Multi-Institutional Prospective Cohort Study of Patients With Pulmonary Hypertension Associated With Respiratory Diseases.

BACKGROUND: There is limited evidence for pulmonary arterial hypertension (PAH)-targeted therapy in patients with pulmonary hypertension associated with respiratory disease (R-PH). Therefore, we conducted a multicenter prospective study of patients with R-PH to examine real-world characteristics of responders by evaluating demographics, treatment backgrounds, and prognosis.Methods and Results:Among the 281 patients with R-PH included in this study, there was a treatment-naïve cohort of 183 patients with normal pulmonary arterial wedge pressure and 1 of 4 major diseases (chronic obstructive pulmonary diseases, interstitial pneumonia [IP], IP with connective tissue disease, or combined pulmonary fibrosis with emphysema); 43% of patients had mild ventilatory impairment (MVI), whereas 52% had a severe form of PH. 68% received PAH-targeted therapies (mainly phosphodiesterase-5 inhibitors). Among patients with MVI, those treated initially (i.e., within 2 months of the first right heart catheterization) had better survival than patients not treated initially (3-year survival 70.6% vs. 34.2%; P=0.01); there was no significant difference in survival in the group with severe ventilatory impairment (49.6% vs. 32.1%; P=0.38). Responders to PAH-targeted therapy were more prevalent in the group with MVI. CONCLUSIONS: This first Japanese registry of R-PH showed that a high proportion of patients with MVI (PAH phenotype) had better survival if they received initial treatment with PAH-targeted therapies. Responders were predominant in the group with MVI.

Predictors of Long-term Outcomes in Patients With Connective Tissue Disease Associated With Pulmonary Arterial Hypertension.

BACKGROUND/OBJECTIVE: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary arterial pressure and pulmonary vascular resistance that can lead to right-sided heart failure. Connective tissue disease-associated PAH (CTD-PAH) often has poorer outcomes than idiopathic or hereditary PAH, suggesting the presence of non-PAH factors that could affect the prognoses. This cohort study aimed to identify prognostic factors for CTD-PAH management. METHODS: Medical records from April 1999 to November 2014 were reviewed to determine the time from treatment initiation to the occurrence of a clinically worsening event and the time elapsed until death. Data at baseline and the final assessment were used to identify prognostic factors associated with events using univariate and multivariate analyses by the stepwise Cox regression method. RESULTS: In 36 patients with CTD-PAH analyzed, the proportions with no clinically worsening events at 1, 2, and 3 years after treatment initiation were 62%, 52%, and 45%, respectively, with survival rates of 88%, 77%, and 77%, respectively. The regression model showed that reduced hemoglobin at baseline, reduced qR pattern in electrocardiogram lead V1, increased 60-minute erythrocyte sedimentation rate, and increased mean pulmonary arterial pressure at the final assessment were risk factors that were significantly associated with clinical worsening. For survival, no prognostic factor was identifiable. CONCLUSIONS: Hemodynamic and non-PAH factors, such as anemia, nutritional status, and inflammatory activity of the underlying CTD, which are not listed in the risk assessment table of PAH guidelines, should be strictly controlled to improve the prognosis of patients with CTD-PAH. A more multifactorial treatment strategy should be developed.

Predictive model of bosentan-induced liver toxicity in Japanese patients with pulmonary arterial hypertension.

Bosentan, an endothelin receptor antagonist, has been widely used as a first-line medication for the treatment of pulmonary arterial hypertension (PAH). It has been shown to improve symptoms of hypertension, exercise capacity, and hemodynamics and prolong time to clinical worsening. However, liver dysfunction is a major side effect of bosentan treatment that could hamper the optimal management of patients with PAH. Previously, we demonstrated, using drug metabolism enzymes and transporters analysis, that the carbohydrate sulfotransferase 3 (CHST3) and CHST13 alleles are significantly more frequent in patients with elevated aminotransferases during therapy with bosentan than they are in patients without liver toxicity. In addition, we constructed a pharmacogenomics model to predict bosentan-induced liver injury in patients with PAH using two single-nucleotide polymorphisms and two nongenetic factors. The purpose of the present study was to externally validate the predictive model of bosentan-induced liver toxicity in Japanese patients. We evaluated five cases of patients treated with bosentan, and one presented with liver dysfunction. We applied mutation alleles of CHST3 and CHST13, serum creatinine, and age to our model to predict liver dysfunction. The sensitivity and specificity were calculated as 100% and 50%, respectively. Considering that PAH is a rare disease, multicenter collaboration would be necessary to validate our model.

