Proactive Semantic Interference Research Articles

The Association Between Plasma Amyloid-β 42/40 and Percentage of Semantic Intrusion Errors in Mild Cognitive Impairment.

Semantic intrusion errors (SIEs) are both sensitive and specific to PET amyloid-β (Aβ) burden in older adults with amnestic mild cognitive impairment (aMCI). Plasma Aβ biomarkers including the Aβ42/40 ratio using mass spectrometry are expected to become increasingly valuable in clinical settings. Plasma biomarkers are more clinically informative if linked to cognitive deficits that are salient to Alzheimer's disease (AD). This study included 119 older adults enrolled in the 1Florida Alzheimer's Disease Research Center (ADRC), 45 aMCI participants scored below the established Aβ42/40 ratio cut-off of 0.160 using the Quest AD-Detect™ assay indicating Aβ positivity (Aβ+), while 50 aMCI participants scored above this cut-off indicating Aβ negative status (Aβ-). Additionally, 24 cognitively unimpaired (CU) persons scored above the cut-off of 0.160 (Aβ-). The aMCI plasma Aβ+ group evidenced the greatest percentage of SIEs, followed by the aMCI Aβ-. The CU Aβ- group exhibited the lowest percentage of SIEs. After adjustment for global cognitive impairment, aMCI plasma Aβ+ continued to demonstrate greater SIEs on tests tapping the failure to recover from proactive semantic interference (frPSI) as compared to the aMCI Aβ-group. Using pre-established cut-offs for frPSI impairment, 8.3% of CU Aβ- participants evidenced deficits, compared to 37.8% of aMCI Aβ-, and 74.0% of aMCI Aβ+. SIEs reflecting frPSI were associated with aMCI Aβ+ status based on the Aβ42/40 ratio. Results suggest the importance of SIEs as salient cognitive markers that map onto underlying AD pathology in the blood.

Vulnerability to semantic and phonological interference in normal aging and amnestic mild cognitive impairment (aMCI).

To determine whether the increased vulnerability to semantic interference previously observed in amnestic mild cognitive impairment (aMCI) is specifically associated with semantic material or if it also affects other types of material, suggesting generalized executive and inhibitory impairment. Seventy-two participants divided into two groups (33 aMCI, 39 normal control [NC]) matched for age and education were included. They completed a comprehensive neuropsychological examination, the French version of the Loewenstein Acevedo Scale for Semantic Interference and Learning (LASSI-L; semantic interference test), and a homologous experimental phonological test, the phonological interference and learning test. Independent sample t tests, mixed analysis of variance (ANOVA), and analysis of covariance (ANCOVA) on memory and interference scores were conducted to compare memory and interference in both conditions for both groups. For memory scores, results revealed significant main effects of group (NC > aMCI) and condition (semantic > phonological) and significant interactions (poorer performance in the semantic condition for aMCI). aMCI committed more phonological false recognition errors, were disproportionately more vulnerable to retroactive semantic interference, and showed a higher percentage of intrusion errors associated with proactive semantic interference than NC. To our knowledge, this is the first study to compare vulnerability to interference in aMCI and normal aging with two similarly designed semantic and phonological word list learning tasks. Taken together, our results suggest that aMCI present with broad difficulties in source memory and inhibition, but that impaired deep semantic processing results in additional semantic intrusion errors during proactive interference and impacts their ability to show good recall after an interference list (greater semantic retroactive interference). Results are discussed according to the level-of-processing and activation/monitoring theories. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Detection of cerebrospinal fluid biomarkers changes of Alzheimer's disease using a cognitive stress test in persons with subjective cognitive decline and mild cognitive impairment.

