Association between serum magnesium levels and cognitive function in patients undergoing hemodialysis.

BACKGROUND: The relationship between chronic kidney disease-mineral and bone disorder (CKD-MBD) and cognitive function remains largely unknown. This cross-sectional study aimed to explore the association between CKD-MBD and cognitive function in patients on hemodialysis. METHODS: Hemodialysis patients aged ≥ 65 years without diagnosed dementia were included. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). CKD-MBD markers, serum magnesium, intact parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OHD), fibroblast growth factor (FGF)-23, and soluble α-klotho were measured. RESULTS: Overall, 390 patients with a median age of 74 (interquartile range, 70-80) years, mean serum magnesium level of 2.4 ± 0.3 mg/dL, and median MoCA and MMSE scores of 25 (22-26) and 28 (26-29), respectively, were analyzed. MoCA and MMSE scores were significantly higher (preserved cognitive function) in the high-magnesium group than in the low-magnesium group according to the unadjusted linear regression analysis (ß coefficient [95% confidence interval (CI)] 1.05 [0.19, 1.92], P = 0.017 for MoCA; 1.2 [0.46, 1.94], P = 0.002 for MMSE) and adjusted multivariate analysis with risk factors for dementia (ß coefficient [95% CI] 1.12 [0.22, 2.02], P = 0.015 for MoCA; 0.92 [0.19, 1.65], P = 0.014 for MMSE). CONCLUSIONS: Higher serum magnesium levels might be associated with preserved cognitive function in hemodialysis patients. Conversely, significant associations were not observed between cognitive function and intact PTH, 25-OHD, FGF-23, or soluble α-klotho levels.

Eating problems in people with dementia with Lewy bodies: Associations with various symptoms and the physician's understanding.

OBJECTIVES: Eating problems frequently occur in people with dementia with Lewy bodies (DLB), but few studies have investigated the clinical background of this phenomenon. This study examined the relationship between eating problems and various symptoms of DLB and the relation between the treatment needs for DLB people with eating problems and the understanding of their eating problems by caregivers and physicians. DESIGN, MEASUREMENTS, AND PARTICIPANTS: This was a subanalysis of a cross-sectional, questionnaire-based survey study. Two hundred sixty-one subjects with DLB were divided into subjects with or without eating problems. Logistic or linear regression analysis was used to investigate the factors influencing eating problems. The treatment needs of DLB people for their eating problems and the understanding of these needs by caregivers and physicians were calculated as participant-caregiver and participant-physician kappa coefficient. RESULTS: Of the 261 participants, 27% suffered from eating problems. The presence of eating problems in participants with DLB was related to depression (p = 0.01, OR : 2.19, 95% CI: 1.23-3.91) and apathy (p = 0.01, OR 2.15, 95% CI: 1.20-3.87), while the worsening of eating problems was related to dysphagia (ß = 0.24, p = 0.03), apathy (ß = 0.23, p = 0.05), and nighttime behavior (ß = 0.24, p = 0.04). The participant-physician kappa coefficient for physician understanding of constipation, weight loss, dysphagia, weight gain, and increase in appetite was significantly lower than the corresponding participant-caregiver kappa coefficient (p-value of five symptoms < 0.01). CONCLUSIONS: Physicians need to pay more attention to eating problems and their neuropsychiatric background in the long-term support and management of DLB subjects.

Education level is associated with neuropsychiatric symptoms in patients with amnestic-mild cognitive impairment.

BACKGROUND: We examined differences in the severity of neuropsychiatric symptom (NPS) subsyndromes according to education level among patients with amnestic-mild cognitive impairment (a-MCI) with the aim of identifying patient demographics related to NPS subsyndromes. METHODS: Overall, 140 patients with a-MCI were included. We divided the patients into three groups according to their educational level (primary education, middle education, and high education) and compared their demographics. To explore the severity of NPS subsyndromes according to educational level, we used the Neuropsychiatric Inventory (NPI) after adjustments for the Mini-Mental State Examination (MMSE) score. Finally, NPS subsyndromes that were identified as being related to educational level were further explored using a general linear model (GLM). RESULTS: Significant differences in several demographics were observed among the three groups. Among the NPS subsyndromes, the scores for aggressiveness were significantly higher in the primary and high education groups than in the middle education group, while the apathy/eating problem scores were significantly higher in the primary education group than in the other groups. The GLM analyses showed that aggressiveness was related to marital status and the Zarit Caregiver Burden Interview (ZBI-J) score, while apathy/eating problems were related to the instrumental activities of daily living (IADL) percentage, the ZBI-J score, and the education level in years. CONCLUSIONS: Among NPS subsyndromes, aggressiveness and apathy/eating problems differed according to education level in patients with a-MCI. A GLM analysis suggested that not only education level, but also various other factors should be considered when determining the need for NPS interventions.

