Late-manifestation of attention-deficit/hyperactivity disorder in older adults: an observational study.

BACKGROUND: The age of attention-deficit/hyperactivity disorder onset is usually during the first 12 years of life; however, there have been recent reports of late-onset attention-deficit/hyperactivity disorder. These reports have been limited to that of young adults, and details in older adults remain unknown. As such, we had previously presented the first case report of "very" late-onset attention-deficit/hyperactivity disorder, wherein the symptoms presented in senile age. In this observational study, we aimed to investigate the prevalence and clinical features of such attention-deficit/hyperactivity disorders in older adults visiting our dementia clinic. METHODS: Four hundred forty-six consecutive patients visiting our specialty outpatient clinic for dementia during the 2-year period from April 1, 2015 to March 31, 2017 were included in this study. First, the patients were examined for the presence or absence of dementia in our specialty outpatient clinic for dementia. Those not diagnosed with dementia were examined for the presence or absence of attention-deficit/hyperactivity disorder in our specialty outpatient clinic for developmental disorders. Finally, these patients who were diagnosed with attention-deficit/hyperactivity disorder were investigated in detail to clarify their clinical characteristics. RESULTS: Of 446 patients (246 women and 200 men), 7 patients were finally diagnosed with attention-deficit/hyperactivity disorder. Although these 7 patients were initially suspected to have Alzheimer's disease (considering their age, 6 of these 7 patients were suspected to have early onset Alzheimer's disease), it was found that these symptoms were due to attention-deficit/hyperactivity disorder. These patients had four characteristics in common: (1) they were significantly younger than the complete study population; (2) they predominantly showed inattention-related symptoms; (3) they showed latent manifestation; and (4) they experienced a stressful life event before manifestation. CONCLUSIONS: Our previous case report suggested that very late-onset attention-deficit/hyperactivity disorder patients could be incorrectly diagnosed with dementia. In this observational study, 1.6% of patients who were initially suspected of having dementia were actually diagnosed with attention-deficit/hyperactivity disorder. This study also showed that the "late-onset" described in our previous report would be better described as "late-manifestation." A clinician should consider late-manifestation of attention-deficit/hyperactivity disorder in the differential diagnosis when encountering dementia patients, especially early onset Alzheimer's disease.

Late-onset attention-deficit/hyperactivity disorder as a differential diagnosis of dementia: a case report.

BACKGROUND: Although adult attention-deficit/hyperactivity disorder has recently gained increased attention, few reports on attention-deficit/hyperactivity disorder in the pre-elderly or elderly have been published. Here, we present the case of a patient with attention-deficit/hyperactivity disorder who gradually developed dementia-like symptoms as she aged, which initially made her condition difficult to distinguish from early onset Alzheimer's disease. This report illustrates that some types of attention-deficit/hyperactivity disorder may be misdiagnosed as dementia. CASE PRESENTATION: The patient was a 58-year-old woman. Although she presented with a tendency for inattentiveness and forgetfulness since childhood, she did not have a history of psychiatric disorders prior to consultation. Around the age of 52 years, her inattentiveness and forgetfulness gradually progressed, and at 57 years of age, she became inattentive and forgetful that it interfered with her work and daily life. For example, she forgot meetings with important clients and transferred money to the wrong bank account; these failures resulted in poor management of her company. At home, she experienced increasing difficulties with remembering prior commitments with her family and misplacing items, which her family members noticed. With the encouragement of her family and employees, who worried that she was suffering from dementia, she visited our memory clinic, whereby she was suspected of having early onset Alzheimer's disease. However, neuropsychological tests and brain imaging evaluations did not reveal any significant abnormalities. After dismissing various possible diagnoses, including dementia, other organic diseases, mood disorders, and delirium, we diagnosed her with attention-deficit/hyperactivity disorder. Treatment with 18 mg of methylphenidate was initiated, and significant improvements in her symptoms were observed within a few days; for example, she stopped losing her things, was able to concentrate for long durations, and could complete more tasks than she could before treatment. Since initiating treatment, she has returned to work and has been able to perform her daily activities without difficulty. CONCLUSIONS: This case supports that some patients with late-onset attention-deficit/hyperactivity disorder may gradually develop dementia-like symptoms during the pre-elderly and elderly stages of life. Therefore, clinicians should consider late-onset attention-deficit/hyperactivity disorder as a differential diagnosis of some types of dementias.