Timely and accurate diagnosis of the earliest manifestations of Alzheimer's disease (AD) is critically important. Cognitive challenge tests such as the Loewenstein Acevedo Scales for Semantic Interference and Learning (LASSI-L) have shown favorable diagnostic properties in a number of previous investigations using amyloid or FDG PET. However, no studies have examined LASSI-L performance against cerebrospinal fluid biomarkers of AD, which can be affected before the distribution of fibrillar amyloid and other changes that can be observed in brain neuroimaging. Therefore, we aimed to evaluate the relationship between LASSI-L scores and CSF biomarkers and the capacity of the cognitive challenge test to detect the presence of amyloid and tau deposition in patients with subjective cognitive decline and amnestic mild cognitive impairment (MCI). One hundred and seventy-nine patients consulting for memory loss without functional impairment were enrolled. Patients were examined using comprehensive neuropsychological assessment, the LASSI-L, and cerebrospinal fluid (CSF) biomarkers (Aβ1-42/Aβ1-40 and ptau181). Means comparisons, correlations, effect sizes, and ROC curves were calculated. LASSI-L scores were significantly associated with CSF biomarkers Aβ1-42/Aβ1-40 in patients diagnosed with MCI and subjective cognitive decline, especially those scores evaluating the capacity to recover from proactive semantic interference effects and delayed recall. A logistic regression model for the entire sample including LASSI-L and age showed an accuracy of 0.749 and an area under the curve of 0.785 to detect abnormal amyloid deposition. Our study supports the biological validity of the LASSI-L and its semantic interference paradigm in the context of the early stages of AD. These findings emphasize the utility and the convenience of including sensitive cognitive challenge tests in the assessment of patients with suspicion of early stages of AD.

Different aspects of failing to recover from proactive semantic interference predicts rate of progression from amnestic mild cognitive impairment to dementia.

This study investigated the role of proactive semantic interference (frPSI) in predicting the progression of amnestic Mild Cognitive Impairment (aMCI) to dementia, taking into account various cognitive and biological factors. The research involved 89 older adults with aMCI who underwent baseline assessments, including amyloid PET and MRI scans, and were followed longitudinally over a period ranging from 12 to 55 months (average 26.05 months). The findings revealed that more than 30% of the participants diagnosed with aMCI progressed to dementia during the observation period. Using Cox Proportional Hazards modeling and adjusting for demographic factors, global cognitive function, hippocampal volume, and amyloid positivity, two distinct aspects of frPSI were identified as significant predictors of a faster decline to dementia. These aspects were fewer correct responses on a frPSI trial and a higher number of semantic intrusion errors on the same trial, with 29.5% and 31.6 % increases in the likelihood of more rapid progression to dementia, respectively. These findings after adjustment for demographic and biological markers of Alzheimer's Disease, suggest that assessing frPSI may offer valuable insights into the risk of dementia progression in individuals with aMCI.

The computerized LASSI-BC Test versus the Standard LASSI-L Paper-and-Pencil Version in Community-Based-Samples.

Proactive Semantic Interference (PSI) and failure to recover from PSI (frPSI), are novel constructs assessed by the LASSI-L. These measures are sensitive to cognitive changes in early Mild Cognitive Impairment (MCI) and preclinical AD determined by Aβ load using PET. The goal of this study was to compare a new computerized version of the LASSI-L (LASSI-Brief Computerized) to the standard paper-and-pencil version of the test. In this study, we examined 110 cognitively unimpaired (CU) older adults and 79 with amnestic MCI (aMCI) who were administered the paper-and-pencil form of the LASSI-L. Their performance was compared with 62 CU older adults and 52 aMCI participants examined using the LASSI-BC. After adjustment for covariates (degree of initial learning, sex, education, and language of evaluation) both the standard and computerized versions distinguished between aMCI and CU participants. The performance of CU and aMCI groups using either form was relatively commensurate. Importantly, an optimal combination of Cued B2 recall and Cued B1 intrusions on the LASSI-BC yielded an area under the ROC curve of .927, a sensitivity of 92.3% and specificity of 88.1%, relative to an area under the ROC curve of .815, a sensitivity of 72.5%, and a specificity of 79.1% obtained for the paper-and-pencil LASSI-L. Overall, the LASSI-BC was comparable, and in some ways, superior to the paper-and-pencil LASSI-L. Advantages of the LASSI-BC include a more standardized administration, suitability for remote assessment, and an automated scoring mechanism that can be verified by a built-in audio recording of responses.

