Originally regarded as exclusive to childhood and adolescence, Attention-Deficit/Hyperactivity Disorder (ADHD) has been recognized as a lifelong neurodevelopmental condition, persisting into old age in 3–4% of the cases (1, 2). However, available data on the natural history of the disorder beyond mid-adulthood are scarce, and the potential interactions between lifetime cognitive dysfunction, including attentional, executive and memory deficits, and age-related cognitive decline are still poorly understood (1, 3–6). Previous reports have suggested that late-life cognitive changes may overlap with these preexisting difficulties, leading to increased problems to manage everyday-life activities, which may mimic neurocognitive disorders, in particular Mild Cognitive Impairment (MCI) (5).

Alternatively, the idea that ADHD may accelerate or predispose to pathological neurogenerative processes is attractive, yet unproven (7). It could be argued that functional and clinical outcomes associated with the condition compared to unaffected individuals are too coincidental with established risk factors for dementia to be unrelated (8). Those include lower educational level (9) and increased prevalence of traumatic brain injury (10), obesity (11), smoking (12), alcohol-related disorders (13), depression (14), social isolation due to peer rejection (15) and physical inactivity (16). In addition, extensive data have indicated the contribution of oxidative stress and neuroinflammation to the pathophysiology of both ADHD and Alzheimer's Disease (17–20).

With that, characterizing the cognitive and behavioral profile of older subjects with ADHD is needed to allow further insight on potentially converging pathological mechanisms in neurodevelopmental and neurodegenerative disorders in late-life and to avoid misdiagnosis of conditions with resembling clinical manifestations. In addition, therapeutic implications of accurately distinguishing these clinical entities could exist, considering that the effectiveness of treatment for ADHD in adults has been proven (21). Hence, the present study aims to compare performances in standardized neuropsychological tests and severity of depression and anxiety across elderly individuals classified as normal controls, ADHD and MCI.

A total of 107 participants (mean age = 67.60 ± 7.50 years; mean schooling = 15.14 ± 2.77 years; 65.4% females) were included in the analyses. Sixty percent (n = 24) of participants in the MCI group were classified as amnestic MCI.

MCI group was significantly older and less educated than controls and ADHD participants. A higher proportion of females were found in the control group (82.9%) than among MCI (60.0%) and ADHD (46.2%) subjects (p < 0.05). Scores in GDS were significantly more elevated in ADHD participants than in controls (p < 0.05). Presence of clinically relevant depressive symptoms (GDS > 5) did not differ across groups (p = 0.14). Neither scores on GAI nor presence of clinical anxiety (GAI > 13) was distinct among diagnostics clusters. Table 1 depicts these results.

After adjustment for age, sex, years of schooling and GDS, mean scores in all memory indices (RAVLT A1-A5, RAVLT A7, RAVLT A6/A5, and RAVLT Rec), TMT B, Digit Span Forward and Digit Span Backwards were significantly different between controls and MCI subjects. Controls performed significantly better than ADHD group in RAVLT A1-A5, RAVLT A7, RAVLT Rec, TMT B and Digit Span Forward. Except for Digit Span Backwards (partial η² = 0.13), effect-sizes were large for all these variables (partial η² > 0.14). No mean difference was observed between ADHD and MCI in the cognitive tasks. Those findings are shown in Table 2.

In this study, a pattern of amnestic-dysexecutive neuropsychological deficits was evidenced in older subjects with ADHD in comparison with normal controls, after controlling for age, years of schooling, sex and severity of depressive symptoms. However, task performances in this group were not distinguishable from MCI, suggesting that these conditions manifest as overlapping cognitive syndromes.

Verbal memory impairments in ADHD were identified for acquisition, delayed recall and recognition processes in relation to controls, which is in line with previous systematic and scoping reviews examining cognitive deficits in adults with the disorder (39, 40). It has been presumed that poor memory strategy selection in those individuals due to a disrupted phonological loop may lead to inefficient encoding of the material to be learned. With the deficient conversion of verbal stimuli into memory, performances in tasks involving retrieval of information both spontaneously and in response to verbal cues predictably fall below the average levels (39, 41).

In addition, scores in executive function tasks were comparable between ADHD and MCI groups. Accordingly, previous reports suggested that severity of frontal-executive impairments in ADHD, whether inherent of the disorder or exacerbated by age-related cognitive decline, might be compatible with subtle, but measurable difficulties to perform everyday life activities, which might mimic MCI presentation (41, 42). Longitudinal investigation of executive control in this diagnostic group may clarify about the contribution of aging to cognitive load and disability in ADHD.

Several limitations of the present study ought to be discussed. Given that awareness of ADHD, especially of later-life cases, has only been recently widespread (43), none of the participants with the condition had been given a diagnosis before the initial assessment in the study. Detection of the disorder was based on retrospective reports of DSM-5 childhood-onset of inattentive and/or hyperactive/impulsive criteria. Evidence of stability of ADHD traits through lifespan might suggest the validity of classification measures developed for younger populations in older samples (44), but more studies addressing this issue are needed (2). Furthermore, the etiological heterogeneity of MCI identified using solely clinical parameters has been widely recognized (45). Future studies applying biomarkers of neurodegenerative and cerebrovascular diseases might reduce selection bias. Finally, the small sample size, the tertiary setting, and the cross-sectional design might also affect validity of our results. Hence, large longitudinal community-based research is needed to confirm our findings.

In conclusion, our data suggest that MCI and ADHD are dissociated clinical entities with overlapping cognitive profiles. Considering the distinct therapeutic implications of the detection of these conditions, clinicians ought to be aware of these converging phenotypes to avoid misdiagnosis. A high level of suspicious and detailed history taking is crucial to allow the differential diagnosis of these disorders.

The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://doi.org/10.6084/m9.figshare.14916888.

The studies involving human participants were reviewed and approved by Research Ethics Committee of the IDOR. The patients/participants provided their written informed consent to participate in this study.

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

This research was supported by intramural grants from the D'Or Institute for Research and Education and Rede D'Or São Luiz Hospital Network, Conselho Nacional de Pesquisa, Coordenação de Aperfeiçoamento de Pessoal de Ensino Superior and Fundação de Amparo à Pesquisa do Rio de Janeiro.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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