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.

Introduction: 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). Methods: 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 (Aß1-42/Aß1-40 and ptau181). Means comparisons, correlations, effect sizes, and ROC curves were calculated. Results: LASSI-L scores were significantly associated with CSF biomarkers Aß1-42/Aß1-40 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. Conclusion: 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.

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 Aß 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.

The upside of cumulative conceptual interference on exemplar-level mnemonic discrimination.

Although long-term visual memory (LTVM) has a remarkable capacity, the fidelity of its episodic representations can be influenced by at least two intertwined interference mechanisms during the encoding of objects belonging to the same category: the capacity to hold similar episodic traces (e.g., different birds) and the conceptual similarity of the encoded traces (e.g., a sparrow shares more features with a robin than with a penguin). The precision of episodic traces can be tested by having participants discriminate lures (unseen objects) from targets (seen objects) representing different exemplars of the same concept (e.g., two visually similar penguins), which generates interference at retrieval that can be solved if efficient pattern separation happened during encoding. The present study examines the impact of within-category encoding interference on the fidelity of mnemonic object representations, by manipulating an index of cumulative conceptual interference that represents the concurrent impact of capacity and similarity. The precision of mnemonic discrimination was further assessed by measuring the impact of visual similarity between targets and lures in a recognition task. Our results show a significant decrement in the correct identification of targets for increasing interference. Correct rejections of lures were also negatively impacted by cumulative interference as well as by the visual similarity with the target. Most interestingly though, mnemonic discrimination for targets presented with a visually similar lure was more difficult when objects were encoded under lower, not higher, interference. These findings counter a simply additive impact of interference on the fidelity of object representations providing a finer-grained, multi-factorial, understanding of interference in LTVM.

Neural Correlates of Semantic Interference and Phonological Facilitation in Picture Naming: A Systematic Review and Coordinate-Based Meta-analysis.

Semantic interference (SI) and phonological facilitation (PF) effects occur when multiple representations are co-activated simultaneously in complex naming paradigms, manipulating the context in which word production is set. Although the behavioral consequences of these psycholinguistic effects are well-known, the involved brain structures are still controversial. This paper aims to provide a systematic review and a coordinate-based meta-analysis of the available functional neuroimaging studies investigating SI and PF in picture naming paradigms. The included studies were fMRI experiments on healthy subjects, employing paradigms in which co-activations of representations were obtained by manipulating the naming context using semantically or phonologically related items. We examined the principal methodological aspects of the included studies, emphasizing the existing commonalities and discrepancies across single investigations. We then performed an exploratory coordinate-based meta-analysis of the reported activation peaks of neural response related to SI and PF. Our results consolidated previous findings regarding the involvement of the left inferior frontal gyrus and the left middle temporal gyrus in SI and brought out the role of bilateral inferior parietal regions in PF.

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

Introduction: 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. Methods: 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). Results: 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. Discussion: 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.

Similarity-induced interference or facilitation in language production reflects representation, not selection.

Researchers have long interpreted the presence or absence of semantic interference in picture naming latencies as confirming or refuting theoretical claims regarding competitive lexical selection. But inconsistent empirical results challenge any mechanistic interpretation. A behavioral experiment first verified an apparent boundary condition in a blocked picture naming task: when orthogonally manipulating association type, taxonomic associations consistently elicit interference, while thematic associations do not. A plausible representational difference is that thematic feature activations depend more on supporting contexts. Simulations show that context-sensitivity emerges from the distributional statistics that are often used to measure thematic associations: residual semantic activation facilitates the retrieval of words that share semantic features, counteracting learning-based interference, and training a production model with greater sequential cooccurrence for thematically related words causes it to acquire stronger residual activation for thematic features. Modulating residual activation, either directly or through training, allows the model to capture gradient values of interference and facilitation, and in every simulation competitive and noncompetitive selection algorithms produce qualitatively equivalent results.

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

Background and objectives: 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. Methods: 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. Results: 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. Discussion: 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.

Semantic interference affects speech production by increasing disfluencies, not errors.

Several studies have shown that different types of disfluency occur depending on the language production stage at which people experience difficulties. The current study combined a network task and a picture-word interference task to analyse whether lexical-semantic difficulty triggers errors and disfluencies in connected-speech production. The participants produced more disfluencies in the presence of a semantically related distractor word than an unrelated distractor word, while few semantic errors were made. These results support the hypothesis that difficulties at distinct stages of language production lead to distinct patterns of disfluency, with lexical-semantic difficulties leading to self-corrections and silent pauses. The results also have implications for the role of the monitoring system in connected-speech production.

Web-based language production experiments: Semantic interference assessment is robust for spoken and typed response modalities.