Clinicodemographic and Psychosocial Factors Related to Presentation or Severity of Delusions of Theft among Females with Amnestic Mild Cognitive Impairment and Alzheimer's Disease.

Objectives: We examined the clinicodemographic and psychosocial factors that relate to the presentation and severity of delusions of theft among female patients with amnestic mild cognitive impairment (a-MCI) and Alzheimer's disease (AD).Methods: We enrolled a total of 177 female patients with a-MCI or AD, of whom 40 presented with delusions of theft. We compared the differences in clinicodemographic and psychosocial factors of the 40 patients (delusions of theft group) with 50 age- and Mini-Mental State Examination (MMSE)-matched controls without delusions (control group). Furthermore, we identified the factors associated with the presentation of delusions of theft using a general linear model (GLM). The severity of delusions of theft was calculated using the Neuropsychiatric Inventory Questionnaire, and correlations between the clinicodemographic and psychosocial factors were examined.Results: Between the two groups, the delusions of theft group had lower scores on the Physical Self-Maintenance Scale and instrumental activities of daily living (IADL) and higher scores on the Japanese version of the Zarit Caregiver Burden Interview (ZBI-J) than the control group. GLM analysis revealed that the IADL score was related to the presentation of delusions of theft. The severity of delusions of theft correlated with the MMSE and the ZBI-J scores in the delusions of theft group.Conclusions: The two groups had several differences regarding clinicodemographic and psychosocial factors. Furthermore, lower IADL scores were related to symptom presentation. Symptom severity correlated with cognitive functioning and caregiver burden.Clinical Implications: In the determination of treatment or care, differences in these factors should be considered.

Distinct early symptoms in neuropathologically proven frontotemporal lobar degeneration.

OBJECTIVES: Frontotemporal lobar degeneration (FTLD) is associated with accumulation of neurodegeneration-related protein, such as tau, TAR DNA-binding protein 43 (TDP-43), or fused in sarcoma protein (FUS). There have been very few systematic studies of the early symptoms of clinical phenotypes: behavioral variant frontotemporal dementia (bvFTD), semantic variant primary progressive aphasia (svPPA). Clinical subtypes and the patterns of atrophy reflect protein-accumulation patterns, but the relationship between early symptoms and pathological findings remains unclear. METHODS: We retrospectively investigated the clinical records and examined the neuropathology of 39 bvFTD and 6 svPPA patients to identify symptoms appearing within 2 years of the first clinically apparent changes. RESULTS: The bvFTD group consisted of 13 FTLD-tau, 18 FTLD-TDP, and 8 FTLD-FUS, and the svPPA group consisted of 6 FTLD-TDP. Age at death is significantly younger in FTLD-FUS (52.8 ± 12.6; P = 0.0104 < 0.05). Over 50% of bvFTD patients show apathy or inertia, and distinct language features appear early in svPPA. Interestingly, bvFTD and svPPA frequently present additional symptoms, not included in the diagnostic criteria, such as physical signs, reticence, dazed condition, and delusions. Stereotyped behaviors, hyperorality and dietary changes are prominent in FTLD-FUS, while linguistic deficits are greater in FTLD-TDP. CONCLUSIONS: Specific symptoms tend to appear in the early stage of FTLD in each pathological background. They might reflect the morphological features and pathological progression, and should be helpful in the stratification of patients for future therapeutic trials based on the proteinopathies.

Frontotemporal Dementia: A Cross-Cultural Perspective.

