Genetic Vulnerability to ADHD Could Signal Risk of Developing Alzheimer’s Later in Life

Although recent large epidemiological studies have hinted at a link between ADHD and Alzheimer’s, this is the first study to tie genetic risk of ADHD to chances of developing late-onset Alzheimer’s disease.

“This study highlights what many in the field are already discussing: The impact of ADHD can be observed throughout the lifespan, and it might be linked to neurodegenerative conditions, such as Alzheimer’s disease,” said lead author Douglas Leffa, M.D., Ph.D.

Not unlike other behavioral disorders, ADHD has a genetic component. But there is no one single gene that will dictate whether its carrier will go on to develop ADHD. Rather, that risk is determined by a combination of small genetic changes.

To measure this risk, researchers used a previously developed tool called ADHD polygenic risk score, or ADHD-PRS, which represents the combined genetic likelihood for developing the disorder, considering the entire genome sequence.

To conduct the study, researchers used a database of 212 adults without cognitive impairments, such as predisposition to other Alzheimer’s related mental health impairments such as dementia, at baseline. The database included brain scans, baseline amyloid and tau levels measured on PET scans and in the cerebrospinal fluid, and results of regular cognitive assessments over the course of six consecutive years. Crucially, researchers also had access to those patients’ genome sequences.

By calculating each patient’s individual ADHD-PRS and matching it with that patient’s signs of Alzheimer’s disease, researchers were able to show that a higher ADHD-PRS can predict subsequent cognitive deterioration and development of Alzheimer’s brain pathophysiology in the elderly who, until then, were not cognitively impaired.

While the study results are intriguing and indicate that the link between ADHD-PRS and Alzheimer’s needs to be researched further, the scientists caution against overgeneralizing their findings and urge families to stay informed but calm.

Because the database demographic was limited to patients who were white and had, on average, more than 16 years of education, more work needs to be done to extend applicability of the findings beyond a thin slice of the American public.

“Right now, we are working on new studies trying to assess ADHD more robustly and enroll childhood ADHD patient cohorts so we can follow them over time for biomarkers of Alzheimer’s disease,” said Pascoal. “These studies take a long time to complete, but they are important for our understanding of multifactorial neurological diseases and how they affect cognitive impairments.”

Sources:

Douglas T. Leffa, João Pedro Ferrari-Souza, Bruna Bellaver, Cécile Tissot, Pamela C. L. Ferreira, Wagner S. Brum, Arthur Caye, Jodie Lord, Petroula Proitsi, Thais Martins-Silva, Luciana Tovo-Rodrigues, Dana L. Tudorascu, Victor L. Villemagne, Ann D. Cohen, Oscar L. Lopez, William E. Klunk, Thomas K. Karikari, Pedro Rosa-Neto, Eduardo R. Zimmer, Brooke S. G. Molina, Luis Augusto Rohde, Tharick A. Pascoal. Genetic risk for attention-deficit/hyperactivity disorder predicts cognitive decline and development of Alzheimer’s disease pathophysiology in cognitively unimpaired older adults. Molecular Psychiatry, 2022; DOI: 10.1038/s41380-022-01867-2

University of Pittsburgh. “Genetic vulnerability to ADHD signals risk of Alzheimer’s disease in old age.” ScienceDaily. ScienceDaily, 8 December 2022. <www.sciencedaily.com/releases/2022/12/221208085834.htm>.

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