Recent Publications by CFE Educators

IMPORTANCE

Identifying the youngest age when Alzheimer disease (AD) influences cognition and the earliest affected cognitive domains will improve understanding of the natural history of AD and approaches to early diagnosis.

OBJECTIVE

To evaluate the age at which cognitive differences between individuals with higher compared with lower genetic risk of AD are first apparent and which cognitive assessments show the earliest difference.

DESIGN, SETTING, AND PARTICIPANTS

This cross-sectional study used data from UK Biobank participants of European genetic ancestry, aged 40 years or older, who contributed genotypic and cognitive test data from January 1, 2006, to December 31, 2015. Data analysis was performed from March 10, 2020, to January 4, 2022.

EXPOSURE

The AD genetic risk score (GRS), which is a weighted sum of 23 single-nucleotide variations.

MAIN OUTCOMES AND MEASURES

Seven cognitive tests were administered via touchscreen at in-person visits or online. Cognitive domains assessed included fluid intelligence, episodic memory, processing speed, executive functioning, and prospective memory. Multiple cognitive measures were derived from some tests, yielding 32 separate measures. Interactions between age and AD-GRS for each of the 32 cognitive measures were tested with linear regression using a Bonferroni-corrected P value threshold. For cognitive measures with significant evidence of age by AD-GRS interaction, the youngest age of interaction was assessed with new regression models, with nonlinear specification of age terms. Models with youngest age of interaction from 40 to 70 years, in 1-year increments, were compared, and the best-fitting model for each cognitive measure was chosen. Results across cognitive measures were compared to determine which cognitive indicators showed earliest AD-related change.

RESULTS

A total of 405 050 participants (mean [SD] age, 57.1 [7.9] years; 54.1% female) were included. Sample sizes differed across cognitive tests (from 12 455 to 404 682 participants). The AD-GRS significantly modified the association with age on 13 measures derived from the pairs matching (range in difference in mean cognition per decade increase in age for 1-SD higher AD-GRS, 2.5%-11.5%), symbol digit substitution (range in difference in mean cognition per decade increase in age for 1-SD higher AD-GRS, 2.0%-5.8%), and numeric memory tests (difference in mean cognition per decade increase in age for 1-SD higher AD-GRS, 8.8%) (P = 1.56 × 10-3). Best-fitting models suggested that cognitive scores of individuals with a high vs low AD-GRS began to diverge by 56 years of age for all 13 measures and by 47 years of age for 9 measures.

CONCLUSIONS AND RELEVANCE

In this cross-sectional study, by early midlife, subtle differences in memory and attention were detectable among individuals with higher genetic risk of AD.

BACKGROUND

Inherited retinal dystrophies describe a heterogeneous group of retinal diseases that lead to the irreversible degeneration of rod and cone photoreceptors and eventual blindness. Recessive loss-of-function mutations in Tubulin Tyrosine Ligase Like 5 (TTLL5) represent a recently described cause of inherited cone-rod and cone dystrophy. This study describes the unusual phenotypes of three patients with autosomal recessive mutations in TTLL5. Examination of these patients included funduscopic evaluation, spectral-domain optical coherence tomography, short-wavelength autofluorescence, and full-field electroretinography (ffERG). Genetic diagnoses were confirmed using whole exome capture. Protein modeling of the identified variants was performed to explore potential genotype-phenotype correlations.

RESULTS

Genetic testing revealed five novel variants in TTLL5 in three unrelated patients with retinal dystrophy. Clinical imaging demonstrated features of sectoral cone-rod dystrophy and cone dystrophy, with phenotypic variability seen across all three patients. One patient also developed high-frequency hearing loss during a similar time period as the onset of retinal disease, potentially suggestive of a syndromic disorder. Retinal structure findings were corroborated with functional measures including ffERG findings that supported these diagnoses. Modeling of the five variants suggest that they cause different effects on protein function, providing a potential reason for genotype-phenotype correlation in these patients.

CONCLUSIONS

The authors report retinal phenotypic findings in three unrelated patients with novel mutations causing autosomal recessive TTLL5-mediated retinal dystrophy. These findings broaden the understanding of the phenotypes associated with TTLL5-mediated retinal disease and suggest that mutations in TTLL5 should be considered as a potential cause of sectoral retinal dystrophy in addition to cone-rod and cone dystrophies.

Deciding when to start and selecting a specific systemic treatment for pediatric psoriasis patients can be a complex process involving many factors. Considerations include type of psoriasis, severity, potential genetic etiologies, comorbidities, triggering events and characteristics unique to each patient. The constellation of clinical features and drug related factors may prompt selection of a specific agent. Systemic treatments may be considered on the basis of those that are "tried and true" (acitretin, methotrexate, cyclosporine, phototherapy) and "new and novel" (the biologic agents). Conventional systemic agents have decades of use to support their safety and efficacy and may be used in very flexible ways with titration of dose when maintenance is achieved or when flares occur. Targeted biologic therapies have overall reassuring safety profiles, can be very efficacious, and require little to no lab monitoring as compared to conventional systemics. However, they can be cost prohibitive and most are administered via injection. Here, we provide data and principles guiding the approach to therapy of moderate to severe psoriasis in children and use case examples to highlight several different clinical scenarios.

Evidence-based education is crucial for meeting the evolving needs of learners in the oncology workforce, given the growing demand for well-trained providers and the rapidly changing complexities of cancer care. With the onset of the severe acute respiratory syndrome coronavirus 2 pandemic, innovative means of delivering educational content in a virtual setting have become a necessary reality. Knowledge of learning science can be translated into concrete, pragmatic methods for using evidence-based education in a virtual world and affords important opportunities for innovation and inclusion across a broad network of educators and learners. We offer key insights and tools to promote attention to and agility with teaching in virtual settings to meet the needs of contemporary educators and learners.