Individualized prediction models in ADHD: a systematic review and meta-regression.

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 (ß = 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.

Attention-deficit/hyperactivity disorder symptoms and subsequent cardiometabolic disorders in adults: investigating underlying mechanisms using a longitudinal twin study.

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.

The diagnosis and treatment of attention-deficit hyperactivity disorder (ADHD) in older adults.

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.

Risk of dementia and mild cognitive impairment in older adults with a criminal background: a population-based register study in Sweden.

Criminal behaviour has previously been associated with an increased risk for several mental health problems, but little is known about the association between criminal behaviour and dementia. We aimed to examine how the criminal background (type of crime, number of convictions, length of the sentence) is associated with dementia and mild cognitive impairment (MCI), and how mental and physical health disorders and educational attainment influenced these associations. A nationwide cohort of 3,617,028 individuals born between 1932 and 1962 were linked with criminal and medical records using Swedish national registers. We used Cox regression models to examine the associations. Increased risks for dementia (Hazard ratios (HRs) 1.54, 95% confidence interval (CI) 1.50-1.57) and MCI (1.55, 1.50-1.61) were found in individuals with criminal background, particularly among those who committed violent or several crimes, or with long sentences. After full adjustment of covariates, the associations attenuated but remained statistically significant for dementia (1.25, 1.22-1.28) and MCI (1.27, 1.22-1.32). The attenuation was mostly explained by mental health problems -depression, anxiety, schizophrenia spectrum disorders, substance use disorder (SUD), and bipolar disorder- (dementia: 1.34, 1.31-1.37; MCI: 1.35, 1.30-1.40). SUD contributed the most to attenuate the associations. Our results may provide important insights to health and penal systems by showing the importance of considering the severity of the criminal background and life-course mental health when assessing the risk of neurodegenerative disorders.

Risk prediction model for cardiovascular diseases in adults initiating pharmacological treatment for attention-deficit/hyperactivity disorder.

BACKGROUND: Available prediction models of cardiovascular diseases (CVDs) may not accurately predict outcomes among individuals initiating pharmacological treatment for attention-deficit/hyperactivity disorder (ADHD). OBJECTIVE: To improve the predictive accuracy of traditional CVD risk factors for adults initiating pharmacological treatment of ADHD, by considering novel CVD risk factors associated with ADHD (comorbid psychiatric disorders, sociodemographic factors and psychotropic medication). METHODS: The cohort composed of 24 186 adults residing in Sweden without previous CVDs, born between 1932 and 1990, who started pharmacological treatment of ADHD between 2008 and 2011, and were followed for up to 2 years. CVDs were identified using diagnoses according to the International Classification of Diseases, and dispended medication prescriptions from Swedish national registers. Cox proportional hazards regression was employed to derive the prediction model. FINDINGS: The developed model included eight traditional and four novel CVD risk factors. The model showed acceptable overall discrimination (C index=0.72, 95% CI 0.70 to 0.74) and calibration (Brier score=0.008). The Integrated Discrimination Improvement index showed a significant improvement after adding novel risk factors (0.003 (95% CI 0.001 to 0.007), p<0.001). CONCLUSIONS: The inclusion of the novel CVD risk factors may provide a better prediction of CVDs in this population compared with traditional CVD predictors only, when the model is used with a continuous risk score. External validation studies and studies assessing clinical impact of the model are warranted. CLINICAL IMPLICATIONS: Individuals initiating pharmacological treatment of ADHD at higher risk of developing CVDs should be more closely monitored.

Attention-deficit/hyperactivity disorder as a risk factor for cardiovascular diseases: a nationwide population-based cohort study.

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.

Attention-deficit/hyperactivity disorder and Alzheimer's disease and any dementia: A multi-generation cohort study in Sweden.

INTRODUCTION: We examined the extent to which attention-deficit/hyperactivity disorder (ADHD), a neurodevelopmental disorder, is linked with Alzheimer's disease (AD) and any dementia, neurodegenerative diseases, across generations. METHODS: A nationwide cohort born between 1980 and 2001 (index persons) were linked to their biological relatives (parents, grandparents, uncles/aunts) using Swedish national registers. We used Cox models to examine the cross-generation associations. RESULTS: Among relatives of 2,132,929 index persons, 3042 parents, 171,732 grandparents, and 1369 uncles/aunts had a diagnosis of AD. Parents of individuals with ADHD had an increased risk of AD (hazard ratio 1.55, 95% confidence interval 1.26-1.89). The associations attenuated but remained elevated in grandparents and uncles/aunts. The association for early-onset AD was stronger than late-onset AD. Similar results were observed for any dementia. DISCUSSION: ADHD is associated with AD and any dementia across generations. The associations attenuated with decreasing genetic relatedness, suggesting shared familial risk between ADHD and AD.

Prevalence of attention-deficit/hyperactivity disorder in older adults: A systematic review and meta-analysis.

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.

The mental and physical health of older offenders: A systematic review and meta-analysis.

A systematic review with meta-analysis was performed to: 1) estimate the prevalence of both mental and physical health problems in older offenders; 2) calculate relative risks for the health conditions in relation to non-offender older adults and; 3) explore the potential confounding role of several variables. We searched five databases up to August 2019. Studies involving offenders older than 50 years old were included. Fifty-five publications met criteria. The pooled prevalence for 18 mental and 28 physical health problems was calculated. In comparison with non-offender older adults, older offenders showed significantly higher risk for Hypertension (RR = 1.16, CI = 1.1, 1.2), Cardiovascular Diseases (RR = 1.24, CI = 1.09, 1.41), Respiratory diseases (RR = 1.75, CI = 1.29, 2.35), and Arthritis (RR = 1.19, CI = 1.12, 1.25). Heterogeneity was significant for all meta-analyses and partially explained by the confounding effect of country, the diagnosis assessment method, and the sample characteristics. Future research should include comparison groups of non-offender older adults and use longitudinal study designs to identify risk factors that can be targeted in preventive programmes.