Adult Attention-Deficit/Hyperactivity Disorder and the Risk of Dementia

Abstract

Importance: Evidence that adult attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk of dementia is scarce and inconsistent, and potential sources of bias are untested.

Objective: To examine the association between adult ADHD and the risk of dementia.

Design, setting, and participants: This prospective national cohort study consisted of 109 218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020. Participants were aged 51 to 70 years in 2003. Statistical analysis was conducted from December 2022 to August 2023.

Exposure: Adult ADHD was a time-varying covariate, classified as present from the age of the first diagnosis (using the International Classification of Diseases, Ninth Revision, and the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision); otherwise, absent.

Main outcome and measures: Cox regression models were fitted to quantify the association between adult ADHD and the risk of incident dementia with hazard ratios (HRs) and their 95% CIs unadjusted and in the primary analysis, using inverse probability weights, adjusted for 18 sources of potential confounding. In 14 complementary analyses, subgroup and sensitivity analyses were implemented.

Results: At the beginning of the follow-up, the sample of 109 218 participants had a mean (SD) age of 57.7 (5.5) years, 56 474 participants (51.7%) were female, and 52 744 (48.3%) were male. During follow-up, 730 participants (0.7%) received a diagnosis of adult ADHD, and 7726 (7.1%) received a diagnosis of dementia. Dementia occurred among 96 of 730 participants (13.2%) with adult ADHD and 7630 of 108 488 participants (7.0%) without adult ADHD. In the primary analysis, compared with the absence of adult ADHD, the presence of adult ADHD was statistically significantly (P < .001) associated with an increased dementia risk (unadjusted HR, 3.62 [95% CI, 2.92-4.49; P < .001]; adjusted HR, 2.77 [95% CI, 2.11-3.63; P < .001]). Twelve of the 14 complementary analyses did not attenuate the conclusions based on the results of the primary analysis. There was, however, no clear increase in the risk of dementia associated with adult ADHD among those who received psychostimulant medication, and evidence of reverse causation was mild.

Conclusions and relevance: In this cohort study of individuals born between 1933 and 1952 and followed up in old age, adult ADHD was associated with an increased risk of dementia. Policy makers, caregivers, patients, and clinicians may wish to monitor reliably for ADHD in old age.

Figure 1.. Study Flow Diagram

Study flow diagram of cohort selection, inclusion, exclusion, and follow-up. ADHD indicates attention-deficit/hyperactivity disorder; HMO, health maintenance organization.

Figure 2.. Primary Analysis of the Association Between Attention-Deficit/Hyperactivity Disorder (ADHD) and the Risk of Dementia

HR indicates hazard ratio from the Cox proportional hazards regression model. 95% CIs are Wald 2-sided 95% CIs. P values are for test of the hypothesis HR = 1 vs the hypothesis HR ≠ 1.

Figure 3.. Complementary Analysis of the Association Between Attention-Deficit/Hyperactivity Disorder (ADHD) and the Risk of Dementia

HR indicates hazard ratio from the Cox proportional hazards regression model. 95% CIs are Wald 2-sided 95% CIs. P values are for test of the hypothesis HR = 1 vs the hypothesis HR ≠ 1.