This was the first part of a longitudinal observational study conducted at 7 community centers or locations in South Florida and 4 in New York City. Following screening and orientation to the study, participants received an in-person assessment to characterize their cognitive status. Participants who met inclusion criteria and adequately completed the initial assessment progressed to later parts of the study.

The sample included English- or Spanish-speaking adults aged 59 years or older who lived in the community, had at least 20/60 vision, were able to read a computer screen, and had adequate hearing for an auditory-based assessment. Men and women were recruited, without restrictions on racial or ethnic status. MCI status was ascertained with a neuropsychological assessment using the Jak-Bondi criteria [31].

Exclusion criteria included a Montreal Cognitive Assessment (MoCA) [32] score of <19 or a reading score, in their dominant language, at less than a 6th grade level. Other exclusions included the inability to undergo assessments in either English or Spanish, having been tested with the LASSI-L in the past 12 months, a diagnosis of a serious psychiatric condition apart from clinical depression, a previous medical history of brain disorder such as stroke, seizures, tumor, or significant traumatic brain injury with extended loss of consciousness.

The literacy level of English speakers was examined with the Wide Range Achievement Test [33], third edition. Spanish speakers were assessed with the Batería III Woodcock-Munoz Identificacion de letras y palabras subtest [34].

Cognitive assessments were used to collect data for the performance-based MCI criteria. The LASSI measures were not used in diagnostic determination. All assessments were performed in each participants’ preferred language (English or Spanish). Montreal Cognitive Assessment (MoCA [32]) examines cognitive performance with scores ranging from 0‐30. Assessments were performed by certified bilingual raters. Using Wechsler Memory Scale- revised, Logical Memory I and II (Anna Thompson Story) [28], participants were asked to read a story and then asked for immediate recall, followed by a 20-minute delayed recall filled with other nonverbal assessments. Hopkins Verbal Learning Test-Revised [29] was administered before assessment with the Brief Assessment of Cognition (BAC), substituting this shorter 12-item, 3 trial verbal learning assessment for the much harder 15-item 5-trial BAC word list test. We also examined delayed recall to contribute to the MCI classification.

Wechsler Memory Scale- revised, Logical Memory I and II (Anna Thompson story) [28]. Participants were asked to read a story and then asked for immediate recall, followed by a 20 -minute delayed recall filled with other non-verbal assessments.

The BAC app version [35] measures domains of cognition known to be related to everyday functioning. The BAC app delivers the same assessments with cloud-connected tablet delivery for ease of administration and standardization. The BAC-app has been widely used in studies of MCI. The cognitive domains assessed include: Digit Sequencing, Token Motor; Verbal Fluency; Symbol Coding; Tower of London. Participants with MoCA scores less than 19 were not tested further and testing also stopped if participants did not have the required literacy level.

Two short tests, Trail-Making Test part A and Animal Naming Fluency were administered immediately before the LASSI-L and the LASSI-D. This assessment was designed to ensure that the participants were ready to be assessed with the somewhat longer LASSI procedure and to provide additional information about the similarities of the participant samples. Performance on these tests were not used for participant selection.

Participants were examined with 2 variants of the LASSI: the legacy technician delivered paper version: the LASSI-L and the LASSI-D, which has identical stimuli to the LASSI-L. The LASSI uses controlled learning and cued recall to maximize encoding of a list of to-be-remembered target words representing three semantic categories. The examinee learns a list of 15 common words comprised of musical instruments, fruits, or articles of clothing (5 words per semantic category) which they are asked to recall immediately after exposure. Critically, exposure to stimuli occurs with the participant being shown each of the words, one at a time, and being asked to read the word aloud, thus ensuring encoding of every stimulus. Words that were read incorrectly are immediately cued in the following way: “The word is XYZ. Please say XYZ.”

After the free recall trial, the examinee is presented with each category cue (eg, clothing) and asked to recall the words from that category, yielding a cued recall score (cued A1). The examinee is then exposed to the same target stimuli for a second learning trial with subsequent cued recall, with a goal of strengthening the acquisition and recall of the list A targets, providing maximum encoding of the to-be-remembered information (cued A2). As the LASSI-L targets identification of semantic intrusions in individuals without major memory challenges, previous studies of the LASSI-L have excluded participants who were unable to learn at least 11 of the 15 list A stimulus words [18-20].

