Posttraumatic stress disorder (PTSD) is often chronic and impairing. Mechanisms that maintain symptoms remain poorly understood because of heterogenous presentation. We parsed this heterogeneity by examining how individual differences in stress-symptom dynamics relate to the long-term maintenance of PTSD.

We studied 7,308 trauma-exposed World Trade Center responders who self-reported PTSD symptoms and stressful life events at annual monitoring visits for up to 20 years (average = 8.8 visits; [range = 4–16]). We used multilevel structural equation models to separate the stable and time-varying components of symptoms and stressors. At the within-person level, we modeled stress reactivity by cross-lagged associations between stress and future symptoms, stress generation by cross-lagged associations between symptoms and future stress, and autoregressive effects represented symptom persistence and stress persistence. The clinical utility of the stress-symptom dynamics was evaluated by associations with PTSD chronicity and mental health care use.

Stress reactivity, stress generation, and symptom persistence were significant on average (bs = 0.03–0.16). There were significant individual differences in the strength of each dynamic (interquartile ranges = 0.06–0.12). Correlations among within-person processes showed some dynamics are intertwined (e.g. more reactive people also generate stress in a vicious cycle) and others represent distinct phenotypes (e.g. people are reactive or have persistent symptoms). Initial trauma severity amplified some dynamics. People in the top deciles of most dynamics had clinically significant symptom levels across the monitoring period and their health care cost 6–17× more per year than people at median levels.

Individual differences in stress-symptom dynamics contribute to the chronicity and clinical burden of PTSD.

It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.

To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.

Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.

IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).

Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.

Increasing daylight exposure might be a simple way to improve mental health. However, little is known about daylight-symptom associations in depressive disorders.

In a subset of the Australian Genetics of Depression Study (N = 13,480; 75% female), we explored associations between self-reported number of hours spent in daylight on a typical workday and free day and seven symptom dimensions: depressive (overall, somatic, psychological); hypo-manic-like; psychotic-like; insomnia; and daytime sleepiness. Polygenic scores for major depressive disorder (MDD); bipolar disorder (BD); and schizophrenia (SCZ) were calculated. Models were adjusted for age, sex, shift work status, employment status, season, and educational attainment. Exploratory analyses examined age-stratified associations (18–24 years; 25–34 years; 35–64 years; 65 and older). Bonferroni-corrected associations (p < 0.004) are discussed.

Adults with depression reported spending a median of one hour in daylight on workdays and three hours on free days. More daylight exposure on workdays and free days was associated with lower depressive (overall, psychological, somatic) and insomnia symptoms (p’s<0.001), but higher hypo-manic-like symptoms (p’s<0.002). Genetic loading for MDD and SCZ were associated with less daylight exposure in unadjusted correlational analyses (effect sizes were not meaningful). Exploratory analyses revealed age-related heterogeneity. Among 18–24-year-olds, no symptom dimensions were associated with daylight. By contrast, for the older age groups, there was a pattern of more daylight exposure and lower insomnia symptoms (p < 0.003) (except for 25–34-year-olds on free days, p = 0.019); and lower depressive symptoms with more daylight on free days, and to some extent workdays (depending on the age-group).

Exploration of the causal status of daylight in depression is warranted.

Psychiatric disorders and type 2 diabetes mellitus (T2DM) are heritable, polygenic, and often comorbid conditions, yet knowledge about their potential shared familial risk is lacking. We used family designs and T2DM polygenic risk score (T2DM-PRS) to investigate the genetic associations between psychiatric disorders and T2DM.

We linked 659 906 individuals born in Denmark 1990–2000 to their parents, grandparents, and aunts/uncles using population-based registers. We compared rates of T2DM in relatives of children with and without a diagnosis of any or one of 11 specific psychiatric disorders, including neuropsychiatric and neurodevelopmental disorders, using Cox regression. In a genotyped sample (iPSYCH2015) of individuals born 1981–2008 (n = 134 403), we used logistic regression to estimate associations between a T2DM-PRS and these psychiatric disorders.