59 Preliminary Findings of Semantic Interference in Learning and Memory Processes in Manifest Huntington’s Disease

Objective:To explore the usefulness of the Lowenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) [Crocco et al, 2013], a novel memory-based cognitive stress test capitalizing on semantic interference, in Huntington’s Disease (HD).Participants and Methods:12 healthy adults (HA) and 14 individuals with manifest HD were administered the LASSI-L as part of an annual research visit with the UCSD Huntington’s Disease Clinical Research Center (HDCRC.) Participants in each group were well matched with regard to age and education. Individuals with manifest HD had an average MoCA score of 26, total functional capacity score of 10, and total motor score of 21 suggesting that they were in the early stages of HD. The LASSI-L examines different types of semantic interference that occur in the learning/encoding process. There are free and cued recall trials for two lists of semantically related words with certain trials specific to different aspects of semantic interference including proactive, retroactive, and failure to recover from proactive interference. T-tests for all recall trials and number of intrusions for each trial were conducted between HA and those with HD to examine whether HD renders one more prone to semantic interference in both encoding and retrieval memory processes.Results:Individuals with HD recalled fewer words on average than HA across all recall trials except for the initial free recall of the first word list. HD individuals recalled significantly fewer (∼1.5) words during the initial (t=-2.8, p=.005, Cohen’s d=2.7) and secondary (t=-2.9, p=.003, Cohen’s d=2.6) cued recall trials from the words on the first list. Individuals with HD also recalled significantly fewer words on initial free recall (t=-2.9, p=.003, Cohen’s d=2.6) and cued recall trials of the second list, with the initial cued recall (t=-2.8, p=.005, Cohen’s d=3.1) sensitive to proactive semantic interference and the second cued recall (t=-3.3, p=.001, Cohen’s d=2.6) sensitive to failure to recover from proactive semantic interference. In addition, individuals with HD also recalled significantly fewer (∼2.2) words on delayed cued recall of the first list, a measure of retroactive semantic interference, than HA (t=-4.8, p<.001, Cohen’s d=2.4). Lastly, individuals with HD recalled fewer (∼4.1) words than HA on delayed free recall of both word lists (t=-3.5, p<.001, Cohen’s d=5.9). The groups did not differ significantly with regard to number of total intrusions per trial.Conclusions:Overall, our study supports the usefulness of the LASSI-L for neuropsychological assessment of HD in clinical and research settings. In comparison to a demographically similar group of HA, individuals with manifest HD showed significant differences in frontally mediated retrieval processes as well as semantic interference processes that affect efficient encoding of novel information.

A - 41 The Association between Education, Literacy, and Performance on the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L) in African American (AA) Older Adults.

The LASSI-L, a cognitive challenge test, has been found to be highly discriminative between AA elders with amnestic mild cognitive impairment (aMCI) versus cognitively unimpaired (CU) counterparts. Given potentially lower levels of formal education and literacy in some AA groups, it is important to determine whether such factors might adversely influence performance. 41 AA adults (53.7% males), with a mean age of 63.9 (SD = 5.1years, range = 54-83) were deemed to be CU after a clinical interview resulted in a CDR = 0, and scores from a neuropsychological battery were deemed normal by experienced neuropsychologists. The LASSI-L was not used in diagnosis. Level of educational attainment was 13.3 (SD = 2.3years: range = 9-20). Level of reading literacy, as assessed by the WRAT-4, yielded an average grade equivalent (GE) of 9.6 (SD = 3.5 range = 2.0-12.9); substantially lower than reported educational attainment. Association between formal education and literacy was 0.52 which accounted for 27% of the shared variance. There were no statistically significant correlations between formal education or WRAT-4 scores in any LASSI-L variables, including initial learning (Cued Recall 2 List A), proactive semantic interference (PSI) (Cued List B1-List B2), failure to recover from PSI, or semantic intrusion errors. Performance on the LASSI-L among AA-CU did not suggest biases associated with formal education or word literacy, making it a promising tool for research. Many neuropsychological measures do not have acceptable diagnostic accuracy when used among individuals that are racially diverse, have lower-education levels, and lower socioeconomic status. This is important in consideration for potential use of LASSI-L in clinical settings.

LASSI-L detects early cognitive changes in pre-motor manifest Huntington's disease: a replication and validation study.