Delusional parasitosis in dementia with Lewy bodies: a case report.

BACKGROUND: Dementia with Lewy bodies (DLB) is characterized by fluctuating cognitive impairments, recurrent visual hallucinations, the motor symptoms of parkinsonism and REM sleep behavior disorder. Various neuropsychiatric symptoms including hallucination and delusions occur frequently; however, delusional parasitosis is rare in DLB. Here, we report a case of DLB patient with delusional parasitosis. CASE PRESENTATION: The patient was an 89-year-old woman. At the age of 88, she began to complain her oral cenesthopathy, and developed cognitive decline, delusional parasitosis and parkinsonism. As a result of examination, she was diagnosed as DLB and treated with combination of donepezil 5 mg/day and aripiprazole 1.5 mg/day, and her complaint was disappeared. CONCLUSIONS: Further studies are needed to investigate the association between delusional parasitosis and underlying pathophysiology of DLB, and the utility of antipsychotics for delusional parasitosis in DLB has to be examined through more cases.

Effect of lamotrigine in the treatment of bipolar depression with psychotic features: a case report.

BACKGROUND: Major depressive episodes with psychotic features are more common in bipolar disorder than in major depressive disorder; however, there is little information on the optimal treatment for bipolar depression with psychotic features. CASE PRESENTATION: The patient was a 69-year-old man. At the age of 66, he was admitted to the hospital for the treatment of bipolar depression with psychotic features. He was treated with a combination therapy of antipsychotics and antidepressants during long-term hospitalization. At the age of 69, he relapsed and was admitted to the hospital again. He was initially treated with olanzapine and lithium for the treatment of bipolar depression with psychotic features. He partially responded to the combination therapy, and psychomotor retardation and delusion of guilt disappeared; however, he developed psychomotor agitation and delusion of persecution, which was a mood-incongruent psychotic feature. Finally, he fully recovered with an additional dosage of lamotrigine, and had no experience of relapse after discontinuation of olanzapine. CONCLUSIONS: This case report implicates the utility of lamotrigine for bipolar depression with psychotic features, and further studies are needed to establish the optimal treatment.

Association between depression, examination-related stressors, and sense of coherence: the Ronin-Sei study.

AIMS: In the Japanese education system, students who fail university entrance exam often go to special preparatory schools to prepare for the following year's exam. These students are called ronin-sei. The purpose of this study was to clarify: (i) depression and somatic complaints in ronin-sei; and (ii) the association between depression, examination-related stressors, and sense of coherence (SOC). METHODS: A total of 914 ronin-sei from two preparatory schools were asked to answer a self-rating questionnaire. Depression was measured using the Center for Epidemiologic Studies Depression Scale (CES-D) and SOC was measured using the SOC-13 Scale. RESULTS: Overall, 57.9% of subjects were considered to have depression (CES-D ≥ 16) and 19.8% had severe depression (CES-D ≥ 26). Higher CES-D scores were associated with a higher rate of somatic complaints. In hierarchical logistic regression analysis, having no one to talk to about his/her worries and having parents who disagree about the first-choice of university and faculty were independent risk factors for depression and severe depression, respectively, even after controlling for SOC. CONCLUSIONS: Preparatory school students have various somatic complaints, and their depression is in part related to examination-related stressors. To maintain mental health, it is important to enhance SOC, to understand their examination-related stressors and to provide adequate support for these students.

Association of advanced glycation end products with A549 cells, a human pulmonary epithelial cell line, is mediated by a receptor distinct from the scavenger receptor family and RAGE.

