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- Dobrosavljevic, Maja, 1986-
(author)
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Attention-Deficit/Hyperactivity Disorder (ADHD) Beyond the Young Age : Investigation of the Prevalence of ADHD in Older Adults and the Risk of Age-related Disorders
- 2023
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Doctoral thesis (other academic/artistic)abstract
- Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder characterized by impairing levels of inattention and/or hyperactivity-impulsivity. Symptoms of ADHD, which typically emerge in childhood, may persist until older age with a substantial adverse impact on health and functionality. Yet there is a notable knowledge gap in research on ADHD in older age and the potential associations of adult ADHD with disorders that are common in older age (i.e., age-related disorders). Thus, this thesis aimed to investigate the prevalence rates of ADHD in older age and whether ADHD in adulthood is associated with an increased risk of age-related disorders. Study I, a systematic review and meta-analysis, suggests that a considerable number of older adults report elevated levels of ADHD symptoms, while the prevalence of treated ADHD is less than half of the prevalence of clinically diagnosed ADHD. In Studies II, III, and IV, we used data from Swedish population registers. We found that ADHD is associated with an increased risk of dementia and mild cognitive impairment (Study II), which substantially attenuates after controlling for psychiatric comorbidity. Further, ADHD symptoms in adulthood are associated with an increased risk of subsequent cardiometabolic disorders (Study III). The associations attenuate after controlling for educational attainment, psychiatric comorbidity, and lifestyle factors, and they are confounded by genetic factors. Finally, the prediction of cardiovascular risk in adults initiating pharmacological treatment for ADHD may improve by considering novel risk factors (i.e., psychiatric comorbidity and use of other psychotropic medications) in addition to traditional predictors (Study IV). Overall, the findings indicate that a substantial number of older adults have increased levels of ADHD symptoms and that ADHD in adults is associated with an increased risk of age-related disorders. Further longitudinal studies, based on both community samples and epidemiological data, are needed to explore the risk of age-related disorders in ADHD, and the underlying mechanisms, until a more advanced older age.
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| 2. |
- Dobrosavljevic, Maja, 1986-, et al.
(author)
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Attention-deficit/hyperactivity disorder as a risk factor for dementia and mild cognitive impairment : a population-based register study
- 2021
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In: European psychiatry. - : Cambridge University Press. - 0924-9338 .- 1778-3585. ; 65:1
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Journal article (peer-reviewed)abstract
- Background: Previous 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.Methods: The study population consisted of 3,591,689 individuals born between 1932 and 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.Results: Individuals 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.Conclusions: ADHD 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.
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| 3. |
- Dobrosavljevic, Maja, 1986-, et al.
(author)
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Attention-deficit/hyperactivity disorder symptoms and subsequent cardiometabolic disorders in adults : investigating underlying mechanisms using a longitudinal twin study
- 2023
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In: BMC Medicine. - : BioMed Central (BMC). - 1741-7015. ; 21:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: Emerging research suggests that attention-deficit/hyperactivity disorder (ADHD) increases the risk for cardiovascular (CVDs) and metabolic disorders (i.e., cardiometabolic disorders) in adulthood. Yet, available studies are scarce and have mainly been focused on individuals receiving clinical ADHD diagnoses. We aimed to investigate the prospective associations of ADHD symptoms in young and mid-adulthood with subsequent cardiometabolic disorders and the underlying mechanisms.METHODS: We studied 10,394 twins from the Swedish Twin Registry (STR), born between 1958 and 1985 without previous medical history of cardiometabolic disorders. They provided self-assessment of ADHD symptoms (score range 0-36) via a validated, DSM-IV-based scale in a web-based questionnaire/telephone interview within the Study of Twin Adults: Genes and Environment (STAGE), in 2005-2006 (aged 19-47 years), and were followed until the end of 2018 (33-59 years) to identify incident clinical diagnoses/medication prescriptions for cardiometabolic disorders acquired from Swedish national registers. We used Cox regression models to investigate the associations between ADHD symptoms score and cardiometabolic outcomes, with and without adjustment for relevant covariates, and a co-twin control design to study familial confounding.RESULTS: A one-unit increase in the level of ADHD symptoms was associated with a 2% increase in the rate of CVDs (hazard ratio [HR] = 1.02, 95% confidence interval 1.01-1.04) and a 3% increase in the rate of metabolic disorders (HR = 1.03, 1.02-1.05), after adjusting for birth year and sex. The associations were no longer significant after adjusting for educational attainment, lifestyle factors, and comorbid psychiatric disorders. The associations remained significant after adjusting for familial factors shared by dizygotic twin pairs but became nonsignificant after adjusting for factors shared by monozygotic twin pairs. However, the strength of the associations attenuated significantly in monozygotic twins compared to dizygotic twins for CVDs only, suggesting genetic confounding.CONCLUSIONS: ADHD symptom score is associated with a higher risk for cardiometabolic disorders, which may be explained by lower educational attainment, adverse lifestyle factors, and psychiatric comorbidities. Moreover, the associations appear to be partly confounded by shared genetic factors, especially for CVDs. Further research is needed to investigate the identified associations at the level of individual cardiometabolic disorders and to follow-up participants until a more advanced older age.
