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ADHD in Older Adults / Seniors

ADHD in Older Adults / Seniors

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Implications for People with ADHD

There are only a few studies on ADHD in older adults. For many people with ADHD, the condition persists into old age, although its prevalence decreases with age. In studies, about 2 to 3% of older adults had ADHD. Only a small proportion of them had been diagnosed, and even fewer had received treatment.

The diagnostic criteria and questionnaires developed for younger adults were also applicable to older adults, but in some cases were less accurate in identifying ADHD in older adults. Since older adults are often no longer employed, it is more difficult to identify impairments. It is recommended that the personal distress experienced be assessed and that information from family members be taken into account.

Treatment with methylphenidate or atomoxetine may also be indicated for older adults. In such cases, attention must be paid to cardiovascular diseases, interactions with other medications, and changes in how the body processes medications with age. Lisdexamfetamine is approved for adults with no upper age limit; however, dose adjustment may be necessary in older adults. A German review article states that methylphenidate is approved for use up to age 60. Beyond that, treatment may be possible on a case-by-case basis as an off-label use, provided the patient is fully informed. The ADxS considers a blanket refusal to prescribe stimulants solely on the basis of age to be unjustifiable.

At a specialized outpatient clinic, about two-thirds of people with ADHD reported that stimulants were effective for them, while just over 40% stopped taking the medication due to side effects or a lack of effectiveness. In a study, amphetamine prescriptions were associated with more cardiovascular events among people over 65. Group cognitive behavioral therapy was just as effective for older adults as it was for younger ones.

ADHD can be associated with memory problems in older adults and may be mistaken for mild cognitive impairment or early-stage dementia. Therefore, when evaluating memory problems in older adults, healthcare providers should ask about lifelong ADHD symptoms. To date, ADHD has rarely been specifically investigated in memory clinics.

Several studies have found an increased risk of dementia in people with ADHD, particularly Lewy body dementia. It remains unclear whether ADHD itself is the cause. In some cases, the association could be explained by other mental health conditions, such as depression or anxiety disorders. A genetic study found no causal link between a predisposition to ADHD and Alzheimer’s disease.

Older adults who were diagnosed late reported lifelong challenges in their careers, relationships, and finances. Among the women surveyed, receiving a diagnosis and treatment later in life fostered self-acceptance. Older drivers with ADHD had more traffic accidents and traffic tickets.

(E 4): There are only a few studies on the symptoms, diagnosis, and treatment of ADHD in older adults. (Narrative review, E 4)1 (Narrative review, E 4)2 (Case report, 2 cases, E 4)3

According to a statement by the Central ADHD Network (2018), treatment with methylphenidate or atomoxetine may also be indicated for older adults. In such cases, attention must be paid to concomitant cardiovascular conditions, drug interactions, and age-related pharmacokinetic changes. (E 4.)4
In a survey, adults aged 50 and older who were currently taking ADHD medication reported significantly better attention than people with ADHD who were not receiving medication. (Cross-sectional study, survey, n = 149, E 3.)5
The efficacy studies of lisdexamfetamine in adults included participants aged 18 to 55. (E 4.)6 However, the absence of studies beyond a certain age limit does not automatically constitute off-label use. (ADxS assessment)

Lisdexamfetamine (Vyvanse Adult) is approved for the treatment of adults with no upper age limit. (E 4.)7 Dexamfetamine clearance was: (E 4.)7

  • about 1 l/h/kg for people aged 18 to 45
  • about 0.7 L/h/kg for people aged 55 to 74
  • 0.55 L/h/kg for people over 75

According to the prescribing information, a dose adjustment may therefore be necessary. (E 4.)7

According to the manufacturer’s instructions, methylphenidate should not be prescribed to older adults. According to a German review, stimulants are approved in Germany for use up to age 60; treatment of older patients is therefore only possible off-label. (Narrative review, E 4.)8 (E 4.)4 Even outside the age-appropriate approval range, medication may be prescribed on a case-by-case basis, provided patients are informed about potential side effects and the off-label use. (Case report, 2 cases, E 4.)3
Consequently, the relevant professional associations are not aware of any recourse proceedings initiated by health insurance funds regarding prescriptions issued after the age of 65.

A blanket refusal to prescribe stimulants after a certain age (particularly for those under 65) without a specific, individual medical reason is likely to constitute a case of medical malpractice. (Assessment by ADxS)

(E 2b): A response to stimulants was observed in older adults with ADHD in: (case series, n = 11, E 4.)9

  • 8 out of 9 patients, based on TOVA scores, were treated with methylphenidate at the dosage typically prescribed for younger adults (11 patients with a first-time diagnosis, aged 55 or older, with a mean age of 61.6 years)
  • 73% according to CGI-Improvement scores, while taking methylphenidate at the standard dose for younger adults (11 patients newly diagnosed at age 55 or older). 10 of the 11 continued taking the medication; no side effects were reported.
  • 65% according to self-reports (ages 55 to 79, specialized outpatient clinic) (retrospective observational study, chart review, n = 113, E 2b.)10 42% discontinued the medication due to side effects or lack of efficacy. While taking methylphenidate, body weight decreased and heart rate increased slightly but significantly.