Among 5 235 300 relative pairs, relatives of individuals with a psychiatric disorder had an increased risk for T2DM with stronger associations for closer relatives (parents:hazard ratio = 1.38, 95% confidence interval 1.35–1.42; grandparents: 1.14, 1.13–1.15; and aunts/uncles: 1.19, 1.16–1.22). In the genetic sample, one standard deviation increase in T2DM-PRS was associated with an increased risk for any psychiatric disorder (odds ratio = 1.11, 1.08–1.14). Both familial T2DM and T2DM-PRS were significantly associated with seven of 11 psychiatric disorders, most strongly with attention-deficit/hyperactivity disorder and conduct disorder, and inversely with anorexia nervosa.

Our findings of familial co-aggregation and higher T2DM polygenic liability associated with psychiatric disorders point toward shared familial risk. This suggests that part of the comorbidity is explained by shared familial risks. The underlying mechanisms still remain largely unknown and the contributions of genetics and environment need further investigation.

Although behavioral mechanisms in the association among depression, anxiety, and cancer are plausible, few studies have empirically studied mediation by health behaviors. We aimed to examine the mediating role of several health behaviors in the associations among depression, anxiety, and the incidence of various cancer types (overall, breast, prostate, lung, colorectal, smoking-related, and alcohol-related cancers).

Two-stage individual participant data meta-analyses were performed based on 18 cohorts within the Psychosocial Factors and Cancer Incidence consortium that had a measure of depression or anxiety (N = 319 613, cancer incidence = 25 803). Health behaviors included smoking, physical inactivity, alcohol use, body mass index (BMI), sedentary behavior, and sleep duration and quality. In stage one, path-specific regression estimates were obtained in each cohort. In stage two, cohort-specific estimates were pooled using random-effects multivariate meta-analysis, and natural indirect effects (i.e. mediating effects) were calculated as hazard ratios (HRs).

Smoking (HRs range 1.04–1.10) and physical inactivity (HRs range 1.01–1.02) significantly mediated the associations among depression, anxiety, and lung cancer. Smoking was also a mediator for smoking-related cancers (HRs range 1.03–1.06). There was mediation by health behaviors, especially smoking, physical inactivity, alcohol use, and a higher BMI, in the associations among depression, anxiety, and overall cancer or other types of cancer, but effects were small (HRs generally below 1.01).

Smoking constitutes a mediating pathway linking depression and anxiety to lung cancer and smoking-related cancers. Our findings underline the importance of smoking cessation interventions for persons with depression or anxiety.

To investigate whether financial constraint and perceived stress modify the effects of food-related taxes on the healthiness of food purchases.

Moderation analyses were conducted with data from a trial where participants were randomly exposed to: a control condition with regular food prices, an sugar-sweetened beverage (SSB) tax condition with a two-tiered levy on the sugar content in SSB (5–8 g/100 ml: €0·21 per l and ≥8 g/100 ml: €0·28 per l) or a nutrient profiling tax condition where products with Nutri-Score D or E were taxed at a 20 percent level. Outcome measures were overall healthiness of food purchases (%), energy content (kcal) and SSB purchases (litres). Effect modification was analysed by adding interaction terms between conditions and self-reported financial constraint or perceived stress in regression models. Outcomes for each combination of condition and level of effect modifier were visualised.

Virtual supermarket.

Dutch adults (n 386).

Financial constraint or perceived stress did not significantly modify the effects of food-related taxes on the outcomes. Descriptive analyses suggest that in the control condition, the overall healthiness of food purchases was lowest, and SSB purchases were highest among those with moderate/high levels of financial constraint. Compared with the control condition, in a nutrient profiling tax condition, the overall healthiness of food purchases was higher and SSB purchases were lower, especially among those with moderate/high levels of financial constraint. Such patterns were not observed for perceived stress.

Further studies with larger samples are recommended to assess whether food-related taxes differentially affect food purchases of subgroups.

Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).

This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.

Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.

The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.

The Stricker Learning Span (SLS) is a computer-adaptive word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). Given recent evidence suggesting the prominence of learning impairment in preclinical Alzheimer’s disease (AD), the SLS places greater emphasis on learning than delayed memory compared to traditional word list memory tests (see Stricker et al., Neuropsychology in press for review and test details). The primary study aim was to establish criterion validity of the SLS by comparing the ability of the remotely-administered SLS and inperson administered Rey Auditory Verbal Learning Test (AVLT) to differentiate biomarkerdefined groups in cognitively unimpaired (CU) individuals on the Alzheimer’s continuum.

