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Genetic risk of ADHD may boost odds of Alzheimer's in old age

A genetic predisposition to attention-deficit/hyperactivity disorder can predict cognitive decline and Alzheimer’s disease in old age, suggests a study led by Drs. Douglas Leffa (L) and Tharick Pascoal, at the University of Pittsburgh. Photo by Julia Graeper/University of Pittsburgh
A genetic predisposition to attention-deficit/hyperactivity disorder can predict cognitive decline and Alzheimer’s disease in old age, suggests a study led by Drs. Douglas Leffa (L) and Tharick Pascoal, at the University of Pittsburgh. Photo by Julia Graeper/University of Pittsburgh

Dec. 8 (UPI) -- Having a genetic predisposition to attention-deficit/hyperactivity disorder, or ADHD, is associated with cognitive decline and may predict Alzheimer's disease in old age, early research released Thursday suggests.

Recent large studies have hinted at a link between ADHD and Alzheimer's, the researchers said a news release, but this is the first study to tie genetic risk of ADHD to chances of developing late-onset Alzheimer's disease.

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Findings from the study, which was led by by University of Pittsburgh School of Medicine researchers, were published Thursday in the journal Molecular Psychiatry.

The study's two lead scientists stressed to UPI, however, that the 200-plus patients whose data were analyzed for the study lacked a clinical diagnosis of ADHD -- because it is very difficult to find studies with large sample sizes composed of elderly patients with clinically diagnosed ADHD.

So, the association between ADHD genetic risk scoring used in their study and Alzheimer's disease must be explored further, the researchers said.

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And more work is needed to link older patients with a confirmed clinical diagnosis of ADHD and the development of dementia due to Alzheimer's disease.

Also, they said, additional research is needed to determine whether interventions to treat ADHD can influence people's risk of Alzheimer's disease in the future -- and it may take several decades to arrive at a definitive answer.

In fact, the scientists cautioned against "overgeneralizing" their findings and urged families to "stay informed but calm."

"It is important to emphasize that the study participants did not have a clinical diagnosis of ADHD. We found that genetic susceptibility to ADHD was associated with cognitive decline and the development of brain pathologies associated with [Alzheimer's disease," Dr. Tharick Pascoal, the study's senior author said in an email.

However, Pascoal, an assistant professor of psychiatry at the University of Pittsburgh, said some people who have this genetic susceptibility to ADHD never develop ADHD symptoms and people who do not have this genetic susceptibility develop ADHD.

"This genetic susceptibility is merely a risk factor for ADHD that is not currently used in clinical practice, which further reinforces that our results have no clinical implications and should not concern patients with ADHD at this early stage," he said.

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Yet, Pascoal cited the importance of determining risk factors to help better identify patients who are likely to progress to severe Alzheimer's disease as new treatments are becoming available at earlier stages of the incurable neurodegenerative illness.

"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," Dr. Douglas Leffa, the study's lead author and a psychiatry resident at the University of Pittsburgh Medical Center, said in the release.

For a long time, ADHD was considered a childhood disease that people grow out of after entering adulthood.

But doctors now know ADHD may persist into adulthood, with perhaps more diverse and subtle symptoms, as compared to children and adolescents, that may make it difficult to diagnose.

Similar to other behavioral disorders, ADHD has a genetic component, the said. And the risk of developing ADHD is determined by a combination of small genetic changes, not a single gene.

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

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The scientists tapped a database of 212 adults, averaging 73 years old, who had no cognitive impairment at baseline. The database included brain scans, baseline amyloid and tau levels measured on PET scans and in the cerebrospinal fluid, and the results of regular cognitive assessments over six consecutive years. Patients' genome sequences also were accessible.

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

However, the scientists noted that most of the patients in the study were White and had, on average, more than 16 years of education. They said they are working to recruit more participants from underrepresented backgrounds and begin follow-up testing.

"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," Pascoal said in the release.

"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."

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The study, which included researchers from Canada, Sweden and Brazil, was funded by the National Institutes of Health and Alzheimer's Association.

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