated with age. Vascular risk factors appear to play a role, but further investigation including exploring genetic markers and MRI is warranted.

Diagnostic Validity of the Smart Aging Serious Game: An Innovative Tool for Digital Phenotyping of Mild Neurocognitive Disorder

Background: The Smart Aging Serious Game (SASG) is an ecologically-based digital platform used in mild neurocognitive disorders. Considering the higher risk of developing dementia for mild cognitive impairment (MCI) and vascular cognitive impairment (VCI), their digital phenotyping is crucial. A new understanding of MCI and VCI aided by digital phenotyping with SASG will challenge current differential diagnosis and open the perspective of tailoring more personalized interventions. Objective: To confirm the validity of SASG in detecting MCI from healthy controls (HC) and to evaluate its diagnostic validity in differentiating between VCI and HC. Methods: 161 subjects (74 HC: 37 males, 75.47±2.66 mean age; 60 MCI: 26 males, 74.20±5.02; 27 VCI: 13 males, 74.22±3.43) underwent a SASG session and a neuropsychological assessment (Montreal Cognitive Assessment (MoCA), Free and Cued Selective Reminding Test, Trail Making Test). A multi-modal statistical approach was used: receiver operating characteristic (ROC) curves comparison, random forest (RF), and logistic regression (LR) analysis. Results: SASG well captures the specific cognitive profiles of MCI and VCI, in line with the standard neuropsychological measures. ROC analyses revealed high diagnostic sensitivity and specificity of SASG and MoCA (AUCs > 0.800) in detecting VCI versus HC and MCI versus HC conditions. A classification accuracy acceptable-to-excellent was found for MCI and VCI (HC versus VCI; RF: 90%, LR: 91%. HC versus MCI; RF: 75%; LR: 87%). Conclusion: SASG allows the early assessment of cognitive impairment through ecological tasks and potentially in a self-administered way. These features make this platform suitable for being considered a useful digital phenotyping tool, allowing a non-invasive and valid neuropsychological evaluation, with evident implications for future digital-health trails and rehabilitation.

Effects of Vibration Training on Cognition and Quality of Life in People with Multiple Sclerosis

Background: Multiple sclerosis (MS) detrimentally affects cognition and quality of life (QOL). Interventions that can improve cognitive deficit and QOL in people with MS are desired. This pilot study investigated the possible effects of vibration training on improving cognition and QOL in people with MS. Methods: Eighteen adults with MS were randomized into two groups: training and control. The training group underwent 6 weeks of vibration training, and the control group maintained their normal lifestyle throughout the study. In both groups, before and after the training course, the disability status was evaluated by the Patient-Determined Disease Steps scale and the Multiple Sclerosis Functional Composite (MSFC), cognitive function was assessed by the Behavior Rating Inventory of Executive Function (BRIEF) and the Selective Reminding Test (SRT), and QOL was gauged by the 36-item Short Form Health Survey (SF-36). Results: The training was well accepted by the participants, and no major adverse event was reported. All participants finished the entire protocol. Compared with the control group, after the training the training group showed greater improvements in MSFC score, Metacognition Index score of the BRIEF, SRT score, and physical domain score of the SF-36. Conclusions: These results suggest that vibration training could be an effective alternative training paradigm to enhance cognition and QOL in people with MS, and they provide an encouraging base to conduct a large-scale clinical trial.

Comparison of Neuropsychological Assessment by Videoconference and Face to Face

Objective: To compare the administration of neuropsychological tests by teleneuropsychology (TeleNP) and face to face (F-F) in order to determine the feasibility and reliability of TeleNP. Method: At the inclusion visit, all participants underwent a traditional F-F neuropsychological assessment as part of their standard care. Four months after inclusion, they were randomized to undergo an additional neuropsychological assessment either by F-F administration or by TeleNP. Results: A total of 150 adults with cognitive complaints, but with no major cognitive or sensorial impairment were included. At 4 months, 69 participants were randomized in the F-F arm and 71 in TeleNP arm (10 lost in the follow-up). The overall satisfaction was high: 87.1% in the TeleNP arm were “very satisfied”, and 82.9% indicated no preference between F-F and TeleNP. In agreement with previous data from the literature, neuropsychological assessments gave similar results across both administration conditions for a large majority of tests [Mini-Mental State Examination (MMSE), Free and Cued Selective Reminding Test (FCSRT) French version, Mahieux gestural praxis battery, Frontal Assessment Battery (FAB), time of completion of the Trail making Test (TMT) A and B, number of errors of the TMT B, Rey complex figure test, categorical et phonological verbal fluency tests] and minor differences for others [80-picture naming test (DO-80), FAB, Digit Span forward and backward and number of errors in the TMT A]. Conclusions: TeleNP is a promising method to be able to test patients as an alternative to F-F condition. Before this procedure can be generalized, it is now necessary to standardize the adaptation of certain tests and to test them in populations with more significant cognitive disorders.

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.

Prognostic Value of Learning and Retention Measures from the Free and Cued Selective Reminding Test to Identify Incident Mild Cognitive Impairment

Objective: To compare the predictive validity of learning and retention measures from the picture version of the Free and Cued Selective Reminding Test with Immediate Recall (pFCSRT + IR) for identifying incident mild cognitive impairment (MCI). Methods: Learning was defined by the sum of free recall (FR) and retention by delayed free recall (DFR) tested 15–20 min later. Totally, 1422 Baltimore Longitudinal Study of Aging (BLSA) participants (mean age 69.6 years, 54% male, mean 16.7 years of education) without dementia or MCI received the pFCSRT + IR at baseline and were followed longitudinally. Cox proportional hazards models were used to evaluate the effect of baseline learning and retention on risk of MCI. Results: In total, 187 participants developed MCI over a median of 8.1 years of follow-up. FR and DFR each predicted incident MCI adjusting for age, sex, and education. Also, each independently predicted incident MCI in the presence of the other with similar effect sizes: around 20% decrease in the hazard of MCI corresponding to one standard deviation increase in FR or DFR. Conclusion: The practice of preferring retention over learning to predict incident MCI should be reconsidered. The decision to include retention should be guided by time constraints and patient burden.