Lung carcinoma-associated cognitive impairment in a patient with Alzheimer's disease pathology: A case report.

A patient with Alzheimer's disease (AD) pathology when cognitive impairment is detected tends to be diagnosed with AD. However, before diagnosing, we make an effort to exclude other diseases, for example, carcinoma.

Longitudinal study of primary progressive aphasia in a patient with pathologically diagnosed Alzheimer's disease: a case report.

BACKGROUND: Alzheimer's disease is a neurodegenerative disease involving the deposition of pathologic amyloid-ß and tau protein in the cerebral cortex. Alzheimer's disease is commonly characterized by progressive impairment of recent memory. Primary progressive aphasia is also often observed in patients with Alzheimer's disease. Moreover, language-associated symptoms, such as primary progressive aphasia, are diverse and varied in Alzheimer's disease. However, nonfluent/agrammatic variant primary progressive aphasia is not generally considered a symptom of Alzheimer's disease. To date, there has been no longitudinal study of primary progressive aphasia in Japanese-speaking patients or in patients speaking other languages with pathologically diagnosed Alzheimer's disease. Here we present a longitudinal study of primary progressive aphasia in a Japanese patient pathologically diagnosed with Alzheimer's disease. CASE PRESENTATION: A 75-year-old Japanese man, whose wife reported that his memory was impaired, also suffered from suspected aphasia. He was pathologically diagnosed with Alzheimer's disease using 11C-Pittsburgh compound-B positron emission tomography and 18F-THK5351 positron emission tomography. Based on clinical observation and the results of the Japanese standard language test of aphasia, he was also diagnosed with nonfluent/agrammatic variant primary progressive aphasia. During the subsequent 2 years, his cognitive impairment, aphasia, and behavioral and psychological symptoms of dementia progressed. Furthermore, progression of pathologic amyloid-ß and tau protein deposition was revealed through 11C-Pittsburgh compound-B positron emission tomography and 18F-THK5351 positron emission tomography. Although the results of [123I] iodoamphetamine single-photon emission computed tomography suggested corticobasal degeneration, this was not observed on the [123I] FP-CIT single-photon emission computed tomography (SPECT) (DaTscan). A previous study had reported that Alzheimer's disease with a nonfluent/agrammatic variant primary progressive aphasia was accompanied by corticobasal degeneration; however, this was not true in our case. CONCLUSIONS: This is possibly the first longitudinal study of nonfluent/agrammatic variant primary progressive aphasia in a Japanese-speaking patient with pathologically diagnosed Alzheimer's disease, but without corticobasal degeneration.

Progressive amnestic cognitive impairment in a middle-aged patient with developmental language disorder: a case report.

BACKGROUND: Developmental disorder and dementia in older adults have been considered unrelated clinical entities because their timing of diagnosis differs greatly; however, recent studies have suggested an association between them. This case describes a middle-aged patient with language disorder exhibiting progressive amnestic cognitive impairment. CASE PRESENTATION: A 44-year-old Japanese man with long-term language dysfunction presented for his first-ever medical evaluation at age 36 years. Although his conversational ability had been impaired since childhood, he was able to graduate from secondary school and gain unskilled employment. At age 36 years, however, his workplace environment became more stressful, which led to behavioral problems that necessitated medical consultation. He consulted two psychiatrists in vain. At age 44 years, the third attending psychiatrist examined him in detail. The major component of his language disorder was amnestic cognitive impairment in the language domain as shown by logical memory subtests of the Wechsler Memory Scale-Revised. Magnetic resonance imaging showed normal findings for his age and no small vessel disease. Global cerebral hypoperfusion versus cerebellar blood flow was shown on (123I) iodoamphetamine single-photon emission computed tomography, and amyloid-ß deposition was negative on positron emission tomography with 11C-Pittsburgh compound B. Pathologic tau accumulation was negative on 18F-THK5351 positron emission tomography imaging. Laboratory tests show no infections, no vitamin deficiencies, and no other diseases that may cause dementia. Clinical features, results of neurocognitive tests and neuroimaging studies showed no well-known neurodegenerative diseases. Collectively, he was diagnosed with language disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. Over a 2-year follow-up period, amnestic cognitive impairment in visual and language domains progressed in parallel with global cerebral hypoperfusion. CONCLUSION: This case suggests a possible link between language disorder as defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria and progressive amnestic cognitive impairment in middle age, which may ultimately lead to dementia, derived from a neurodegenerative disease.

