Genetic predisposition to ADHD linked to Alzheimer’s risk

A genetic predisposition to attention deficit/hyperactivity disorder (ADHD) may increase the risk of cognitive decline and Alzheimer diseasesuggests new research.

The researchers note that the study, which included more than 200 participants, is the first to show an association between the genetic risk of ADHD and odds of developing late-onset Alzheimer’s.

Those with higher ADHD polygenic risk scores (ADHD-PRS) who also had evidence of amyloid-β (Aβ) deposits at baseline experienced greater cognitive decline over the 6-year study period.

However, none of the participants had been clinically diagnosed with ADHD, and the researchers were quick to point out that their findings do not imply that people with ADHD develop Alzheimer’s disease.

Because this was an observational study and was not designed to test for cause and effect, it is not clear whether a genetic predisposition to ADHD increases the risk of Alzheimer’s or simply makes people more susceptible to damage from the disease.

“At this point, our data shows that both could be true,” said lead investigator Teixeira Leffa, MD, PhD, a psychiatry resident at the University of Pittsburgh Medical Center, Pennsylvania. Medscape Medical News.

“We found that a higher genetic risk of ADHD was associated with cognitive decline and the development of Alzheimer’s disease, suggesting that it may increase the risk of developing AD,” Leffa said.

“At the same time, these effects were seen primarily in individuals with amyloid pathology at baseline, pointing to genetic risk for ADHD as a susceptibility to damage caused by Alzheimer’s,” he added.

The findings were posted online December 8 in Molecular Psychiatry.

A proxy for ADHD

Recent studies have suggested a possible link between ADHD and Alzheimer’s and other dementias. But exploring the association has been challenging because there are few large data sets on adults with ADHD.

So the researchers found a proxy for ADHD: a polygenic risk score that represents the combined genetic probability of developing ADHD.

They took advantage of the Alzheimer’s Disease Neuroimaging Initiative (ADNI), a longitudinal multicenter study, to identify 212 adults aged 55 to 90 years who did not have cognitive impairment and who had not been clinically diagnosed with ADHD.

At baseline, all participants underwent longitudinal cerebrospinal fluid (CSF) phosphorylated Aβ, tau positron emission tomography (PET) scan at threonine 181 (p-tau181) evaluation, MRI and a cognitive evaluation. All returned at 6 months, 1 year, and annually thereafter.

The results showed that a high PRS score for ADHD was associated with worse cognitive performance, but only among those with Aβ deposits at baseline.

Furthermore, higher ADHD-PRS was associated with increased CSF p-tau181 levels and frontoparietal atrophy in Aβ-positive individuals without cognitive impairment.

“Previous studies indicate that the effects of amyloid pathology on cognitive decline may depend on individual mechanisms of resilience and susceptibility,” Laffe said.

“Our findings suggest that participants with a higher genetic risk for ADHD may be more susceptible to cognitive impairment associated with amyloid deposition,” he added.

more research is needed

Commenting on the findings of Medscape Medical News, Heather Snyder, PhD, vice president of medical and scientific relations for the Alzheimer’s Association, said it’s important to note that the study participants had genetic markers associated with ADHD risk but had not been diagnosed with ADHD.

“This could suggest that mechanisms that may be abnormal in ADHD are also mechanisms that are affected in cognitive decline,” he said.

Snyder emphasized that the findings “do not necessarily mean that people with ADHD are at increased risk of cognitive decline. Larger and more diverse population studies are needed to further examine this potential association.”

Laffe agreed, noting that “it’s important to note that while genetics have a strong influence on the development of ADHD,” environmental factors also play a role.

He noted that some people with a lower genetic risk score develop ADHD, while others with a higher score never show symptoms.

“This is an important limitation, and we would like to highlight that more work is needed to link clinically confirmed ADHD symptoms and the development of Alzheimer’s disease dementia,” Laffe said.

The study was not funded. Leffa and Snyder report having no relevant financial relationships.

Mole Psych. Published online on December 8, 2022. Summary

Kelli Whitlock Burton is a reporter for Medscape Medical News, covering neurology and psychiatry.

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