Cognitive decline is an important early sign in pre-motor manifest Huntington's disease (preHD) and is characterized by deficits across multiple domains including executive function, psychomotor processing speed, and memory retrieval. Prior work suggested that the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L)-a verbal learning task that simultaneously targets these domains - could capture early cognitive changes in preHD. The current study aimed to replicate, validate and further analyze the LASSI-L in preHD using larger datasets. LASSI-L was administered to 50 participants (25 preHD and 25 Healthy Controls) matched for age, education, and sex in a longitudinal study of disease progression and compared to performance on MMSE, Trail A & B, SCWT, SDMT, Semantic Fluency (Animals), and CVLT-II. Performance was then compared to a separate age-education matched-cohort of 25 preHD participants. Receiver operating curve (ROC) and practice effects (12 month interval) were investigated. Group comparisons were repeated using a preHD subgroup restricted to participants predicted to be far from diagnosis (Far subgroup), based on CAG-Age-Product scaled (CAPs) score. Construct validity was assessed through correlations with previously established measures of subcortical atrophy. PreHD performance on all sections of the LASSI-L was significantly different from controls. The proactive semantic interference section (PSI) was sensitive (p = 0.0001, d = 1.548), similar across preHD datasets (p = 1.0), reliable on test-retest over 12 months (spearman rho = 0.88; p = <0.00001) and associated with an excellent area under ROC (AUROC) of 0.855. In the preHD Far subgroup comparison, PSI was the only cognitive assessment to survive FDR < 0.05 (p = 0.03). The number of intrusions on PSI was negatively correlated with caudate volume. The LASSI-L is a sensitive, reliable, efficient tool for detecting cognitive decline in preHD. By using a unique verbal learning test paradigm that simultaneously targets executive function, processing speed and memory retrieval, the LASSI-L outperforms many other established tests and captures early signs of cognitive impairment. With further longitudinal validation, the LASSI-L could prove to be a useful biomarker for clinical research in preHD.

Using the LASSI-L to Detect Robust Interference Effects in Premanifest Huntington Disease.

Diagnosis of manifest Huntington disease (HD) is based primarily on motor symptoms, but premanifest HD (preHD) is often associated with subtle cognitive decline. The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) is a validated verbal learning test that can be used to detect early cognitive decline. To determine the utility of the LASSI-L for detecting early cognitive decline in individuals with preHD and to compare the results of the LASSI-L with those of commonly used neuropsychological tests in HD. We administered the LASSI-L to 13 individuals with preHD and 13 healthy controls matched for age, sex, and education as part of a longitudinal study of disease progression. For comparison purposes, we administered the Mini-Mental State Examination; Stroop Color and Word Test; Symbol Digit Modalities Test; Trail-Making Test, Parts A and B; and category fluency (animals) task. Five of the seven sections on the LASSI-L captured group differences: Proactive Semantic Interference (PSI; P < 0.001), Failure to Recover From PSI (P = 0.038), Retroactive Semantic interference (RSI; P = 0.013), Delayed Recall (P < 0.001), and B1 Cued Recall Intrusions (P = 0.036). Using a false discovery rate of <0.05, PSI, RSI, and Delayed Recall remained significant. The LASSI-L is a sensitive instrument for detecting early interference effects in individuals with preHD that outperforms commonly used neuropsychological tests. The LASSI-L could be a useful addition to clinical and research protocols involving individuals with preHD.

A Novel Computerized Cognitive Test for the Detection of Mild Cognitive Impairment and Its Association with Neurodegeneration in Alzheimer's Disease Prone Brain Regions.

During the prodromal stage of Alzheimer's disease (AD), neurodegenerative changes can be identified by measuring volumetric loss in AD-prone brain regions on MRI. Cognitive assessments that are sensitive enough to measure the early brain-behavior manifestations of AD and that correlate with biomarkers of neurodegeneration are needed to identify and monitor individuals at risk for dementia. Weak sensitivity to early cognitive change has been a major limitation of traditional cognitive assessments. In this study, we focused on expanding our previous work by determining whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Semantic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. A second focus was to correlate LASSI-BC performance to volumetric reductions in AD-prone brain regions. Data was gathered from 111 older adults who were comprehensively evaluated and administered the LASSI-BC. Eighty-seven of these participants (51 CU; 36 aMCI) underwent MR imaging. The volumes of 12 AD-prone brain regions were related to LASSI-BC and other memory tests correcting for False Discovery Rate (FDR). Results indicated that, even after adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) on the LASSI-BC differentiated between CU and aMCI groups. An optimal combination of frPSI and initial learning strength on the LASSI-BC yielded an area under the ROC curve of 0.876 (76.1% sensitivity, 82.7% specificity). Further, frPSI on the LASSI-BC was associated with volumetric reductions in the hippocampus, amygdala, inferior temporal lobes, precuneus, and posterior cingulate.

