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.

Effects of restriction of activities and social isolation on risk of dementia in the community

ABSTRACT Objective: Social isolation and emotional isolation, i.e. loneliness, have been associated with dementia or cognitive decline. In contrast, the relationship of restriction of physical and instrumental activities of daily living to cognitive decline and dementia has been less studied. Design: We examined multiple quality of life (QoL) indicators, including isolation and restriction of activities, utilizing two validated scales in elders without dementia to determine their associations with cognitive decline and incident dementia that were followed longitudinally over 6 years. We comprehensively controlled for other symptom constellations, including depression and anergia. Setting: A large multi-ethnic prospective study was conducted in northern Manhattan, NYC. Participants: An ethnically diverse sample of 855 non-demented individuals at baseline participated. Measures: The following QoL scales were utilized: Restriction, Anergia, Isolation, Loneliness, and Affective Suffering. Results: Both Restriction (HR = 2.22, 95% CI [1.42, 3.47], P < .001) and Isolation (HR = 1.78, 95% CI [1.17, 2.70], P = 0.007) were associated with episodic memory and incident dementia, controlling for age, sex, and education. Loneliness and Affective Suffering (depression) were not associated with these outcomes (P’s > .1) with both Restriction and Isolation in the same model for the prediction of dementia, only Restriction remained significant (HR = 1.97, 95% CI [1.24, 3.14], P = 0.004). In cross-lagged panel analyses, Restriction and Isolation had reciprocal influences (P’s < .001), indicating that Restriction at the previous time point influenced current Isolation. Importantly, Restriction (but not Isolation) and Selective Reminding total recall memory demonstrated highly significant direct and reciprocal influences over time (P’s < .001). Conclusions: Restriction and Isolation were associated with incident dementia. Restriction played a more prominent role in its impact on memory decline. The development of these impairments in QoL, particularly Restriction, may provide warning signs of future cognitive decline and dementia and provide multiple and novel avenues for therapeutic interventions with the goal of delaying the development of cognitive decline and dementia.

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.

The Free and Cued Selective Reminding Test Predicts Braak Stage

Background: The ultimate validation of a clinical marker for Alzheimer’s disease (AD) is its association with AD neuropathology. Objective: To identify clinical measures that predict pathology, we evaluated the relationships of the picture version of the Free and Cued Selective Reminding Test (pFCSRT + IR), the Mini-Mental State Exam (MMSE), and the Clinical Dementia Rating scale Sum of Boxes (CDR-SB) to Braak stage. Methods: 315 cases from the clinicopathologic series at the Knight Alzheimer’s Disease Research Center were classified according to Braak stage. Boxplots of each predictor were compared to identify the earliest stage at which decline was observed and ordinal logistic regression was used to predict Braak stage. Results: Looking at the assessment closest to death, free recall scores were lower in individuals at Braak stage III versus Braak stages 0 and I (combined) while MMSE and CDR scores for individuals did not differ from Braak stages 0/I until Braak stage IV. The sum of free recall and total recall scores independently predicted Braak stage and had higher predictive validity than MMSE and CDR-SB in models including all three. Conclusion: pFCSRT + IR + IR scores may be more sensitive to early pathological changes than either the CDR-SB or the MMSE.