Being genetically predisposed to attention-deficit/hyperactivity disorder (ADHD) could increase the risk of Alzheimer’s disease in later life, research suggests.
The study revealed that well-established ADHD biomarkers were collectively associated with cognitive declines, particularly in memory, among previously unaffected older adults.
Cognitive decline was most common in those displaying amyloid (A)β peptide on brain scans, which is a protein widely implicated in Alzheimer’s.
Further research indicated that people genetically vulnerable to ADHD could be particularly susceptible to the harmful effects of Aβ, thereby providing a link with Alzheimer’s disease.
The findings, in Molecular Psychiatry, could help identify at-risk individuals who might benefit from the new treatments becoming available at earlier stages in Alzheimer’s progression.
“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 researcher Douglas Leffa, PhD, a psychiatry resident at the University of Pittsburgh Medical Center.
Leffa and coworkers used a polygenic risk score to determine overall genetic predisposition to ADHD in 212 adults without cognitive impairments who were taking part in a study into the early detection of Alzheimer’s disease.
All participants were aged 55 to 90 years, underwent scans and had regular cognitive assessments over a period of six years.
The team found that a higher ADHD polygenic risk score was associated with greater cognitive decline during follow up.
The combined effect of a high ADHD risk score and brain Aβ deposition on cognitive deterioration was more significant than when each measure was taken in isolation.
Among participants positive for Aβ peptide, a higher ADHD polygenic risk score was associated with increased phosphorylated (p)tau protein pathology in cerebrospinal fluid (CSF), which has been linked with neurodegenerative disease, and it was also linked with brain atrophy in frontal and parietal brain regions.
“These findings suggest that the genetic liability to ADHD increases the susceptibility to cognitive decline, tau pathology, and neurodegeneration in the presence of Aβ pathology in the brain of older individuals,” the researchers summarize.
They suggest the ADHD polygenic risk score could be used to assess the risk of cognitive decline in Aβ-positive older adults who are currently cognitively unimpaired.
It could also be used to predict cognitive deterioration in the absence of biomarkers for Alzheimer’s disease.
They add: “Importantly, ADHD-[polygenic risk score] was associated with longitudinal CSF p-tau hyperphosphorylation and brain atrophy in frontoparietal but not temporal regions in Aβ-positive individuals, suggesting that an ADHD-related brain susceptibility to the harmful effects of Aβ plays a role in the early development of [Alzheimer’s disease] in genetically vulnerable patients.”
