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

Zhang, Le; Rietz, Ebba Du; Kuja‐Halkola, Ralf; Dobrosavljevic, Maja; Johnell, Kristina; Pedersen, Nancy L.; Larsson, Henrik; Chang, Zheng

doi:10.1002/alz.12462

Cited by 23 publications

(27 citation statements)

References 52 publications

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“…A second possibility is that the inclusion of non-ADHD cases in the exposed group is driving observed effects. As previously noted, many non-ADHD hyperkinetic disorders—which were included in the exposed cohort in four of the five cohort studies (Curtin et al, 2018 ; Tzeng et al, 2019 ; Du Rietz et al, 2021 ; Zhang et al, 2021 )—are caused by damage to the basal ganglia (Wichmann and DeLong, 2010 ) and may conceivably predispose one to further later-life basal ganglia dysfunction (a hallmark of LBD, e.g., McKeith et al, 2017 ). To tease apart these issues will require careful and systematic assessment of ADHD across all participants within future studies, and an examination of neurodegenerative disease risk in ADHD and non-ADHD hyperkinetic syndromes separately.…”

Section: Critical Appraisal Of Methodological Approachesmentioning

confidence: 90%

“…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.…”

Section: Discussionmentioning

confidence: 99%

“…In four studies (Curtin et al, 2018 ; Fluegge and Fluegge, 2018 ; Tzeng et al, 2019 ; Du Rietz et al, 2021 ), ADHD participants were identified via health record diagnostic codes from the International Classification of Diseases (ICD), and the authors evaluated the risk of subsequent basal ganglia diseases including LBD (Curtin et al, 2018 ; Du Rietz et al, 2021 ) or Lewy body or Alzheimer’s dementias (Fluegge and Fluegge, 2018 ; Tzeng et al, 2019 ; Du Rietz et al, 2021 ) associated with these codes. Another study (Zhang et al, 2021 ) investigated the relationship between familial aggregation of ADHD and dementia using both ICD-9 and ICD-10 codes. Not all studies, however, included consistent or intuitive operationalizations of ADHD ( Table 1 ).…”

Section: Critical Appraisal Of Methodological Approachesmentioning

confidence: 99%

“…Not all studies, however, included consistent or intuitive operationalizations of ADHD ( Table 1 ). For instance, two (Tzeng et al, 2019 ; Zhang et al, 2021 ) considered inattentive, hyperactive, and combined ADHD presentations (codes 314.00-01), while another (Fluegge and Fluegge, 2018 ) only considered hyperactivity presentations (314.01). Thus, ADHD cases presenting without hyperactivity—which represent between 20% (Salvi et al, 2019 ) and 40% (Gibbins et al, 2010 ) of adult cases—were not captured in the Fluegge and Fluegge ( 2018 ) study, suggesting the sample was an incomplete representation of ADHD.…”

Section: Critical Appraisal Of Methodological Approachesmentioning

confidence: 99%

“…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. Two smaller retrospective case-control studies have similarly reported increased earlier-life ADHD symptoms in individuals with Parkinson’s disease relative to controls (Walitza et al, 2007 ; Golimstok et al, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

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

Becker

Sharma

Callahan

2022

Front. Aging Neurosci.

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In this review, we undertake a critical appraisal of eight published studies providing first evidence that a history of attention-deficit/hyperactivity disorder (ADHD) may increase risk for the later-life development of a neurodegenerative disease, in particular Lewy body diseases (LBD), by up to five-fold. Most of these studies have used data linked to health records in large population registers and include impressive sample sizes and adequate follow-up periods. We identify a number of methodological limitations as well, including potential diagnostic inaccuracies arising from the use of electronic health records, biases in the measurement of ADHD status and symptoms, and concerns surrounding the representativeness of ADHD and LBD cohorts. Consequently, previously reported risk associations may have been underestimated due to the high likelihood of potentially missed ADHD cases in groups used as “controls”, or alternatively previous estimates may be inflated due to the inclusion of confounding comorbidities or non-ADHD cases within “exposed” groups that may have better accounted for dementia risk. Prospective longitudinal studies involving well-characterized cases and controls are recommended to provide some reassurance about the validity of neurodegenerative risk estimates in ADHD.

