Cued Selective Reminding Test Research Articles

Brain Resources: How Semantic Cueing Works in Mild Cognitive Impairment due to Alzheimer's Disease (MCI-AD).

Semantic cues in the Free and Cued Selective Reminding Test (FCRST) play a key role in the neuropsychological diagnosis of Amnesic Mild Cognitive Impairment due to Alzheimer’s Disease (MCI-AD); however, the neural bases of their impact of recall abilities are only partially understood. Here, we thus decided to investigate the relationships between brain metabolism and the FCSRT Index of Sensitivity of Cueing (ISC) in patients with MCI-AD and in healthy controls (HC). Materials: Thirty MCI-AD patients (age: 74.7 ± 5.7 years; education: 9.6 ± 4.6 years, MMSE score: 24.8 ± 3.3, 23 females) and seventeen HC (age: 66.5 ± 11.1 years; education: 11.53 ± 4.2 years, MMSE score: 28.4 ± 1.14, 10 females) who underwent neuropsychological evaluation and brain F-18 fluorodeoxyglucose Positron Emission Tomography (FDG-PET) were included in the study. Results: ISC was able to differentiate HC from MCI-AD subjects as shown by a ROC analysis (AUC of 0.978, effect size Hedges’s g = 2.89). MCI-AD subjects showed significant hypometabolism in posterior cortices, including bilateral inferior Parietal Lobule and Precuneus and Middle Temporal gyrus in the left hemisphere (VOI-1) compared to HC. ISC was positively correlated with brain metabolism in a single cluster (VOI-2) spanning the left prefrontal cortex (superior frontal gyrus) and anterior cingulate cortex (ACC) in the patient group (R2 = 0.526, p < 0.001), but not in HC. Mean uptake values of VOI-2 did not differ between HC and MCI-AD. The structural connectivity analysis showed that VOI-2 is connected with the temporal pole, the cingulate gyrus and the posterior temporal cortices in the left hemisphere. Conclusion: In MCI-AD, the relative preservation of frontal cortex metabolic levels and their correlation with the ISC suggest that the left frontal cortices play a significant role in maintaining a relatively good memory performance despite the presence of posterior hypometabolism in MCI-AD.

Relationship between brain AD biomarkers and episodic memory performance in healthy aging

The presence of brain biomarkers can be observed decades before the first clinical symptoms of Alzheimer’s disease (AD). We aimed to determine whether associations between biomarkers and episodic memory performance already exist in a healthy late middle-aged population or only in participants over 60 years old. Performance at the Free and Cued Selective Reminding Test [FCSRT], the Logical Memory test and the Mnemonic Similarity Task [MST] was determined in sixty healthy participants (50–70 y.) with a negative status for amyloid-beta (Aβ) biomarker. We assessed Aβ cortical level and tau/neuroinflammation burden using PET scanner, and hippocampal atrophy with MRI scanner. Generalized linear mixed models showed that MST scores (recognition and pattern separation) were positively associated with hippocampal volume in participants over 60 years. No association between memory performance and Aβ and tau/neuroinflammation burden was found in the older or in the younger age group. This suggests that visual recognition memory and discrimination of lures may constitute early cognitive markers of memory decline in an older population.

Impairment of episodic memory in genetic frontotemporal dementia: A GENFI study.

IntroductionWe aimed to assess episodic memory in genetic frontotemporal dementia (FTD) with the Free and Cued Selective Reminding Test (FCSRT).MethodsThe FCSRT was administered in 417 presymptomatic and symptomatic mutation carriers (181 chromosome 9 open reading frame 72 [C9orf72], 163 progranulin [GRN], and 73 microtubule‐associated protein tau [MAPT]) and 290 controls. Group differences and correlations with other neuropsychological tests were examined. We performed voxel‐based morphometry to investigate the underlying neural substrates of the FCSRT.ResultsAll symptomatic mutation carrier groups and presymptomatic MAPT mutation carriers performed significantly worse on all FCSRT scores compared to controls. In the presymptomatic C9orf72 group, deficits were found on all scores except for the delayed total recall task, while no deficits were found in presymptomatic GRN mutation carriers. Performance on the FCSRT correlated with executive function, particularly in C9orf72 mutation carriers, but also with memory and naming tasks in the MAPT group. FCSRT performance also correlated with gray matter volumes of frontal, temporal, and subcortical regions in C9orf72 and GRN, but mainly temporal areas in MAPT mutation carriers.DiscussionThe FCSRT detects presymptomatic deficits in C9orf72‐ and MAPT‐associated FTD and provides important insight into the underlying cause of memory impairment in different forms of FTD.