The Cognitive Stress Test (CST): An Innovative Tool to Differentiate Cognitively Unimpaired (CU) Older Adults from those with Pre‐Mild Cognitive Impairment (Pre‐MCI) and Amnestic MCI (aMCI).

AbstractBackgroundThe CST is a novel assessment that was designed to measure cognitive changes during preclinical and prodromal stages of AD, that include aMCI and PreMCI, where deficits do not meet MCI. The CST employs semantically competing word lists to measure the impact of semantic interference, failure to recover from proactive semantic interference (frPSI), and its persistent effects, despite multiple trials. We hypothesized that frPSI deficits on the CST would be persistent in pre‐MCI and aMCI groups when compared to cognitively unimpaired (CU) controls.Method50 aMCI, 31 pre‐MCI, and 69 CU elders were administered the CST. Participants were presented with List A (18 semantically related words: occupations, household items, or transportation methods) for three initial learning trials, followed by three learning trials of List B, a categorically similar wordlist, to examine PSI and frPSI. Retroactive Semantic Interference (RSI) was assessed by using category cues to elicit recall of List A targets, followed by an additional learning trial to examine failure to recover from RSI (frRSI).ResultSignificant differences were observed between all diagnostic groups across CST Cued Recall trials that measure maximum learning, PSI, frPSI, and persistent frPSI. PreMCI and aMCI participants experienced deficits in learning List B despite two additional opportunities; a deficit that was observed even after adjusting for initial learning strength. Older adults with greater risk (preMCI and aMCI) performed similarly on indices that measures PSI, frPSI, and persistent frPSI as compared to controls. There were differences in RSI among CU and aMCI groups yet measuring frRSI did not differentiate groups. aMCI participants made more semantic intrusion errors on recall trials that cued List B words. Pre‐MCI and CU made a similar number of intrusion errors.ConclusionThe CST extends our work by assessing persistent effects of frPSI, which have been shown to predict neurodegenerative progression and have been associated with multiple biomarkers of AD. The finding that persistent frPSI could differentiate CU from preMCI groups is a promising indicator that semantic interference deficits persist in older adults that present a heightened risk for progression to dementia and is worthy of further research.

Neuropsychological, Metabolic, and Connectivity Underpinnings of Semantic Interference Deficits Using the LASSI-L.

LASSI-L is a novel neuropsychological test specifically designed for the early diagnosis of Alzheimer's disease (AD) based on semantic interference. To examine the cognitive and neural underpinnings of the failure to recover from proactive semantic and retroactive semantic interference. One hundred and fifty-five patients consulting for memory loss were included. Patients underwent neuropsychological assessment, including the LASSI-L, and FDG-PET imaging. They were categorized as subjective memory complaints (SMC) (n=32), pre-mild cognitive impairment (MCI) due to AD (Pre-MCI) (n=39), MCI due to AD (MCI-AD) (n=71), and MCI without evidence of neurodegeneration (MCI-NN) (n=13). Voxel-based brain mapping and metabolic network connectivity analyses were conducted. A significant group effect was found for all the LASSI-L scores. LASSI-L scores measuring failure to recover from proactive semantic interference and retroactive semantic interference were predicted by other neuropsychological tests with a precision of 64.1 and 44.8%. The LASSI-L scores were associated with brain metabolism in the bilateral precuneus, superior, middle and inferior temporal gyri, fusiform, angular, superior and inferior parietal lobule, superior, middle and inferior occipital gyri, lingual gyrus, and posterior cingulate. Connectivity analysis revealed a decrease of node degree and centrality in posterior cingulate in patients showing frPSI. Episodic memory dysfunction and the involvement of the medial temporal lobe, precuneus and posterior cingulate constitute the basis of the failure to recover from proactive semantic interference and retroactive semantic interference. These findings support the role of the LASSI-L in the detection, monitoring and outcome prediction during the early stages of AD.

Persistent Failure to Recover from Proactive Semantic Interference on the Cognitive Stress Test Differentiates Between Amnestic Mild Cognitive Impairment, Pre-Mild Cognitive Impairment, and Cognitively Unimpaired Older Adults.

