Alzheimer's risk linked to genetic propensity for ADHD

Alzheimer’s risk linked to genetic propensity for ADHD

A genetic predisposition to attention-deficit/hyperactivity disorder (ADHD) has been linked to an increased risk of cognitive decline and Alzheimer’s disease in older adults, according to a new study from the University of Pittsburgh. The findings are the first to link the genetic risk of ADHD to age-related cognitive impairment.

The hypothesis that ADHD might increase the risk of dementia later in life is relatively new. Only in recent years have researchers begun to point to a possible association between the two conditions.

The problem facing researchers 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 types of hyperactivity disorder in children, from what was called “minimal brain dysfunction” in the 1950s to the “childhood hyperkinetic reaction” in the 1950s. 1960. It was not until the late 1980s that the formal clinical term ADHD appeared, and even since then its diagnostic criteria have remained vague.

Thus, effective longitudinal studies linking ADHD to Alzheimer’s disease have been difficult. The few studies that pointed to a relationship couldn’t 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 dementia risk, including diabetes, depression and low education.

More recent clues come from new genetic research. A 2021 study, for example, found that parents of children with ADHD were at greater risk of dementia and Alzheimer’s disease than parents of children without ADHD, suggesting there may be a potential genetic relationship between the two conditions.

Another intriguing crossover between the two conditions came in a very recent study which found that drugs commonly used to treat ADHD showed promise for improving cognition in patients with Alzheimer’s disease.

This new study relied on recently developed ADHD genetic risk scores as a way to explore possible links between Alzheimer’s disease and ADHD in older adults. According to the researchers, the ADHD Genetic Risk Score “represents the combined genetic responsibility for the disorder and is strongly associated with ADHD diagnosis and associated traits in independent clinical and population samples.”

So, instead of looking at whether older people had received an official diagnosis of ADHD in their youth, the researchers measured their genetic predisposition to the disease, regardless of the clinical diagnosis.

The study looked at data from an ongoing longitudinal research project in Alzheimer’s disease that follows cognitively healthy subjects into old age. About 200 subjects were included in the study, all of whom initially had good cognitive health but showed minor imaging signs of early amyloid protein deposits in the brain.

Over a six-year follow-up period, researchers found that a high ADHD genetic risk score was correlated with higher rates of cognitive decline. The study also found that the greater the brain deposits of amyloid (Aβ) at the start of the study, the faster the cognitive decline in subjects at genetic risk for ADHD.

“Our results suggest that the genetic responsibility for ADHD is associated with cognitive deterioration and the development of AD pathophysiology,” the researchers write in the study. “The findings were primarily seen in Aβ-positive individuals, suggesting that genetic responsibility for ADHD increases susceptibility to the harmful effects of Aβ pathology.”

Tharick Pascoal, lead author of the new study, is careful not to overstate these results. Although ADHD can present itself as a risk factor for dementia, it may only be a minor risk factor among the multitude of factors that determine whether someone will develop Alzheimer’s disease.

“Right now, we’re working on new studies trying to assess ADHD more robustly and enrolling cohorts of childhood ADHD patients so we can follow them over time for biomarkers of Alzheimer’s disease,” Pascoal added. “These studies are time-consuming, but they are important for our understanding of multifactorial neurological diseases and how they affect cognitive impairment.”

The new study was published in Molecular psychiatry.

Source: University of Pittsburgh

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