Mayo Clinic Study of Aging CU participants (N=319; mean age=71, SD=11; mean education=16, SD=2; 47% female) completed a brief remote cognitive assessment (∼0.5 months from in-person visit). Brain amyloid and brain tau PET scans were available within 3 years. Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (A+, n=110) or not (A-, n=209), and for 2) those with biological AD (A+T+, n=43) vs no evidence of AD pathology (A-T-, n=181). Primary neuropsychological outcome variables were sum of trials for both the SLS and AVLT. Secondary outcome variables examined comparability of learning (1-5 total) and delay performances. Linear model ANOVAs were used to investigate biomarker subgroup differences and Hedge’s G effect sizes were derived, with and without adjusting for demographic variables (age, education, sex).

Both SLS and AVLT performances were worse in the biomarker positive relative to biomarker negative groups (unadjusted p’s<.05). Because biomarker positive groups were significantly older than biomarker negative groups, group differences were attenuated after adjusting for demographic variables, but SLS remained significant for A+ vs A- and for A+T+ vs A-T- comparisons (adjusted p’s<.05) and AVLT approached significance (p’s .05-.10). The effect sizes for the SLS were slightly better (qualitatively, no statistical comparison) for separating biomarker-defined CU groups in comparison to AVLT. For A+ vs A- and A+T+ vs A-T- comparisons, unadjusted effect sizes for SLS were -0.53 and -0.81 and for AVLT were -0.47 and -0.61, respectively; adjusted effect sizes for SLS were -0.25 and -0.42 and for AVLT were -0.19 and -0.26, respectively. In secondary analyses, learning and delay variables were similar in terms of ability to separate biomarker groups. For example, unadjusted effect sizes for SLS learning (-.80) was similar to SLS delay (.76), and AVLT learning (-.58) was similar to AVLT 30-minute delay (-.55) for the A+T+ vs AT- comparison.

Remotely administered SLS performed similarly to the in-person-administered AVLT in its ability to separate biomarker-defined groups in CU individuals, providing evidence of criterion validity. The SLS showed significantly worse performance in A+ and A+T+ groups (relative to A- and A-T-groups) in this CU sample after demographic adjustment, suggesting potential sensitivity to detecting transitional cognitive decline in preclinical AD. Measures emphasizing learning should be given equal consideration as measures of delayed memory in AD-focused studies, particularly in the preclinical phase.

Neuronal dysfunction of the locus coeruleus (LC), the primary producer of norepinephrine, has been identified as a biomarker of early Alzheimer's disease (AD) pathophysiology. Norepinephrine has been implicated in attentional control, and its reduced cortical circulation in AD may be associated with selective attentional difficulties. Additionally, greater pupil dilation indicates greater effort needed to perform a cognitive task, and greater compensatory effort to perform the digit span task has been found in individuals at risk for AD. In this study, we examined associations between a neuroimaging biomarker of the LC and pupil dilation during the Stroop task as a sensitive measure of attentional control.

64 older adults without dementia were recruited from the San Diego community (mean [SD] age = 74.3 [6.3]; 39 cognitively unimpaired and 25 with mild cognitive impairment). All participants underwent magnetic resonance imaging of the LC and generated behavioral data from a computerized Stroop task that included 36 incongruent trials (e.g., GREEN presented in red ink), 36 congruent trials (e.g., GREEN presented in green ink), and 32 neutral trials (e.g., LEGAL presented in green ink) in a randomized presentation. Mean pupil dilation for each trial (change relative to baseline at the start of each trial) was measured at 30 Hz using the Tobii X2-30 system (Tobii, Stockholm, Sweden) and averaged within each Stroop condition. Paired t-tests assessed for differences in mean pupil dilation across incongruent and congruent Stroop conditions. Iterative re-weighted least squares regression was used to assess the association between a rostral LC contrast ratio measure derived from manually marked ROIs and mean pupil dilation during incongruent trials divided by congruent trials, adjusting for age, sex, and education. Follow-up analyses also assessed the association of these variables with mean reaction time (RT) for incongruent trials divided by congruent trials.

