In our previous case report, we reported on late-onset ADHD with dementia-like symptoms. In this study, we discussed the possibility of several such patients presenting to the dementia outpatient clinic. We also demonstrated that it might be difficult to distinguish ADHD from other types of dementia, especially EOAD, in such patients.
There could be various reasons for these patients with ADHD to be initially suspected of having EOAD. One reason was that the age range of patients matched between the ADHD and EOAD groups (Table 1). Another reason may be the clinical course. As mentioned in Table 2 and in the Results section, all ADHD patients manifested inattentiveness and forgetfulness at the senile stage. Perhaps, this clinical course of ADHD symptoms that began to interfere with the patient’s social lives in the senile age were similar to the onset of dementia from a relative’s point of view, and this is the reason why they attended dementia clinic recommended from their surroundings. Similarly, EOAD often presents with symptoms of forgetfulness and inattention rather than behavioral and psychological symptoms of dementia, such as visual hallucinations and personality changes, and the onset of EOAD is often detected by surrounding people due to disturbed social activity of the affected patients [25]. Furthermore, patients with EOAD are known to often present with the above symptoms before the development of brain atrophy (including the hippocampus). Therefore, it is not surprising that ADHD patients in the present study who visited our specialty outpatient clinic for dementia with chief complaints of forgetfulness and inattention were initially suspected of having EOAD despite the absence of obvious morphological abnormalities.
How can ADHD be differentiated from EOAD? First, the procedures that were helpful included the PiB-PET and the determination of the phosphorylated tau/amyloid beta-42 ratio in the CSF. Both are known to have high sensitivity and high specificity. If negative results are obtained in both examinations, there is an extremely high likelihood that EOAD is absent [26]. Thus, EOAD was excluded through the use of PiB-PET and CSF, as described in our previous case report [18]. However, the problem is that these tests are special and not every hospital can do it. Therefore, in this study, there were only three patients with ADHD who could be ruled out as having EOAD even after these tests were performed. Another point is the type of forgetfulness observed in the patient. In cases of EOAD, patients become forgetful in the way that they cannot recall whether they went out the previous day, or they cannot memorize the name of the attending physician, irrespective of how many times they see the physician. However, in this study, patients with ADHD were forgetful in that they inadvertently forgot things because they were preoccupied with something else, or they forgot to perform one task while simultaneously performing several other tasks. Both types of forgetfulness were the same in terms of interfering with the patients’ living activities; however, forgetfulness in EOAD involves the lack of episodic memories, whereas that in ADHD is forgetfulness attributable to inadvertence. Given this difference, it would appear that it was easy for the specialists to distinguish between the two; however, this difference is only apparent in relatively advanced EOAD. In the case of very early EOAD, the lack of episodes is not quite obvious; hence, it remains difficult to distinguish.
In terms of treatment, 60% of the patients with ADHD responded to the treatment. In general, the main focus of dementia treatment is to prevent progression. However, in the case of ADHD, there are cases where treatment clearly improves symptoms and quality of life, as in the case shown in the previous case report. The difference in medication is one of the most important factors in differentiating between the two. Moreover, ADHD medications have also been suggested to be effective in treating diseases other than ADHD [27,28,29]; therefore, effective treatment does not necessarily indicate that the patient has ADHD.
Moreover, there is a persistent question that should be considered. It is now well-established that a considerable subset of people with mild cognitive impairment (MCI) remain cognitively stable over a number of years without ever progressing to dementia. It is possible that some or all of the ADHD patients constituted cases of stable MCI. This can be explained by the third finding in Table 2, which has been elaborated in detail in the Results section. Considering the clinical course of gradual worsening of ADHD-like characteristics, it is more reasonable to explain them as a manifestation of ADHD rather than as a stable MCI. However, in current practice, there may be cases in which ADHD and stable MCI cannot be distinguished with certainty, and this is an issue warranting further studies.