Validation and Norms for a Recognition Task for the Spanish Version of the Free and Cued Selective Reminding Test.

The aim of the present work was to develop and validate a recognition task to be used with the Spanish version of the 16 items Free and Cued Selective Reminding Test (FCSRT). A total of 96 (67.7% women) cognitively healthy, functionally independent community-dwelling participants aged 55years or older underwent a comprehensive neuropsychological assessment. A recognition task for the FCSRT was developed that included the original 16 items, 16 semantically related items, and eight unrelated foils. Indices of discriminability (d') and response bias (C), as well as 95% confidence intervals for chance-level responding were calculated. On average, our sample was 65.71years old (SD=6.68, range: 55-87), had 11.39years of formal education (SD=3.37, range: 3-19), and a Mini-Mental State Examination score=28.42 (SD=1.49, range: 25-30). Recognition scores did not differ statistically between sexes, nor did they correlate with demographics. Participants scored at ceiling levels (mean number of Hits=15.52, SD=0.906, mean number of False Alarms=0.27, SD=0.589). All the participants scored above chance levels. Normative data from a novel recognition task for the Spanish version of the FCSRT are provided for use in clinical and research settings. Including a recognition task in the assessment of memory functioning might help uncover the pattern of memory impairments in older adults, and can help improve the memory profile of people with amnestic Mild Cognitive Impairment. Future research is warranted to validate and expand the recognition task.

Cultural validity of cognitive markers for Alzheimer’s disease (AD): Evidence for global strategies

AbstractBackgroundAvailability of culture‐free cognitive tests with marker properties for AD has proved a barrier to global harmonization strategies. The European Neurodegenerative Diseases Working Group suggested that the Short‐Term Memory Binding Test (STMBT) and the Free and Cued Selective Reminding Test (FCSRT) are useful tests for the early detection of AD (Costa et al., 2017). Yassuda et al. (2019) showed that STMB is insensitive to age and education among healthy Brazilian adults. Parra et al. (2019) suggested that these tests should enter global strategies to aid the early detection of AD. Evidence is still needed to ascertain that such a validity translates to the assessment of affected individuals from underrepresented populations. The current study aimed to shed new light on such an outstanding question.MethodsWe recruited 64 healthy controls (HC), 60 patients with Mild Cognitive Impairment (MCI), and 63 patients with mild AD from Lima, regional area health clinics (DIRESA) between 06/2018‐05/2019. They were all illiterate. We considered Illiterate individuals who (1) attended no school or were enrolled for less than one year and (2) could not read or write (a booklet was given which showed a simple sentence). We assessed them with the STMBT, the visual FCSRT, and a brief clinical‐neuropsychological protocol.ResultsThe assessment confirmed the healthy (CDR=0.0, pFAQ=2.2, BDI=5.9), MCI (CDR=0.5, pFAQ=3.7, BDI=6.2), and dementia (CDR=1.3, pFAQ=16.5, BDI=7.2) status of our groups. Significant between‐group differences were found with both the STMBT (F(2,184)=590.1, p&lt;0.001) and Free Recall during the visual FCSRT (F(2,184)=3936.2, p&lt;0.001), with HC&gt;&gt;&gt;MCI&gt;&gt;&gt;AD. ROC analysis with STMB revealed AUC=0.98 for HC vs. MCI, AUC=1.00 for HC vs. AD, and AUC=0.97 for MCI vs. AD. For the visual FCSRT, an AUC=1.00 was found for HC vs (MCI &amp; AD), and AUC=0.99 for MCI vs AD.ConclusionThe two cognitive markers recently recommended for harmonisation of neuropsychological assessment in neurodegenerative dementias in Europe seem suitable to support such practices in illiterate populations. Parra et al. (2019) recently suggested that only global strategies will help meet global challenges. Here we provide evidence of cognitive markers for AD that can reliably enter such strategies.