It is predictable that syndromes of frontotemporal dementia (FTD) may have a worldwide distribution; however, data available on their incidence and prevalence are variable. This variability most likely reflects disparities across regions in the distribution of the expertise, technology, and resources available for FTD research and care. Important discoveries have been made regarding FTD's phenotypes, genetics, and cultural influences on the expression of symptoms; however, in many countries, there are barriers posed by a dearth of resources. There are pressing needs to further develop research on FTD: including first, population studies designed to fill the gaps in our knowledge about FTD's frequency and risk factors in developing regions and among minority groups in developed countries. It is also necessary to facilitate the psychometric characterization of contemporary diagnostic criteria and their translation to different languages and cultural contexts. Furthermore, much needed is the analysis of differences in the genetic risk factors for FTD, particularly non-Mendelian susceptibility factors. It is hoped that reflections on FTD from an international perspective will spur an extension of the vibrant multicenter collaborations, that exist in North America and Europe, toward new centers to be established and supported in the developing regions of the world.

Sex differences in the severity of neuropsychiatric symptoms and their relationship with clinico-demographic and psychosocial factors in patients with amnestic mild cognitive impairment and mild Alzheimer's disease.

Objectives: We examined differences in the severity of neuropsychiatric symptoms (NPS) according to sex and identified NPS-related clinico-demographic and psychosocial factors among community-living patients with amnestic-mild cognitive impairment (a-MCI) or mild Alzheimer's disease (AD).Method: Overall, 111 patients (44 males, 67 females) with mild a-MCI (n = 64) or mild AD (n = 47) were included. We divided the patients according to sex and compared their clinico-demographic and psychosocial factors, explored the severity of NPS using the subscales from the Neuropsychiatric Inventory-Questionnaire (NPI-Q), and further identified variables related to NPS.Results: Significant differences in several clinico-demographic and psychosocial characteristics were observed between the sexes. The severity of delusions was higher among females (mean, 0.48; SD, 1.60) than males (mean, 0.23; SD, 1.07; p = .02), while the severity of irritability was higher among males (mean, 0.97; SD, 1.92) than females (mean, 0.49; SD, 1.40; p = .03). The severity of delusions among females was related to the duration of cognitive decline (B = 0.37, p = .03), while the severity of irritability among males was related to general cognition (B = -0.40, p = .003).Conclusion: The severity of NPS among patients with a-MCI or mild AD differed according to sex. We identified NPS-related clinico-demographic factors among these patients. Sex differences should be considered when determining the need for NPS interventions.

Anosognosia in patients with Alzheimer's disease: current perspectives.

Alzheimer's disease (AD) is a neurodegenerative disease characterised by neurocognitive impairments, especially memory impairment, as core symptoms linked to reductions in activities of daily life. As marginal symptoms, neuropsychiatric symptoms (NPSs) appear during the progressive course of the disease. A lack of self-awareness (anosognosia) of cognitive and functional impairments is often seen in patients with AD, and associations between anosognosia and other NPSs have been previously reported. To account for anosognosia pathogenesis neurocognitively, the cognitive awareness model (CAM) has been helpful for explaining the stream of events from sensory input to behavioural/affective and metacognitive outputs. According to CAM, there are three types of anosognosia: (i) primary anosognosia, (ii) executive anosognosia, and (iii) mnemonic anosognosia. These types of anosognosia are generated from different neurocognitive modulations leading to metacognitive outputs or behavioural/affective regulations. Primary anosognosia is considered to be caused by deficits in the metacognitive awareness system (MAS). While preserved MAS function is associated with milder depression and anxiety in AD, a severer depressive mood in patients with mild AD can inversely cause self-underestimation. The modulation of executive anosognosia is thought to be associated with dangerous/disinhibition behaviours and apathy among NPS sub-symptoms, via impairments of comparator mechanism (Cm) within the central executive system. Other neurobehavioral reactions linked to self-awareness include 'denying' and 'confabulation', and each of these reactions is thought to be affected by the MAS and a Cm. Denial of one's own memory impairments appears as a defensive reaction to protect against dysphoric feelings, and the confabulatory comment is instantly reaction constructed by fabrications according to misinterpretations of memory information about oneself. Similarly, the innovative development of a theoretical model (CAM) has contributed to explaining the mechanism of anosognosia and some neurobehavioral outputs from a neurocognitive perspective.