Following the second presentation of list A, the participant is presented a semantically related list (list B) which consists of 15 words which are different from list A, with 5 from each of the same categories and again asked to read them aloud. Following the list B presentation, the examiner asks the participant for free recall of the list B words (B1 free recall); reduced learning compared with list A defines immediate proactive semantic interference (PSI). Then, the participants are cued to recall the list B words. Next, the participants read the list B words again, followed by a second cued recall trial (cued recall B2). Recall performance on this second learning trial measures whether the examinee’s manifests failure to recover from PSI (frPSI). Refer to Figure 1 for the sequence of assessments contained in the LASSI.

An additional critical set of outcomes are intrusion scores. During both free and cued recall conditions for list B any recalled words that are not from the are recorded. This dependent variable is calculated into an index, dividing the number of intrusion errors by the total words recalled, including words correctly recalled and intrusions, yielding “percentage of intrusion errors” (PIE) This index captures the proportion of all recalled information that constitutes intrusions. PIE has been shown to be the most sensitive predictor of risk for subsequent cognitive decline [16,36]. The LASSI-L has been translated into multiple languages, including Spanish. We used the English and Spanish versions in this study.

The digital assessments with the LASSI-D were computerized, cloud-based, and completely self-administered. To ensure that the LASSI-D is a valid equivalent of the LASSI-L, several important steps were undertaken in the migration. The first was piloting and refining the (Google) voice recognition software through pilot testing to ensure accurate of identification of words read and recalled by participants (taking into consideration different English and Spanish accents, physical environments, etc). Second was the development of a realistic AI generated humanoid avatar. The avatar vocalizes the instructions and feedback during assessment that are read by the human tester during LASSI-L assessments. Third was the development of a digitally administered pretesting orientation and preparation session to ensure attentiveness and understanding on the part of the participant. This orientation serves to ready the user to properly interface with the LASSI-D application, while testing the functionality of the user’s internet connection, the microphone, and speakers. In the orientation, the participant is asked to name some simple shapes that appear on the device’s screen, continuing until correct responses are detected by the software. Thus, the resulting software program interactively provides instructions and feedback to participants, presenting all stimuli and identifying and collating the words spoken by the examinee.

Participants were screened for cognitive functioning as described above. Participants were designated as having normal cognition (NC) or 1 of 3 different MCI subtypes: aMCI (impairments on 2 or more memory tests but no other cognitive domains); multidomain mild cognitive impairment (2 or more impairments on both memory and other cognitive domains); nonamnestic mild cognitive impairment (NAMCI; impairments on 2 nonmemory cognitive domains, but no more than 1 memory domain). Normative standards for the screening tests were used to evaluate performance, with impairment defined as SD 1 below normative values on each test. The LASSI data for participants with NAMCI were collected, but their data was not examined because the LASSI-L is focused on aMCI. We did not inform the research participants whose data were being excluded because they may have known other participants and discussed the research procedures with them. NC participants were required to have a MoCA score of 26 or more, which was downwardly adjusted due to low levels of education/literacy present in the samples at our community centers.

A fully bilingual testing assistant was present during all assessment sessions and administered all the paper-and-pencil screening tests as well as the LASSI-L. At the end of the first assessment with the LASSI, participants also were administered the ADAS-Cog. Testing order of the LASSI variants was sequentially based, presented in Figure S1 in Multimedia Appendix 1, and is separated by 2 weeks. We started with the LASSI-L and tested until we had at least 50 confirmed eligible participants (MoCA >19, list A2 recognition >10, does not meet criteria for NAMCI). Next, we administered the LASSI-D-form A, until we were certain we had 50 eligible participants. Because of delays in confirmation of MCI status, more than 50 cases were in each of the final samples. We did not attempt to balance the samples for potential factors (language, aMCI vs NC, sex). Baseline performance on forms B and C and weeks 2, 4, and 6 reassessments with the alternative forms of the LASSI-D will be presented in a comprehensive paper on alternative forms and test-retest effects when the study is completed.