Cellular interactions with advanced glycation end products (AGE)-modified proteins are known to induce several biological responses, not only endocytic uptake and degradation, but also the induction of cytokines and growth factors, combined responses that may be linked to the development of diabetic vascular complications. In this study we demonstrate that A549 cells, a human pulmonary epithelial cell line, possess a specific binding site for AGE-modified bovine serum albumin (AGE-BSA) (K(d) = 27.8 nM), and additionally for EN-RAGE (extracellular newly identified RAGE binding protein) (K(d) = 118 nM). Western blot and RT-PCR analysis showed that RAGE (receptor for AGE) is highly expressed on A549 cells, while the expression of other known AGE-receptors such as galectin-3 and SR-A (class A scavenger receptor), are below the level of detection. The binding of (125)I-AGE-BSA to these cells is inhibited by unlabeled AGE-BSA, but not by EN-RAGE. In contrast, the binding of (125)I-EN-RAGE is significantly inhibited by unlabeled EN-RAGE and soluble RAGE, but not by AGE-BSA. Our results indicate that A549 cells possess at least two binding sites, one specific for EN-RAGE and the other specific for AGE-BSA. The latter receptor on A549 cells is distinct from the scavenger receptor family and RAGE.

Effects of testosterone therapy on bipolar disorder with Klinefelter syndrome.

Klinefelter syndrome (KS) is widely associated with cognitive impairment and language problems. KS patients may also exhibit psychiatric symptoms. We present the case of an 18-year-old man with KS who experienced rapidly repeating relapses of manic episodes. He was unresponsive to the usual pharmacotherapies for bipolar disorders such as mood stabilizers and second-generation antipsychotics. Mood was eventually improved with testosterone therapy in addition to pharmacotherapy, with no relapse of manic episodes for 3 years after discharge. Testosterone therapy may prevent relapsing manic episodes of bipolar disorder in patients with KS.

Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1) serves as an endothelial receptor for advanced glycation end products (AGE).

Advanced glycation end products (AGE) are known to serve as ligands for the scavenger receptors such as SR-A, CD36 and SR-BI. In the current study, we examined whether AGE is recognized by lectin-like oxidized low density lipoprotein receptor-1 (LOX-1). Cellular binding experiments revealed that AGE-bovine serum albumin (AGE-BSA) showed the specific binding to CHO cells overexpressing bovine LOX-1 (BLOX-1), which was effectively suppressed by an anti-BLOX-1 antibody. Cultured bovine aortic endothelial cells also showed the specific binding for AGE-BSA, which was suppressed by 67% by the anti-BLOX-1 antibody. Thus, LOX-1 is identified as a novel endothelial receptor for AGE.

Nepsilon-(Carboxymethyl)lysine and 3-DG-imidazolone are major AGE structures in protein modification by 3-deoxyglucosone.

The levels of plasma 3-deoxyglucosone (3-DG) increase under hyperglycemic conditions and are associated with the pathogenesis of diabetic complications because of the high reactivity of 3-DG with proteins to form advanced glycation end products (AGE). To investigate potential markers for 3-DG-mediated protein modification in vitro and in vivo, we compared the yield of several 3-DG-derived AGE structures by immunochemical analysis and HPLC and measured their localization in human atherosclerotic lesions. When BSA was incubated with 3-DG at 37 degrees C for up to 4 wk, the amounts of N(epsilon)-(carboxymethyl)lysine (CML) and 3-DG-imidazolone steeply increased with incubation time, whereas the levels of pyrraline and pentosidine increased slightly by day 28. In contrast, significant amounts of pyrraline and pentosidine were also observed when BSA was incubated with 3-DG at 60 degrees C to enhance AGE-formation. In atherosclerotic lesions, CML and 3-DG-imidazolone were found intracellularly in the cytoplasm of most foam cells and extracellularly in the atheromatous core. A weak-positive immunoreaction with pyrraline was found in the extracellular matrix and a few foam cells in aortic intima with atherosclerotic lesions. Our results provide the first evidence that CML and 3-DG-imidazolone are major AGE structures in 3-DG-modified proteins, and that 3-DG-imidazolone provides a better marker for protein modification by 3-DG than pyrraline.

Sleep duration and its association with sleepiness and depression in "ronin-sei" preparatory school students.