Relationships between socio-clinico-demographic factors and global cognitive function in the oldest old living in the Tokyo Metropolitan area: Reanalysis of the Tokyo Oldest Old Survey on Total Health (TOOTH).

BACKGROUND: Despite a steady increase in life expectancy, a few studies have investigated cross-sectional correlates and longitudinal predictors of cognitive function, a core domain of the successful aging, among socio-clinico-demographic factors in the oldest-old exclusively. OBJECTIVES: The aims of this study were to examine socio-clinico-demographic characteristics associated with global cognition and its changes in the oldest-old. METHODS: We reanalyzed a dataset of cognitively preserved community-dwelling subjects aged 85 years and older in the Tokyo Oldest Old Survey on Total Health, a 6-year longitudinal observational study. This study consisted of (1) baseline cross-sectional analyses examining correlates of global cognition (n = 248) among socio-clinico-demographic factors and (2) longitudinal analyses examining baseline predictors for changes of global cognition in 3-year follow-up (n = 195). The Mini-Mental State Examination was used as a screening test to assess global cognition. RESULTS: At baseline, higher weights were related to higher cognitive function in the oldest-old. The baseline predictors of global cognitive decline in 3-year follow-up were higher global cognition, shorter education period, and lower sociocultural activities and lower instrumental activity of daily living, in this order. CONCLUSIONS: The present study suggests that it is crucial to attain higher education during early life and avoid leanness or obesity, participate in sociocultural cognitive activities during late life, and maintain instrumental activity of daily living to preserve optimal cognitive function in the oldest-old, which will facilitate developing prevention strategies for cognitive decline and promoting successful aging in this increasing population.

Anosognosia in mild Alzheimer's disease is correlated with not only neural dysfunction but also compensation.

BACKGROUND: Anosognosia in Alzheimer's disease (AD) is a complicated, non-unitary phenomenon. In a clinical setting, patients with mild AD often preserve their awareness partially. We hypothesized that compensation, as well as neural dysfunction, could be correlated with anosognosia in mild AD. METHODS: The severity of anosognosia was evaluated using the Anosognosia Questionnaire for Dementia in 37 subjects with mild AD or mild cognitive impairment due to AD. The subjects also underwent single-photon emission computed tomography with N-isopropyl-p-[123 I]iodoamphetamine. Correlation between the severity of anosognosia and perfusion was assessed, and anosognosia (+) and (-) groups were compared. RESULTS: The severity of anosognosia was relatively mild; the mean Anosognosia Questionnaire for Dementia score was 6.76 ± 14.16. Subjects were divided into two groups: anosognosia (+) (n = 11) and anosognosia (-) (n = 26). In the single-photon emission computed tomography data analysis, the severity of anosognosia was correlated with both lower regional cerebral blood flows of the right prefrontal cortex and higher regional cerebral blood flows of the parietal cortex, especially the left temporo-parietal junction. CONCLUSIONS: Our results suggest that anosognosia in mild AD could be correlated with compensation as well as neural dysfunction. We speculate that this compensation may be related to the retrieval of outdated autobiographical memory.

Psychosocial or clinico-demographic factors related to neuropsychiatric symptoms in patients with Alzheimer's disease needing interventional treatment: analysis of the CATIE-AD study.

