Published Research

Early detection of amnestic mild cognitive impairment (aMCI) is crucial for early intervention. The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) identify risk for cognitive decline by measuring proactive semantic interference (PSI). PSI correlates with critical Alzheimer’s disease (AD) biomarkers, predicting decline. A digital version of the LASSI™, the LASSI-D™, was highly convergent with the LASSI-L in older participants. We developed three alternative forms of the LASSI-D™, examining convergence across forms and retest changes, to evaluate utility as a repeated-measure

The three digital alternative forms of the LASSI™ (LASSI-D™) were highly convergent with each other and the LASSI-L. The findings provide evidence of the utility of a cloud-based, self-administered cognitive challenge test with alternative forms.

This study reports on the development and initial validation of a self-administered computerized version of the Loewenstein-Acevedo Scales for Semantic Interference (LASSI), the digital LASSI (LASSI-D). A self-administered digital version, with an artificial intelligence–generated avatar assistant, was the migrated assessment.

The results for the digital migration of the LASSI-D were highly convergent with the legacy LASSI-L. Across all indices of similarity, including sensitivity, criterion validity, classification accuracy, and performance, the versions converged across languages. The current data provide convincing evidence of the use of a fully self-administered digitally migrated cognitive challenge test.

Huntington’s disease (HD) is characterized by progressive cognitive decline, with early deficits often preceding motor symptoms. The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) captures many types of deficits in verbal memory including susceptibility to interference. The current study aims to delineate the progression of these deficits across different stages of HD.

The LASSI-L appears to be a useful tool for detecting early and progressive cognitive changes in Huntington’s disease, particularly by capturing the sequential nature of verbal memory deficits, including early vulnerability to interference. These findings suggest that the LASSI-L may help refine HD staging by integrating sequential neuropsychological markers of cognitive decline.

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.

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.

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.

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.

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.

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 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.  LASSI-L had high reliability and promising predictive value in the diagnosis of aMCI and mild AD due to AD.

The objective was 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.

The 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).

In this study, the focus was on expanding 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.

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. Further, frPSI on the LASSI-BC was associated with volumetric reductions in the hippocampus, amygdala, inferior temporal lobes, precuneus, and posterior cingulate.

Cognitive decline is an important early sign in premotor 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.

The study found that LASSI-L is a sensitive, reliable, efficient tool for detecting cognitive decline in preHD.

Diagnosis of manifest Huntington disease (HD) is based primarily on motor symptoms, but premanifest HD (preHD) is often associated with subtle cognitive decline. Objective of the study was 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.

The study found that 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.

The psychometric properties and clinical utility of the brief computerized version of the LASSI-L was evaluated, together with its ability to differentiate older adults who are cognitively normal (CN) from those with amnestic Mild Cognitive Impairment (aMCI).

The conclusion was that the LASSI-BC, a brief computerized version of the LASSI-L is a valid and useful cognitive tool for the detection of aMCI among older adults.

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).

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.

The 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.

The Loewenstein-Acevedo Scales for Semantic Interference and Learning (LASSI-L) is an increasingly utilized cognitive stress test designed to identify early cognitive changes associated with incipient neurodegenerative disease. The objective was to examine previously derived cut-points for cognitively unimpaired older adults that were suggestive of performance impairment on multiple subscales of the LASSI-L.

Only 7.7% of HC were incorrectly classified as having impairments. A modest number of LASSI-L subscales taking approximately 8 minutes to administer, had excellent discriminative ability using established cut-offs among individuals with presumptive stages of AD. This has potential implications for both clinical practice and clinical research settings targeting AD during early prodromal stages.

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). 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.

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.

The development and validation of clinical outcome measures to detect early cognitive decline associated with Alzheimer’s disease (AD) biomarkers is imperative. Semantic intrusions on the Loewenstein Acevedo Scales of Semantic Interference and Learning (LASSI-L) has outperformed widely used cognitive measures as an early correlate of elevated brain amyloid in prodromal AD and has distinguished those with amnestic mild cognitive impairment (aMCI) and high amyloid load from aMCI attributable to other non-AD conditions.

Since intrusion errors on memory tasks vary widely, we employed a novel method that accounts for the percentage of intrusion errors (PIE) in relation to total responses. Individuals with either high or low amyloid load across the spectrum of aMCI and dementia and amyloid negative cognitively normal older adults (CN) were studied.

PIE, a novel and sensitive index of early memory dysfunction, demonstrated high levels of sensitivity and specificity in differentiating CN from amyloid positive persons with preclinical AD. Mean levels of PIE are higher for amyloid positive aMCI and dementia participants relative to their amyloid negative counterparts.

