Impact of genetic counseling and testing in individuals at high risk of familial Alzheimer's disease from Latin America: a non-randomized controlled trial

Abstract

Introduction: This study involved evaluating a tailored genetic counseling and testing (GCT) protocol for families at risk of autosomal dominant Alzheimer's disease (ADAD) in Latin America (LatAm), focusing on essential cultural and regional adaptations.

Methods: We conducted a non-randomized controlled trial among ADAD families in Colombia and Argentina. Participants were categorized based on their decision to learn their genetic status (GS), with further comparisons between mutation-positive versus mutation-negative participants who learned their status. Psychological impacts were measured using validated scales for anxiety and depression.

Results: Of the 122 eligible participants, 97 completed the GCT protocol, and 87 opted to learn their GS. There were no clinically significant differences in psychological distress between those who learned their status and those who did not, nor between mutation-positive and mutation-negative individuals.

Discussion: The GCT protocol effectively managed psychological impacts in ADAD families and was positively received, demonstrating the importance of culturally adapted GCT protocols.

Highlights: We examined the adaptation and efficacy of a GCT protocol in LatAm for families at risk of ADAD.The GCT protocol mitigated psychological distress among at-risk ADAD families.The study confirms the protocol's cultural appropriateness and psychological safety.Future studies should explore the long-term psychological and public health impacts of GCT and use of GCT for treatment options.

Keywords: Latin America; autosomal dominant Alzheimer's disease; cultural adaptation; genetic counseling and testing; psychological impact; vulnerabilities.

FIGURE 1

Overview of genetic counseling and testing protocol for ADAD in Latin America. (A) General recommendations at institutional level: foundational guidelines for centers and institutions initiating genetic counseling and testing (GCT) services. (B) Overview of PRAGA pilot program GCT protocol, Section 1: initial protocol assessment – evaluating readiness and requirements for GCT. Sections 2, 3, 4: core GCT process – detailed depiction of GCT sessions including sample collection, genetic disclosure, and post‐disclosure assessments. Section 5: final protocol assessment – assessing effectiveness of entire GCT protocol. Section 6: recommended follow‐up – conducted by a team member to discuss GCT process and assess further support needs. At an institutional level, this section serves to evaluate the overall emotional impact and effectiveness of the genetic counseling received. (C) General recommendations for GCT and considerations for encounters 2, 3, 4. Provides overarching guidelines and specific considerations for effectively managing the core sessions of the GCT process, ensuring consistency and adaptability to patient needs.

FIGURE 2

Participant flow diagram in study. The diagram illustrates the initial recruitment, various phases of the study, and the number of participants who discontinued the study due to being lost to follow‐up or not recommended for genetic testing.

FIGURE 3

Change in distress measures in test group relative to control group and within the test troup by DIAD mutation status (A–F). (A–C) Changes in distress measures between the test group (red line) and control group (blue line) at baseline and 3 months after status disclosure. (A) Depression score. (B) General anxiety score. (C) Health‐related anxiety score. (D–F) Change in distress measures within test group: DIAD mutation‐positive (straight red line) versus mutation‐negative (dashed red line) at baseline and 3 months after status disclosure. (D) Depression score. (E) General anxiety score. (F) Health‐related anxiety score. ** Significant differences between groups; ++ significant within‐group difference relative to baseline. Depression scores were assessed using Montgomery–Åsberg Depression Rating Scale (MADRS). MADRS severity thresholds are set as follows: 14 to 18 for mild depression, 19 to 23 for moderate, 24 to 36 for marked, 37 to 39 for severe, and 40 or higher for extreme depression., General anxiety scores were evaluated using a brief version of the Zung Anxiety Scale, where a score of 24 or higher indicates clinically significant anxiety., Health‐related anxiety was measured using the Short Health Anxiety Inventory (SHAI). For the SHAI, a score of 18 or higher suggests a significant shift in health anxiety levels. For all scales used, higher scores represent more severe clinical outcomes, and changes of approximately five points from baseline, even without surpassing the thresholds, are considered clinically meaningful.