Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.

Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).

Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

Radiation dermatitis (RD) is a frequent toxicity during radiotherapy (RT) for head and neck cancer (HNC). We report the first use of KeraStat® Cream (KC), a topical, keratin-based wound dressing, in patients with HNC receiving RT.

This pilot study randomized HNC patients treated with definitive or postoperative RT (≥60 Gy) to KC or standard of care (SOC), applied at least twice daily during and for 1-month after RT. Outcomes of interest included adherence to the assigned regimen (at least 10 applications per week of treatment), clinician- and patient-reported RD, and skin-related quality of life.

24 patients were randomized and completed the study. Most patients had stage III-IV disease and oropharynx cancer. Median RT dose was 68 Gy; the bilateral neck was treated in 19 patients, and 18 patients received concurrent chemotherapy. Complete adherence was observed in 7/12 (SOC) vs. 10/12 (KC, p = 0.65).  Adherence by patient-week was 61/68 versus 64/67, respectively (p = 0.20). No differences in RD were observed between groups.

A randomized trial of KC versus SOC in HNC patients treated with RT is feasible with good adherence to study agent. An adequately powered randomized study is warranted to test the efficacy of KC in reducing RD.

We assess the association between self-reported history of periodontal disease diagnosis with self-reported cognitive and functional decline at age ∼60. We also investigate (1) the roles of social background, demographic characteristics, education, and adolescent test scores in confounding that association and (2) the role of cardiovascular disease in mediating that association.

We use data from a nationally representative sample of 13,525 people who participated in the 2021 wave of the High School & Beyond (HSB) cohort study. HSB began in 1980 with a nationally-representative sample of American 10th and 12th grade students; these students have been followed up on six occasions since 1980, yielding extraordinary and prospectively-collected life course data on all key measures for a large, multicultural sample.

In 2021, HSB sample members were evaluated with neuropsychological tests that evaluated list learning and memory, semantic and letter fluency, and working memory. They were also asked to self-report memory and functional decline using the AD8, using a cutoff of 2 or more items for significant concerns. Mild Cognitive Impairment will be identified using an algorithm validated in a similar sample of middle aged participants.

Sample members were also asked in 2021 whether a medical professional had ever diagnosed them with periodontal disease; those responding affirmatively were then asked the years in which they started and stopped having periodontal disease.

Measures of social and economic background; demographic characteristics; and educational contexts, opportunities, and attainments were measured prospectively—and in great detail—in the surveys administered in the 1980s. Critically, almost all sample members completed a series of cognitive tasks during adolescence, allowing us to address a key set of confounders in the relationship between periodontal disease and MCI. Markers of cardiovascular disease were measured in both 2013 and 2021.

We estimate logistic regression models predicting significant cognitive and functional concerns as a function of periodontal disease history; we also estimate models that account for confounders, including social background, demographic characteristics, education, and cognitive skills during adolescence; finally, we estimate models that account for the mediating role of cardiovascular disease. All models account for the clustered sampling design of HSB and employ sampling weights to account for HSB’s complex sampling design and selective attrition from the panel.

About 15% of the cohort has been diagnosed with periodontal disease, and nearly one in five had significant cognitive and functional concerns.

People with a history of periodontal disease were more likely to report significant cognitive and functional concerns. This association remains substantive and statistically significant after adjusting for confounders. All else equal, the odds of people with a history of periodontal disease having an AD8 score of 2 or higher were about 60% greater than the odds of those not reporting periodontal disease. Very little of this association can be attributed to cardiovascular disease as a mediating pathway.

People with a history of periodontal disease are at greatly elevated risk of self-reported cognitive and functional concerns at age ∼60. This supports evidence— never before collected at this scale in a long-term, representative cohort study—that oral pathogens may contribute to cognitive well-being over the life course.

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.

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.

Anxiety disorders are the most frequently diagnosed psychiatric conditions in children and adolescents. Cognitive behavioural therapy (CBT) is a well-established and effective treatment for anxiety and related disorders across the lifespan. Expectations of psychotherapy have been demonstrated to affect outcomes, yet there is sparse existing literature on adolescent patient and parent perspectives of CBT prior to engagement with treatment.

This study aimed to qualitatively explore the expectations and perceptions of CBT for anxiety and related disorders among adolescent patients and parents.

Fourteen adolescent patients and 16 parents participated in semi-structured individual interviews or focus groups consisting of 2–3 participants. Interview transcripts were analysed using inductive analysis.

Three themes were identified: worries about CBT, expectations and knowledge of the CBT process, and the role of parents and families. Overall, we found that adolescents and parents had generally positive views of CBT. The outset of CBT saw adolescents and parents express concern about stigma as well as the ambiguity of CBT. Parents continued to express a lack of understanding of what CBT entailed during their child’s treatment course.

These results suggest that both adolescents and parents would benefit from early discussion and reinforcement of expectations for CBT treatment. Further research efforts are warranted and should be directed towards determining appropriate expectations for parental involvement in a child’s CBT course and effective communication of treatment expectations to both adolescents and parents.

The cardiovascular adaptations associated with structured exercise training in Fontan patients remain unknown. We hypothesised that short-term training causes cardiac remodelling and parallel improvement in maximal exercise capacity (VO2 max) in these patients.

Five patients, median age 19.5 (17.6–21.3) years, with a history of Fontan operation meeting inclusion/exclusion criteria, participated in a 3-month training programme designed to improve endurance. Magnetic resonance images for assessment of cardiac function, fibrosis, cardiac output, and liver elastography to assess stiffness were obtained at baseline and after training. Maximal exercise capacity (VO2 max) and cardiac output Qc (effective pulmonary blood flow) at rest and during exercise were measured (C2H2 rebreathing) at the same interval. VO2 max increased from median (IQR) 27.2 (26–28.7) to 29.6 (28.5–32.2) ml/min/kg (p = 0.04). There was an improvement in cardiac output (Qc) during maximal exercise testing from median (IQR) 10.3 (10.1–12.3) to 12.3 (10.9–14.9) l/min, but this change was variable (p = 0.14). Improvement in VO2 max correlated with an increase in ventricular mass (r = 0.95, p = 0.01), and improvement in Quality-of-life inventory (PedsQL) Cardiac scale scores for patient-reported symptoms (r = 0.90, p = 0.03) and cognitive problems (r = 0.89, p = 0.04). The correlation between VO2 max and Qc showed a positive trend but was not significant (r = 0.8, p = 0.08). No adverse cardiac or liver adaptations were noted.

Short-term training improved exercise capacity in this Fontan pilot without any adverse cardiac or liver adaptations. These results warrant further study in a larger population and over a longer duration of time.

NCT03263312, Unique Protocol ID: STU 122016-037; Registration Date: 18 January, 2017.