ADHD medications were not significantly associated with cardiovascular disease in any age group. A moderately increased risk, particularly for cardiac arrest or tachyarrhythmias (RR 1.60, 95% CI 0.94 to 2.72), could not be ruled out. The cardiovascular risk associated with ADHD medications was as follows: (meta-analysis, k = 19, N = 3,931,532, evidence level 2b.)11

  • Amphetamine prescriptions among individuals over 65 with ADHD after propensity score matching, OR 6.16 (95% CI 4.22 to 8.99), 38 versus 6 events per 1,000, absolute risk difference 3.31% (retrospective cohort study, n = 13,233, up to 3 years, E 2b.)12 Blood pressure was elevated while on amphetamine. Myocardial infarctions were rare and did not differ between groups.
  • ADHD medications in older adults, RR 1.59 (0.62 to 4.05)
  • ADHD medications in children and adolescents, RR 1.18 (95% CI 0.91 to 1.53)
  • ADHD medications in young and middle-aged adults, RR 1.04 (0.43 to 2.48)

Adults aged 50 and older responded just as well as younger adults to a 12-week, manualized CBT group therapy program focused on executive functions related to inattention. However, among older adults, symptoms also improved significantly in the non-specific support group, so the difference between CBT and the control condition was smaller for them. (RCT, secondary analysis by age group, n = 81, of whom n = 26 were aged 50 and older, 12 weeks, author employed by the manufacturer, E 1b.)13 For CBT compared to the support group, the following were found:

  • Effect sizes (d’) for: (RCT, secondary analysis by age group, n = 81, of which n = 26 were aged 50 or older, 12 weeks, author employed by the manufacturer, E 1b.)13
    • Time management, organization, planning (AISRS-TMOP), younger participants, d’ = 1.2
    • Inattention in the blinded interview (AISRS-IN), younger participants, d’ = 0.93
    • Observer-rated inattention/memory (CAARS-O), older participants, d’ = 0.51
    • Observer-rated inattention/memory (CAARS-O), younger participants, d’ = 0.47
    • Time management, organization, planning (AISRS-TMOP), older participants, d’ = 0.43
    • Inattention in the blinded interview (AISRS-IN), older participants, d’ = 0.34
  • Response rates for inattention (AISRS-IN, 30% reduction) with CBT in: (RCT, secondary analysis by age group, n = 81, of whom n = 26 were aged 50 or older, 12 weeks, author employed by the manufacturer, E 1b.)13
    • 43.8% among younger participants (control group: 6.9%)
    • 38.5% among older participants (control group: 21.4%), not statistically significant

In Denmark, ADHD medications were primarily used off-label in people aged 50 and older as part of palliative care; no more than 2% of new users had been diagnosed with ADHD. The incidence of new users rose from 12.5 to 49.3 per 100,000 person-years between 2000 and 2010 and fell to 30.3 by 2015. Characteristics of new users according to: (register-based study, cohort study, n = 6,690, 2000 to 2012, E 2b.)14

  • Methylphenidate, 98% (of which 91% is in immediate release)
  • Opioid co-medication, 54%
  • Previous cancer diagnosis, 52% (up to 70% for those aged 65 and older)
  • 1-year mortality rate, 50% (primarily among cancer patients)
  • Median age 62 years (IQR 55 to 71)

The quality of care for adults with ADHD (as measured by quality indicators in electronic health records) improved from 2010 to 2020 for both younger and older people with ADHD. However, by the end of the period, older people with ADHD met most quality indicators less frequently than younger people with ADHD. (Cohort study, full text not available to us, E 2b.)15

There is barely any data available on the effects of stimulants during the peri- and postmenopausal periods. The authors speculate that the effects are less pronounced after menopause due to low estrogen levels. (Theoretical review, E 4.)16

(E 3): The prevalence of ADHD decreased with age. (Meta-analysis, k = 40, E 3.)17 (Meta-analysis, k = 6, E 3.)18 The meta-analysis with k = 6 found the decline to occur with a balanced gender ratio; age and gender interacted in this effect. The prevalence of ADHD was