CHST3 and CHST13 polymorphisms as predictors of bosentan-induced liver toxicity in Japanese patients with pulmonary arterial hypertension.

Bosentan, an endothelin receptor antagonist, has been widely used as a first-line drug for the treatment of pulmonary arterial hypertension (PAH). In addition, bosentan is approved for patients with digital ulcers related to systemic sclerosis. Liver dysfunction is a major adverse effect of bosentan and may lead to discontinuation of therapy. The purpose of this study was to identify genomic biomarkers to predict bosentan-induced liver injury. A total of 69 PAH patients were recruited into the study. An exploratory analysis of 1936 single-nucleotide polymorphisms (SNPs) in 231 genes involved in absorption, distribution, metabolism, and elimination of multiple medications using Affimetrix DMET™ (Drug Metabolism Enzymes and Transporters) chips was performed. We extracted 16 SNPs (P < 0.05) using the Jonckheere-Terpstra trend test and multiplex logistic analysis; we identified two SNPs in two genes, CHST3 and CHST13, which are responsible for proteoglycan sulfation and were significantly associated with bosentan-induced liver injury. We constructed a predictive model for bosentan-induced liver injury (area under the curve [AUC]: 0.89, sensitivity: 82.61%, specificity: 86.05%) via receiver operating curve (ROC) analysis using 2 SNPs and 2 non-genetic factors. Two SNPs were identified as potential predictive markers for bosentan-induced liver injury in Japanese patients with pulmonary arterial hypertension. This is the first pharmacogenomics study linking proteoglycan sulfating genes to drug-induced liver dysfunction, a frequently observed clinical adverse effect of bosentan therapy. These results may provide a way to personalize PAH medicine as well as provide novel mechanistic insights to drug-induced liver dysfunction.

Echocardiography during preload stress for evaluation of right ventricular contractile reserve and exercise capacity in pulmonary hypertension.

OBJECTIVES: Pulmonary hypertension (PH) is characterized by marked and sustained elevation of pulmonary vascular resistance and pulmonary artery pressure, and subsequent right-sided heart failure. Right ventricular (RV) function and exercise capacity have been recognized as important prognostic factors for PH. Our aim was to investigate RV contractile reserve and exercise capacity during a leg-positive pressure (LPP) maneuver. METHODS: The study population comprised 43 PH patients and 17 normal controls. All patients underwent echocardiography at rest and during LPP stress. Exercise capacity was assessed by 6-minute walk distance for PH patients. RV relative wall thickness was calculated from dividing by RV free wall thickness by basal RV linear dimensions at end-diastole. RV function was calculated by averaging peak speckle-tracking longitudinal strain from the RV free wall. RV contractile reserve was assessed as the difference in RV free wall strain at rest and during LPP stress. Changes in left ventricular stroke volume (ΔSV) during LPP stress were also calculated. RESULTS: ΔSV and RV contractile reserve of PH patients were significantly lower than of controls (3.6 ± 6.0 mL vs 8.5 ± 2.3 mL, and 8.2 ± 11.9% vs 14.5 ± 6.6%; both P < 0.01). RV contractile reserve of PH patients with ΔSV <3.3 mL was significantly lower than of PH patients with ΔSV >3.3 mL (3.9 ± 13.2% vs 12.3 ± 8.9%; P = 0.02). ΔSV had also significant correlation with 6-minute walk distance (r = 0.42, P = 0.006). Multivariate regression analysis showed that RV relative wall thickness was an independent determinant parameter of ΔSV during LPP stress for PH patients (ß = 3.2, P = 0.003). CONCLUSIONS: Preload stress echocardiography in response to LPP maneuver, a noninvasive and easy-to-use procedure for routine clinical use, proved to be useful for the assessment of RV contractile reserve and exercise capacity of PH patients.