Mean pupil dilation significantly differed across conditions (t = 3.74, mean difference = .13, 95% CI [.06, .20]) such that dilation was higher during the incongruent condition (mean [SD] dilation = .18 [.38] mm) relative to the congruent condition (mean [SD] dilation = .05 [.35] mm). A significant association was observed between pupil dilation and LC contrast ratio, such that increased levels of mean dilation during incongruent trials relative to congruent trials were observed at lower levels of LC contrast ratio (i.e., lower LC integrity; r = -.37, 95% CI [-.55, -.13]). This association was not observed for mean dilation during only congruent trials (r = -.08, 95% CI [-.31, .18]). Additionally, neither LC contrast ratio [r = .24, 95% CI [-.02, .46]) nor mean incongruent/congruent pupil dilation (r = .14, 95% CI [-.13, .37]) were associated with incongruent/congruent RT.

Findings suggest that increased pupil dilation during a demanding attentional task is indicative of increased compensatory effort needed to achieve the same level of performance for individuals with reduced LC biomarker integrity. Pupillometry assessment offers a low-cost, non-invasive, and scalable biomarker of LC dysfunction that may be indicative of preclinical AD.

Mayo Test Drive (MTD): Test Development through Rapid Iteration, Validation and Expansion, is a web-based multi-device (smartphone, tablet, personal computer) platform optimized for remote self-administered cognitive assessment that includes a computer-adaptive word list memory test (Stricker Learning Span; SLS; Stricker et al., 2022; Stricker et al., in press) and a measure of processing speed (Symbols Test: Wilks et al., 2021). Study aims were to determine criterion validity of MTD by comparing the ability of the MTD raw composite and in-person administered cognitive measures to differentiate biomarkerdefined groups in cognitively unimpaired (CU) individuals on the Alzheimer’s continuum.

Mayo Clinic Study of Aging CU participants (N=319; mean age=71, SD=11, range=37-94; mean education=16, SD=2, range=6-20; 47% female) completed a brief remote cognitive assessment (∼0.5 months from in-person visit). Brain amyloid and brain tau PET scans were available within 3 years. Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (A+, n=110) or not (A-, n=209), and for 2) those with biological AD (A+T+, n=43) or with no evidence of AD pathology (A-T-, n=181). Primary outcome variables were MTD raw composite (SLS sum of trials + an accuracy-weighted Symbols response time measure), Global-z (average of 9 in-person neuropsychological measures) and an in-person screening measure (Kokmen Short Test of Mental Status, STMS; which is like the MMSE). Linear model ANOVAs were used to investigate biomarker subgroup differences and Hedge’s G effect sizes were derived, with and without adjusting for demographic variables (age, education, sex).

Remotely administered MTD raw composite showed comparable to slightly larger effect sizes compared to Global-z. Unadjusted effect sizes for MTD raw composite for differentiating A+ vs. A- and A+T+ vs. A-T- groups, respectively, were -0.57 and -0.84 and effect sizes for Global-z were -0.54 and -0.73 (all p’s<.05). Because biomarker positive groups were significantly older than biomarker negative groups, group differences were attenuated after adjusting for demographic variables, but MTD raw composite remained significant for A+T+ vs A-T- (adjusted effect size -0.35, p=.007); Global-z did not reach significance for A+T+ vs A-T- (adjusted effect size -0.19, p=.08). Neither composite reached significance for adjusted analyses for the A+ vs A- comparison (MTD raw composite adjusted effect size= -.22, p=.06; Global-z adjusted effect size= -.08, p=.47). Results were the same for an alternative MTD composite using traditional z-score averaging methods, but the raw score method is preferred for comparability to other screening measures. The STMS screening measure did not differentiate biomarker groups in any analyses (unadjusted and adjusted p’s>.05; d’s -0.23 to 0.05).

Remotely administered MTD raw composite shows at least similar ability to separate biomarker-defined groups in CU individuals as a Global-z for person-administered measures within a neuropsychological battery, providing evidence of criterion validity. Both the MTD raw composite and Global-z showed greater ability to separate biomarker positive from negative CU groups compared to a typical screening measure (STMS) that was unable to differentiate these groups. MTD may be useful as a screening measure to aid early detection of Alzheimer’s pathological changes.

The locus coeruleus (LC) plays a key role in cognitive processes such as attention, executive function, and memory. The LC has been identified as an early site of tau accumulation in Alzheimer’s disease (AD). LC neurons are thought to survive, albeit with limited functionality, until later stages of the disease, though how exactly this limited functionality impacts cognition through the course of AD is still poorly understood. We investigated the interactive effects of an imaging biomarker of the LC and AD-related cerebrospinal fluid (CSF) biomarkers on attention, executive function, and memory.

