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Diabetic patients are at increased risk for stroke, but little is known about the presence of other brain lesions. We studied the association of magnetic resonance imaging-detected brain lesions to diabetes in 1,252 individuals aged 65-75 years who were randomly selected from eight European population registries or defined working populations. All scans were centrally read for brain abnormalities, including infarcts, white matter lesions, and atrophy. We used a three-point scale to rate periventricular white matter lesions, and the volume of subcortical lesions was calculated according to their number and size. Subjective grading of cortical atrophy by lobe and summation of the lobar grades resulted in a total cortical atrophy score. The mean of three linear measurements of the ventricular diameter relative to the intracranial cavity defined the severity of subcortical atrophy. After adjustment for possible confounders, diabetes was associated with cortical brain atrophy but not with any focal brain lesions or subcortical atrophy. There was a strong interaction of diabetes and hypertension, such that the association between diabetes and cortical atrophy existed only in hypertensive but not in normotensive participants. Cognitive and pathological data are needed to determine the clinical significance of these findings as well as to understand the mechanisms underlying these associations. [ABSTRACT FROM AUTHOR]

Cascade genetic testing of relatives from families with pathogenic variants associated with hereditary breast and ovarian cancer (HBOC) or Lynch syndrome (LS) has important implications for cancer prevention. We compared the characteristics of relatives from HBOC or LS families who did not have genetic testing (GT (-) group) with those who had genetic testing (GT (+) group), regardless of the outcome. Self-administered surveys collected cross-sectional data between September 2017 and December 2021 from relatives participating in the CASCADE cohort. We used multivariable logistic regression with LASSO variable selection. Among n = 115 relatives who completed the baseline survey, 38% ( n = 44) were in the GT (-) group. Being male (OR: 2.79, 95% CI: 1.10-7.10) and without a previous cancer diagnosis (OR: 4.47, 95% CI: 1.03-19.42) increased the odds of being untested by almost three times. Individuals from families with fewer tested relatives had 29% higher odds of being untested (OR: 0.71, 95% CI: 0.55-0.92). Reasons for forgoing cascade testing were: lack of provider recommendation, lack of time and interest in testing, being afraid of discrimination, and high out-of-pocket costs. Multilevel interventions designed to increase awareness about clinical implications of HBOC and LS in males, referrals from non-specialists, and support for testing multiple family members could improve the uptake of cascade testing.

Cascade screening for Tier 1 cancer genetic conditions is a significant public health intervention because it identifies untested relatives of individuals known to carry pathogenic variants associated with hereditary breast and ovarian cancer (HBOC) and Lynch syndrome (LS). The Swiss CASCADE is a family-based, open-ended cohort, including carriers of HBOC- and LS-associated pathogenic variants and their relatives. This paper describes rates of cascade screening in relatives from HBOC- and LS- harboring families, examines carriers' preferences for communication of testing results, and describes theory-based predictors of intention to invite relatives to a cascade screening program. Information has been provided by 304 index cases and 115 relatives recruited from September 2017 to December 2021. On average, 10 relatives per index case were potentially eligible for cascade screening. Approximately 65% of respondents wanted to invite relatives to the cohort, and approximately 50% indicated a preference for patient-mediated communication of testing results, possibly with the assistance of digital technology. Intention to invite relatives was higher for first- compared to second- and third-degree relatives, but was not different between syndromes or based on relatives' gender. The family environment and carrying pathogenic variants predicts intention to invite relatives. Information helps optimize delivery of tailored genetic services.