  • for symptomatic or subclinical ADHD in cases of:
    • 4.51% (95% CI 2.15 to 9.32) for those aged 60 and older (18- to 24-year-olds: 8.99%, 95% CI 6.12 to 13.03) (Meta-analysis, k = 40, E 3.)17
    • 4.2% (below the threshold) among people aged 60 to 94 in the Netherlands (weighted) (cross-sectional study, n = 1,494, manufacturer-funded, E 3.)19
  • for ADHD based on diagnostic criteria (full-blown or research diagnosis) in cases of:
    • 3.1% among 40- to 59-year-olds (n = 256) in Germany (cross-sectional study, n = 539, E 3.)20
    • 2.8% (DSM-IV full-blown diagnosis) among 60- to 94-year-olds in the Netherlands (weighted) (cross-sectional study, n = 1,494, manufacturer-funded, E 3.)19
    • 2.6% among 40- to 80-year-olds in Germany (cross-sectional study, n = 539, E 3.)20
    • 2.5% (95% CI 2.1 to 3.1) for adults overall (pooled) (meta-analysis, k = 6, E 3.)18
    • 2.18% (95% CI 1.51 to 3.16) in people aged 50 and older based on a research diagnosis using validated scales (pooled) (meta-analysis, k = 20, N = 20,999,871, E 3.)21
    • 2.1% among 60- to 80-year-olds (n = 283) in Germany, with no significant difference compared to 40- to 59-year-olds (cross-sectional study, n = 539, E 3.)20
  • as lifetime prevalence (self-reported) in: (cohort study, n = 2,832, up to 44 months, E 2b.)22
    • 2.6% among active drivers aged 65 to 79
  • for persistent ADHD (onset in childhood) in: (meta-analysis, k = 40, E 3.)17
    • 0.77% (95% CI 0.3 to 1.96) for those aged 60 and older (18- to 24-year-olds: 5.05%, 95% CI 3.12 to 8.07)
  • as a clinical diagnosis for: (meta-analysis, k = 20, N = 20,999,871, E 3.)21
    • 0.23% (95% CI 0.12 to 0.43) among people aged 50 and older (pooled)

The ADHD treatment rate among people aged 50 and older was 0.09% (95% CI 0.06 to 0.15). Accordingly, less than half of those with a clinical diagnosis were receiving treatment. Heterogeneity among the studies was significant across all survey methods. (Meta-analysis, k = 20, N = 20,999,871, E 3.)21

(E 3): Older participants reported significantly fewer ADHD symptoms than younger participants. (Cross-sectional study, n = 3,443, E 3.)23 No difference between men and women (cross-sectional study, n = 1,494, manufacturer-funded, E 3.)19 People aged 60 to 70 more than those aged 71 to 94

Overall ADHD symptom scores did not differ between the age groups (40 to 59 and 60 to 80 years) in the German population sample; however, impulsivity/emotional lability and self-concept problems did differ. People with ADHD had more psychopathological abnormalities than people without ADHD (moderate to large effect sizes). In 92.1% of cases, a third-party assessment confirmed the self-report regarding current symptoms. (Cross-sectional study, n = 539, E 3.)20

In the general population, the following percentage of individuals scored 14 or higher on the ADHD Self-Report Scale (ASRS) (screening cutoff): (Cross-sectional study, n = 3,443, E 3.)23

  • 6.2% of people aged 48 to 52
  • 2.2% of people aged 68 to 74

(E 2b): Older adults were diagnosed with ADHD less frequently than younger adults. (Cohort study, insurance data, n = 5,282,877 adults, 10 years, E 2b.)24 (Registry study, n = 3,536,476, E 3.)25 In England, the documented ADHD diagnosis rate in primary care was 1.19% in 2025 (95% CI 1.18 to 1.21) and decreased with age. (Registry study, n = 3,536,476, E 3.)25 The lower diagnosis rate was evident

  • in the probability of an ADHD diagnosis for: (cohort study, insurance data, n = 5,282,877 adults, 10 years, E 2b.)24
    • Retirees versus working-age adults, OR = 0.278
    • People aged 65 and older compared with those aged 18 to 24, OR = 0.094 (95% CI 0.088 to 0.101), about ten times less likely
  • regarding the discrepancy between the documented diagnosis rate (England) and published prevalence estimates from: (registry study, n = 3,536,476, E 3.)25
    • 93.51% for men and women aged 65 and older
    • 73.03% among men and women aged 55 to 64
    • 28.71% among men aged 18 to 24

The incidence of documented diagnoses was lowest among people aged 65 and older and remained consistently low from 2000 to 2024. (Registry study, n = 3,536,476, E 3.)25

(E 3): ADHD was found

  • childhood ADHD, assessed retrospectively using the Wender Utah Rating Scale (WURS), in cases of:
    • 25% (9 out of 36) of older patients at a memory clinic with mild cognitive impairment (MCI, average age 72.4 years), probable ADHD, cut-off 30 points (cross-sectional study, n = 36, Study 3)26
    • 22.5% of psychiatric patients aged 65 and older, probable childhood ADHD (WURS score of 36 or higher) (cross-sectional study, n = 261, full text not available to us, E 3.)27 This was associated with more suicide attempts, legal problems, and traffic violations.
    • 4.4% of older adults (ranging from those with normal cognitive function to those with dementia) tested positive for childhood ADHD (cross-sectional study, n = 310, E 3.)28
    • 3.3% of people aged 65 to 80 (WURS 36 or higher) (cross-sectional study, N = 2,500, n = 1,599, E 3.)29 Men reported significantly more symptoms. More childhood symptoms were associated with general problems during childhood and poorer current health.
  • as currently diagnosed ADHD in clinical samples among:
    • 9.7% of psychiatric patients aged 65 and older (SCID-5, controls 1.5%) (Cross-sectional study, n = 261, full text not available to us, E 3.)27 ADHD predicted higher levels of attentional impulsivity regardless of age, gender, and education (p = 0.003).
    • 13 of 583 patients with cognitive symptoms (ages 22 to 75) at a memory clinic (case series, n = 13, E 4.)30