The Landscape Montage Technique for diagnosing frontotemporal dementia starting as primary progressive aphasia: a case report.

BACKGROUND: The Landscape Montage Technique was originally developed by Hisao Nakai, a Japanese psychiatrist, to pursue the possibility and application of a psychotherapeutic approach using drawing for patients with schizophrenia. Drawing was initially adopted to evaluate patients with an impaired ability for verbal expression, particularly for the diagnosis and treatment of patients with schizophrenia. Since its development, the Landscape Montage Technique has been utilized in various clinical settings throughout Japan. This study aimed to evaluate the psychiatric conditions of a patient diagnosed as having primary progressive aphasia using the Landscape Montage Technique at a 3-year follow-up. CASE PRESENTATION: We present the case of a 64-year-old, right-handed Japanese woman initially diagnosed as having logopenic variant primary progressive aphasia or logopenic aphasia. At a 3-year follow-up, logopenic aphasia progressed to behavioral variant frontotemporal dementia or frontotemporal dementia. According to her husband, she began to have speech difficulties approximately 5 years before her first visit. The results of neurocognitive tests suggested mild cognitive impairment or early stages of dementia. Her clinical dementia rating score was 0.5, suggesting a diagnosis of mild cognitive impairment. She had a Raven's Colored Progressive Matrices score of 31 out of 36, which indicated a nonverbal cognitive ability that was greater than the 90th percentile for her age. The Japanese Standard Language Test of Aphasia, which was performed at two points during the follow-up, indicated the possibility for a diagnosis of primary progressive aphasia given the progression of her aphasia. Based on her clinical symptoms and Japanese Standard Language Test of Aphasia results, a diagnosis of logopenic variant primary progressive aphasia was established. Magnetic resonance imaging revealed severe predominant left frontal and anterior temporal atrophy, as well as bilateral parietal atrophy. Amyloid beta deposition was negative. At the 3-year follow-up, logopenic variant primary progressive aphasia had progressed to behavioral variant frontotemporal dementia. However, the Landscape Montage Technique allowed for the diagnosis of behavioral variant frontotemporal dementia only 2 years after baseline. CONCLUSIONS: The present study showed that the Landscape Montage Technique can be useful for diagnosing behavioral variant frontotemporal dementia that starts as logopenic variant primary progressive aphasia at earlier stages.

Tau accumulation in two patients with frontotemporal lobe degeneration showing different types of aphasia using 18F-THK-5351 positron emission tomography: a case report.

ABSTRACTTau deposits in Alzheimer's disease and corticobasal syndrome have been reported using 18F-THK-5351 positron emission tomography (PET). To our knowledge, our study is the first to demonstrate tau deposits in patients with frontotemporal lobe degeneration (FTLD), using 18F-THK-5351 PET. This case report presents two patients, both of whom showed positive Tau deposition using 18F-THK-5351 PET. One patient was diagnosed with semantic variant primary progressive aphasia (PPA) and the other diagnosed with logopenic variant PPA. Our results suggest an association in the pathology of Alzheimer's disease, corticobasal syndrome, and FTLD, and could plan more effective clinical care in advance.

Cognitive impairment before changes appear on [18F]-fluoro-D-glucose positron emission tomography images in a patient with possible early-stage cerebellar-predominant multiple system atrophy.

