29 Vascular Burden Mediates the Relationship Between ADHD and Cognition in Older Adults
Bibliographic record
Abstract
Objective: Accumulating evidence from case-control and population studies suggests attention-deficit/hyperactivity disorder (ADHD) confers a 2- to 5-fold risk of all-cause dementia later in life. Here, we investigate vascular burden as a potential mediator of this relationship, because vascular integrity is well known to be compromised in ADHD (due to chronic obesity, diabetes, and hypertension) and is also a robust risk factor for neurodegeneration (due to reduced cerebral blood flow). We use brain white matter hyperintensities (WMH) as a measure of vascular burden. Participants and Methods: Thirty-nine adults aged 48-81 years with clinical ADHD, and 37 matched controls, completed neuropsychological testing and 1.5 T structural neuroimaging. None had stroke. Cognitive tests were demographically-adjusted to Z scores using regression-based norms generated from the control group, and averaged across tests within domains of short- and long-term verbal memory (forward digit span, California Verbal Learning Test, Logical Memory), visual memory (Visual Recognition, Rey Complex Figure), processing speed (coding, trails A, Stroop word-reading and color-naming), language (Boston Naming Test, semantic fluency), visuoconstruction (clock drawing, Rey Complex Figure copy), and executive function (backward digit span, trails B, phonemic fluency, Stroop inhibition, Wisconsin Card Sorting Test). Total WMH volumes (i.e., combined periventricular and deep) within subcortical, temporal, frontal, parietal, and occipital regions were individually divided by regional volumes to produce a proportion of each region representing WMH, then log-transformed to correct for skew. Age-corrected linear regression quantified total effects of ADHD on cognition; when these were significant, mediation models quantified the direct effects of ADHD on WMH volumes and the direct effect of WMH volumes on cognition. Sobel’s test estimated indirect effects of ADHD on cognition via WMH. Results: Group had a significant total effect on Processing Speed (ß=-1.154, p<.001) and on Executive Functioning (ß=-0.587, p=.004), where ADHD participants had lower composite scores (M=-1.10, SD=1.76 and M=-0.54, SD=1.14 respectively) than controls (M=0.02, SD=0.74; M=0.00, SD=0.49). Only frontal-lobe WMH had direct effects on Processing Speed (ß=-0.315, p=.012) and Executive Functioning (ß=-0.273, p<.001). The direct effect of ADHD on frontal WMH was significant (ß=-0.734, p=.016), and Sobel’s tests supported an indirect effect of ADHD on Executive Functioning (z=2.079, p=.038) but not Processing Speed (z=1.785, p=.074) via WMH. Because the effect of ADHD on WMH was negative (i.e., fewer WMH in ADHD) despite worse cognition than controls, we tested the a posteriori hypothesis that WMH burden may be relatively more deleterious for ADHD than controls. We found considerably stronger negative correlations between total WMH volumes and Processing Speed (r=-.423, p=.009) and Executive Functioning (r=-.528, p<.001) in the ADHD group than in controls (r=-.231, p=.175 and r=-.162, p=.346, respectively), even though total whole-brain proportion of WMH (M=0.15%, SD=0.27; Mann-Whitney l/=430.0, p=.002) and frontal-lobe proportion of WMH volumes (M=0.33%, SD=0.51; Mann-Whitney U=464.0, p=.007) were lower in ADHD than in controls (M=0.29%, SD=0.42 and M=0.66%, SD=0.88, respectively). Conclusions: WMH burden contributes significantly to the relationship between ADHD and cognition, but ADHD remains an independent contributor to worse processing speed and executive functioning in older adults. Vascular burden may have relatively more deleterious effects on cognition in ADHD, potentially due to decades of accumulated allostatic load, whereas healthy controls can accumulate greater amounts of WMH before cognition is impacted.
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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 | 0.001 | 0.006 |
| Meta-epidemiology (narrow) | 0.000 | 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 | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.004 | 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".