The goal of the analyses was to examine the similarity of the LASSI-L and LASSI-D, form A (identical stimuli to LASSI-L). Analyses were performed on the 6 critical variables, cued recall of list B trial 1 (B1), cued recall 2 of list B (B2), intrusions on list B trials 1 (B1) and 2 (B2), and percentage of intrusion errors (PIE) for list B trials 1 and 2 (PIE1 and PIE2) for participants who achieved a qualifying cued A2 score. We used t tests to compare performance of NC and aMCI participants on all 6 variables in each of the 2 forms (LASSI-L vs LASSI-D form A). We then compared the difference between aMCI and NC for each of the 6 variables within each version. Then we examined the correlations of the 6 variables with other indicators of cognitive impairment (ADAS-Cog and MoCA) separately for the LASSI-L and LASSI-D. To confirm that the samples were comparable in their overall cognitive performance, the NC and aMCI within the were compared for similarity of performance on the MoCA, the TMT-A, and animal naming. Final analyses included examination of classification accuracy, using forward entry stepwise discriminant function analyses to examine the ability of the 6 LASSI variables in each version to classify participants as aMCI versus NC. We then added ADAS-Cog scores to the classification model to see if classification was improved by a standard cognitive assessment targeting AD/ADRD. We used receiver-operating characteristic curve analyses to examine correct classification of aMCI and NC, collapsing across the 2 versions of the LASSI.

The Western Coppernicus Group Institutional Review Board approved the study (approval number 2022‐1540) and all participants provided signed informed consent. All data were fully anonymized for storage and analysis. Participants received $40.00 in compensation for each assessment session.

There were 9 NAMCI participants scheduled for initial testing with the LASSI-L and 4 NAMCI participants scheduled for initial assessment with the LASSI-D. There were also 30 participants who did not meet the list A learning criteria. When the MoCA scores of the 30 participants who did not meet the minimum LASSI learning score were compared with those who did, those who failed to qualify had significantly lower MoCA scores (mean 21.03, SD 2.8), compared with those who qualified (mean 24.21, SD 2.8; t₁₄₀=5.45; P<.001).

Table 1 presents information on the eligible participants, characterized by which version of the LASSI they received at their assessment. There were no significant differences in age, education, and MoCA scores across the participant samples. There were slightly more Spanish speakers in the LASSI-D cohort, but there were no differences in any of the 6 critical LASSI variables, age, or MoCA scores across the Spanish and non-Spanish speakers (all t₁₁₁<1.64; all P>.10).

Table 2 presents the results of the comparison of performance across the 2 forms of the LASSI.

The largest difference between the LASSI-L and LASSI-D on any variable was cued recall B1 for the MCI group, with an effect size of d=0.3 (t₅₆=1.13; P=.13), with better performance on the LASSI-L. All of the other 5 t tests were also nonsignificant (P>.05). Scores on the 2 critical variables of percentage intrusion errors were essentially identical across both versions of the LASSI for both participant groups (P>.71).

Table 3 presents the results of comparisons of form differences across NC and MCI participants for all the critical variables as well as diagnostic differences for each of these variables.

Performance of the aMCI participants was worse than the NC participants on all LASSI variables with the 2 forms combined. The smallest difference between aMCI and NC participants across the forms was for intrusions on cued recall B2, which had an effect size of d=0.68 (t₅₆=2.3; P=.03). All other tests had larger effect sizes, higher t statistics, and lower P values.

As can be seen in Table 4, every LASSI-L and LASSI-D variable was significantly correlated with MoCA and ADAS-Cog scores in the combined sample. Correlations were smaller for the intrusion variables than for the learning variables comprised of correct responses.

We performed comparative analyses of the 2 samples across the cognitive variables administered at each assessment and at baseline and present them in Table S1 in Multimedia Appendix 2. As can be seen in that table, there were no significant differences in any of the variables across the 2 samples of participants.

Finally, Figure 2 presents the results of discriminant analyses using the PIE intrusion variables to classify cases into aMCI versus NC status. The PIE2 intrusion variable was the only one to enter the analysis (Wilks Lambda=7.03; χ²₁=38.6; Pillas approx. F_1,110=46.49; P<.001). Correct classification of the cases was 88% (51/58) for NC (7/58, 12% false positive) and 78% (42/54) for MCI (12/54, 22% false negative) for total correct classification of cases of 83% (93/112). Adding the ADAS-Cog as an additional predictor did not change the results, as it did not enter the equation (F_1,110 =3.85; P=.06). The area under the receiver operating characteristic curve (AUC) statistics are also presented in Figure 2. Importantly, the AUC statistic overall was 0.82, consistent with the overall correct classification rate.

When the samples were split into subgroups based on LASSI-L or LASSI-D first and the analyses rerun, only PIE2 intrusion errors again entered the analysis at P<.001 in both subgroups. Classification accuracy was 77% (23/30) for NC and 66% (16/24) for aMCI in the LASSI-L first group and 82%(23/28) for NC and 77% (23/30) for aMCI. Despite the smaller size of these samples, the data suggest quite similar classification accuracy for each version of the LASSI.