Subjective cognitive decline correlates with medial temporal lobe and hippocampal subfield volumetry in cognitively unimpaired participants

AbstractBackgroundSubjective cognitive decline (SCD) is a risk factor for cognitive decline and AD. SCD individuals display lower medial temporal lobe (MTL) volumes. Some features of SCD (SCDplus), such as specific worry and recent onset, have been proposed as more related to AD pathology. In this study we aimed to explore the differences in MTL volumes between SCD and control individuals and their associations with memory performance in a large sample of cognitively unimpaired subjects.Methods603 cognitively unimpaired individuals from a population‐based study (age: [47‐76], mean: 60.04∓6.57) underwent structural MRI, clinical and neuropsychological assessments. 184 were classified as SCD or 419 as Controls by their answers to the question “Do you perceive difficulties in memory or cognition as compared to how they used to be?”. A subgroup of 31 fulfilling two SCDplus criteria (Worry and Onset within last 5 years) was defined. Memory performance was assessed with the Free and Cued Selective Reminding Test (FCSRT).MTL and HS were segmented using ASHS using T1 and IR sequences. We compared regional volumes across SCD groups using linear models. Age, sex, education, APOE carriership and total intracranial volume were included as covariates. SCD group*memory scores interactions were assessed.ResultsSCD subjects showed lower volumes than Controls in right CA1 (p=0.031) and subiculum (p=0.026) (Figure 1). SCDplus subjects showed larger BA36 volumes in both hemispheres (Figure 2). In models comparing Controls and SCDplus we found a significant interaction (p=0.021) between SCDplus status and parahippocampal (PHC) bilateral volumes on FCSRT free recall score, with positive association in Controls and negative in SCDplus (poorer performance associated with larger PHC) (Figure 3).ConclusionAs previously reported in smaller and older samples (Schwarz et al, AAIC 2019) a reduction of CA1 and subiculum was found in SCD subjects. Moreover, PHC volume correlates negatively with memory performance in SCDplus: this may pinpoint a transitional phase in the AD continuum with increments of cortical volume, as described in (Gispert et al., 2015; Fortea et al., 2011). Further work including CSF biomarkers will assess how these associations may be mediated by AD pathology.

What’s in a name? Semantic, as well as episodic, memory plays an important role in the diagnostic sensitivity of the free and cued selective reminding test in MCI

AbstractBackgroundThe Free and Cued Selective Reminding Test (FCSRT) is highly sensitive in the detection of AD, even at early stages (Grober, et al., 2008; Papp et al., 2015; Slachevsky et al., 2018). By controlling encoding and retrieval, the task is especially sensitive to memory consolidation deficits that characterize AD. During the learning phase, patients name items that are paired with semantic cues aimed to boost encoding and retrieval. However, benefit from the semantic cues requires intact semantic memory and access. As the “cognitive signature” of AD includes reduced semantic processing (Henry and Crawford, 2004.), we asked whether this reduction impacts FCRST performance.Method170 patients (M age=74.1±6.2, M edu=16±3.0; 57% male) clinically referred for neuropsychological evaluation to address cognitive decline completed the FCSRT and semantic access measures, the Boston Naming Test (BNT) and semantic (animal) fluency. Neuropsychologists independently and blindly assigned diagnosis specifying NCD severity (Mild v. Major) and type (amnestic v. non‐amnestic). To determine the impact of semantic processing on FCRST performance we examined whether naming accuracy (NA): (1) differed between patient groups on first FCSRT learning trial; (2) was impacted by item prototypicality, 3) was predicted by BNT and semantic fluency performances, and (4) predicted subsequent FCSRT performance (total free, and total cued recall accuracy).ResultSs included 50 Mild NCD, amnestic; 59 Mild NCD, non‐amnestic; 23 Major NCD, amnestic; and 38 Major NCD, non‐amnestic. NA on the first FCSRT learning trial was higher for Mild than Major NCD and non‐amnestic than amnestic patients without severity x type interaction. Across all groups: NA was predicted by BNT (p &lt; .05) and semantic fluency (p &lt; .05), and was better for high than for low prototypicality items. Also across all groups, NA predicted subsequent memory for the items, including total free recall accuracy (p &lt; .001) and total cued recall accuracy (p &lt; .001).ConclusionThe diagnostic sensitivity of the FCSRT in AD is likely impacted not only by reduced episodic memory but also by reduced semantic memory and access. Understanding what underlies the sensitivity of the FCSRT may ultimately help improve the detection of early cognitive changes in AD.

White matter integrity linked to memory retrieval deficits in posterior cortical atrophy