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.

Optimal image reconstruction using multidetector-row computed tomography to facilitate cardiac resynchronization therapy.

Preprocedural recognition of the segment of latest mechanical contraction along with the anatomy of the coronary venous system is important for successful and effective cardiac resynchronization therapy. We present a case of ischemic cardiomyopathy who underwent implantation of a cardiac resynchronization therapy device with a defibrillator, which was facilitated by preprocedural computed tomographic images reconstructed to visualize the left ventricular slab and the coronary venous system simultaneously on the cardiac contour. The present reconstruction method using computed tomography is optimal and feasible method to incorporate the echocardiographic findings into the procedure performed under fluoroscopy appropriately.

Human herpesvirus 6 and 7 are biomarkers for fatigue, which distinguish between physiological fatigue and pathological fatigue.

Fatigue reduces productivity and is a risk factor for lifestyle diseases and mental disorders. Everyone experiences physiological fatigue and recovers with rest. Pathological fatigue, however, greatly reduces quality of life and requires therapeutic interventions. It is therefore necessary to distinguish between the two but there has been no biomarker for this. We report on the measurement of salivary human herpesvirus (HHV-) 6 and HHV-7 as biomarkers for quantifying physiological fatigue. They increased with military training and work and rapidly decreased with rest. Our results suggested that macrophage activation and differentiation were necessary for virus reactivation. However, HHV-6 and HHV-7 did not increase in obstructive sleep apnea syndrome (OSAS), chronic fatigue syndrome (CFS) and major depressive disorder (MDD), which are thought to cause pathological fatigue. Thus, HHV-6 and HHV-7 would be useful biomarkers for distinguishing between physiological and pathological fatigue. Our findings suggest a fundamentally new approach to evaluating fatigue and preventing fatigue-related diseases.

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.

["Anger" Seen in Obsessive-compulsive Disorder : A Study of 40 Subjects Who Underwent Inpatient Morita Therapy].

We conducted a study on "anger" seen in obsessive-compulsive disorder (OCD). Subjects were 40 men and women (age range: 20-58 years) admitted to the Jikei University Center for Morita Therapy who had been diagnosed with OCD (DSM-IV-TR) and undergone inpatient Morita therapy. The Japanese version of the Structured Clinical Interview for DSM-IV (SCID) (DSM-IV Axis I and Axis II diagnoses), the Yale-Brown Obsessive Compulsive Scale (Y- BOCS) (changes in OCD severity), the State-Trait Anger Expression Inventory (STAXI-2) using "anger" as the indicator, and the State-Trait Anxiety Inventory (STAI) using "anxiety" as the indicator were used, and the data were subjected to statistical analysis. Improvements were seen in the Y-BOCS for all of the following : total score, obsessional idea, compulsive act, insight, and avoidance. These results indicate that inpatient Morita ther- apy improves OCD. In the STAI, improvements were seen for both state anxiety and trait anxiety. Improvement of trait anxiety may be considered an indicator of the cultivation of a hypochondriacal temperament. In the STAXI-2, improvements were seen for anger reaction and anger expression-in, which are both aspects of the obsessive-compulsive style (Salzman, L.). Improvements in these items therefore indicate that inpatient Morita therapy improves aspects of the obsessive-compulsive style. A correlation with the degree of OCD improvement was observed for the insight level. Poor insight was a factor associated with poor outcomes of inpatient Morita therapy. Furthermore, two cases were presented, and the actual condition of treatment for OCD and "anger" in inpatient Morita therapy was elucidated.

Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAH. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH.

The short-term effects of C-peptide on the early diabetes-related ultrastructural changes to the podocyte slit diaphragm of glomeruli in rats.