A probable diagnosis of ADHD in individuals with MCI was more common among: (cross-sectional study, n = 36, E 3.)26

  • male, OR = 22.3 (1.5 to 325.5)
  • current hyperactivity (ADHD RS-IV), OR = 2.8 (1.2 to 6.9)

(E 4): Had a psychiatric comorbidity:

  • 85% of the 13 patients diagnosed at the Memory Center, primarily with anxiety and depression (case series, n = 13, E 4.)30
  • 54% of 11 patients diagnosed for the first time who were 55 years of age or older (with at least one psychiatric comorbidity) (case series, n = 11, E 4.)9

In the same 11 patients (mean age 61.6 years), the following proportions were found for: (case series, n = 11, E 4.)9

  • predominantly inattentive subtype, 55%
  • Mixed type, 45%

Among 65- to 80-year-olds with retrospectively high childhood symptom scores (WURS 36 or higher), 53.3% (16 out of 30) also met the clinical cutoff commonly used in Sweden for current ADHD symptoms (WRASS 70 or higher); none of those with lower childhood scores did. The authors interpret this as evidence of significant persistence of ADHD symptoms into old age. (Cross-sectional study, N = 1,599, n = 60, E 3.)31

Among individuals aged 65 to 80, the Wender Scales, Barkley Scales, and DSM-IV criteria were largely consistent in their assessment of childhood and current ADHD symptoms. Met DSM-IV criteria (6 or more symptoms): (cross-sectional study, N = 1,599, n = 60, E 3.)32

  • 70.0% retrospective rate for inattention in childhood among children with high childhood scores (WURS 36 or higher)
  • 68.8% for current inattention when current scores are high (WRASS 70 or higher)
  • 56.3% for current hyperactivity/impulsivity with high current scores (WRASS 70 or higher)
  • 13.6% for current hyperactivity/impulsivity with lower current scores (WRASS below 70)
  • 11.4% for current inattention when current scores are lower (WRASS below 70)

(E 3): The diagnostic criteria and instruments developed for younger adults were also applicable to older adults. (Cross-sectional study, retrospective data, N = 231, n = 23, manufacturer-funded, E 3.)33 (Validation study, n = 324, E 3.)34

Among older adults with ADHD, the number of current ADHD symptoms did not differ from the number reported retrospectively for childhood (9.91 versus 10.43 out of 18). The authors therefore considered the diagnostic criteria developed for younger adults to be applicable to older adults as well. (Cross-sectional study, retrospective data, N = 231, n = 23, industry-funded, E 3.)33

The ADHD Self-Assessment Scale (ADHD-SB) and the Wender-Reimherr Interview (WRI) were also suitable as diagnostic tools for people aged 60 to 99 (correct classification rates of 89.5% and 86.1%, respectively; specificity ranging from 81% to 94%). However, both methods underestimated the number of people with ADHD compared to expert assessment (8% versus 14% of the total sample) and demonstrated lower psychometric quality in older adults than in younger adults (AUC 0.67 and 0.72, respectively). (Validation study, n = 324, E 3.)34

Longitudinal data with repeated measurements have so far only been collected up to the fifth decade of life, while prospective data from childhood (MTA) extend to an average age of 25. In older adults who are not employed, it is more difficult to assess the degree of impairment. It is proposed that, as with depression, the personally experienced distress be evaluated and information from third-party medical histories be included. (Comment, E 4.)35

For adults aged 50 and older, a hierarchical model of ADHD symptoms—with a higher-order general ADHD factor and the subfactors of inattention, hyperactivity, and impulsivity—best described the data (CFI = 0.96, TLI = 0.98, RMSEA = 0.04). The model also fit well for individuals without cognitive impairment or dementia. The general factor was associated with cognitive function, depressive symptoms, and polygenic ADHD risk. (Cross-sectional study, n = 1,562, E 3.)36

Among 18- to 59-year-olds (n = 645) and 60- to 85-year-olds (n = 233), the factor structure of ADHD symptoms (CAARS, two-factor model with inattention, hyperactivity, and impulsivity) was age-invariant. Hyperactivity and impulsivity were slightly lower among older adults. Among older adults, ADHD symptoms predicted poorer working memory, whereas among younger adults, inattention was associated with better cognitive flexibility. The authors considered the validity of the ADHD concept in older adults to be confirmed but recommended age-appropriate normative values. (Cross-sectional study, N = 878, E 3.)37

