Attention-deficit/hyperactivity disorder as a risk factor for dementia and mild cognitive impairment: A population-based register study

Abstract

BackgroundPrevious research has indicated that attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk for dementia, but studies are scarce and inconclusive. We aimed to investigate the association between ADHD, and dementia, and mild cognitive impairment (MCI). Additionally, we aimed to investigate the impact of comorbid conditions, educational attainment, head injuries, other developmental disorders, and sex, on the association. MethodsThe study population consisted of 3,591,689 individuals born between 1932-1963, identified from Swedish population-based registers. Cases of ADHD, dementia and MCI were defined according to ICD diagnostic codes and ATC codes for medication prescriptions. A Cox proportional hazards model was used to test the associations between ADHD, and dementia and MCI. ResultsIndividuals with ADHD had an increased risk for dementia and MCI. After adjusting for sex and birth year, a hazard ratio (HR) was 2.92 (95% confidence interval 2.40-3.57) for dementia, and 6.21 (5.25-7.35) for MCI. Additional adjustment for psychiatric disorders (depression, anxiety, substance use disorder, and bipolar disorder) substantially attenuated the associations, HR=1.62 (1.32-1.98) for dementia, and 2.54 (2.14-3.01) for MCI. Common metabolic disorders (hypertension, type 2 diabetes, and obesity), sleep disorders, head injuries, educational attainment, and other developmental disorders, had a limited impact on the association. The association between ADHD and dementia was stronger in men. ConclusionsADHD is a potential risk factor for dementia and MCI, although the risk significantly attenuates after controlling for psychiatric disorders. Further research is needed to confirm these findings and to explore underlying mechanisms of the associations.

Genetic Risk for Attention-Deficit/Hyperactivity Disorder Predicts Cognitive Decline and Development of Alzheimer’s Disease Pathophysiology in Cognitively Unimpaired Older Adults

“…Importantly, our study provides unique evidence that higher ADHD-PRS was associated with progressive cognitive decline, predominantly in the memory domain. Since the prototypical clinical phenotype of AD is progressive amnestic symptoms (23), our results support previous epidemiological findings demonstrating that ADHD might be a risk factor for cognitive decline, potentially leading to MCI and dementia syndromes due to AD (6–8).…”

“…Additionally, cognitive function in older adults with ADHD may closely resemble early manifestations of neurodegenerative conditions (5). Recent population-based large epidemiological studies suggested that ADHD is associated with a higher risk for mild cognitive impairment (MCI) and Alzheimer’s disease (AD) (6–8). However, these findings rely primarily on electronic health records and consequently can present biased estimates of ADHD and dementia prevalence.…”

“…Recent population-based large epidemiological studies suggested that ADHD is associated with a higher risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD) (6)(7)(8).…”

From attention-deficit hyperactivity disorder to sporadic Alzheimer’s disease—Wnt/mTOR pathways hypothesis

“…In the current paper, we present our hypothesis of the Wnt/mTOR pathway playing a role both in ADHD and sAD pathophysiology, which may explain the recent findings of ADHD as a risk for sAD ( Tzeng et al, 2019 ; Dobrosavljevic et al, 2021 ; Zhang et al, 2022 ). Furthermore, we discuss the possible therapeutic potentials of the psychostimulant methylphenidate (MPH) which, by affecting the Wnt/mTOR pathway, might be beneficial in both disorders.…”

Predicting childhood and adolescent attention-deficit/hyperactivity disorder onset: a nationwide deep learning approach

“…Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder characterized by impairing levels of inattention, hyperactivity/impulsivity, or both, with an estimated worldwide prevalence of 5-10% in children and 2-5% in adults [1]. The disorder, which frequently co-occurs with other psychiatric and medical conditions [2][3][4][5][6], among others, leads to economic and interpersonal problems, academic impairments, delinquency, and injuries [4,[7][8][9][10] that are associated with a significant individual and healthcare burden [11]. An extensive body of work shows that pharmacologic treatment for ADHD protects against a wide range of adverse outcomes [10] (e.g., injuries and accidents, criminality, substance use disorders, suicide, and traumatic brain injury), at least in the short term.…”