AbstractBackgroundPosterior cortical atrophy (PCA) is an atypical form of Alzheimer’s disease characterised by visuospatial abilities, with episodic memory traditionally thought to be relatively preserved. However, recent work suggests that verbal memory is impaired at clinical presentation (Ahmed et al., 2016) associated with changes in functional connectivity of parietal attention networks (Veldsman et al., 2018). It is currently unclear how structural connectivity changes may contribute to memory functioning within this patient group. Here, we examine the relationship between white matter integrity and verbal episodic memory in PCA.MethodEighteen patients with PCA and eighteen healthy controls underwent diffusion tensor imaging (DTI) MRI scanning. Episodic memory of patients was assessed with the Free and Cued Selective Reminding Test with Immediate Recall (FCSRT‐IR). Voxel‐wise statistical analyses of fractional anisotropy and mean diffusivity measures in patient and control groups were carried out using tract‐based spatial statistics. Relationships between white matter microstructure and memory performance were examined with partial correlations controlling for age.ResultThere was no difference in encoding of verbal items between patients and healthy controls. However, PCA patients presented with significant impairments of memory retrieval on the FCSRT‐IR. In line with previous neuroimaging research, white matter degeneration in PCA was restricted to posterior regions of the cortex. Within the patient group, reduced integrity of the splenium of the corpus callosum was associated with less free recall of task items.ConclusionThis study demonstrates that splenial atrophy may contribute to deficits in episodic memory retrieval in PCA. The findings have implications for supporting diagnostic profiling in PCA.

The ketogenic diet as a potential prevention or therapeutic strategy for AD

AbstractBackgroundDiet is a powerful modulator of brain health. The ketogenic diet (KD), a very low carbohydrate diet, is remarkably effective in treating refractory epilepsy; 50‐70% of patients have &gt;50% seizure reduction and 30% have &gt;90% seizure reduction. Although the mechanisms underlying its effectiveness are not definitively known, reduction of neuronal hyperexcitability and neuroprotective effects of ketones have been demonstrated, as has reduction in AD pathology in rodent models. We tested the effect of a 6‐week Modified Mediterranean‐like KD (MMKD) compared with a low‐fat American Heart Association Diet (AHAD) on AD biomarkers and memory.MethodThe study used a randomized crossover design in which participants consumed either a MMKD (5‐10% of total daily calories obtained from carbohydrates) or the control AHAD (∼15% of calories obtained from fat per day) for 6 weeks, followed by a 6‐week washout period during which participants were instructed to resume their pre‐study diet, after which the second diet was consumed for 6 weeks. Diets were equicaloric with participants’ normal diet. Compliance was verified by measuring blood ketone levels. CSF collection, pseudocontinuous arterial spin label (pcASL) MRI, 11C‐AcAc/18F FDG Positron Emission Tomography (PET), and memory testing (Z score composite constructed from Story Recall and Free and Cued Selective Reminding Test) were performed at baseline and at the end of each intervention.ResultA total of 20 participants completed both diets, with 3 participants discontinuing the study early. Mean compliance rates for completers were 90% for the MMKD and 95% for AHAD. The MMKD was associated with increased CSF Aβ42 and decreased tau. Cerebral perfusion increased after the MMKD in AD regions of interest, and whole‐brain ketone uptake increased on 11C‐AcAc PET. No changes in these outcomes were observed following the AHAD. Memory performance improved after both diets.ConclusionThe MKKD intervention favorably influenced CSF AD biomarkers, cerebral perfusion, and memory. These results provide the basis for an ongoing Phase II study using a longer intervention in a larger sample of adults with MCI.

Component process analysis of verbal memory in a sample of students with a binge drinking pattern

BackgroundMany studies have emphasized the harmful impact of binge drinking on several cognitive functions, including memory. However, the exact nature of the memory processes involved is still unknown. The present study was designed to assess verbal working memory and verbal episodic memory, especially its encoding, storage and retrieval processes, in binge drinking to identify the processes impacted by this behavior. MethodsParticipants were 48 community-recruited college students aged 18–25 years and categorized as either binge drinkers (BDs) or social drinkers (SDs). They were assessed with (a) subtests of the Wechsler scale (digit span, letter–number sequencing) measuring verbal working memory, and (b) a modified version of the Free and Cued Selective Reminding Test (FCSRT), which measures verbal episodic memory functioning in various conditions of encoding (controlled) and recollection (free recall, cued recall, and recognition). ResultsVerbal working memory was unaffected by binge drinking, whereas verbal episodic memory performances were reduced. In particular, analysis of the modified FCSRT scores suggested that BDs had less proficient storage and retrieval processes. Furthermore, correlational analyses indicated that the proficiency of these memory components was negatively correlated with several indicators of binge drinking behavior. ConclusionsResults suggest that binge drinking behavior affects the storage and recollection processes of verbal episodic memory. The academic failure described in binge drinkers could be partly related to this harmful effect. Our results on the negative impact of binge drinking on memory should be used to develop information campaigns targeting students.

