Adult ADHD is Linked to an Increased Risk of Incident Dementia
—Results from a national cohort study demonstrated the presence of adult ADHD was associated with a 2.77-fold increased risk of dementia. These findings suggest the importance of monitoring for ADHD in older age.
Adult attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk of dementia, a recent study suggests.1
“The association between adult ADHD and dementia risk remains a topic of interest because of inconsistent results and key factors are yet to be studied,” first author Stephen Z. Levine, PhD, School of Public Health, University of Haifa, Haifa, Israel, and colleagues noted in JAMA Network Open. “These factors include prescribed psychostimulant medications and reverse causation.”
Study design and participant characteristics
This cohort population came from electronic health records of all patients with a clinical diagnosis of dementia since 2000 at a single nonprofit health maintenance organization. The prospective birth cohort included Israeli citizens born between 1933 and 1952, with follow-up from January 1, 2003, to death, dementia, leaving the HMO, or the end of the study (February 28, 2020). Dementia and ADHD diagnoses were based on ICD-9 and ICD-10 codes. The authors noted that the diagnosis for ADHD requires a standard neuropsychological assessment, often performed in specialized testing centers.
Mean age at the beginning of follow-up was 57.7 years (n=109,218) and 51.7% were female. Participants with adult ADHD were younger than those without adult ADHD (55.7 vs 57.7 years). During the 17.2-year follow-up for incident dementia, 7726 (7.1%) participants were diagnosed with dementia and 730 (0.7%) participants received a diagnosis of adult ADHD. Of those with adult ADHD, 163 (22.3%) participants received treatment with a psychostimulant.
Among those with adult ADHD, 96 (13.2%) had an incident dementia diagnosis. Among those without adult ADHD, 7630 of 108,488 (7.0%) participants had an incident dementia diagnosis. Rates of dementia were estimated at 5.19 and 1.44 per 10,000 person-years for those with and without adult ADHD, respectively. Among participants with an ADHD diagnosis, 42.9% (6 of 14) received a dementia diagnosis at 85 years of age versus 15.2% (1223 of 8032) of participants without ADHD.
Risk of dementia and complementary analyses
Participants with adult ADHD had a significantly higher risk of incident dementia compared with participants without adult ADHD (unadjusted HR, 3.62 [95% CI, 2.92-4.49; P<.001]; adjusted HR, 2.77 [95% CI, 2.11-3.63; P<.001]).
To challenge the primary analysis, the adjusted Cox proportional hazards regression model was refitted to perform complementary analyses. This included investigating interactions between adult ADHD and sex, smoking status, age at study start of 60 years or younger, and age at study start of older than 60 years. The results of these analyses did not attenuate the findings of the primary analysis. Additional sensitivity analyses investigating the impact of a single ADHD diagnosis or more than one adult ADHD diagnosis compared with individuals without ADHD did not attenuate the primary conclusions.
The authors also looked at early vs later-onset dementia. This analysis did not affect primary results. In addition, no clear association was found between ADHD and risk of dementia among participants who received psychostimulant medication.
Models conducted to investigate reverse causation, stratified by three 5-year successive follow-up durations, did not attenuate the primary conclusions. As the duration became closer to the dementia diagnosis, the HR quantifying the association between ADHD and dementia risk became higher.
Conclusions
In this study, Levine and colleagues demonstrated that an adult diagnosis of ADHD was associated with a 2.77-fold increase in the risk of incident dementia.
Future studies are needed to investigate the role of psychostimulant medication use in older age, which may include assessing adult ADHD symptom severity.
Limitations of this study include the lack of information on childhood-onset ADHD, the potential underascertainment of the rate of adult ADHD, the inability to examine the symptoms of ADHD, the probably underascertainment of dementia, and the inability to assess academic achievement, cognitive reserve, cognitive impairment, and the possibility of some diagnostic overlap between ADHD and dementia.
“In this cohort study of 109,218 participants followed up to 17.2 years, after adjustment for 18 potential sources of confounding, the primary analysis indicated that an adult ADHD diagnosis was associated with a 2.77-fold increased dementia risk,” the authors concluded in JAMA Network Open. “Complementary analyses generally did not attenuate the conclusion of the primary analysis. This finding suggests that policy makers, caregivers, patients, and clinicians may wish to monitor ADHD in old age reliably.”
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