(E 3): Older adults with ADHD performed worse on episodic memory tasks than healthy peers of the same age. (Systematic review, k = 10, E 3.)38 (Cross-sectional study, n = 107, E 3.)39

Older adults (aged 50 and older) with ADHD performed worse on measures of attention and episodic memory than younger people with ADHD and healthy peers of the same age. Findings regarding executive functions were inconsistent (working memory was sometimes worse than in healthy older adults, and sometimes as good as or better than in younger adults with ADHD). (Systematic review, k = 10, E 3.)38

Older adults with ADHD performed worse than controls on episodic memory and executive functions (partial η² > 0.14, backward digit span 0.13) and did not differ from individuals with MCI in any cognitive domain. (Cross-sectional study, n = 107, E 3.)39

Among older adults (ages 68 to 74), ADHD symptoms primarily affected cognitive performance indirectly through depressive symptoms. Higher levels of hyperactivity were associated with better task-switching ability among older adults. (Cross-sectional study, n = 3,443, E 3.)23

Even in middle age (47 to 54 years), ADHD symptoms—including subclinical ones—were associated with slower reaction and processing speeds and reduced cognitive flexibility. (Cross-sectional study, population cohort, N = 2,091, E 3.)40

Retrospectively recorded childhood ADHD symptoms were weakly associated with poorer executive functions in individuals aged 18 to 85 (r = -0.10). Vascular risk factors (diabetes, smoking, obesity, high blood pressure, hypercholesterolemia) independently influenced cognition; however, they did not explain the association between ADHD symptoms and cognition either as mediators or as moderators. Age (under or over 65 years) did not moderate these associations. (Cross-sectional study, n = 1,092, E 3.)41

Older patients at a cognitive-neurological clinic with ADHD and mild cognitive impairment (MCI) both exhibited memory impairments with different underlying mechanisms (in MCI, a storage deficit with relatively smaller hippocampi; in ADHD, an encoding deficit with thinning of the frontal cortex). Both groups had normal executive functions. Semantic retrieval was impaired only in the MCI group. The authors did not consider ADHD to be a precursor to dementia, but rather a pathophysiologically distinct phenocopy. (Cross-sectional study, n = 40 ADHD, 29 MCI, 37 controls, E 3.)42

Older adults with ADHD showed a relatively isolated deficit in working memory compared to age-matched controls, whereas individuals with Lewy body dementia (DLB) exhibited broad-based impairments. Comparison of performance profiles (late-life ADHD / DLB) in: (Systematic review, k = 28 (3 ADHD studies with a total of 127 people with ADHD, 25 DLB studies), E 3.)43

  • Working memory, impaired in 2 out of 2 / 7 out of 10 studies
  • Inhibition control, impaired in 1 out of 3 / 3 out of 5 studies
  • cognitive flexibility, impaired in 1 out of 2 / 11 out of 13 studies
  • Planning: normal in 1 out of 1 study; impaired in 15 out of 16 studies
  • semantic and phonemic word fluency: unremarkable in 2 out of 2 studies; impaired in 15 out of 15 and 17 out of 17 studies, respectively
  • Psychomotor speed: normal in 1 out of 1 study; impaired in 11 out of 12 studies

The reduced NoGo-P3 observed in young adults with ADHD largely normalized by middle adulthood and then declined again. The authors view this as consistent with the “last in, first out” hypothesis, according to which brain regions that mature late undergo early degeneration. ADHD could therefore be associated not only with delayed brain maturation but also with premature age-related decline. (Cross-sectional study, N = 86, n = 45, E 3.)44

In a sustained attention task, older adults without ADHD reported fewer instances of mind wandering than younger adults, with comparable behavioral consequences (including reaction time variability). On the EEG, the P3 amplitude was reduced during inattentive trials in both age groups, though to a lesser extent in older adults. (Experimental cross-sectional study using EEG, n = 89, EEG analysis n = 50, full text not available to us, E 3.)45

In adults aged 35 and older with a clinical, symptomatic, or genetic risk for ADHD, changes were found in the frontostriatal, frontoparietal, and limbic systems compared to controls. Middle-aged adults with a diagnosis of ADHD showed more widely distributed cortical structural differences, while older adults exhibited predominantly frontal abnormalities, possibly due to an age-related attenuation of these differences. Two functional studies found reduced frontal activation alongside increased parietal activation, consistent with compensatory recruitment. In undiagnosed samples, genetic ADHD risk interacted with Alzheimer’s-related pathology to affect the brain and cognition. (Systematic review, k = 13, E 3.)46

Among older adults (ages 56 to 84), the association between ASS and ADHD symptoms was weaker (r = 0.39) than during adolescence (r = 0.60) and middle adulthood (r = 0.50). The authors hypothesize a de-differentiation of executive functions with age. (Narrative review with empirical analysis of 17,173 paired symptom assessments, ages 0 to 84, E 4.)47

(E 4): Persistent ADHD may manifest in older age as cognitive difficulties (memory, attention, organization) and may be misinterpreted as a mild cognitive disorder (MCI) or an early-stage neurodegenerative disease. (Narrative review, E 4.)48 (Case series, n = 13, E 4.)30 (Case reports, E 4.)49 Lifelong deficits in attention, working memory, processing speed, and executive functions may otherwise be misinterpreted as cognitive decline.