Sulcal morphology as predictor of cognitive decline over a 3‐year period in elderly at risk to develop Alzheimer’s disease

AbstractBackgroundCerebral sulci openings have been consistently observed as larger in Alzheimer’s disease (AD) patients than in cognitively normal elderly. However, it remains unknown whether large openings may have predictive value of cognitive trajectories. We aimed to determine whether sulci openings might be predictors of changes in cognition over a 3‐year period in elderly people at risk to develop AD (at‐AD‐risk).MethodParticipants were recruited in memory and research centers in France between 2008 and 2011 in the framework of the MRI‐Multidomain Alzheimer Preventive Trial (MRI‐MAPT) ancillary study. They were non‐demented community‐dwelling women and men aged ≥ 70 years, and presented memory complaints and frailty criteria. In 20 sulci distributed throughout the brain, openings were extracted from Magnetic Resonance Imaging (MRI) T1‐weighted images obtained at baseline in 433 participants, using the Morphologist pipeline of BrainVISA [http://brainvisa.info, version 4.5.1]. Cognition was evaluated at baseline, 6, 12, 24, and 36 months of follow‐up with a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini‐Mental State Examination (MMSE) orientation items, Digit Symbol Substitution Test, and Category Naming Test). Linear mixed regression models explored the composite score variation over time according to the baseline openings magnitude.ResultAt baseline, participants were on average 74.8 (4.0) years old. The mean MMSE was 28.1 (1.5) and the mean composite cognitive score was 0.11 (0.62). Sulci openings were categorized into tertiles (T1, T2, T3) for the statistical analyses. The participants showing the largest openings (T3) in the left anterior inferior temporal sulcus presented a greater decline in the composite cognitive score over the 3‐year period of follow‐up (β=‐0.07, 95%CI [‐0.12; ‐0.02]) than the participants with lower openings values.ConclusionLarge openings of sulci within the lateral temporal area of the brain might be predictors of cognitive decline within 3 years in at‐AD risk individuals. These results may have strong applications in clinical setting and for preventive strategies.

Late‐life literacy training for improving memory and brain connectivity: Baseline results

AbstractBackgroundHigher education acquired through the lifespan is believed to buffer the cognitive decline associated with neurodegenerative diseases. However, whether acquiring education later in life can improve memory is unknown.MethodsWe recruited illiterate adults that enroll in a late‐life literacy program to determine the impact of literacy training in adulthood on memory. Participants underwent baseline literacy tests and episodic memory was assessed with the Free and Cued Selective Reminding test (with pictures).ResultsAt baseline, 43 illiterate adults that did not know how to read and write participated in the study. They had a mean age of 50.3 (SD 14.3) year‐old, 19 (44%) were males, 37 (90%) were non‐Caucasians and 24 (57%) were from low‐socioeconomic background. The main reason they did not attended school when they were young was that they had to work (n=21, 49%). Baseline clinical characteristics of participants were smoking in 26%, depression in 25% and anxiety in 16%. The mean free delayed‐recall was 10.6 (SD 3.1), out of 16 figures.ConclusionHere we present the baseline characteristics of this group of illiterate adults that engage in a late‐life literacy program. The results show that the participants recruitment is feasible and representative of such illiterate adult populations. Although episodic memory is normal, there is room for memory improvement to be studied in the follow up visit.

Distinct contributions of longitudinal tau and amyloid to decline in various cognitive domains in preclinical AD

AbstractBackgroundWe sought to assess the preclinical contributions of longitudinal Aβ and tau accumulation at different baseline Aβ levels to decline across multiple cognitive domains.Method124 clinically normal older adults from the Harvard Aging Brain Study with longitudinal Aβ (PIB), tau (FTP) and cognition (PACC) were included (median follow‐up=8.0±1.0 years). The following linear mixed models examined neocortical PIB and inferior temporal (IT) FTP change effects on PACC and its component tasks and included age, sex, APOE and education as covariates: 1) Time*PIB level t0*PIB change t0‐3 on cognition t0‐8, with post‐hoc regional analyses. 2) Time*PIB level t3*FTP change t3‐8 on cognition t3‐8, because FTP was introduced at t3. Mediation analyses assessed whether the effect of PIB change t0‐3 on subsequent cognitive decline t3‐8 was mediated by IT‐FTP at t3. ResultIncreasing PIB change‐t0‐3 was associated with declining cognition‐t0‐8 across all tasks at higher PIB‐t0 levels (Figure 1). The Digit Symbol Substitution Test (DSST) also declined with increasing PIB change at low PIB‐t0 levels (β=‐1.99, p=.002). FTP change‐t3‐5 was associated with declines at high PIB‐t3 levels for all PACC components except DSST (Figure 2). Only free recall (Free and Cued Selective Reminding Test; FCsrt‐FR) exhibited FTP change‐related decline in low PIB adults (β=‐1.70, p=.02). Mediation analyses demonstrated that FTP‐t3 mediated the effect of PIB change t0‐3 on cognitive decline t3‐8 for all PACC components except DSST, which remained associated only with PIB change (Figure 3). Regional analyses revealed different patterns of increasing PIB change associated with FCsrt‐FR and DSST decline (Figure 4).ConclusionTwo different patterns of cognitive decline were observed: 1) A tau‐mediated pattern of steeper decline across multiple domains in individuals with high Aβ. Free recall declined starting at low Aβ levels, in association with tau and accumulating Aβ in regions important for memory retrieval. 2) A decline on the DSST associated with accumulating Aβ, but not IT tau, even in those with low Aβ. DSST involves processing speed and executive function. The broader pattern of Aβ accumulation was associated with DSST decline suggests it may reflect a general cognitive slowing in response to Aβ‐mediated changes in synaptic transmission.