Previous studies on late-onset ADHD have proposed two types of late-onset ADHD; however, these studies have been limited to young adults. One type is “new-onset” ADHD [8, 9] and another type is “manifestation” of the disease [10, 12]. The result of our study corresponds to the latter. Moreover, what we described previously in our case report as “very late-onset ADHD” is actually more accurately termed as “the late-manifestation of ADHD”. Then, why did ADHD symptoms manifest in the senile age? In this regard, “aging alteration” and “stressful life events (SLE)” showed in Table 2 may play an important role. In the senile age, the brain function may have been declining due to age-related changes. In addition to these age-related changes, SLE may have accelerated decline of brain function. The relationship among SLE, late life, and cognitive decline has already been reported in another study [30]. Due to the functional brain decline caused by these factors, symptoms of ADHD may have manifested as these could not be compensated anymore. Higher intelligence quotient (IQ) of patients with ADHD has been demonstrated in previous research [9]. Our study did not compare the IQs because we were unable to apply the Wechsler Adult Intelligence Scale; however, we observed a statistically significant difference in the years of education (Table 1). Probably, some older adults with ADHD may efficiently compensate their ADHD tendency by utilizing their aptitude.
Therefore, ADHD cases in older adults can be summarized as follows. First, there are people who live with high intellectual ability and compensate ADHD well. As these people reach senile age, their brain function begins to deteriorate owing to aging alteration, and SLE further reduces their brain function. The diminished brain function is no longer able to compensate for ADHD symptoms as it used to previously. When ADHD symptoms become apparent at senile age and interfere with daily life, those around the patient may suspect development of dementia and advise the patient to see a doctor. This is probably how the patients with ADHD in this study came to visit the dementia outpatient clinic.
Limitations
The study had certain limitations. First, there was the possibility of missed diagnosis of ADHD. In this study, all the patients underwent several routine tests, and similar to routine practice by specialists, we ruled out diseases that had the potential to contribute to cognitive decline (e.g., depression, brain tumor, vitamin B12 deficiency, and hypothyroidism). When these diseases were suspected, the patients were excluded from the study. However, we cannot deny the possibility that some of the excluded patients had ADHD as a comorbidity. For example, a previous study reported that older adults with ADHD often had depression [31]. Moreover, it was also problematic that the developmental disorder specialists began the intervention with verification of medical records prepared by the dementia specialists. Since impulsivity, inattention, and forgetfulness were also important symptoms in the evaluation of dementia, the dementia specialists examined these symptoms. However, since the interview was not conducted with ADHD in mind, it might not have been sufficient. Furthermore, it is possible that the medical records were inadequately documented and therefore, patients with ADHD were not considered by the specialists in developmental disorder. Therefore, a developmental disorder specialist could ideally directly examine all the outpatients and evaluate them for the presence of ADHD. However, this was not practical in routine clinical practice, neither in terms of patient consent nor in terms of manpower on the part of the researcher. Therefore, it was necessary to narrow down the list of patients to some extent by screening the medical records. The next limitation is that sufficient information before the age of 12 was not obtained because the patients were old and fewer people knew about their childhood. Unlike the screening phase, the policy during the diagnosis phase was to accurately adhere to the diagnostic criteria. However, owing to the aforementioned reasons, it was difficult to ascertain the characteristics before the age of 12 years; hence, we had to exclude this item from the diagnosis. The third limitation pertains to the diagnosis performed by two developmental disorder specialists. During the direct examination of the patients themselves or the information provided by their family performed by a developmental disorder specialist, each patient was not separately diagnosed by two specialists. In practice, the patient had first been diagnosed by a specialist, and then the result was discussed between the first specialist and a second specialist. Moreover, both specialists participated in the study with knowledge of the study’s aims. These features may have created a bias in diagnosis. The fourth limitation was about the follow-up survey. The follow-up survey permitted detailed verification of only the patient who continued to visit the clinic; however, patients who had not visited the clinic were managed over the telephone. Many details cannot be confirmed over the phone and certain findings could be missed.