OBJECTIVE: This study sought to determine psychosocial and clinico-demographic factors related to each symptomatic cluster (i.e., aggressiveness, psychosis, apathy/eating problems, and emotion/disinhibition) of neuropsychiatric symptoms (NPSs) in patients with Alzheimer's disease (AD) needing interventional treatment against their agitation or psychotic symptoms. These clusters were classified from 12 Neuropsychiatric Inventory (NPI) subscores in our previous study using the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) dataset. METHODS: Based on clinical data from 421 AD outpatients with agitation or psychotic symptoms needed interventional treatment enrolled in the CATIE-AD, we conducted logistic regression analyses to examine the relationships between each symptomatic cluster and three psychosocial (marital status, residence, and caregivers' burden) and nine clinico-demographic (age, gender, education year, general cognition, activity of daily living [ADL], general medical health, race, and intake of anti-dementia drugs or psychotropics) factors. RESULTS: While no factor contributed to aggressiveness, psychosis was associated with several clinico-demographic factors: female gender, non-Caucasian race, and lower cognitive function. Apathy/eating problems was associated with more severe caregiver burden, living in one's own home, lower ADL level, and male gender, while emotion/disinhibition was predicted by more severe caregiver burden, lower education level, not-married status, and younger age. CONCLUSIONS: Among the four NPS clusters, apathy/eating problems and emotion/disinhibition were associated with psychosocial as well as clinico-demographic factors in AD patients with psychotic symptoms or agitation needed interventional treatment. Copyright © 2016 John Wiley & Sons, Ltd.

Genetic association between RAGE polymorphisms and Alzheimer's disease and Lewy body dementias in a Japanese cohort: a case-control study.

BACKGROUND/AIMS: Interaction of receptor for advanced glycation end products (RAGE) with amyloid-ß increases amplification of oxidative stress and plays pathological roles in Alzheimer's disease (AD). Oxidative stress leads to α-synuclein aggregation and is also a major contributing factor in the pathogenesis of Lewy body dementias (LBDs). Therefore, we aimed to investigate whether RAGE gene polymorphisms were associated with AD and LBDs. METHODS: Four single nucleotide polymorphisms (SNPs)-rs1800624, rs1800625, rs184003, and rs2070600-of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBDs patients, and 105 age-matched controls. RESULTS: Linkage disequilibrium (LD) examination showed strong LD from rs1800624 to rs2070600 on the gene (1.1 kb) in our cases in Japan. Rs184003 was associated with an increased risk of AD. Although there were no statistical associations for the other three SNPs, haplotypic analyses detected genetic associations between AD and the RAGE gene. Although relatively few cases were studied, results from the SNPs showed that they did not modify the risk of developing LBDs in the Japanese population. CONCLUSION: Our findings suggested that polymorphisms in the RAGE gene are involved in genetic susceptibility to AD. Copyright © 2016 John Wiley & Sons, Ltd.

Benzodiazepine Use Attenuates Cortical ß-Amyloid and is Not Associated with Progressive Cognitive Decline in Nondemented Elderly Adults: A Pilot Study Using F18-Florbetapir Positron Emission Tomography.

OBJECTIVE: It is inconclusive as to whether benzodiazepines (BZDs) are related to cognitive deterioration in the elderly populations. Animal studies suggest that γ-aminobutyric acid A receptor agonists, such as BZDs, may prevent Aß-neurotoxicity and reduce ß-amyloid (Aß). However, no studies have investigated the effects of BZD use on Aß in humans. METHODS: This cross-sectional, prospective study using Alzheimer's Disease Neuroimaging Initiative sites in the United States and Canada on nondemented elderly adults between 55 and 90 years of age assessed cortical Aß levels by positron emission tomography radiotracer F18-Florbetapir. Changes in global cognitive function and verbal memory performance over 2 years were assessed using scores on Montreal Cognitive Assessment and five domains of Rey Auditory Verbal Learning Test, respectively. RESULTS: Previous BZD users (N = 15) had lower cortical Aß levels in frontal (F(1, 26) = 8.82, p = 0.006), cingulate (F(1, 26) = 8.58, p = 0.007), parietal (F(1, 26) = 7.31, p = 0.012), and temporal (F(1, 26) = 7.67, p = 0.010) regions compared with matched BZD nonusers (N = 15), after controlling for history of psychiatric disorders and antidepressant use. Also, no differences were found in global cognitive function and changes in cortical Aß over 2 years between continuous BZD users (N = 15) andthe matched nonuser group (N = 15). CONCLUSION: Previous BZD use was associated with lower cortical Aß levels in nondemented elderly control subjects. Future studies with larger samples are required to replicate our findings.

When a Little Knowledge Can Be Dangerous: False-Positive Diagnosis of Behavioral Variant Frontotemporal Dementia among Community Clinicians.