VAMP2 is a cerebrospinal fluid marker of selective hippocampal synapse loss and episodic memory performance in Alzheimer’s disease

AbstractBackgroundAn early objective cerebrospinal fluid (CSF) marker of cognitive decline in preclinical Alzheimer’s disease (AD) would be a useful addition to the current AD biomarker arsenal. We recently identified VAMP2 as a potential CSF marker of AD‐related synapse loss. The aim of this study was 1) to evaluate the regional brain expression of VAMP2 in human postmortem tissue and 2) to assess the correlation of CSF VAMP2 levels with cognitive performance in cognitively normal controls and AD patients.MethodParaffin fixed brain sections from hippocampus, frontal, posterior‐cingulate and temporal inferior cortices from AD cases (n=10) and non‐pathological controls (n=10) were stained with anti‐VAMP2 (Cell Signaling) and an HRP‐conjugated (Dako) secondary antibody. VAMP2 was quantified using MATLAB software (MA, USA). CSF from the Sant Pau Initiative in Neurodegeneration (SPIN) cohort was selected from cognitively normal controls (n=68), preclinical AD stages 1 (n=31) and 2 (n=8), prodromal AD (n=80) and AD dementia patients (n=39). Cognitive performance was evaluated using the total score in the Free and Cued Selective Reminding Test (Buschke et al). We quantified VAMP2 in CSF by Single MOlecule Array (SIMOA).ResultIn control and AD brains, VAMP2 showed a neuropil‐like expression pattern consistent with a synapse marker and was widely expressed in cortical and subcortical regions (hippocampus&gt;frontal cortex&gt;cingulate cortex&gt;temporal cortex). VAMP2 expression in AD brains was reduced 0.6‐fold compared to controls in the hippocampus (p=0.01) but comparable to controls in all other regions tested (all p&gt;0.1). Reduced hippocampal VAMP2 levels correlated with increased Braak (r2=0.4, p=0.006) and CERAD (r2=0.3, p=0.03) staging. In CSF, VAMP2 levels were decreased compared to controls in preclinical AD and sequentially elevated over the course of AD, plateauing at the prodromal stage. Worse episodic memory was associated with increased CSF VAMP2 in controls (r2=0.09, p=0.009). In AD, the best fit was a nonlinear model (r2=0.07, p=0.0009) in which worse episodic memory was associated with increased CSF VAMP2 in preclinical AD but decreased VAMP2 in clinical AD.ConclusionThese data support VAMP2 as a promising CSF marker of selective hippocampal synapse loss and episodic memory performance in Alzheimer’s disease and healthy controls.

Neuroanatomical signature of super‐ageing: Structural brain study of youthful episodic memory in people over the age of 80

