Elevated Biomarkers of Alzheimer Disease Present in Patients with ADHD at Midlife: Poster Data From APSARD

Patients with a history of attention deficit hyperactive disorder (ADHD) showed elevated values of biomarkers of Alzheimer disease at midlife, from a recent presentation at the American Professional Society of ADHD and Related Diseases, in San Diego, California, January 15-18, 2026.¹ Cross-sectional preliminary data analysis suggested pathophysiological processes related to later in life cognitive decline are present in midlife ADHD.

The study tested whether adults diagnosed with ADHD in childhood show early Alzheimer disease markers in midlife. Cognition and plasma biomarker data were taken from the Pittsburgh ADHD Longitudinal Study (PALS), a longitudinal collection of patients with and without ADHD.² The study pool follows individuals diagnosed with ADHD in childhood and demographically similar individuals without ADHD.³ PALS collects cognitive function data with the Montreal Cognitive Assessment, Trail Making Test, Number Span, Digit Symbol Substitution Test, and Rey Auditory Verbal Learning Test. Blood-based biomarkers are measured with the NULISAseqTM CNS Disease Panel. The PALS data pool includes 50 individuals, 25 with ADHD and 25 without. The mean age of ADHD and control groups is 44.1 and 44 years, respectively. In total, participants are 80% male, 76% White, 16% Black, 8% mixed-race, and 56% attained a 4-year college degree.

Upon evaluation, individuals with ADHD history showed elevated values of established biomarkers of Alzheimer disease, with larger differences between the ADHD and control groups than expected at midlife. Individuals with a history of ADHD presented worse executive function, attention, and processing speed. Between the ADHD and non-ADHD groups, no significant differences in memory were found. Participants with ADHD showed lower Digit Symbol Substitution Test scores and longer Trail Making Test completion times, confirming differences in processing speed, attention, and executive function.

With blood biomarkers, the ADHD group showed lowered plasma A-beta 42 and A-beta 40, along with higher p-tau 181. P-tau 217 and p-tau 231 showed a similar increasing trend. These patterns are consistent with greater Alzheimer disease biomarker burden in midlife. Higher markers of neurodegeneration (neurofilament light chain) were seen in the ADHD group, but no significant differences in astrocyte reactivity (glial fibrillary acidic protein) or microglial activation (triggering receptor expressed on myeloid cells 2) were seen. Plasma biomarkers are considered able to detect the presence of Alzheimer disease pathology years before the onset of clinical symptoms.⁴

According to poster data presented, these findings “suggest that pathophysiological processes linked to later cognitive decline are already present in midlife ADHD.” The PALS study will continue towards its enrollment goal of 100 participants aged 40 or older. Findings here are preliminary, and authors noted full study enrollment and longitudinal follow up is needed to confirm trajectories and mechanisms.

References

1. Leffa DT, Kipp H, Connor K, et al. Cognition and blood-based biomarkers of Alzheimer’s disease in adults with and without childhood ADHD: preliminary results from the Pittsburgh ADHD longitudinal study. Poster presented at: American Professional Society of ADHD and Related Diseases; January 15-18, 2025; San Diego, California. Accessed January 15, 2026.

2. The Pittsburgh ADHD longitudinal study. Youth and Family Research Program, University of Pittsburgh. Accessed January 15, 2026. http://yfrp.pitt.edu/pals

3. Molina BSG, Sibley MH, Pedersen SL, et al. The Pittsburgh ADHD Longitudinal Study (PALS). In L. Hechtman (Ed.), Attention deficit hyperactivity disorder: adult outcome and its predictors (pp. 105–155). Oxford University Press; 2017.

4. Pascoal TA, Aguzzoli CS, Lussier FZ, et al. Insights into the use of biomarkers in clinical trials in Alzheimer's disease. EBioMedicine. 2024;108:105322.