The following is a summary of “Prevalence of Pathogenic Variants and Eligibility Criteria for Genetic Testing in Patients Who Visit a Memory Clinic,” published in the February 2025 issue of Neurology by Lee et al.
Genetic testing helps detect dementia-related variants for patient care and family planning. Traditional criteria may overlook carriers of pathogenic variants.
Researchers conducted a retrospective study to identify missed carriers of pathogenic variants in patients for genetic counseling in memory clinic.
They retrospectively tested patients visiting the Alzheimer Center Amsterdam from 2010 to 2012 using a 54-gene dementia panel, focusing on class IV/V variants according to American College of Medical Genetics and Genomics guidelines. They assessed APP duplications and C9ORF72 repeat expansion, determined the prevalence of pathogenic variants, and proposed new eligibility criteria for genetic testing. The criteria were applied prospectively for 1 year (2021–2022), with results compared to the retrospective cohort.
The results showed that genetic tests were performed on 1,022 of 1,138 patients (90%, [mean age 62.1 ± 8.9 years; 40.4% were female]) who visited the memory clinic. Among them, 34 pathogenic variant carriers (3.3%) were identified, 24 of whom were symptomatic. Previous clinical criteria identified 15 carriers (44% of all carriers, 65% of symptomatic carriers). The proposed criteria identified 22 carriers (62.5% of all carriers, 91% of symptomatic carriers). In the prospective cohort, 148 of 515 patients (28.7%) were eligible for testing under the new criteria. Of the 90 eligible patients who consented, 13 pathogenic carriers were identified, representing a 73% increase compared to the previous criteria.
Investigators found that patients with pathogenic genetic variants visiting memory clinics were often not eligible for genetic testing. The new criteria improved the identification of patients with a genetic cause for cognitive complaints.
Source: neurology.org/doi/10.1212/WNL.0000000000210273