For experimental research on language production, temporal precision and high quality of the recorded audio files are imperative. These requirements are a considerable challenge if language production is to be investigated online. However, online research has huge potential in terms of efficiency, ecological validity and diversity of study populations in psycholinguistic and related research, also beyond the current situation. Here, we supply confirmatory evidence that language production can be investigated online and that reaction time (RT) distributions and error rates are similar in written naming responses (using the keyboard) and typical overt spoken responses. To assess semantic interference effects in both modalities, we performed two pre-registered experiments (n = 30 each) in online settings using the participants' web browsers. A cumulative semantic interference (CSI) paradigm was employed that required naming several exemplars of semantic categories within a seemingly unrelated sequence of objects. RT is expected to increase linearly for each additional exemplar of a category. In Experiment 1, CSI effects in naming times described in lab-based studies were replicated. In Experiment 2, the responses were typed on participants' computer keyboards, and the first correct key press was used for RT analysis. This novel response assessment yielded a qualitatively similar, very robust CSI effect. Besides technical ease of application, collecting typewritten responses and automatic data preprocessing substantially reduce the work load for language production research. Results of both experiments open new perspectives for research on RT effects in language experiments across a wide range of contexts. JavaScript- and R-based implementations for data collection and processing are available for download.

The unseen, the seen, and the spoken: Latent and overt priming in cyclic picture naming.

Language production entails selecting words in the face of internally, and sometimes externally, driven competition that influences the long-term accessibility of both selected words and competitors. Because both endogenous and externally presented competitors usually result in semantic interference, it is often assumed that they engage the same underlying processes. We question this assumption. Specifically, we propose that latent primes may more naturally commingle with endogenous lexical activation whereas overt primes elicit strong control processes. Two experiments examined the effects of latent (masked) and overt (picture-word) priming in combination with cyclic picture naming of small sets of taxonomically or thematically related or unrelated pictures. A subsequent continuous picture naming phase was designed to assess enduring effects of service as a prime or target. Only taxonomic relations showed substantial interference in cyclic naming. Latent priming tended to increase interference for taxonomic relations, but it produced facilitation for thematic relations. In contrast, overt priming induced interference for both types of relation, indicating exertion of cognitive control. In the continuous picture naming phases, accessibility was hindered for previously presented latent primes (Experiment 1) but enhanced for previously overt primes (Experiment 2). Surprisingly, interference in cyclic naming did not carry forward to the continuous phase. These findings suggest that masked priming may be a viable intervention in the internal dynamics of lexical selection. In contrast, they also add to the body of evidence questioning the validity of using picture-word procedures to study inherent semantic interference.

Learning and vulnerability to phonological and semantic interference in normal aging: an experimental study.

ABSTRACTThis study compares semantic and phonological interference vulnerability across the full range of learning processes. Method: 43 controls aged 61-88 underwent a neuropsychological examination, French adaptation of the LASSI-L, and an experimental phonological test, the TIP-A. Paired sample t-tests, factorial ANOVA and hierarchical regressions were conducted, psychometric properties were calculated. Results: TIP-A efficiently generated phonological interference between concurrent word lists and was associated with short-term memory, unlike LASSI-L. On LASSI-L, proactive interference was higher than retroactive interference; the opposite pattern was found on TIP-A. Memory performance was better explained by age in the semantic than in the phonological task. Age was not associated with interference vulnerability. Intrusions and false recognition were associated with cognitive functioning regardless of age, particularly in the semantic context. Conclusion: To our knowledge, this is the first study to assess phonological and semantic interference using homologous concurrent word list tasks, and not a working memory build-up or DRM paradigm. The pattern obtained illustrates the weak initial memory trace in a phonological context and results are discussed according to depth-of-processing and dual-process theories. Similar paradigms could be studied among various pathologies for a better understanding of generalised interference vulnerability vs. specific semantic or phonological impairment.

Neighing dogs: Semantic context effects of environmental sounds in spoken word production - a replication and extension.

Semantic context effects are well established using both words and pictures as stimuli. One such effect, semantic interference, is observed in naming latencies when a categorically related distractor word or picture is presented together with a target picture (e.g., dog-LION). Recently, this effect has also been shown to occur when an environmental sound (e.g., a dog barking) is presented as an auditory distractor during picture naming and when a distractor picture is presented with a target sound for naming. The purpose of the current study was twofold: (1) to replicate the semantic interference effect in the picture-sound interference (PSI) paradigm and (2) determine whether a semantic interference effect is also observable when distractor words are presented with environmental sounds as target auditory objects for naming, using a novel sound-word interference (SWI) paradigm. We replicated the semantic interference effect in Experiment 1 with environmental sound distractors. Experiment 2 demonstrated significant semantic interference during an SWI paradigm for the first time. We discuss the implications of these results for our understanding of the origin and locus of the semantic interference effect according to current theories of lexical selection.

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.

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.