Multiple system atrophy (MSA) is a sporadic, rapidly progressive neurodegenerative disorder characterized by autonomic dysfunction combined with parkinsonism or cerebellar ataxia. Patients with MSA typically suffer from cognitive disorders and rapid eye movement sleep behaviour disorder. 18 F-fluorodeoxyglucose-positron emission tomography is used to assess MSA. However, the relationship between the clinical features and findings on 18 F-fluorodeoxyglucose-positron emission tomography in patients with MSA has not yet been investigated. Here we report a case of possible early-stage cerebellar-type MSA. We concluded that cerebellar-type MSA or other factors, such as rapid eye movement sleep behaviour disorder or obstructive sleep apnoea cognitive impairment, could appear before changes are visible on 18 F-fluorodeoxyglucose-positron emission tomography images. Additionally, we concluded that the cognitive impairment could derive from cerebellar-type MSA itself, not from other factors such as rapid eye movement sleep behaviour disorder or sleep apnoea syndrome.

Right temporal activation differs between melancholia and nonmelancholic depression: a multichannel near-infrared spectroscopy study.

The aim of this study was to determine whether melancholia differs from nonmelancholic depression in frontotemporal functioning by means of multichannel near-infrared spectroscopy. We recruited 32 major depressive disorder (MDD) patients with melancholic features (MDD-MF), 28 MDD patients with nonmelancholic features (MDD-NMF), and 24 healthy controls. Regional hemodynamic changes induced by a verbal fluency task (VFT) were monitored, and their correlations with depressive symptoms were examined. In comparison with the controls, significant differences were observed in mean oxygenated hemoglobin (oxy-Hb) changes induced by VFT in patients with MDD-MF in 25 channels (p = 0.000-0.047) and in those with MDD-NMF in 12 channels (p = 0.000-0.023). Moreover, patients with MDD-MF had significantly smaller mean oxy-Hb changes than those with MDD-NMF in 8 channels of the right temporal region (p = 0.001-0.048). No significant correlations were observed between mean oxy-Hb changes and the Hamilton rating scale for depression (HAMD) 17 total score in both groups of patients with MDD. On examining each item of HAMD17, psychomotor retardation in patients with MDD-MF showed a significant positive correlation with mean oxy-Hb changes in the right temporal region (ch43; ρ = 0.55; p = 0.001), whereas that in patients with MDD-NMF showed a significant negative correlation with mean oxy-Hb changes in the frontal and left temporal regions in 3 channels (ρ = -0.60 to -0.53; p = 0.000-0.004). In conclusion, our results indicate that melancholia is qualitatively distinct from nonmelancholic depression both clinically and biologically.

[Abnormal eating behaviors in elderly people].

Olfaction of even healthy elderly people is impaired, compared to younger people. This might lead to preference for food in elderly people. Patients having dementia have been reported to show several types of features in eating, according to types of dementia. For example, patients having dementia of Alzheimer's type often show olfaction impairment. Patients having dementia with Lewy bodies often show swallowing problems. Patients having frontotemporal dementia often suffer from binge eating. These features should be considered in caring for patients with dementia.

Memantine treatment for neuropsychiatric symptoms in a patient with probable idiopathic normal pressure hydrocephalus: a case report.

INTRODUCTION: Patients with idiopathic normal pressure hydrocephalus often show neuropsychiatric symptoms besides the triad of 'classic' symptoms. Memantine has been reported to have positive effects on the neuropsychiatric symptoms of patients with Alzheimer's disease and patients with dementia with Lewy bodies. We administered memantine to a Japanese patient with probable idiopathic normal pressure hydrocephalus, hoping that this treatment would have positive effects on the neuropsychiatric symptoms of his idiopathic normal pressure hydrocephalus. CASE PRESENTATION: An 80-year-old right-handed Japanese man was diagnosed as having probable idiopathic normal pressure hydrocephalus and showed neuropsychiatric symptoms as well as the triad of classic symptoms of idiopathic normal pressure hydrocephalus. We treated our patient with memantine by increasing, decreasing, and then again increasing the dose of memantine. We evaluated his neuropsychiatric symptoms using the Neuropsychiatric Inventory at baseline, after the dose was increased to 20mg/day, after the dose was decreased to 5mg/day, and after the dose was increased again to 15mg/day. We simultaneously evaluated the triad of symptoms and conducted neuropsychological tests. In addition, we evaluated the psychological distress of our patient's caregiver using the Zarit Caregiver Burden Interview. CONCLUSIONS: Memantine had positive effects on the neuropsychiatric symptoms of our patient with idiopathic normal pressure hydrocephalus. Although none of his triad of classic symptoms, including cognitive abilities, improved, the psychological distress of our patient's caregiver improved.