Susceptibility to proactive semantic interference (PSI) and the inability to ameliorate these difficulties with one additional learning trial have repeatedly been implicated as early features of incipient Alzheimer's disease (AD). Unfortunately, persistent failure to recover from PSI (frPSI) after repeated learning trials, are not captured by existing memory measures, or been examined in pre-mild cognitive impairment (PreMCI). A novel Cognitive Stress Test (CST) was employed to measure the impact of PSI, initial failure to recover from PSI and persistent effects of PSI, despite multiple learning trials of the new to-be-remembered material (pfrPSI). We hypothesized that PSI deficits on the CST would persist in both PreMCI and amnestic MCI (aMCI) groups over repeated learning trials when compared to cognitively unimpaired (CU) older adults. One hundred fifty older adults (69 CU, 31 PreMCI, and 50 aMCI) underwent a standardized clinical and neuropsychological evaluation. The CST was independent of diagnostic classification. Even after adjusting for strength of initial learning, aMCI and PreMCI groups demonstrated greater persistent PSI (pfrPSI) relative to the CU group despite repeated learning trials of List B. Further, the aMCI group made a higher number of semantic intrusion errors relative to the PreMCI and CU groups on all List B Cued Recall trials. Persistent PSI appears to be a common feature of aMCI and PreMCI. The possible theoretical mechanisms and empirical implications of these new findings are discussed.

Developing a Danish version of the LASSI-L test – reliability and predictive value in patients with mild cognitive impairment, mild dementia due to AD and subjective cognitive decline

ABSTRACT Tests measuring proactive semantic interference as The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), has shown promising diagnostic properties for the diagnosis of Mild Cognitive Impairment (MCI) and dementia. LASSI-L may also be efficient in predicting cognitive decline in at-risk individuals. There is an unmet need to examine the diagnostic properties of the LASSI-L in a Danish context where traditional neuropsychological tests are typically applied when diagnosing possible dementia disorders. To investigate the reliability, convergent validity, and predictive value of the new Danish LASSI-L version in aMCI and mild dementia due to Alzheimer’s disease (AD). From a memory clinic we included 17 aMCI patients, 15 patients with mild dementia (AD), 17 patients with Subjective Cognitive Decline (SCD), and 30 healthy controls. Neuropsychological assessment was applied in all patients, and biomarker analyses were performed for patients with aMCI and mild AD. Cronbach’s alpha was 0.94. Patients with aMCI and mild dementia differed significantly from healthy controls on all LASSI-L measures. ROC analyses showed a very high AUC value for both patients with aMCI [0.85–0.97] and mild dementia [0.93–0.99]. SCD patients generally did not differ from controls, except for significantly lower scores on one item (Cued Recall A1) LASSI-L had high reliability and promising predictive value in the diagnosis of aMCI and mild AD due to AD. SCD patients diagnosed in a memory clinic did not differ significantly from healthy on the LASSI-L.

A-214 A Novel Computerized Cognitive Test for the Detection of MCI and its Association with Neurodegeneration in Alzheimer’s Disease Prone Brain Regions

Abstract Objective: First, to determine whether a digitized cognitive stress test, the Loewenstein-Acevedo Scales for Sematic Interference and Learning, Brief Computerized Version (LASSI-BC) could differentiate between Cognitively Unimpaired (CU) and amnestic Mild Cognitive Impairment (aMCI) groups. Second, to correlate LASSI-BC performance to volumetric reductions in Alzheimer’s disease (AD)-prone regions. Methods: 111 elders underwent a clinical and neuropsychological evaluation, along with the LASSI-BC. All participants were independent community-dwellers, had knowledgeable informants, and did not meet DSM-V criteria for any active neuropsychiatric disorder, Mood Disorder or Psychotic Disorder. Eighty-seven participants (51 CU; 36 aMCI) underwent MRI imaging. The volumes of 12 AD-prone regions were related to LASSI-BC and other memory indices correcting for False Discovery Rate (FDR). Results: After adjusting for initial learning ability, the failure to recover from proactive semantic interference (frPSI) of LASSI-BC successfully differentiated between groups. Measures of frPSI were associated with volumetric reductions in AD-prone regions (hippocampus, amygdala, inferior temporal-lobes, precuneus and posterior cingulate) in aMCI cohort. A combination of maximum learning capacity and frPSI on the LASSI-BC yielded an area under ROC curve of 0.876 with greater sensitivity and specificity when compared to other traditional tests (e.g., HVLT). Conclusions: Performance on the LASSI-BC successfully discriminated between diagnostic groups and is significantly associated with volumetric loss among aMCI individuals. This is significant as diagnostic cognitive tests of preclinical and prodromal AD should also be required to exhibit sensitivity to biomarkers of AD (e.g., amyloid, tau, and neurodegeneration in AD-prone regions), which may address some of the most critical challenges facing clinical trials.