BACKGROUND: 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). OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Salient Cognitive Paradigms to Assess Preclinical Alzheimer's Disease.

Despite the growing emphasis to identify early biological markers that can detect the progressive accumulation of brain pathology in the complex pathophysiologic cascade that occurs in Alzheimer's disease (AD), we continue to employ the same neuropsychological paradigms that were developed to detect dementia or frank cognitive impairment. It has become increasingly clear that we cannot expect to measure clinically meaningful change in relationship to these emerging preclinical biomarkers using these traditional cognitive assessment paradigms, nor will we advance the efforts to identify the earliest cognitive changes that emerge in AD. Over the last decade, a few novel promising cognitive assessment paradigms have emerged that have shown promise in identifying subtle cognitive deficits in AD which aids in early detection and monitoring of meaningful cognitive change over time. Some of these cognitive assessment paradigms are reviewed here, including semantic interference, semantic intrusion errors, memory binding, and binding of face and name associations. These paradigms may be useful for AD clinical trials focused on secondary prevention if there is sufficient rigor to suggest that they correlate with AD biomarkers, having robust sensitivity, specificity, and predictive utility among culturally and linguistically diverse populations at-risk for AD.

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

OBJECTIVE: 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. DESIGN: Cross-sectional study. SETTING: 1Florida Alzheimer's Disease Research Center baseline study. PARTICIPANTS: 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). MEASURES: 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. RESULTS: 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. CONCLUSIONS: 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.

Distributional properties of semantic interference in picture naming: Bayesian meta-analyses.

Studies of word production often make use of picture-naming tasks, including the picture-word-interference task. In this task, participants name pictures with superimposed distractor words. They typically need more time to name pictures when the distractor word is semantically related to the picture than when it is unrelated (the semantic interference effect). The present study examines the distributional properties of this effect in a series of Bayesian meta-analyses. Meta-analytic estimates of the semantic interference effect first show that the effect is present throughout the reaction time distribution and that it increases throughout the distribution. Second, we find a correlation between a participant's mean semantic interference effect and the change in the effect in the tail of the reaction time distribution, which has been argued to reflect the involvement of selective inhibition in the naming task. Finally, we show with simulated data that this correlation emerges even when no inhibition is used to generate the data, which suggests that inhibition is not needed to explain this relationship.

BONEs not CATs attract DOGs: Semantic context effects for picture naming in the lesioned language network.

The breakdown of rapid and accurate retrieval of words is a hallmark of aphasic speech and a prime target of therapeutic intervention. Complementary, psycho- and neurolinguistic research have developed a spectrum of models, how and by which neuronal network uncompromised speakers can rely on remarkable lexical retrieval capacities. Motivated by both lines of research we invited 32 participants with a chronic left hemispheric brain lesion to name pictures in the presence of distractor words. This picture-word-interference (PWI) paradigm is widely used in psycho- and neurolinguistic research. We find that also after brain lesion categorically related words (CAT â†’ [dog]picture) impede naming, while associatively related words (BONE â†’ [dog]picture) ease access, when compared to unrelated distractor words. The effects largely affecting latencies in neurotypical populations, are reproduced for error rate in our participants with lesions in the language network. Unsurprisingly, overall naming abilities varied greatly across patients. Notably, however, the two effects (categorical interference / associative facilitation) differ between participants. Correlating performance with lesion patterns we find support for the notion of a divergence of brain areas affording different aspects of the task: (i) lesions in the left middle temporal gyurs (MTG) deteriorate overall naming, confirming previous work; more notably, (ii) lesions comprising the inferior frontal hub (inferior frontal gyrus, IFG) of the language-network increase the interference effect for the categorical condition; on the contrary, (iii) lesions to the mid-to-posterior temporal hub (posterior middle and superior temporal gyri, pMTG/ pSTG) increase the facilitatory effect for the associative condition on error rates. The findings can be accommodated in a neuro-linguistic framework, which localizes lexical activation but also lexical interference in posterior parts of the language network (pMTG/pITG); conversely, selection between co-activated categorically related entries is afforded by frontal language areas (IFG). While purely experimental in nature our study highlights that lesion site differentially influences specific aspects of word retrieval. Since confrontational naming is a cornerstone of aphasia rehabilitation, this may be of note when designing and evaluating novel therapeutic regimes.

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.

An Information-Theoretic Account of Semantic Interference in Word Production.

I present a computational-level model of semantic interference effects in online word production within a rate-distortion framework. I consider a bounded-rational agent trying to produce words. The agent's action policy is determined by maximizing accuracy in production subject to computational constraints. These computational constraints are formalized using mutual information. I show that semantic similarity-based interference among words falls out naturally from this setup, and I present a series of simulations showing that the model captures some of the key empirical patterns observed in Stroop and Picture-Word Interference paradigms, including comparisons to human data from previous experiments.