According to the authors, the association between ADHD and MCI is more of a confounding factor than a cause. Genetic, imaging, and pharmacological findings do not support a direct link between ADHD and Alzheimer’s disease, but leave open the possibility of a connection to Lewy body dementia and Parkinson’s disease. (Narrative review, E 4.)48

(E 4): When evaluating memory problems or a neurodegenerative disorder in older adults, it is important to inquire about or rule out pre-existing ADHD. (Case reports, E 4.)49 Inquire about ADHD or learning disabilities (case series, n = 86; full text not available to us, E 4.)50 When patients complain of declining short-term memory, differentiate from mild cognitive impairment (MCI) (Narrative review, E 4.)48 ADHD screening in cases of MCI with predominant attention deficit

Cognitive screenings (MMSE, MoCA) do not adequately distinguish between pre-existing and newly emerging deficits; neuropsychological testing with follow-up evaluations is recommended. The authors present a screening questionnaire for this purpose. (Case reports, E 4.)49

Forgetfulness and distractibility were the main complaints of adults with ADHD at a memory clinic. (Case series, n = 86; full text not available to us, E 4.)50

The WURS scores were not associated with a diagnosis of mild cognitive disorder (MCI) or dementia, but showed nonlinear associations with tasks of sustained attention. Therefore, attention deficits in older adults do not necessarily indicate a neurodegenerative disease. (Cross-sectional study, n = 310, E 3.)28

A 72-year-old man with mild neurocognitive disorder due to Alzheimer’s disease had apparently exhibited symptoms of inattention since childhood. A structured interview did not allow for a definitive ADHD diagnosis due to memory distortions. The authors suspected ADHD that had previously been compensated for by high cognitive abilities but had become decompensated due to the onset of a neurodegenerative process. An unexplained worsening of ADHD symptoms in old age should raise suspicion of a neurodegenerative process. (Case report, n = 1, full text not available to us, E 4.)51

54% of the U.S. memory clinics that responded had already identified cases of ADHD, and about half made the ADHD diagnosis themselves for the first time. Only 19% routinely screened for ADHD, and barely any clinic described treatment methods. ADHD in older adults is therefore likely underdiagnosed in memory clinics. (Survey, n = 62 memory clinics, E 3.)52

(E 2b): The risk associated with ADHD was

  • dementia (all forms of dementia):
    • HR 4.01 (95% CI 2.53 to 6.36), adjusted, within 10 years in adults compared with age- and sex-matched controls (5.48% vs. 4.0%) (Cohort study, n = 2,700, 10 years, E 2b.)53 Methylphenidate and atomoxetine were not associated with a lower risk of dementia.
    • HR 0.98 to 4.01 as the range of adjusted HRs for dementia from any cause in the included studies (systematic review, k = 7, E 2b.)54 The magnitude of the direct effect remained unclear due to methodological heterogeneity (no meta-analysis possible).
    • HR 3.33 (95% CI 1.09 to 10.17), adjusted, in a memory clinic cohort over up to 15 years (27 of 161 adults with ADHD and 4 of 109 non-affected individuals) (cohort study, n = 270, 15 years, E 2b.)55
    • HR 3.15 (95% CI 2.33 to 4.25, I² = 22.9%) in a pooled analysis excluding the Swedish registry study identified as an outlier (meta-analysis, k = 5, N = 3,704,277, E 2b.)56
    • HR 2.92 (2.40 to 3.57) starting at age 50 (register-based cohort study, N = 3,591,689, n = 9,532, median 14.1 years, E 2b.)57
    • HR 2.77 (95% CI 2.11 to 3.63), adjusted, among 51- to 70-year-olds diagnosed with adult ADHD (dementia in 13.2% versus 7.0%) (Cohort study, n = 109,218, 17 years, E 2b.)58 No clear increase in risk was found among people with ADHD who received psychostimulants. Evidence of reverse causality (ADHD diagnosis as an early sign of incipient dementia) was limited.
    • HR 2.52 (95% CI 1.51 to 4.22), pooled, with very high heterogeneity (I² = 87.7%) (Meta-analysis, k = 5, N = 3,704,277, E 2b.)56 A meta-analysis was not possible for Alzheimer’s, vascular, and Lewy body dementia due to an insufficient number of studies.
    • HR 1.62 (1.32 to 1.98) starting at age 50, after additional adjustment for depression, anxiety disorder, substance use disorder, and bipolar disorder (Register-based cohort study, N = 3,591,689, n = 9,532, median 14.1 years, E 2b.)57
    • HR 0.98 in one included study after adjusting for education, metabolic disorders, sleep disorders, head injuries, and mental disorders (previously 2.93) (Systematic review, k = 7, E 2b.)54
  • a Lewy body disease:
    • HR 54.54 (95% CI 7.48 to 397.50), adjusted, in the memory clinic cohort (the most common form of dementia was Lewy body dementia with 20 cases, 19 of which were in the ADHD group) (cohort study, n = 270, 15 years, E 2b.)55
    • OR 5.1 (95% CI 2.7 to 9.6) for a history of ADHD symptoms in adulthood compared with controls (case-control study, n = 509, E 3.)59
    • OR 4.9 (95% CI 2.8 to 8.4) for a history of ADHD symptoms in adulthood compared with Alzheimer’s dementia (case-control study, n = 509, E 3.)59
    • up to five times the risk of developing a neurodegenerative disease later in life, particularly Lewy body diseases (initial evidence from 8 studies) (Narrative review, k = 8, E 4.)60
  • mild cognitive impairment (MCI) beginning at age 50: (Register-based cohort study, N = 3,591,689, n = 9,532, median 14.1 years, E 2b.)57
    • HR 6.21 (5.25 to 7.35)
    • HR 2.54 (2.14 to 3.01) after additional adjustment