Episodic memory is frequently impaired in Multiple Sclerosis (MS), but the cognitive characteristics and neuropsychological processes involved remain controversial. Our aim was to study episodic memory dysfunction in MS, using the LASSI-L, a novel memory-based cognitive stress test that uses a new paradigm that capitalizes on semantic interference

We found that deficits in maximum learning, difficulties in recovery from the effects of proactive semantic interference and retroactive semantic interference are three important breakdowns in episodic memory deficits among patients with MS. The LASSI-L showed good psychometric and diagnostic properties. Overall, our study supports the utility of the LASSI-L, as a new cognitive test, useful for neuropsychological assessment in MS in clinical and research settings.

Semantic intrusion errors on memory tests may represent very early cognitive changes associated with elevated Alzheimer’s disease pathology within the brain, including amyloid-β (Aβ). Subscales that measure proactive semantic interference (PSI) and intrusions related to PSI on the Loewenstein Acevedo Scales of Semantic Interference and Learning (LASSI-L) have been associated with high levels of brain amyloid load, structural changes on brain MRI in Hispanic and non-Hispanic groups. It is presently unknown whether intrusion errors or other measures of the LASSI-L can differentiate between African-American (AA) older adults diagnosed with amnestic mild cognitive impairment (aMCI) or classified as cognitively normal (CN).

With and without statistical adjustment for literacy, AA aMCI participants scored lower on all LASSI-L measures. ROC analyses revealed an area under the curve exceeding 90% and correctly classified 86% of AA aMCI with 82% specificity for AA CN participants.  Percentage of intrusion errors on the LASSI-L subscales susceptible to PSI differentiated AA aMCI from AA CN. This adds to emerging evidence indicating that the LASSI-L may be culturally appropriate and can differentiate between aMCI and CN in diverse ethnic/cultural groups.

Failure to recover from proactive semantic interference (frPSI) has been shown to be more sensitive than traditional cognitive measures in different populations with preclinical Alzheimer’s disease. The authors sought to characterize the structural and amyloid in vivo correlates of frPSI in cognitively normal offspring of patients with late-onset Alzheimer’s disease (O-LOAD), compared with individuals without a family history of neurodegenerative disorders (CS).

Recovery from proactive semantic interference (frPSI) and RAVLT delayed recall were lower in O-LOAD cases. Better recovery from retroactive semantic interference was associated with less amyloid load in the left temporal lobe in O-LOAD but not CS. In middle-aged cognitively normal individuals with one parent affected with LOAD, frPSI was impaired compared with persons without a family history of LOAD.

Culturally fair cognitive assessments sensitive to detecting changes associated with prodromal Alzheimer’s disease are needed. Performance of Hispanic and non-Hispanic older adults on the Loewenstein-Acevedo Scale of Semantic Interference and Learning (LASSI-L) was examined in persons with amnestic mild cognitive impairment (aMCI) or normal cognition. The association between a novel cognitive marker, the failure to recover from proactive semantic interference (frPSI), and cortical thinning was explored.

In diverse populations, LASSI-L performance differentiated patients with aMCI from cognitively normal older adults and was associated with thinning in Alzheimer’s disease-prone regions, suggesting its clinical utility.

Semantic intrusion (SI) errors may highlight specific breakdowns in memory associated with preclinical Alzheimer disease (AD); however, there have been no investigations to determine whether SI errors occur with greater frequency in persons with amnestic mild cognitive impairment (aMCI) confirmed as amyloid positive (Amy+) vs those who have clinical symptoms of aMCI-AD with negative amyloid scans (suspected non-AD pathology [SNAP]) or persons who are diagnosed with other brain disorders affecting cognition.

SIs on the LASSI-L related to PSI and frPSI uniquely differentiated Amy+ and Amy- participants with aMCI and likely reflect deficits with inhibition and source memory in preclinical AD not captured by traditional cognitive measures. This may represent a specific, noninvasive test successful at distinguishing cases with true AD from those with SNAP.

Accumulating evidence indicates that the failure to recover from the effects of proactive semantic interference [frPSI] represents an early cognitive manifestation of preclinical Alzheimer’s disease. A limitation of this novel paradigm has been a singular focus on the number of targets correctly recalled, without examining co-occurring semantic intrusions [SI] that may highlight specific breakdowns in memory. We focused on SI and their relationship to amyloid load and regional cortical thickness among persons with amnestic mild cognitive impairment (aMCI).

Semantic intrusions on measures susceptible to frPSI related to greater brain amyloid load and lower cortical thickness. These findings further support the hypothesis that frPSI, as expressed by the percentage of intrusions, may be a cognitive marker of initial neurodegeneration and may serve as an early and distinguishing test for preclinical AD that may be used in primary care or clinical trial settings.