BACKGROUND: Accurate diagnosis of behavioral variant frontotemporal dementia (bvFTD) is important as patients' behavioral symptoms have profound implications for their families and communities. Since the diagnosis of bvFTD derives from behavioral features, accurate identification of patients can be difficult for non-specialists. Concrete rates of diagnostic accuracy among non-specialists are unavailable. METHODS: To examine the accuracy of community clinicians' diagnoses of bvFTD and to identify patient characteristics leading to misdiagnosis, we reviewed the charts and referral letters of 3,578 patients who were seen at our specialized center. Referral diagnosis and reasons, manifesting symptoms, demographic data, Mini-Mental State Examination score, Clinical Dementia Rating score and Neuropsychiatric Inventory score were extracted. RESULTS: 60% of patients assigned a single diagnosis of bvFTD by community clinicians did not have bvFTD according to specialists. Compared to specialist-confirmed bvFTD patients, false bvFTD patients were more likely to be depressed and to be non-Caucasian, showed less euphoria, apathy, disinhibition and abnormal eating behaviors, had milder disease severity and better overall cognition. bvFTD was mentioned by referring clinicians in 86% of specialist-confirmed bvFTD cases, but missed cases were called Alzheimer's, Parkinson's or Huntington's disease, or progressive aphasia. CONCLUSION: These results revealed a widespread lack of familiarity with core diagnostic symptoms among non-specialists and suggest that community clinicians require specialized diagnostic support before providing a definitive diagnosis of bvFTD.

Executive Dysfunction Correlated With 2-Year Treatment Response in Patients With Late-Life Undifferentiated Somatoform Disorders.

BACKGROUND: Late-life somatoform disorders (SDs) are characterized by various aging-associated factors. Recently, cognitive decline, including executive dysfunction, has been reported as an etiological factor of late-life SDs. The response to treatment for late-life SDs varies from one patient to another. Treatment strategies for late-life SDs require these etiological factors to be considered. We hypothesized that the treatment response in patients with late-life SDs was associated with executive dysfunction. OBJECTIVE: The aim of the present study was to confirm the changes in disease severity over a 2-year follow-up period and to determine which etiological factors are related to the treatment response in patients with late-life SDs. METHODS: We examined 55 patients with late-life SDs who were treated with pharmacotherapy and supportive psychotherapy at baseline. The changes in the disease severity and cognitive profiles over a 2-year follow-up period were evaluated. Additionally, we investigated which etiological factors at baseline were related to treatment resistance. RESULTS: Of the 55 patients who were enrolled in the present study, 31 completed the 2-year follow-up period. Overall, the disease severity improved significantly in patients with late-life SDs. On the contrary, executive function decreased throughout the research period. Moreover, we found that executive dysfunction and the presence of hyperlipidemia at baseline were related to treatment resistance. CONCLUSIONS: These results suggest that aging-associated etiological factors be considered for the treatment of late-life SDs.

Classifying eating-related problems among institutionalized people with dementia.

AIMS: Various eating-related problems are commonly observed among people with dementia, and these problems place a huge burden on the caregivers. An appropriate classification of these problems is important in order to understand their underlying mechanisms and to develop a therapeutic approach for managing them. The aim of this study was to develop a possible classification of eating-related problems and to reveal the background factors affecting each of these problems across various conditions causing dementia. METHODS: The participants were 208 institutionalized patients with a diagnosis of dementia. Care staff were asked to report all kinds of eating-related problems that they observed. After the nurses' responses were analyzed, 24 items relating to eating-related problems were extracted. A factor analysis of these 24 items was conducted, followed by a logistic regression analysis to investigate the independent variables that most affected each of the eating-related factors. RESULTS: Four factors were obtained. Factor 1 was overeating, factor 2 was swallowing problems, factor 3 was decrease in appetite, and factor 4 was obsession with food. Each factor was associated with different background variables, including Mini-Mental State Examination scores, Clinical Dementia Ratings, and neuropsychiatric symptoms. CONCLUSIONS: This study suggests that eating-related problems are common across conditions causing dementia and should be separately considered in order to understand their underlying mechanisms.

Clinicopathological Study of Patients With C9ORF72-Associated Frontotemporal Dementia Presenting With Delusions.