Metabolic disorders, sleep disorders, head injuries, educational level, and other developmental disorders barely affected the association. The association with dementia was stronger among men; among women with ADHD, the risk of dementia was 42% lower than among men with ADHD. (Register-based cohort study, N = 3,591,689, n = 9,532, median 14.1 years, E 2b.)57

Non-amnestic mild cognitive disorder occurred in 67.1% of people with ADHD and 17.4% of people not with ADHD in the memory clinic cohort. (Cohort study, n = 270, 15 years, E 2b.)55

Methodological weaknesses (diagnoses based on billing data, unrecognized cases of ADHD in control groups, inclusion of hyperkinetic syndromes not related to ADHD, confounding factors due to comorbidities) can cause risk estimates to be either underestimated or overestimated. (Narrative review, k = 8, E 4.)60

The following reported having had ADHD symptoms in adulthood: (case-control study, n = 509, E 3.)59

  • 47.8% of people with Lewy body dementia
  • 15.2% of people with Alzheimer’s disease
  • 15.1% of the inspections

Relatives of people with ADHD had an increased risk of Alzheimer’s disease and dementia from any cause. The association weakened as the degree of genetic relatedness decreased, suggesting shared familial risk factors. Risk among relatives of people with ADHD for: (cohort study, multigenerational registry, n = 2,132,929, E 2b.)61

  • Early-onset Alzheimer’s disease in parents, HR 1.69 (95% CI 1.34 to 2.13)
  • Alzheimer’s disease in parents, adjusted HR 1.55 (95% CI 1.26 to 1.89)
  • Dementia of any cause in parents, HR 1.34 (95% CI 1.11 to 1.63)
  • Early-onset Alzheimer’s disease in grandparents, HR 1.27 (95% CI 1.19 to 1.36)
  • Late-onset Alzheimer’s disease in parents, HR 1.20 (95% CI 0.82 to 1.77)
  • Alzheimer’s disease in uncles and aunts, HR 1.15 (95% CI 0.85 to 1.56), not significant
  • Alzheimer’s disease in grandparents, HR 1.11 (95% CI 1.08 to 1.13)
  • Dementia of any cause in grandparents, HR 1.10 (95% CI 1.08 to 1.12)
  • Late-onset Alzheimer’s disease in grandparents, HR 1.09 (95% CI 1.07 to 1.11)

A genetic predisposition to ADHD had no causal effect on the risk of Alzheimer’s disease (OR 1.00, 95% CI 0.98 to 1.02), nor did it have such an influence when adjusted for education (OR 1.00, 95% CI 0.99 to 1.01) and IQ (OR 1.00, 95% CI 0.99 to 1.02). Conversely, a genetic predisposition to Alzheimer’s disease did not influence the risk of ADHD (OR 1.12, 95% CI 0.86 to 1.44). (Mendelian randomization, GWAS data from 20,183 ADHD cases, 35,191 controls, 71,880 Alzheimer’s cases, and 383,378 controls, E 2b.)62

A higher polygenic ADHD risk (ADHD-PRS) was associated with greater cognitive decline over a period of up to 6 years among cognitively intact older adults without a diagnosis of ADHD (ages 55 to 90) (global cognition, PACC: β = -0.10, 95% CI -0.16 to -0.03, Cohen’s f² = 0.21). This association was observed only in individuals with amyloid-β deposits. In amyloid-positive individuals, a higher ADHD-PRS was also associated with changes in: (cohort study, n = 212, up to 6 years, E 2b.)63

  • Elevated levels of p-Tau181 in cerebrospinal fluid, β = 0.05 (0.01 to 0.08)
  • frontoparietal atrophy
  • greater memory decline (ADNI-Mem), interaction with amyloid-β: β = -0.02 (-0.05 to -0.0001)

