Journal Article Annotations
2023, 4th Quarter

Child and Adolescent Psychiatry/Pediatrics

Annotations by Sneha Jadhav, MD
January, 2024

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

PUBLICATION #1 — Child and Adolescent Psychiatry/Pediatrics

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

Stephen Z Levine, Anat Rotstein, Arad Kodesh, Sven Sandin, Brian K Lee, Galit Weinstein, Michal Schnaider Beeri, Abraham Reichenberg

Abstract: JAMA Netw Open. 2023 Oct 2;6(10):e2338088. doi: 10.1001/jamanetworkopen.2023.38088.

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.

Annotation

The finding:
In this electronic health record (EHR)-based prospective study included over 100,000 individuals followed between 2003 to 2020, the researchers found a 2.77-fold increase in risk of incident dementia in individuals with adult ADHD. There are new findings of mild evidence of reverse causation, namely dementia diagnosis in later life may predispose to ADHD-like symptoms early in life and that ADHD treated with psychostimulants medication was not associated with an increased dementia risk. Factors such as patient sex, smoking status, early or late onset dementia did not attenuate the conclusions from the primary analysis.

Strength and weaknesses:
A prospective study spanning over a decade with a large cohort provides a strong basis for studying a disease which has relatively low rate of diagnosis and treatment among adults. The starting point of the study with no pre-existing ADHD or dementia diagnoses minimizes several potential biases. The diagnostic assessment by trained professionals lends credibility to the diagnoses which are highly clinical and can have overlapping symptoms. The limitations of the study were the lack of information about childhood-onset ADHD and lack of details about ADHD symptom profile, which may vary widely but also may specifically change the risk stratification for future diagnosis of dementia. There are many known dementia risk factors that were not included in the study such as impact of low academic achievement (impaired cognitive reserve), APOE e4 status, and cerebrovascular disease.

Relevance:
It will be critical to assess adults with ADHD early and frequently for dementia symptoms. Since the symptoms of the two conditions can overlap, structuring assessments to account for and differentiate both symptom clusters and establishing thresholds for each diagnosis. It is plausible that the pathological process of ADHD or the day-to-day symptoms themselves reduce the ability of the individual to compensate for later-in-life neurodegenerative and cerebrovascular processes.