BACKGROUND: Several clinical studies point to a high prevalence of psychotic symptoms in frontotemporal dementia associated with C9ORF72 mutations, but clinicopathological studies addressing the association between C9ORF72 mutations and delusions are lacking. METHOD: Seventeen patients with pathologically proven frontotemporal lobar degeneration (FTLD) associated with C9ORF72 mutations were identified from Neurodegenerative Disease Brain Bank. Of the 17 cases with C9ORF72 mutation, 4 exhibited well-defined delusions. The clinical history, neurological examination, neuropsychological testing, neuroimaging analysis, and postmortem assessment of the patients with delusions were evaluated and compared with the other cases. RESULT: The content of the delusions was mixed including persecution, infidelity, and grandiosity. All cases showed parkinsonism; voxel-based morphometry analysis showed greater precuneus atrophy in patients with delusions than those without delusions. All 4 had unclassifiable FTLD with TAR DNA-binding protein inclusions, with characteristics of both type A and type B. Three cases had additional τ pathology and another had α-synuclein pathology. CONCLUSION: C9ORF72 carriers with well-defined delusions likely associated with additional pathologies and parietal atrophy in neuroimaging. Patients presenting with middle-aged onset of delusions should be screened for C9ORF72 mutations, especially if family history and parkinsonism are present.

Cognitive Dysfunction in Patients With Late-Life Somatic Symptom Disorder: A Comparison According to Disease Severity.

BACKGROUND: Late-life somatic symptom disorder (SSD) is characterized by various aging-associated factors, such as a functional decline, psychosocial problems, and cognitive dysfunction. However, the details of the cognitive dysfunction that occur in late-life SSD are still unknown. OBJECTIVE: The aims of this study were to reveal the cognitive profile of patients with late-life SSD and to evaluate how cognitive dysfunction affects disease severity. METHODS: We compared the cognitive profiles of patients with late-life SSD (n = 40) with those of normal control subjects (n = 21). In addition, we divided the patients with late-life SSD into mild-to-moderate (n = 24) and severe (n = 16) groups and compared the cognitive profiles of the 3 groups. RESULTS: Patients with late-life SSD exhibited a lower Mini-Mental State Examination total score and attention decline. In the 3-group comparison, the severe group had a lower Mini-Mental State Examination score and Frontal Assessment Battery score than the normal control group, whereas no significant difference was seen between the mild-to-moderate and the normal control groups. CONCLUSIONS: Our data suggest that different cognitive patterns may exist depending on disease severity, possibly indicating differences in pathogenesis.

Association between the catechol-O-methyltransferase polymorphism Val158Met and Alzheimer's disease in a Japanese population.

OBJECTIVE: Catechol-O-methyltransferase (COMT) plays an important role in dopamine degradation, which is associated with the pathophysiology of Alzheimer's disease (AD) and alcoholism. A functional COMT polymorphism, Val158Met (rs4680 G > A), affects the onset of AD and is associated with alcohol dependence through dopamine receptor sensitivity in the prefrontal cortex. METHODS: The aim of this case-control study (398 cases and 149 controls) was to investigate whether Val158Met polymorphism influences the onset of AD stratified according to alcohol consumption and apolipoprotein E (APOE) status. We also used single photon-emission computed tomography (SPECT) to analyse 26 patients with AD with the polymorphism. RESULTS: As a function of APOE status, the genotypic frequencies of rs4680 in patients with AD did not differ from those in controls. We detected a significant association between high alcohol consumption in patients with AD (HAC-AD group) and the polymorphism in genotypic and allelic frequencies. Logistic regression analyses demonstrated that the presence of the APOE genotype with rs4680 increased the risk for HAC-AD synergistically. Hyperperfusion in the right sub-lobar insula of patients with the G/G genotype was found compared with that of patients with the G/A genotype. SPECT studies showed a relationship between the polymorphism and compensatory reactions for dysfunctions of dopaminergic neurotransmission in AD pathophysiology. CONCLUSION: Although genetic association between the polymorphism and the onset of AD in a Japanese population were not observed, the polymorphism affected the risk for HAC-AD.