The effects of memantine on a patient having preclinical dementia with Lewy bodies.

OBJECTIVE: Memantine has been reported to have positive effects on visual hallucinations and cognition in patients with dementia with Lewy bodies (DLB). We hypothesized that memantine would have similar effects on a patient having Charles Bonnet syndrome, preclinical DLB. METHOD: We evaluated the effect of memantine on visual hallucination, cognitive abilities and so on from baseline to 4 months after the start of medication. RESULTS: Treatment of the patient with memantine resulted in the disappearance of visual hallucinations but could not stop the progression to dementia. CONCLUSIONS: Our results suggested that, for a patient having preclinical DLB, memantine had some degree of positive effects, but the mechanism remains to be revealed.

Different characteristics of cognitive impairment in elderly schizophrenia and Alzheimer's disease in the mild cognitive impairment stage.

We compared indices of the revised version of the Wechsler Memory Scale (WMS-R) and scaled scores of the five subtests of the revised version of the Wechsler Adult Intelligence Scale (WAIS-R) in 30 elderly schizophrenia (ES) patients and 25 Alzheimer's disease (AD) patients in the amnestic mild cognitive impairment (aMCI) stage (AD-aMCI). In the WMS-R, attention/concentration was rated lower and delayed recall was rated higher in ES than in AD-aMCI, although general memory was comparable in the two groups. In WAIS-R, digit symbol substitution, similarity, picture completion, and block design scores were significantly lower in ES than in AD-aMCI, but the information scores were comparable between the two groups. Delayed recall and forgetfulness were less impaired, and attention, working memory and executive function were more impaired in ES than in AD-aMCI. These results should help clinicians to distinguish ES combined with AD-aMCI from ES alone.

Decreased α event-related synchronization in the left posterior temporal cortex in schizophrenia: a magnetoencephalography-beamformer study.

Alpha rhythm is one of the most prominent electromagnetic changes in the brain, and electroencephalography (EEG) alpha reactivity disturbance may sometimes represent an early sign of cerebral dysfunction. Although magnetoencephalography (MEG) has a better spatial resolution than EEG, it has not extensively been used to explore alpha-power change deficits in schizophrenia as a possible neurophysiological marker of the disease. The purpose of this study was to use MEG to identify abnormalities in alpha synchronization induced by eye-closing in schizophrenia patients compared to healthy controls, and to investigate whether alpha reactivity deficits correlate with clinical features of the disorder. MEG data were recorded in 22 schizophrenia patients and 20 age- and gender-matched controls during eyes-open/eyes-closed resting states. Cortical sources of event-related synchronization (ERS) were estimated using multiple source beamformer, and BrainVoyager was used for statistic group analysis. A significant decrease in ERS in the upper alpha band (10-13 Hz) was found in the left posterior temporal region in schizophrenia patients relative to controls, and this activity showed correlation with visual memory scores. This upper alpha ERS deficit may indicate left temporal dysfunction and visual-information processing impairment in schizophrenia, and upon further confirmation it might represent a neurophysiological state marker of the disorder.

KIBRA genetic polymorphism influences episodic memory in Alzheimer's disease, but does not show association with disease in a Japanese cohort.

