Can Genetic Risk for ADHD Predict Cognitive Decline in Older Adults?

What you need to know

• Genetic risk for ADHD is associated with faster cognitive decline in older adults, even without an ADHD diagnosis
• This cognitive decline is most pronounced in people who also have signs of amyloid protein buildup in the brain
• Higher genetic risk for ADHD is linked to increased tau protein and brain atrophy over time in those with amyloid buildup
• The findings suggest ADHD genetic risk may increase susceptibility to Alzheimer’s disease processes in older adults

ADHD and cognitive decline in older adults

Attention-deficit/hyperactivity disorder (ADHD) is typically thought of as a condition that begins in childhood. However, researchers are increasingly recognizing that ADHD symptoms can persist into older adulthood for some people. There is also growing interest in whether ADHD or a genetic predisposition to ADHD might be linked to cognitive decline and dementia risk later in life.

This study looked at whether genetic risk for ADHD was associated with cognitive decline in older adults who did not have an ADHD diagnosis. The researchers used a measure called a polygenic risk score, which combines information from many genetic variants associated with ADHD into a single score reflecting a person’s overall genetic risk.

They found that older adults with higher genetic risk scores for ADHD showed faster decline in cognitive function over a 6-year period, particularly in memory. This cognitive decline was most pronounced in people who also had signs of amyloid protein buildup in their brains. Amyloid plaques are one of the hallmark brain changes in Alzheimer’s disease.

Executive function deficits

One interesting finding was that higher genetic risk for ADHD was associated with lower executive function scores from the beginning of the study. Executive functions are higher-level cognitive skills that help us plan, focus attention, switch between tasks, and control impulses. These types of deficits are commonly seen in people diagnosed with ADHD.

Unlike memory, which declined faster over time in those with higher ADHD genetic risk, executive function deficits were relatively stable. This suggests the executive function differences may reflect longstanding traits related to ADHD risk, rather than a progressive decline.

Biomarkers of Alzheimer’s disease

In addition to cognitive testing, the researchers looked at biological markers in the brain associated with Alzheimer’s disease. They found that in people who had signs of amyloid protein buildup, higher genetic risk for ADHD was associated with:

1. Faster increases in tau protein levels in cerebrospinal fluid over time. Tau tangles are another key brain change in Alzheimer’s disease.

2. More rapid brain shrinkage (atrophy) in frontal and parietal regions of the brain.

These findings suggest that genetic risk for ADHD may increase susceptibility to Alzheimer’s disease-related brain changes in older adults who have amyloid accumulation.

The amyloid cascade hypothesis

To understand these results, it’s helpful to know about a prominent theory of Alzheimer’s disease progression called the amyloid cascade hypothesis. This theory proposes that accumulation of amyloid protein in the brain is an early trigger that sets off a cascade of other damaging brain changes, including tau tangles, brain atrophy, and cognitive decline.

However, many older adults have amyloid buildup without developing dementia. This has led researchers to look for other factors that might make the brain more vulnerable to amyloid’s harmful effects.

The current study suggests that genetic risk for ADHD could be one such vulnerability factor. The combination of high ADHD genetic risk and amyloid buildup was associated with faster progression of tau, brain atrophy, and cognitive symptoms compared to either factor alone.

Implications for understanding cognitive aging

These findings add to growing evidence that ADHD and ADHD-related traits may be relevant to cognitive aging and dementia risk. Some key implications include:

1. Genetic risk for ADHD may influence cognitive trajectories in older adults, even in the absence of an ADHD diagnosis. This highlights the importance of considering neurodevelopmental factors when studying cognitive aging.

2. ADHD genetic risk could potentially help identify older adults who are more susceptible to Alzheimer’s disease processes and cognitive decline. This information might be useful for early detection or determining who might benefit most from interventions.

3. The results raise questions about whether treating ADHD or ADHD-like symptoms in older adults could potentially help maintain cognitive function or slow decline. However, more research would be needed to determine if this is the case.

4. The findings provide clues about biological mechanisms that might link ADHD risk to cognitive decline, such as increased vulnerability to amyloid-related brain changes. This could point to new directions for understanding the causes of cognitive decline.

Limitations and future directions

It’s important to note some limitations of this study. The participants were mostly white and highly educated, so the findings may not generalize to all populations. Additionally, the study looked at genetic risk for ADHD rather than diagnosed ADHD, so we can’t conclude that these findings necessarily apply to older adults with ADHD.

Future research could explore whether similar patterns are seen in more diverse populations and in people diagnosed with ADHD. It would also be valuable to study whether interventions targeting ADHD symptoms or related cognitive processes could help maintain cognitive function in older adults at higher genetic risk.

Conclusions

• Genetic risk for ADHD is associated with faster cognitive decline in older adults without ADHD diagnoses, particularly in those with signs of amyloid accumulation in the brain
• This cognitive decline is accompanied by increases in tau protein and brain atrophy in regions associated with both ADHD and Alzheimer’s disease
• The findings suggest ADHD genetic risk may increase vulnerability to Alzheimer’s disease processes in the aging brain
• More research is needed to understand the implications for cognitive health in older adults with ADHD and to explore potential interventions