The association between proactive semantic interference and blood sugar levels

AbstractBackgroundGlucose levels, together with hemoglobin A1c (HA1c), have been associated with reduced cognitive performance, particularly on executive functioning and memory measures. Numerous studies using the Loewenstein‐Acevedo Scales for Semantic Interference and Learning (LASSI‐L) have demonstrated that proactive semantic interference (PSI) and failure to recover from PSI (frPSI) are sensitive to early cognitive changes present in the preclinical stages of Alzheimer's disease (AD).MethodThe aim of the present study was to examine the association between PSI, frPSI, blood glucose levels, and hemoglobin A1c (HA1c) among cognitively normal middle‐aged adults. Seventy‐five adults (Age: 50.8 ± 6.67; Education: 16.23 ± 2.93; Sex: 68% female) without psychological disorders, substance use disorders, or previous cognitive diagnoses were recruited as part of a memory and aging study. Sixty‐seven participants identified as White (89%) and eight as African American (11%). They were fluent in English and/or Spanish and were tested in their dominant and preferred language (65% English, 35% Spanish), as assessed by the Language Experience and Proficiency Questionnaire. All participants underwent a neuropsychological evaluation and administration of the Clinical Dementia Rating Scale (CDR); all were diagnosed as cognitively normal by trained neuropsychologists. Participants fasted six to eight hours prior to providing a blood sample. Comparisons were made between participants using t‐tests and Chi‐square tests. An additional Spearman correlation was used to determine the relationship between the variables. Blood glucose and HA1c levels were compared to LASSI‐L scores, including the number of words correctly recalled and the number of intrusion errors (IE) on the PSI (List B Cued Recall 1) and frPSI (List B Cued Recall 2) trials.ResultThere was no significant association between glucose and the LASSI‐L Scales. However, higher HA1c levels were correlated with lower intrusion errors sensitive to proactive semantic interference.ConclusionOur findings are inconsistent with previous research, as an increase of blood glucose and HA1c levels have been formerly found to lead to reduced cognitive performance. Based on these findings, further investigations are warranted to better understand the associations between HA1C levels, proactive semantic interference, and varying cognitive domains.

Changes in LASSI-L performance over time among older adults with amnestic MCI and amyloid positivity: A preliminary study

There is a pressing need to develop measures that are sensitive to the earliest subtle cognitive changes of Alzheimer's disease (AD) to improve early detection and track disease progression. The Loewenstein-Acevedo Scales of Semantic Interference (LASSI-L) has been shown to successfully discriminate between cognitively unimpaired (CU) older adults and those with amnestic mild cognitive impairment (MCI) and to correlate with total and regional brain amyloid load. The present study investigated how the LASSI-L scores change over time among three distinct diagnostic groups. Eighty-six community-dwelling older adults underwent a baseline evaluation including: a clinical interview, a neuropsychological evaluation, Magnetic Resonance Imaging (MRI), and amyloid Positron Emission Tomography (PET). A follow up evaluation was conducted 12 months later. Initial mean values were calculated using one-way ANOVAs and chi-square analyses. Post-hoc comparisons were conducted using Tukey's Honestly Significant Difference (HSD). A 3 × 2 repeated measures analysis was utilized to examine differences in LASSI-L performance over time. The MCI amyloid positive group demonstrated a significantly greater decline in LASSI-L performance than the MCI amyloid negative and CU groups respectively. The scales that best differentiated the three groups included the Cued A2, which taps into maximum learning capacity, and Cued B2, which assesses the failure to recover from proactive semantic interference. Our findings further support the LASSI-L's discriminative validity.

