Attention-Deficit/Hyperactivity Disorder and Late-Life Cognitive Impairment.

IMPORTANCE

Attention-deficit/hyperactivity disorder (ADHD) affects tens to hundreds of millions of adults worldwide, and preliminary evidence suggests it may be associated with increased risk of mild cognitive impairment (MCI) and dementia. However, concerns regarding diagnostic ascertainment and residual confounding remain.

OBJECTIVE

To investigate the association of ADHD with incident cognitive impairment, defined as MCI or dementia, using electronic health record (EHR) diagnoses and genetic liability measured using genome-wide ADHD polygenic risk score (ADHD PRS) in the same individuals.

DESIGN, SETTING, AND

PARTICIPANTS

This cohort study used data from the US All of Us Research Program (enrollment May 6, 2018, to October 1, 2023; EHR data from January 4, 1985, to October 1, 2023; mean [SD] follow-up 10.26 [6.75] years). A total of 187 341 participants aged 50 years and older with available EHR and genomic data were included. Data were analyzed from October 2025 to July 2026.

EXPOSURES: ADHD diagnosis and ADHD PRS.

MAIN OUTCOMES AND MEASURES: Incident MCI or dementia.

RESULTS

Among 187 341 participants (mean [SD] age, 56.41 [7.88] years; 107 266 [57%] female), 3026 (1.6%) had ADHD. Among participants with ADHD, 203 (6.7%) developed cognitive impairment, compared with 6259 (3.4%) among those without ADHD. In adjusted Cox models, ADHD was associated with a more than 4-fold higher hazard of cognitive impairment (hazard ratio [HR], 4.60; 95% CI, 3.99-5.29; P < .001). Adjustments for comorbidities, educational attainment, and health care utilization attenuated but did not eliminate the association. Similarly, ADHD PRS was associated with incident cognitive impairment (highest vs lowest quintile: HR, 1.35; 95% CI, 1.25-1.46; P < .001). Among participants who developed cognitive impairment, comorbid ADHD diagnosis was associated with a nearly 2-fold higher odds of suboptimal mental health (odds ratio [OR], 1.69; 95% CI, 1.18-2.39; P = .01), quality of life (OR, 1.66; 95% CI, 1.14-2.39; P = .02), social satisfaction (OR, 2.39; 95% CI, 1.69-3.37; P < .001), and 20% higher health care utilization (incidence rate ratio, 1.20; 95% CI, 1.09-1.34; P = .003), suggesting greater care burden beyond the elevated incidence risk.

CONCLUSIONS AND RELEVANCE: In this cohort study, convergent clinical and genetic evidence revealed ADHD was associated with a markedly increased risk of late-life cognitive impairment. Among those who develop cognitive impairment, an ADHD diagnosis was associated with worse health outcomes and greater health care utilization, supporting the need for targeted monitoring and integrated care in this population.