AbstractBackgroundSuperagers are people over the age of 80 that possess an episodic memory function of a person 20‐30 years younger. By drawing on a large (N=1213) longitudinal cohort of elderly individuals, we aimed to identify a superager subgroup and to determine key differences, including brain structure, between superagers and peers with normal episodic memory for their age.MethodA sample of 64 superagers (mean age 81.9 years, 59.4% women) and 19 age‐matched controls (mean age 82.6 years, 57.9% women) from the Vallecas Project cohort based at Fundación CIEN were selected according to their episodic memory score in the Free and Cued Selective Reminding Test; superagers scored at or above the mean value of a 50‐56yo person and controls scored within one standard deviation for their age. Demographic, genetic (APOE), lifestyle, clinical and neuropsychological variables were compared. Structural whole‐brain measures of grey matter volume are analised across groups at baseline and over time for up to 5 years (2‐6 time points) using CAT12 toolbox in SPM12.ResultThere were no differences in age, sex, years of education, current frequency of physical exercise or APOE genotype across groups. A history of anxiety, depression and cardiopathy was less frequent in superagers. At baseline, a higher grey matter volume in superagers compared to controls was shown in the bilateral anterior thalamus and regions within the temporal lobe including bilateral effects in the hippocampus, the amygdala, the entorhinal cortex, the parahippocampal gyrus and the fusiform gyrus (p &lt; 0.05 FWE corrected). The longitudinal analysis revealed reduced grey matter volume loss over time in superagers in bilateral hippocampus, entorhinal cortex, parahippocampal gyrus, the left amygdala, bilateral basal forebrain, caudate, anterior insula, and right posterior cingulate (p &lt; 0.05 FWE corrected).ConclusionBaseline differences between these two populations were located in a neuroanatomical network linked with memory function including key areas within the temporal lobe and also the anterior thalamus. The atrophy rate over time in these temporal regions is slower for the superager group, suggesting that they are more resistant than controls to the ageing decline of memory‐related areas.

Metabolic correlates of neuropsychological assessment in behavioral variant frontotemporal dementia

AbstractBackgroundNeuropsychological assessment is an essential tool in the diagnosis and monitoring of patients with neurodegenerative disorders. Cognitive functions underlying neuropsychological tests are complex, and accordingly interpretation is often challenging. In behavioral variant frontotemporal dementia (bvFTD), neural correlates of cognitive testing are largely unknown, and they could be different to other settings such as Alzheimer’s disease (AD). In this study, we aimed to analyze the metabolic underpinnings of neuropsychological test results in a series of patients with bvFTD.MethodSeventy‐two patients with bv‐FTD according to the consensus criteria were included. Patients were examined with a comprehensive neuropsychological protocol and 18F‐FDG‐PET. Voxel‐based analysis was used to study the correlation between regional brain metabolism and cognitive performance of the following tests: Boston Naming Test (BNT), Trail Making Test (TMT), Rey‐Osterrieth Complex Figure, verbal fluency (semantic and phonological), Free and Cued Selective Reminding Test (FCSRT), Stroop Color Word Interference test, Tower of London, and Visual Object and Space Perception Battery (VOSP). Age, sex, and years of education were introduced as nuisance covariates. A healthy control and Alzheimer’s disease groups were also examined with the same protocol for comparison. Neuroimaging analyses were conducted using SPM12.ResultMean age in the bvFTD group was 71.33+/‐7.75 years, and 43 (59.7%) were men. In bvFTD, BNT was positively correlated with the left anterior temporal lobe; FCSRT was correlated with the left frontal cortex; Phonological fluency with left frontal lobe and right superior frontal; semantic fluency with left frontal, temporal and thalamus; TMT‐B was negatively correlated with bilateral medial frontal lobes, especially with the right side; VOSP was correlated with the right frontal lobe.ConclusionWe showed the brain regions associated to the performance of different standardized neuropsychological tests in bvFTD. The differences observed between bvFTD and AD suggests that neural underpinnings underlying these tests are different according to each disease, confirming the multiple cognitive processes involved during performance of each particular test. Overall, our study provides useful information to achieve a better understanding of neuropsychological examination in patients with bvFTD. In addition, these findings could be useful to detect cognitive subtypes within the syndrome of bvFTD.

Episodic Memory Impairment in Parkinson's Disease: Disentangling the Role of Encoding and Retrieval.

The source of episodic memory (EM) impairment in Parkinson's disease (PD) is still unclear. In the present study, we sought to quantify specifically encoding, consolidation, and retrieval process deficits in a list-learning paradigm by a novel method, the item-specific deficit approach (ISDA). We applied the ISDA method to the Free and Cued Selective Reminding Test (FCSRT) in a sample of 15 PD patients and 15 healthy participants. The results revealed differences in free recall performance between PD patients and controls. These patients, however, benefited from cues as much as controls did, and total recall did not differ between groups. When analyzing the ISDA indices for encoding, consolidation, and retrieval deficits, the results showed a general memory deficit, but with a clear focus on encoding and retrieval, as revealed by the sensitivity values. Moreover, controlling for initial learning did not eliminate group effects in retrieval. Our findings reveal a mixed pattern in PD patients, with deficits in both encoding and retrieval processes in memory. Also, despite the fact that an encoding dysfunction may explain some of the deficits observed at retrieval, it cannot fully account for the differences, highlighting that both encoding and retrieval factors are necessary to understand memory deficits in PD.