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| 5. |
- Dobrosavljevic, Maja, 1986-, et al.
(author)
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Prevalence of attention-deficit/hyperactivity disorder in older adults : A systematic review and meta-analysis
- 2020
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In: Neuroscience and Biobehavioral Reviews. - : Elsevier. - 0149-7634 .- 1873-7528. ; 118, s. 282-289
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Research review (peer-reviewed)abstract
- There is a significant knowledge gap in research on Attention-Deficit/Hyperactivity Disorder (ADHD) in older adults. Via a systematic review and meta-analysis, we aimed to investigate the prevalence of ADHD in older adults, considering different assessment methods. We searched five electronic databases up to June 26, 2020. We identified 20 relevant studies with 32 datasets providing a total sample size of 20,999,871 individuals (41,420 individuals with ADHD). The pooled prevalence estimates differed significantly across assessment methods: 2.18 % (95 % CI = 1.51, 3.16) based on research diagnosis via validated scales, 0.23 % (0.12, 0.43) relying on clinical ADHD diagnosis, and 0.09 % (0.06, 0.15) based on ADHD treatment rates. Heterogeneity was significant across studies for all assessment methods. There is a considerable number of older adults with elevated levels of ADHD symptoms as determined via validated scales, and the prevalence of treated ADHD is less than half of the prevalence of clinically diagnosed ADHD. This highlights the need for increased awareness of ADHD clinical diagnosis and treatment in older adults.
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| 6. |
- Dobrosavljevic, Maja, 1986-, et al.
(author)
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Risk prediction model for cardiovascular diseases in adults initiating pharmacological treatment for attention-deficit/hyperactivity disorder
- 2022
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In: Evidence-Based Mental Health. - : BMJ Publishing Group Ltd. - 1362-0347 .- 1468-960X. ; 25, s. 185-190
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Journal article (peer-reviewed)abstract
- Background: Available prediction models ofcardiovascular diseases (CVDs) may not accuratelypredict outcomes among individuals initiatingpharmacological treatment for attention-deficit/hyperactivity disorder (ADHD).Objective: To improve the predictive accuracyof traditional CVD risk factors for adults initiatingpharmacological treatment of ADHD, by consideringnovel CVD risk factors associated with ADHD (comorbidpsychiatric disorders, sociodemographic factors andpsychotropic medication).Methods: The cohort composed of 24 186 adultsresiding in Sweden without previous CVDs, born between1932 and 1990, who started pharmacological treatmentof ADHD between 2008 and 2011, and were followedfor up to 2 years. CVDs were identified using diagnosesaccording to the International Classification of Diseases,and dispended medication prescriptions from Swedishnational registers. Cox proportional hazards regressionwas employed to derive the prediction model.Findings: The developed model included eighttraditional and four novel CVD risk factors. Themodel showed acceptable overall discrimination (Cindex=0.72, 95% CI 0.70 to 0.74) and calibration(Brier score=0.008). The Integrated DiscriminationImprovement index showed a significant improvementafter adding novel risk factors (0.003 (95% CI 0.001 to0.007), p<0.001).Conclusions: The inclusion of the novel CVD riskfactors may provide a better prediction of CVDs in thispopulation compared with traditional CVD predictorsonly, when the model is used with a continuous riskscore. External validation studies and studies assessingclinical impact of the model are warranted.Clinical implications: Individuals initiatingpharmacological treatment of ADHD at higher risk ofdeveloping CVDs should be more closely monitored.
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| 7. |
- Dobrosavljevic, Maja, 1986-, et al.
(author)
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The diagnosis and treatment of attention-deficit hyperactivity disorder (ADHD) in older adults
- 2023
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In: Expert Review of Neurotherapeutics. - : Expert Reviews Ltd.. - 1473-7175 .- 1744-8360. ; 23:10, s. 883-893
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Research review (peer-reviewed)abstract
- INTRODUCTION: There is a striking knowledge gap on ADHD in older adults, and the diagnosis as well as treatment for ADHD in this age group.AREAS COVERED: The authors first review the literature on the prevalence, functional impairment, and health comorbidities of ADHD across the lifespan. Next, they address the diagnostic criteria for ADHD in adults according to the DSM/ICD, available screening/diagnostic tools, differential diagnosis, and the validity of diagnostic criteria for ADHD in older adults. Finally, the authors focus on empirical evidence on the prevalence rates, medication response, and safety of pharmacological treatment of ADHD in older adults, and national and international clinical guidelines on the treatment of ADHD in this age group. EXPERT OPINION: It is expected that future editions of the DSM and ICD will provide specifiers to the standard ADHD criteria, to better inform the diagnosis of ADHD in older adults. It is also expected that the increasing number of epidemiological studies will provide rigorous estimates on the prevalence, incidence, and burden of ADHD in older adults. One may expect an increasing number of RCTs assessing the efficacy/effectiveness and tolerability/safety of pharmacological as well as non-pharmacological interventions which will inform future guidelines on ADHD in older adults.
