Impact of the polygenic risk scores for attention‐deficit/hyperactivity disorder in Alzheimer's disease
Bibliographic record
Abstract
Abstract INTRODUCTION Epidemiological studies indicate a link between attention‐deficit/hyperactivity disorder (ADHD) and elevated risk of dementia. However, the impact of ADHD on cognition and Alzheimer's disease (AD) biomarkers in individuals with cognitive impairment remains unclear. METHODS We computed weighted ADHD polygenic risk scores (ADHD‐PRS) in 938 cognitively impaired participants (674 mild cognitive impairment [MCI] and 264 dementia; mean age 73.5 years). A subset underwent cerebrospinal fluid (CSF) analysis for amyloid beta (Aβ) and phosphorylated tau, as well as fluorodeoxyglucose positron emission tomography ([ 18 F]FDG‐PET). RESULTS We observed lower executive function in individuals with high ADHD‐PRS for both MCI and dementia participants. Higher levels of CSF phosphorylated tau, but not Aβ, were observed in dementia participants with higher ADHD‐PRS. Increased ADHD‐PRS was associated with glucose hypometabolism in the frontal and parietal cortices. DISCUSSION ADHD‐PRS is associated with a more severe disease presentation in individuals with cognitive impairment due to dementia, characterized by impaired executive function, elevated tau pathology, and hypometabolism in the frontal and parietal cortices. Highlights We calculated the genetic liability for attention‐deficit/hyperactivity disorder (ADHD) using polygenic risk scores (ADHD‐PRS). Elevated ADHD‐PRS was associated with executive function deficits in individuals with mild cognitive impairment (MCI) or Alzheimer's disease (AD) dementia. Higher levels of cerebrospinal fluid (CSF) phosphorylated tau, but not amyloid beta (Aβ), were observed in dementia participants with higher ADHD‐PRS. Higher ADHD‐PRS was associated with brain hypometabolism in individuals with AD dementia. Hypometabolism in the parietal cortex mediated the effects of ADHD‐PRS on executive function.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.006 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".