PURPOSES: The Japanese word "ronin-sei" refers to a student who has failed their university entrance examination and is preparing to re-take the examination in the following year. We aimed to determine how sleep duration is associated with daytime sleepiness or depression in ronin-sei because impaired daytime performance is known to result from sleep deprivation. METHODS: The participants in this cross-sectional study were 1075 ronin-sei and 285 university students. Sleepiness and depressive symptoms were assessed using the Epworth Sleepiness Scale (ESS) and the Center for Epidemiologic Studies Depression Scale (CES-D), respectively. RESULTS: Ronin-sei had significantly shorter sleep duration and earlier bed- and rise-times than university students. There was no significant difference in CES-D between the groups; however, the ESS score of university students was significantly higher than that of ronin-sei. Ronin-sei who slept for 5 to <6h had higher ESS scores than those who slept for 6 to <7h. The mean CES-D score in ronin-sei who slept <5h was significantly higher than in those who slept for 5 to <6h, from 6 to <7h, and from 7 to <8h. Ronin-sei who slept for more than 8h also had higher depression scores. CONCLUSIONS: Sleep deprivation appears to be common among ronin-sei. Furthermore, a U-shaped relationship was found between sleep duration and depressive symptoms, revealing that ronin-sei who had too little or too much sleep were more likely to exhibit an increase in depressive symptoms.

Relationship among VEGF, VEGF receptor, AGEs, and macrophages in proliferative diabetic retinopathy.

PURPOSE: We studied the roles of vascular endothelial growth factor (VEGF), its receptor (flt-1), advanced glycation end products (AGEs), and macrophages in the development of proliferative diabetic retinopathy. METHODS: Ocular fluid and small specimens of iris and neovascular membrane were obtained from 30 patients who underwent vitreous surgery (19 eyes with proliferative diabetic retinopathy [PDR], 11 eyes with non-diabetic ocular diseases). VEGF and AGE levels in ocular fluid were assayed by ELISA. Immunohistochemical studies of VEGF, flt-1, AGEs, and macrophage were performed on the ocular tissues. RESULTS: The mean VEGF and AGE levels in the vitreous (695.7pg/ml and 2.4mg/ml, respectively) were significantly higher in diabetic than in non-diabetic eyes (25.9pg/ml, p=0.0007 and 1.3mg/ml, p=0.005, respectively). Likewise, in the aqueous humor, VEGF and AGE levels were significantly higher in diabetic than in non-diabetic eyes. VEGF levels in the vitreous and aqueous humor were correlated significantly (r=0.6; p=0.02), but AGEs were not. The VEGF levels were not correlated with AGE levels in the aqueous or vitreous. In the iris, VEGF, AGEs, and macrophages were stained more prominently in the specimens from patients with diabetes than from patients without diabetes, while flt-1 staining did not differ. The Neovascular membranes were stained much more prominently for all (VEGF, flt-1, AGEs and macrophages) even when compared with the iris from patients with diabetes. CONCLUSIONS: By analyzing aqueous and vitreous humor, proliferative membranes, and iris from the same patients, the current clinical study strongly supports previous reports that showed the role of VEGF, macrophages, and AGEs in the development of diabetic proliferative retinopathy. From the results of the current study, we showed that flt-1 plays an important role in the development of retinal neovascular membranes but the role is uncertain in the iris and retina.

Accumulation of imidazolone, pentosidine and N(epsilon)-(carboxymethyl)lysine in hippocampal CA4 pyramidal neurons of aged human brain.

Previous studies from our laboratory demonstrated that N(epsilon)-(carboxymethyl)lysine (CML), one of the major advanced glycation end products (AGE), was accumulated in human pyramidal neurons in the hippocampus in an age-dependent manner. This suggests a potential link between AGE-accumulation and the aging process in neurons. The purpose of the present study was to examine whether this notion could be extended to other AGE structures, such as imidazolone and pentosidine. This was done using 19 human brains that were not affected by dementia. The immunohistochemical survey on distribution in brain tissues of imidazolone and pentosidine was carried out with monoclonal antibodies specific for imidazolone and pentosidine. A parallel control experiment was carried out with anti-CML antibody. The results showed that pentosidine and imidazolone were localized in neurons in different areas of human brain tissue, especially in neurons of CA4 in the hippocampus. The characteristic distribution of pentosidine and imidazolone is very similar to that of CML. Furthermore, when the accumulation of these AGE structures was compared with the age of individual brains it was found that accumulation of imidazolone, pentosidine and CML in the CA4 region increased with age. These findings taken together support the notion that the accumulation of AGE structures in the CA4 region might be closely related to the aging process in neurons.