Clinical Manifestations

Area of Science:

• Neuroscience
• Genetics
• Psychiatry

Background:

• Attention-deficit/hyperactivity disorder (ADHD) and Alzheimer's disease (AD) are distinct neurological disorders.
• Emerging evidence suggests shared genetic and molecular mechanisms may link ADHD and AD.
• ADHD is characterized by inattention and hyperactivity, while AD involves progressive neurodegeneration and dementia.

Purpose of the Study:

• To systematically review and investigate potential genetic overlaps between ADHD and AD.
• To identify shared genetic factors and molecular pathways implicated in both conditions.
• To explore the potential role of ADHD polygenic risk scores (PRS) in AD pathology.

Main Methods:

• A systematic review adhering to PRISMA guidelines was conducted.
• Searches were performed in major scientific databases (PubMed, Embase, PsychInfo, Web of Science).
• Studies utilizing genetic analyses, particularly ADHD PRS in human participants with confirmed AD diagnoses, were included.

Main Results:

• Two studies met inclusion criteria, revealing correlations between ADHD-PRS and cognitive decline, tau pathology, and brain atrophy in Aβ-positive individuals.
• ADHD-PRS was also associated with increased risks for cardiometabolic and autoimmune conditions.
• Key genes like FOXP2, APOE ε4, and SNAP25 were implicated in both ADHD and AD, involved in synaptic plasticity.

Conclusions:

• Genetic liability for ADHD may exacerbate AD pathology, especially in the presence of amyloid-beta (Aβ).
• Shared pathways, including Wnt/mTOR signaling and neuroinflammation, present potential therapeutic targets.
• Longitudinal studies are crucial to confirm causal relationships and identify at-risk populations using PRS.