ADHD and Neurodegenerative Disease Risk: A Critical Examination of the Evidence

In this review, we undertake a critical appraisal of eight published studies providing first evidence that a history of attention-deficit/hyperactivity disorder (ADHD) may increase risk for the later-life development of a neurodegenerative disease, in particular Lewy body diseases (LBD), by up to five-fold. Most of these studies have used data linked to health records in large population registers and include impressive sample sizes and adequate follow-up periods. We identify a number of methodological limitations as well, including potential diagnostic inaccuracies arising from the use of electronic health records, biases in the measurement of ADHD status and symptoms, and concerns surrounding the representativeness of ADHD and LBD cohorts. Consequently, previously reported risk associations may have been underestimated due to the high likelihood of potentially missed ADHD cases in groups used as controls, or alternatively previous estimates may be inflated due to the inclusion of confounding comorbidities or non-ADHD cases within exposed groups that may have better accounted for dementia risk. Prospective longitudinal studies involving well-characterized cases and controls are recommended to provide some reassurance about the validity of neurodegenerative risk estimates in ADHD.

Automated summary

Methodological limitations, including diagnostic inaccuracies, bias in symptom measurement, and concerns about representativeness, may have led to underestimation or overestimation of the association between ADHD and neurodegenerative disease risk in previous studies.