BACKGROUND/AIMS: A single-nucleotide polymorphism (SNP) in the KIBRA gene, rs17070145, was reported to be significantly associated with episodic memory in cognitively normal cohorts. This observation has expanded genetic studies on KIBRA to Alzheimer's disease (AD). Importantly, the association between KIBRA and episodic memory in AD has never been addressed. In this study, we investigated whether the KIBRA rs17070145 SNP influences AD episodic memory and the disease in a Japanese cohort. METHODS: Blood samples from 346 AD patients and 375 normal cognitive controls were collected and genotyped for rs17070145. Episodic memory was measured in 32 AD patients, diagnosed for the first time, by use of the Rivermead Behavioral Memory Test (RBMT). RESULTS: We found that KIBRA C allele carriers scored significantly lower than KIBRA non-C carriers on both RBMT total profile score (p = 0.042, effect size = 0.84) and RBMT total screening score (p < 0.001, effect size = 1.42). The KIBRA gene did not show association with AD in our Japanese cohort. CONCLUSION: Our results evidence a strong association between the KIBRA gene and episodic memory impairment in AD, but show no influence on AD in our Japanese cohort. We propose that KIBRA might have an effect similar to cognitive reserve.

The impact of a genome-wide supported psychosis variant in the ZNF804A gene on memory function in schizophrenia.

A recent genome-wide association study showed that a variant (rs1344706) in the ZNF804A gene was associated with schizophrenia and bipolar disorder. Replication studies supported the evidence for association between this variant in the ZNF804A gene and schizophrenia and that this variant is the most likely susceptibility variant. Subsequent functional magnetic resonance imaging studies in healthy subjects demonstrated the association of the high-risk ZNF804A variant with neural activation during a memory task and a theory of mind task. As these cognitive performances are disturbed in patients with schizophrenia, this gene may play a role in cognitive dysfunction in schizophrenia. The aim of the current study was to investigate the potential relationship between this ZNF804A polymorphism and memory function. The effects of the high-risk ZNF804A genotype, diagnosis, and genotype-diagnosis interaction on verbal memory, visual memory (VisM), attention/concentration, and delayed recall (measured by the Wechsler Memory Scale-Revised) were analyzed by two-way analysis of covariance in 113 patients with schizophrenia and 184 healthy subjects. Consistent with previous studies, patients with schizophrenia exhibited poorer performance on all indices as compared to healthy control subjects (P < 0.001). A significant ZNF804A genotype-diagnosis interaction was found for VisM performance (P = 0.0012). Patients with the high-risk T/T genotype scored significantly lower on VisM than G carriers did (P = 0.018). In contrast, there was no genotype effect for any index in the healthy control subjects (P > 0.05). Our data suggest that rs1344706 may be related to memory dysfunction in schizophrenia. © 2010 Wiley-Liss, Inc.

Global cerebral hypoperfusion in preclinical stage of idiopathic normal pressure hydrocephalus.

In patients with idiopathic normal pressure hydrocephalus (iNPH), ventriculomegaly and narrowed subarachnoid spaces at the high convexity appear in magnetic resonance (MR) images before the occurrence of objective symptoms. In addition, quantitative regional cerebral blood flow (rCBF) has been reported to be reduced in iNPH patients with objective symptoms. To determine whether reduced rCBF is responsible for the appearance of symptoms, we compared rCBF in patients with suspected iNPH with no objective triad symptoms (NOS), iNPH patients with apparent objective triad symptoms (AOS) and normal control subjects (NC). Regional CBF was quantified in 35 Regions-of-interest (ROIs) by 123I-IMP single photon emission computed tomography (SPECT) using the autoradiography (ARG) method. Multiple comparisons showed that, in all brain regions examined except for in the frontal white matter, rCBF in the NOS group was significantly lower than that in the NC group, but in all brain regions, not significantly different from that of the AOS group. These results suggest that factors other than rCBF in the resting state are responsible for the occurrence of objective symptoms of iNPH.

[Language and semantic memory impairment in a patient with motor neuron disease and semantic dementia: a case report].