We recruited 67 older adults from the San Diego community (mean age=74.52 years; 38 cognitively normal, 23 with mild cognitive impairment, and 6 with probable AD). Participants had LC-sensitive magnetic resonance imaging (MRI) used to obtain a measure of LC signal relative to surrounding tissue, with lower LC signal possibly indicating limited functionality. Participants also underwent a lumbar puncture to obtain CSF measurements of amyloid-beta 42 (Ab42) and phosphorylated tau (p-tau). We calculated the p-tau/Ab42 ratio, which is positively correlated with AD progression. Finally, participants were administered a comprehensive neuropsychological battery, and cognitive composites were created for attention (Digit Symbol, Digit Span Forward, Trails A), executive function (Digit Span Backward, Trails B, Color-Word Inhibition Switching), and two measures of verbal memory [learning (CVLT List A 1-5, Logical Memory Immediate Recall) and delay (CVLT Long Free Recall, Logical Memory Delayed Recall)]. Four multiple linear regressions modeled the relationship between each composite with age, gender, education, p-tau/Ab42, average LC contrast, and interactions between average LC contrast and p-tau/Ab42. For models that were statistically significant, additional regressions were assessed to determine which segment of the LC (caudal, middle, rostral) contributed to the relationship.

Our model predicted attention (p=.001, R2=.298) with main effects of average LC signal, p-tau/Ab42, and LC by p-tau/Ab42 interaction. Follow-up regressions revealed that each LC segment contributes to this relationship. Our model predicted executive function (p=.006, R2=.262) with a main effect of average LC signal and LC by p-tau/Ab42 interaction. Follow-up regressions revealed that this relationship was limited to the caudal and middle LC. Our models predicted both verbal learning (p<.001, R2=.512) and delayed memory (p<.001, R2=.364); both with main effects of gender and education. Follow-up regressions revealed that the rostral LC signal interacts with p-tau/Ab42 to predict both verbal learning and delayed memory. For all interactions, those with low p-tau/Ab42 exhibited a positive relationship between LC signal and cognition, whereas those with higher p-tau/Ab42 showed a negative relationship.

MR-assessed LC signal relates to attention, executive function, and verbal learning and memory in a manner that depends on CSF levels of p-tau and Ab42. The relationship between LC signal and cognition is positive at low levels and negative at higher levels of p-tau/Ab42. If lower LC signal indicates reduced integrity, these findings imply that MR-assessed LC signal may be a more meaningful marker of AD progression in earlier stages of the disease. Alternatively, this measure may capture a different underlying mechanism depending on tau and amyloid biomarker status.

The Stricker Learning Span (SLS) is a computer-adaptive digital word list memory test specifically designed for remote assessment and self-administration on a web-based multi-device platform (Mayo Test Drive). We aimed to establish criterion validity of the SLS by comparing its ability to differentiate biomarker-defined groups to the person-administered Rey’s Auditory Verbal Learning Test (AVLT).

Participants (N = 353; mean age = 71, SD = 11; 93% cognitively unimpaired [CU]) completed the AVLT during an in-person visit, the SLS remotely (within 3 months) and had brain amyloid and tau PET scans available (within 3 years). Overlapping groups were formed for 1) those on the Alzheimer’s disease (AD) continuum (amyloid PET positive, A+, n = 125) or not (A-, n = 228), and those with biological AD (amyloid and tau PET positive, A+T+, n = 55) vs no evidence of AD pathology (A−T−, n = 195). Analyses were repeated among CU participants only.

The SLS and AVLT showed similar ability to differentiate biomarker-defined groups when comparing AUROCs (p’s > .05). In logistic regression models, SLS contributed significantly to predicting biomarker group beyond age, education, and sex, including when limited to CU participants. Medium (A− vs A+) to large (A−T− vs A+T+) unadjusted effect sizes were observed for both SLS and AVLT. Learning and delay variables were similar in terms of ability to separate biomarker groups.

Remotely administered SLS performed similarly to in-person-administered AVLT in its ability to separate biomarker-defined groups, providing evidence of criterion validity. Results suggest the SLS may be sensitive to detecting subtle objective cognitive decline in preclinical AD.