The Association Between Parkinson’s Disease and Attention-Deficit Hyperactivity Disorder

Abstract

While Parkinson’s disease (PD) and attention-deficit hyperactivity disorder (ADHD) are two distinct conditions, it has been hypothesized that they share several overlapping anatomical and neurochemical changes. In order to investigate that hypothesis, this study used claims data from Taiwan’s Longitudinal Health Insurance Database 2000 to provide the significant nationwide population-based evidence of an increased risk of PD among ADHD patients, and the connection between the two conditions was not the result of other comorbidities. Moreover, this study showed that the patients with PD were 2.8 times more likely to have a prior ADHD diagnosis compared with those without a prior history of ADHD. Furthermore, an animal model of ADHD was generated by neonatally injecting rats with 6-hydroxydopamine (6-OHDA). These rats were subjected to behavior tests and the 99mTc-TRODAT-1 brain imaging at the juvenile stage. Compared to control group rats, the 6-OHDA rats showed a significantly reduced specific uptake ratio in the striatum, indicating an underlying PD-linked pathology in the brains of these ADHD phenotype-expressing rats. Overall, these results support that ADHD shares a number of anatomical and neurochemical changes with PD. As such, improved knowledge of the neurochemical mechanisms underlying ADHD could result in improved treatments for various debilitating neurological disorders, including PD.

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

“…Strengths include well-powered analyses and extensive follow-up periods (>10 years) in most studies. However, six (Curtin et al, 2018 ; Fluegge and Fluegge, 2018 ; Tzeng et al, 2019 ; Fan et al, 2020 ; Du Rietz et al, 2021 ; Zhang et al, 2021 ) rely on ICD diagnostic codes extracted from electronic health records, and there are limitations around the validity and accuracy of these codes, particularly for a disorder that is notoriously difficult to detect in adults (Newcorn et al, 2007 ; Ginsberg et al, 2014 ). The remaining two (Walitza et al, 2007 ; Golimstok et al, 2011 ) are limited by potentially biased and inaccurate self-reported retrospective childhood ADHD symptoms in small samples of cognitively impaired participants.…”

“…Despite these sex differences, only three of the studies considered sex as a covariate in their statistical models (Curtin et al, 2018 ; Tzeng et al, 2019 ; Du Rietz et al, 2021 ) and one matched groups on sex (Golimstok et al, 2011 ). Lastly, all articles except two (Tzeng et al, 2019 ; Fan et al, 2020 ) disregarded obvious risk factors for developing dementia, such as traumatic brain injury, hypertension, physical inactivity, cardiovascular risk factors, excessive alcohol consumption, and smoking (Bergland et al, 2017 ; Livingston et al, 2020 ). Many of these risk factors are increased in ADHD, including traumatic brain injury (Liou et al, 2018 ), hypertension (Fuemmeler et al, 2011 ), cardiovascular risk factors (Cortese et al, 2013 ; Irmisch et al, 2013 ; Chen et al, 2018 ; Du Rietz et al, 2021 ), and smoking (Galéra et al, 2017 ), and these factors may be accounting for a substantial portion of the putative association between ADHD and later-life neurodegenerative disease (as in Bendayan et al, 2020 , for example).…”

“…We conducted a formal evaluation of the quality of the eight studies in this review using the Newcastle-Ottawa Scale (Wells et al, 2011 ), and found many strengths across each ( Table 2 ). All case-control studies had clear criteria for the selection of controls, and two ensured that participants were age- and sex-matched (Golimstok et al, 2011 ; Fan et al, 2020 ). Consensus criteria were used in two of the three case-control studies to ascertain neurodegenerative disease outcomes (Walitza et al, 2007 ; Golimstok et al, 2011 ).…”

“…In the last 15 years, eight published studies have suggested that ADHD may be a risk factor for incident neurodegeneration (Walitza et al, 2007 ; Golimstok et al, 2011 ; Curtin et al, 2018 ; Fluegge and Fluegge, 2018 ; Tzeng et al, 2019 ; Fan et al, 2020 ; Du Rietz et al, 2021 ; Zhang et al, 2021 ; see Table 1 ). These studies have primarily used data from population registers with linked health information (Curtin et al, 2018 ; Du Rietz et al, 2021 ; Zhang et al, 2021 ), healthcare utilization databases (Fluegge and Fluegge, 2018 ), or health insurance databases (Tzeng et al, 2019 ), and have reported increased risk for neurodegeneration—particularly LBD—in individuals with antecedent ADHD.…”

Longitudinal Cognitive Performance of Older Adults With ADHD Presenting to a Cognitive Neurology Clinic: A Case Series of Change Up to 21 Years

“…A potential limitation of this study was its retrospective design, which resulted in a biased sample of cognitively stable older adults with persistent ADHD. Several studies have raised the possibility that ADHD in early or mid-life may confer risk for neurodegenerative disease in later life ( Walitza et al, 2007 ; Golimstok et al, 2011 ; Curtin et al, 2018 ; Fluegge and Fluegge, 2018 ; Tzeng et al, 2019 ; Fan et al, 2020 ; Du Rietz et al, 2021 ). However, any patient with significant cognitive impairment or documented decline would be classified in clinic charts as having mild cognitive impairment or dementia (i.e., not “suspected of having ADHD”), and thus would not be captured by our sampling method.…”