Potential Genetic Intersections Between ADHD and Alzheimer's Disease: A Systematic Review

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Attention-deficit/hyperactivity disorder (ADHD) and Alzheimer's disease (AD) are distinct neurological disorders with potential shared genetic and molecular pathways.
• ADHD is a neurodevelopmental disorder affecting children and adults, while AD is a leading cause of dementia in older adults.
• Emerging evidence points to overlapping contributors, including synaptic plasticity, neuroinflammation, and oxidative stress pathways.

Purpose of the Study:

• To systematically review and investigate potential genetic predispositions linking ADHD and AD.
• To identify original human studies employing genetic analyses and ADHD polygenic risk scores (PRS) for ADHD and AD.

Main Methods:

• A systematic literature search was conducted across multiple databases (Web of Science, Embase, PsycINFO, PubMed) following PRISMA guidelines.
• Keywords included ADHD, AD, and genetic factors. Inclusion criteria specified original human studies with genetic analyses and confirmed AD diagnoses.
• Screening and relevance assessment were performed using Rayyan software, excluding non-original studies, animal research, and articles lacking genetic links.

Main Results:

• Two studies met the inclusion criteria from an initial 1450 records.
• One study found that ADHD-PRS was associated with cognitive decline, increased tau pathology, and brain atrophy in amyloid-beta (Aβ)-positive individuals.
• Another large study found no direct link between ADHD-PRS and dementia, with associations mediated by lifestyle factors like BMI, education, and substance use.

Conclusions:

• Preliminary evidence for a genetic intersection between ADHD and AD is conflicting.
• ADHD genetic liability may exacerbate AD pathology in specific contexts (e.g., Aβ-positive individuals), but lifestyle factors play a significant mediating role.
• Further longitudinal research integrating genetics, biomarkers, and detailed lifestyle data is crucial to elucidate the complex ADHD-AD relationship.