The Free and Cued Selective Reminding Test (FCSRT) is the most accurate test for the diagnosis of prodromal Alzheimer’s disease (AD). Recently, a novel cognitive test, the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L), has been developed in order to provide an early diagnosis. The objective was to compare the diagnostic accuracy of the FCSRT and the LASSI-L for the diagnosis of AD in its preclinical and prodromal stages using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) as a reference.

The LASSI-L, a cognitive stress test, was superior to FCSRT in the prediction of AD features on FDG-PET. This emphasizes the possibility to advance toward an earlier diagnosis of AD from a clinical perspective.

In spite of advances in neuroimaging and other brain biomarkers to assess preclinical Alzheimer’s disease (AD), cognitive assessment has relied on traditional memory paradigms developed well over six decades ago. This has led to a growing concern about their effectiveness in the early diagnosis of AD which is essential to develop preventive and early targeted interventions before the occurrence of multisystem brain degeneration. We describe the development of novel tests that are more cognitively challenging, minimize variability in learning strategies, enhance initial acquisition and retrieval using cues, and exploit vulnerabilities in persons with incipient AD such as the susceptibility to proactive semantic interference, and failure to recover from proactive semantic interference.

The advantages of various novel memory assessment paradigms are examined as well as how they compare with traditional neuropsychological assessments of memory. Finally, future directions for the development of more effective assessment paradigms are suggested.

The main objective of this study was to assess cognitive and depressive manifestations associated with Alzheimer’s disease in middle-aged asymptomatic individuals with maternal versus paternal family history of the disease using standardly used neuropsychological measures and a novel cognitive stress test, the Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L).

This study highlights the value of semantic interference paradigms in early detection of Alzheimer’s and emphasizes the importance of studying maternal versus paternal transmission of the disease.

The study attempted to replicate and extend our previous findings that frPSI is a sensitive marker of early AD, and related to a unique pattern of volumetric loss in AD prone areas.

Unique and strong associations between volumetric reductions and frPSI as observed by Loewenstein and colleagues were replicated. Together with cortical thickness findings, these results indicate that frPSI is worthy of further study as a sensitive and early cognitive marker of AD.

This study investigated the association between PSI, recovery from PSI, and reduced MRI volumes in AD signature regions among cognitively impaired and unimpaired older adults.

LASSI-L indices eliciting failure to recover from PSI were more highly associated with more MRI regional biomarkers of AD than other traditional cognitive measures.

We have obtained previous evidence of limbic dysfunction in middle-aged, asymptomatic offspring of late-onset Alzheimer’s disease (LOAD) patients, and failure to recover from proactive semantic interference has been shown to be a sensitive cognitive test in other groups at risk for LOAD. The objective was to assess the effects of specific proactive semantic interference deficits as they relate to functional magnetic resonance imaging (fMRI) neocortical and limbic functional connectivity in middle aged offspring of individuals with LOAD (O-LOAD) and age-equivalent controls.

The present results suggest that both semantic interference deficits and connectivity abnormalities might reflect limbic circuit dysfunction as a very early clinical signature of LOAD pathology, as previously demonstrated for other limbic phenotypes, such as sleep and circadian alterations.

The Loewenstein-Acevedo Scale for Semantic Interference and Learning (LASSI-L) is a novel cognitive test that measures recovery from proactive semantic interference, which may be an early cognitive marker of Alzheimer’s disease (AD). The objective was to generate normative data for a Spaniard population and to validate the LASSI-L for the diagnosis of amnestic mild cognitive impairment (aMCI) and mild AD.

The LASSI-L is a reliable and valid test for the diagnosis of aMCI and mild AD. The age and education influences on the performance of the test and normative data are provided. LASSI-L merits further studies to evaluate its ability to detect preclinical AD and predict progression to aMCI and early dementia.

The objective was to examine the utility of a novel “cognitive stress test” to detect subtle cognitive impairments and amyloid load within the brains of neuropsychologically normal community-dwelling elders.

LASSI-L deficits were identified among 89% of those with MCI, 47% with PreMCI, 33% with SMI, and 13% classified as CN. Failure to recover or compensate for the effects of PSI on the LASSI-L distinguishes the LASSI-L from other widely used neuropsychological tests and appears to be sensitive to subtle cognitive impairments and increasing amyloid load.

A number of older adults obtain normal scores on formal cognitive tests, but present clinical concerns that raise suspicion of cognitive decline. Despite not meeting full criteria for Mild Cognitive Impairment (MCI), these PreMCI states confer risk for progression to Alzheimer’s disease (AD). This investigation addressed a pressing need to identify cognitive measures that are sensitive to PreMCI and are associated with brain biomarkers of neurodegeneration.

PreMCI participants evidenced greater LASSI- L deficits, particularly with regards to frPSI and delayed recall, relative to the CN group.