A-187 Is Once Enough? First Trial Performance on the Free and Cued Selective Reminding Test in a Clinical Sample of Older Adults with Neurocognitive Disorders

Abstract Objective There is urgent need for tools that quickly identify neurocognitive disorders (NCD). The Free and Cued Selective Reminding Test (FCSRT) has high sensitivity for detecting NCD severity (Mild vs. Major) and type (amnestic vs. non-amnestic). However, full administration of three learning trials makes it relatively lengthy. We examined whether first trial performance detects NCD type and severity. Method 187 patients (Mage = 74.7 ± 6.9, Medu = 16 ± 3.1; 58% male) were clinically evaluated. Diagnoses were Mild NCD—amnestic (N = 55), Mild NCD—non-amnestic (N = 67), Major NCD -amnestic (N = 23), and Major NCD –non-amnestic (N = 42). Free recall accuracy (FRA) [number freely recalled/16 *100] and cued recall accuracy (CRA) [(number of cues provided—number recalled with cues)/16 *100] were calculated for each of 3 learning trials. Results First trial performance predicted NCD severity (2 (2) = 7.84, p &amp;lt; .03) and type (2 (1) = 59.0, p &amp;lt; .001). First trial FRA predicted NCD severity (B = −3.29, p &amp;lt; .01). First trial FRA and CRA predicted NCD type (CRA better than FRA, (B = −4.54, p &amp;lt; .001). Third trial accuracy did not predict NCD severity [2 (2) = 5.75, p = .06). Third trial accuracy predicted NCD type [2 (2) = 56.6, p &amp;lt; .001]; third trial FRA performed similarly to first trial FRA. Conclusions Our results suggest that first trial FCSRT performance may be enough to screen for neurocognitive disorders. Findings identify free recall accuracy as a better predictor of type and cued recall accuracy a better predictor of NCD severity.

Age-related change in episodic memory: role of functional and structural connectivity between the ventral posterior cingulate and the parietal cortex.

While the neural correlates of age-related episodic memory decline have been extensively studied, the precise involvement of the Posterior Cingulate Cortex (PCC) and posterior parietal cortex (the precuneus and the angular gyrus), remains unclear. The present study examined functional and structural neural correlates of age-related episodic memory change assessed over 12years in 120 older adults (range 76-90years). Episodic memory performance was measured using the Free and Cued Selective Reminding Test (FCSRT); functional connectivity metrics were computed from resting-state fMRI images and structural connectivity metrics were assessed through microstructural properties of reconstructed tract using a native space pipeline. We found that FCSRT change was significantly associated with the functional connectivity between the ventral PCC and three parietal regions, the ventral superior, the inferior part of the precuneus, and the rostro dorsal part of the angular gyrus. This association was independent of hippocampal volume. In addition, we found the that change in FCSRT scores was associated with fractional anisotropy of the tract connecting the ventral PCC and the ventral superior part of the precuneus. Change in episodic memory in aging was therefore related to a combination of high functional connectivity and low structural connectivity between the ventral PCC and the ventral superior part of the precuneus.

Associative memory and in vivo brain pathology in asymptomatic presenilin-1 E280A carriers.

To determine whether performance on the Free and Cued Selective Reminding Test (FCSRT) is associated with PET in vivo markers of brain pathology and whether it can distinguish those who will develop dementia later in life due to autosomal-dominant Alzheimer disease (AD) from age-matched controls. Twenty-four cognitively unimpaired Presenilin-1 E280A carriers (mean age 36 years) and 28 noncarriers (mean age 37 years) underwent Pittsburg compound B-PET (amyloid), flortaucipir-PET (tau), and cognitive testing, including the FCSRT (immediate and delayed free and cued recall scores). Linear regressions were used to examine the relationships among FCSRT scores, age, mean cortical amyloid, and regional tau burden. Free and total recall scores did not differ between cognitively unimpaired mutation carriers and noncarriers. Greater age predicted lower free recall and delayed free and total recall scores in carriers. In cognitively impaired carriers, delayed free recall predicted greater amyloid burden and entorhinal tau, while worse immediate free recall scores predicted greater tau in the inferior temporal and entorhinal cortices. In turn, in all carriers, lower free and total recall scores predicted greater amyloid and regional tau pathology. FCSRT scores were associated with in vivo markers of AD-related pathology in cognitively unimpaired individuals genetically determined to develop dementia. Difficulties on free recall, particularly delayed recall, were evident earlier in the disease trajectory, while difficulties on cued recall were seen only as carriers neared the onset of dementia, consistent with the pathologic progression of the disease. Findings suggest that the FCSRT can be a useful measure to track disease progression in AD.