OBJECTIVE: This study aimed to investigate the structural changes in the slit diaphragm, caused by early diabetes, and the nephroprotective effect of C-peptide. METHODS: Streptozotocin-induced type 1 diabetic Wistar rats were divided into control, control plus C-peptide, early diabetes, and early diabetes plus C-peptide groups. C-peptide was infused into rats for one day. The slit diaphragm component proteins podocin, CD2AP, and nephrin, were stained immunofluorescently and their distribution quantitatively analyzed by determining the overlapping area ratio. The interfoot process gap length was measured from electron microscopic images. RESULTS: Diabetic duration correlated best with the area ratio of podocin and CD2AP (r = 0.626), followed by other protein combinations, showing progressive change in the slit diaphragm structure. C-peptide-treatment did not alter area ratios. The interfoot process gap length was wider in diabetic rats (p < 0.05) and did not narrow with C-peptide-treatment in either control or diabetic rats (both p < 0.05). CONCLUSIONS: Diabetes widened the interfoot process gap length and distorted the slit diaphragm structure progressively and heterogeneously in rats with early diabetes; this was not altered by C-peptide-treatment. The nephroprotective effect of C-peptide in decreasing the glomerular filtration rate appears to be functional rather than structural.

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.

Correlation between cognition and symptomatic severity in patients with late-life somatoform disorders.

OBJECTIVES: Various aging associated factors, such as functional decline, psychosocial problems, and cognitive dysfunction, are risk factors for somatoform disorders (SDs) in the elderly. The aim of the present study was to evaluate how cognition is correlated with the severity of late-life SDs from a neuropsychological viewpoint. METHODS: Fifty-three patients over 60 years of age who had been diagnosed as having SDs were examined in this study. The severity of the somatic symptoms was assessed using the Hamilton Anxiety Rating Scales (HAMA). Cognitive functions were assessed using the Mini-Mental State Examination (MMSE), the Frontal Assessment Battery (FAB), and the Japanese version of the Neurobehavioral Cognitive Examination (J-COGNISTAT). RESULTS: The J-COGNISTAT subtest score for attention was below the cutoff point (8 points) but was not correlated with the severity of the somatic symptoms in the patients with late-life SDs. The severity of anxiety as assessed using the HAMA was significantly correlated with the calculation scores (P < 0.005) among the J-COGNISTAT subtests, the FAB total (P < 0.05), and the FAB subtest scores (similarities and motor series) (P < 0.01). Other factors, including the benzodiazepine dosage, antidepressant dosage, the duration of illness, and the onset age, were not significantly correlated with the symptomatic severities. CONCLUSION: Patients with late-life SDs showed attention deficits, but no correlation was seen between the attention deficits and symptomatic severities. Attention deficits might be associated with the appearance of symptoms. Executive dysfunction and working memory might be associated with the severity of symptoms.

White matter hyperintensities are associated with the severity of late-life somatoform disorders and executive functions.

BACKGROUND: Medically unexplained symptoms are often seen in the elderly. Recently, correlations between medically unexplained symptoms and somatoform disorders (SDs) have been reported. The existence of many interactive psychiatric aetiologies is known among SDs. Late-life SDs might be influenced by some aetiological factors caused by ageing processes, such as structural changes in the brain and cognitive dysfunctions. AIMS: Under such circumstances, we investigated the presence of subcortical white matter hyperintensities (WMHs), which increase with ageing, and hypothesized that subcortical WMHs are related to the disease severity of late-life SDs. Furthermore, we confirmed whether cognitive dysfunction influences this process. METHODS: To evaluate these hypotheses, we examined patients with medically unexplained symptoms who met the criteria for undifferentiated somatoform disorder and divided the patients into three groups according to the degree of subcortical WMHs: grade 0, grade 1, and grade 2. The subcortical WMHs were rated using Fazekas grading. Differences in symptom severity and cognitive functions were compared among the three groups. RESULTS: The grade 2 group had the severest symptoms. Furthermore, the grade 2 group had lower cognitive function scores than the other groups. CONCLUSIONS: The present study showed that the presence of subcortical WMHs in patients with late-life SDs was a predictor of disease severity. Moreover, cognitive dysfunction appeared to play a role in the advancement of disease severity.