Intrusion Errors and Progression of Cognitive Deficits in Older Adults with Mild Cognitive Impairment and PreMCI States

Introduction: Among persons with amnestic mild cognitive impairment (aMCI), intrusion errors on subscales that measure proactive semantic interference (PSI) may be among the earliest behavioral markers of elevated Alzheimer’s disease brain pathology. While there has been considerable cross-sectional work in the area, it is presently unknown whether semantic intrusion errors are predictive of progression of cognitive impairment in aMCI or PreMCI (not cognitively normal but not meeting full criteria for MCI). Methods: This study examined the extent to which the percentage of semantic intrusion errors (PIE) based on total responses on a novel cognitive stress test, the Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L), could predict clinical/cognitive outcomes over an average 26-month period in older adults initially diagnosed with aMCI, PreMCI, and normal cognition. Results: On the LASSI-L subscale sensitive to PSI, a PIE cut point of 44% intrusion errors distinguished between those at-risk individuals with PreMCI who progressed to MCI over time compared to individuals with PreMCI who reverted to normal on longitudinal follow-up. Importantly, PIE was able to accurately predict 83.3% of aMCI individuals who later progressed to dementia. Discussion: These preliminary findings indicate that PIE on LASSI-L subscales that measure PSI may be a useful predictor of clinical progression overtime in at-risk older adults.

Semantic intrusion errors as a function of age, amyloid, and volumetric loss: a confirmatory path analysis.

To examine the direct and indirect effects of age, APOE ϵ4 genotype, amyloid positivity, and volumetric reductions in AD-prone brain regions as it relates to semantic intrusion errors reflecting proactive semantic interference (PSI) and the failure to recover from proactive semantic interference (frPSI) on the Loewenstein-Acevedo Scales of Semantic Interference and Learning (LASSI-L), a cognitive stress test that has been consistently more predictive of preclinical and prodromal Alzheimer's disease (AD) than traditional list-learning tests. Cross-sectional study. 1Florida Alzheimer's Disease Research Center baseline study. Two-hundred and twelve participants with Mini-Mental State Examination (MMSE) score above 16 and a broad array of cognitive diagnoses ranging from cognitively normal (CN) to dementia, of whom 58% were female, mean age of 72.1 (SD 7.9). Participants underwent extensive clinical and neuropsychological evaluations, MR and amyloid Positron Emission Tomography/Computer/Computer Tomography (PET/CT) imaging, and analyses of APOE ϵ4 genotype. Confirmatory path analyses were conducted in the structural equation modeling framework that estimated multiple equations simultaneously while controlling for important covariates such as sex, education, language of evaluation, and global cognitive impairment. Both amyloid positivity and decreased brain volumes in AD-prone regions were directly related to LASSI-L Cued B1 and Cued B2 intrusions (sensitive to PSI and frPSI effects) even after controlling for covariates. APOE ϵ4 status did not evidence direct effects on these LASSI-L cognitive markers, but rather exerted their effects on amyloid positivity, which in turn related to PSI and frPSI. Similarly, age did not have a direct relationship with LASSI-L scores, but exerted its effects indirectly through amyloid positivity and volumes of AD-prone brain regions. Our study provides insight into the relationships among age, APOE ϵ4, amyloid, and brain volumetric reductions as it relates to semantic intrusion errors. The investigation expands our understanding of the underpinnings of PSI and frPSI intrusions in a large cohort.

The relationship of semantic intrusions to different etiological subtypes of MCI and cognitively healthy older adults.

Introduction: There is increasing evidence that susceptibility to proactive semantic interference (PSI) and the failure to recover from PSI (frPSI) as evidenced by intrusion errors may be early cognitive markers of both preclinical and prodromal Alzheimer's disease (AD).Methods: One hundred forty‐five participants were administered extensive clinical and neuropsychological evaluations including the Loewenstein‐Acevedo Scales for Semantic Interference and Learning (LASSI‐L), a sensitive cognitive stress test measuring PSI and frPSI. Participants also underwent structural magnetic resonance imaging (MRI) and amyloid positron emission tomography/computed tomography (PET/CT) imaging.Results: PSI and frPSI errors were much more prevalent in the mild cognitive impairment (MCI)‐AD (amyloid positive) group than the other diagnostic groups. The number of intrusion errors observed across the other MCI groups without amyloid pathology and those with normal cognition were comparable.Discussion: Semantic intrusion errors on the LASSI‐L occur much less frequently in persons who have different types of non–AD‐related MCI and may be used as an early cognitive marker of prodromal AD.