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| 9. |
- Li, Lin, 1989-, et al.
(author)
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Attention-deficit/hyperactivity disorder as a risk factor for cardiovascular diseases : a nationwide population-based cohort study
- 2022
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In: World Psychiatry. - : Masson SpA. - 1723-8617 .- 2051-5545. ; 21:3, s. 452-459
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Journal article (peer-reviewed)abstract
- Accumulating evidence suggests a higher risk for cardiovascular diseases among individuals with mental disorders, but very little is known about the risk for overall and specific groups of cardiovascular diseases in people with attention-deficit/hyperactivity disorder (ADHD). To fill this knowledge gap, we investigated the prospective associations between ADHD and a wide range of cardiovascular diseases in adults. In a nationwide population-based cohort study, we identified 5,389,519 adults born between 1941 and 1983, without pre-existing cardiovascular diseases, from Swedish registers. The study period was from January 1, 2001 to December 31, 2013. Incident cardiovascular disease events were identified according to ICD codes. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards regression model, with ADHD as a time-varying exposure. After an average 11.80 years of follow-up, 38.05% of individuals with ADHD versus 23.57% of those without ADHD had at least one diagnosis of cardiovascular disease (p<0.0001). ADHD was significantly associated with increased risk of any cardiovascular disease (HR=2.05, 95% CI: 1.98-2.13) after adjusting for sex and year of birth. Further adjustments for education level, birth country, type 2 diabetes mellitus, obesity, dyslipidemia, sleep problems and heavy smoking attenuated the association, which however remained significant (HR=1.84, 95% CI: 1.77-1.91). Further adjustment for psychiatric comorbidities attenuated but could not fully explain the association (HR=1.65, 95% CI: 1.59-1.71). The strongest associations were found for cardiac arrest (HR=2.28, 95% CI: 1.81-2.87), hemorrhagic stroke (HR=2.16, 95% CI: 1.68-2.77), and peripheral vascular disease/arteriosclerosis (HR=2.05, 95% CI: 1.76-2.38). Stronger associations were observed in males and younger adults, while comparable associations were found among individuals with or without psychotropic medications and family history of cardiovascular diseases. These data suggest that ADHD is an independent risk factor for a wide range of cardiovascular diseases. They highlight the importance of carefully monitoring cardiovascular health and developing age-appropriate and individualized strategies to reduce the cardiovascular risk in individuals with ADHD.
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| 10. |
- Salazar de Pablo, Gonzalo, et al.
(author)
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Individualized prediction models in ADHD : a systematic review and meta-regression
- 2024
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In: Molecular Psychiatry. - : Springer. - 1359-4184 .- 1476-5578.
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Research review (peer-reviewed)abstract
- There have been increasing efforts to develop prediction models supporting personalised detection, prediction, or treatment of ADHD. We overviewed the current status of prediction science in ADHD by: (1) systematically reviewing and appraising available prediction models; (2) quantitatively assessing factors impacting the performance of published models. We did a PRISMA/CHARMS/TRIPOD-compliant systematic review (PROSPERO: CRD42023387502), searching, until 20/12/2023, studies reporting internally and/or externally validated diagnostic/prognostic/treatment-response prediction models in ADHD. Using meta-regressions, we explored the impact of factors affecting the area under the curve (AUC) of the models. We assessed the study risk of bias with the Prediction Model Risk of Bias Assessment Tool (PROBAST). From 7764 identified records, 100 prediction models were included (88% diagnostic, 5% prognostic, and 7% treatment-response). Of these, 96% and 7% were internally and externally validated, respectively. None was implemented in clinical practice. Only 8% of the models were deemed at low risk of bias; 67% were considered at high risk of bias. Clinical, neuroimaging, and cognitive predictors were used in 35%, 31%, and 27% of the studies, respectively. The performance of ADHD prediction models was increased in those models including, compared to those models not including, clinical predictors (β = 6.54, p = 0.007). Type of validation, age range, type of model, number of predictors, study quality, and other type of predictors did not alter the AUC. Several prediction models have been developed to support the diagnosis of ADHD. However, efforts to predict outcomes or treatment response have been limited, and none of the available models is ready for implementation into clinical practice. The use of clinical predictors, which may be combined with other type of predictors, seems to improve the performance of the models. A new generation of research should address these gaps by conducting high quality, replicable, and externally validated models, followed by implementation research.
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