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Section: Critical Appraisal Of Methodological Approachesmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Critical Appraisal Of Methodological Approachesmentioning

confidence: 99%

Section: Critical Appraisal Of Methodological Approachesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Becker

Sharma

Callahan

2022

Front. Aging Neurosci.

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Adult Attention-Deficit/Hyperactivity Disorder and the Risk of Dementia

Levine,

Rotstein,

Kodesh

et al. 2023

JAMA Netw Open

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ImportanceEvidence that adult attention-deficit/hyperactivity disorder (ADHD) is associated with an increased risk of dementia is scarce and inconsistent, and potential sources of bias are untested.ObjectiveTo examine the association between adult ADHD and the risk of dementia.Design, Setting, and ParticipantsThis prospective national cohort study consisted of 109 218 members of a nonprofit Israeli health maintenance organization born between 1933 and 1952 who entered the cohort on January 1, 2003, without an ADHD or dementia diagnosis and were followed up to February 28, 2020. Participants were aged 51 to 70 years in 2003. Statistical analysis was conducted from December 2022 to August 2023.ExposureAdult ADHD was a time-varying covariate, classified as present from the age of the first diagnosis (using the International Classification of Diseases, Ninth Revision, and the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision); otherwise, absent.Main Outcome and MeasuresCox regression models were fitted to quantify the association between adult ADHD and the risk of incident dementia with hazard ratios (HRs) and their 95% CIs unadjusted and in the primary analysis, using inverse probability weights, adjusted for 18 sources of potential confounding. In 14 complementary analyses, subgroup and sensitivity analyses were implemented.ResultsAt the beginning of the follow-up, the sample of 109 218 participants had a mean (SD) age of 57.7 (5.5) years, 56 474 participants (51.7%) were female, and 52 744 (48.3%) were male. During follow-up, 730 participants (0.7%) received a diagnosis of adult ADHD, and 7726 (7.1%) received a diagnosis of dementia. Dementia occurred among 96 of 730 participants (13.2%) with adult ADHD and 7630 of 108 488 participants (7.0%) without adult ADHD. In the primary analysis, compared with the absence of adult ADHD, the presence of adult ADHD was statistically significantly (P &lt; .001) associated with an increased dementia risk (unadjusted HR, 3.62 [95% CI, 2.92-4.49; P &lt; .001]; adjusted HR, 2.77 [95% CI, 2.11-3.63; P &lt; .001]). Twelve of the 14 complementary analyses did not attenuate the conclusions based on the results of the primary analysis. There was, however, no clear increase in the risk of dementia associated with adult ADHD among those who received psychostimulant medication, and evidence of reverse causation was mild.Conclusions and RelevanceIn this cohort study of individuals born between 1933 and 1952 and followed up in old age, adult ADHD was associated with an increased risk of dementia. Policy makers, caregivers, patients, and clinicians may wish to monitor reliably for ADHD in old age.

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Epidemiology, diagnostics and treatment of attention deficit-hyperactivity disorder (ADHD) in advanced age

Praus,

Moldavski,

Alm

et al. 2023

Nervenarzt

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ZusammenfassungAktuelle Studien belegen eine vergleichsweise hohe Prävalenz der Aufmerksamkeitsdefizit-Hyperaktivitäts-Störung (ADHS) bis ins höhere Lebensalter. Ältere Betroffene leiden unter einer hohen Belastung mit psychiatrischer und somatischer Komorbidität sowie erheblichen Einschränkungen ihres psychosozialen Funktionsniveaus und subjektiven Wohlbefindens. Die differenzialdiagnostische Abgrenzung gegenüber neurodegenerativen Erkrankungen ist besonders in dieser Altersgruppe schwierig. Die vorliegende narrative Übersichtsarbeit will den aktuellen Wissensstand zur Epidemiologie der ADHS im höheren Lebensalter und zu möglichen Zusammenhängen zwischen ADHS und dem Risiko für Neurodegeneration zusammenfassen. Darüber hinaus werden Empfehlungen zur Diagnostik der ADHS im höheren Lebensalter und Behandlungsoptionen dargestellt.

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

Cited by 23 publications

References 52 publications

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

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

Adult Attention-Deficit/Hyperactivity Disorder and the Risk of Dementia

Epidemiology, diagnostics and treatment of attention deficit-hyperactivity disorder (ADHD) in advanced age

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