A genetic predisposition to attention-deficit/hyperactivity disorder (ADHD) has been linked to an increased risk of cognitive decline and Alzheimer's disease in old age, according to new research from the University of Pittsburgh. The findings are the first to associate ADHD genetic risk with age-related cognitive impairment.
The hypothesis ADHD could increase risk of later-life dementia is relatively new. It has only been over the past few years that researchers have begun to point to a possible association between the two conditions.
The problem researchers face in understanding this potential association is that ADHD, as we currently understand it, is a relatively new diagnostic condition. For decades clinicians have defined many different kinds of hyperactivity disorders in children, from what was called "minimal brain dysfunction" in the 1950s to "hyperkinetic reaction of childhood" in the 1960s. It wasn't until the late 1980s that the formal clinical term ADHD appeared, and even since then its diagnostic criteria has been vague.
So, effective longitudinal studies linking ADHD with Alzheimer's have been challenging. The few studies that have gestured to a relationship could not come close to proving a shared physiological cause. ADHD, for example, is often associated with a number of environmental and lifestyle factors known to increase one's risk for dementia, including diabetes, depression and low educational attainment.
More recent clues have come from new genetic research. A 2021 study, for example, found parents of children with ADHD were at higher risk of dementia and Alzheimer's compared to parents of children without ADHD, suggesting there could be a potential genetic relationship between the two conditions.
Another intriguing crossover between the two conditions came in a very recent study that found drugs commonly used to treat ADHD have shown promise in improving the cognition of Alzheimer's patients.
This new study leveraged recently developed ADHD genetic risk scores as a way of exploring possible links between Alzheimer's and ADHD in older adults. According to the researchers, the ADHD genetic risk score, "represents the combined genetic liability for the disorder and is highly associated with ADHD diagnosis and related traits in independent clinical and population samples."
So instead of looking at whether older adults had been formally diagnosed with ADHD in their younger years, the researchers measured their genetic predisposition to the condition, regardless of any clinical diagnosis.
The study looked at data from an ongoing longitudinal Alzheimer's research project tracking cognitively healthy subjects into old age. Around 200 subjects were included in the study, all cognitively healthy at baseline but displaying minor imaging signs of early amyloid protein deposits in the brain.
Over a six-year follow-up period the researchers found a high ADHD genetic risk score correlated with greater rates of cognitive decline. The study also found the greater the amyloid (Aβ) brain deposits at the beginning of the study, the faster the cognitive decline in subjects with ADHD genetic risk.
"Our results suggest that genetic liability for ADHD is associated with cognitive deterioration and the development of AD pathophysiology," the researchers write in the study. "Findings were mostly observed in Aβ-positive individuals, suggesting that the genetic liability for ADHD increases susceptibility to the harmful effects of Aβ pathology."
Tharick Pascoal, senior author on the new study, is cautious not to overstate these findings. Although ADHD could present as a risk factor for dementia, it may only be a minor risk factor amongst the multitude of factors that dictate whether someone goes on to develop Alzheimer's.
“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,” added 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.”
The new study was published in Molecular Psychiatry.
Source: University of Pittsburgh