We report the rare case of a 59-year-old man with motor neuron disease and semantic dementia (SD-MND); SD-MND was in a very early stage, and its clinical progression, especially with regard to language impairment, and abnormalities on neuroimages were evaluated for 3 years. The patient complained only of difficulties in recalling names of acquaintances and in writing kanji characters. After 1 year, he experienced difficulty in describing common objects. He developed two-way anomia only in some words, which varied from day to day. His anomia was not category-specific and was noted even with respect to words that describe color. In addition to experiencing difficulty in writing kanji characters, he experienced difficulty in writing kana characters. Muscle atrophy was observed, and he experienced weakness in his limbs, especially in the right upper limb; however, bulbar symptoms were not observed. At this point, he fulfilled the diagnostic criteria for MND. In the next year, semantic memory impairment became apparent, and he was subsequently diagnosed with SD. Deterioration in his ability to name objects in all categories, except body parts, was noted. Further, the ability of writing both kana and kanji characters was increasingly impaired. He developed bulbar symptoms and experienced increased muscle weakness. The characteristics of this patient differed from those of SD patients without MND with regard to the difficulty in writing kana characters and naming colors even though the SD-MND was in the early stage. Further, the pattern of brain hypoperfusion was different from that observed for SD patients without MND. In the case of this patient, brain hypoperfusion was found not only in the left anterior temporal lobe but also in the frontal lobe. The characteristics of his language symptoms might be related to the specific pattern of brain hypoperfusion, which might be commonly observed in patients with dementia and MND.

Neuropsychiatric symptoms in patients with idiopathic normal pressure hydrocephalus.

OBJECTIVE: To clarify the characteristics of neuropsychiatric symptoms in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Neuropsychiatric symptoms of 64 iNPH patients with mild triad symptoms from three kinds of hospitals were evaluated with the Neuropsychiatric Inventory (NPI) and compared with 126 patients with Alzheimer's disease (AD). RESULTS: The most frequently observed neuropsychiatric symptom in the iNPH patients was apathy followed by anxiety and aggression. No symptom was more prevalent or more severe in iNPH than in AD. The severity of cognitive impairment was correlated with both aberrant motor activity and apathy. CONCLUSIONS: Neuropsychiatric symptoms were mild in patients with iNPH and apathy was the most prevalent symptom. The correlation between neuropsychiatric symptoms and cognitive impairment in iNPH appears to arise from a common pathology in the frontal lobe.

Neuroimaging studies in patients with Charles Bonnet Syndrome.

Charles Bonnet Syndrome (CBS) is characterized by complex formed and recurrent visual hallucinations in psychologically normal people, and is often associated with eye pathology. Many psychiatrists have taken an interest in CBS because this syndrome could provide clues to the mechanisms underlying visual hallucinations. In the present paper, we review previous neuroimaging studies in patients with CBS and summarize the results of these studies. There could be a fundamental dysfunction in the primary and secondary visual cortices in some patients with CBS, and transient cortical activation occurs in the inferior lateral temporal cortex during the appearance of visual hallucinations in CBS patients. External visual stimuli are perceived in the retina and are transmitted to the primary visual cortex (Brodmann area (BA) 17). The stimuli are transmitted from BA 17 to the secondary visual cortex (BA 18) and then to the visual association cortices (BA 19 and BA 37). In general, our perception of external visual stimuli normally has an inhibitory effect on the endogenous activation of the visual cortex. Visual loss due to certain conditions, of which eye pathology is the most commonly postulated in CBS patients, produces a state of sensory deprivation that releases the visual cortex from regulation by external stimuli, resulting in visual hallucinations (cortical release phenomenon). The results of previous neuroimaging studies suggest that the cortical release phenomenon hypothesis for the occurrence of visual hallucinations in patients with CBS is plausible. In addition, the results indicate that not only eye pathology, but also dysfunction in the primary and secondary visual cortices could result in deprivation of external visual stimuli.