A systematic review of genetic overlaps between ADHD and Alzheimer’s disease identified only 2 eligible studies with conflicting results. Among cognitively normal older adults (n = 212), a higher polygenic ADHD risk score in amyloid-positive individuals was associated with progressive cognitive decline, greater tau pathology, and frontoparietal atrophy. In contrast, in a cohort of 10,645 Swedish twins, no direct association was found between polygenic ADHD risk and dementia; observed associations with somatic diseases were mediated by BMI, education, smoking, and alcohol abuse. (Systematic review, k = 2, E 2b.)64

Among older adults with cognitive impairment (mean age 73.5 years), a high polygenic ADHD risk score was associated with more severe clinical features, as shown in: (cross-sectional study, n = 938, Table 3.)65

  • executive functions in mild cognitive disorder, β = -0.15 (95% CI -0.30 to -0.008)
  • executive functions in Alzheimer’s dementia, β = -0.28 (95% CI -0.52 to -0.03)
  • CSF p-tau181 in Alzheimer’s dementia, β = 0.48 (95% CI 0.20 to 0.75)
  • CSF amyloid-β1-42, no difference

In Alzheimer’s dementia, a higher polygenic ADHD risk score was also associated with frontal and parietal hypometabolism (FDG-PET), with parietal hypometabolism mediating the effect on executive functions. (Cross-sectional study, n = 938, E 3.)65

(E 3): Older adults with ADHD reported lifelong impairments. (Cross-sectional study, n = 296, of whom 11 had ADHD, E 3.)66 stable throughout life (Qualitative study, n = 24, author(s) employed by the manufacturer, E 3.)67 cumulative burden throughout life in cases of late diagnosis (63%) due to lower income and retirement savings, missed career opportunities, and social isolation (Qualitative interview study, n = 9, E 4.)68 Women diagnosed with ADHD after age 60 experience lifelong difficulties in their careers and relationships

Older adults with ADHD reported the following current impairments: (Cross-sectional study, n = 296, including 11 with ADHD, E 3.)66

  • social relationships (46%)
  • Organizing daily life (36%)
  • Family life (18%)
  • Managing money (18%)

Compared to younger adults with ADHD, older adults with a late diagnosis had lower productivity (AAQoL 51.7 vs. 61.9) but a more positive outlook on life (67.7 vs. 60.6). 21% feared that their ADHD symptoms were actually age-related cognitive problems or dementia. (Qualitative study, n = 24, author(s) employed by the manufacturer, E 3.)67

Women diagnosed after the age of 60 also described creative coping strategies. Being diagnosed and treated later in life fostered their self-acceptance. (Qualitative interview study, n = 9, E 4.)68

Adults with ADHD (aged 18 to 52 at the start of follow-up) exhibited greater instability in their daily lives. These associations increased with age and were strongest in the oldest group (aged 40 to 52). (Registry study, N = 3,448,440, n = 31,081, manufacturer-funded, author(s) employed by the manufacturer, E 2b.)69 Elevated incidence rates were found

  • for ADHD: (registry study, N = 3,448,440, n = 31,081, manufacturer-funded, author(s) employed by the manufacturer, E 2b.)69
    • Relocations, IRR 2.35 (95% CI 2.32 to 2.37)
    • Relationship instability (children with different partners), IRR 1.07 (1.06 to 1.08)
    • Change of job, IRR 1.03 (1.02 to 1.04)
  • in the oldest group compared to the middle group (ages 30 to 39), both significantly, for: (Registry study, N = 3,448,440, n = 31,081, manufacturer-funded, author(s) employed by the manufacturer, E 2b.)69
    • Relocations, IRR 1.50 (1.47 to 1.54)
    • Relationship instability, IRR 1.11 (1.08 to 1.14)
    • Change of job, IRR 1.09 (1.06 to 1.12)

Women with ADHD experienced greater relationship instability than men with ADHD across all age groups. (Registry study, N = 3,448,440, n = 31,081, industry-funded, author(s) employed by the manufacturer, E 2b.)69

Older drivers (ages 65 to 79) with ADHD had an increased risk (adjusted incidence rate ratio, aIRR) after adjustment for: (cohort study, n = 2,832, up to 44 months, E 2b.)22

  • Traffic tickets (self-reported), aIRR 2.02 (95% CI 1.42 to 2.88)
  • Traffic accidents (self-reported), aIRR 1.74 (95% CI 1.26 to 2.40)
  • Emergency braking, aIRR 1.07 (95% CI 1.02 to 1.12)

Children with ADHD symptoms at age 7 (3.1%) had an increased risk of dying by age 58 (OR 1.86, 95% CI 1.08 to 3.17, 251 deaths). The risk was largely explained by smoking and a higher waist-to-hip ratio at age 44. (Cohort study, n = 8,016, 51 years, E 2b.)70

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