Clinical applications of digital angiography with the harmonization function in body interventional radiology.

Digital subtraction angiography (DSA) is frequently applied in interventional radiology (IR). When DSA is not useful due to misregistration, digital angiography (DA) as an alternative option is used. In DA, the harmonization function (HF) works in real time by harmonizing the distribution of gray steps or reducing the dynamic range; thus, it can compress image gradations, decrease image contrast, and suppress halation artifacts. DA with HF as a good alternative to DSA is clinically advantageous in body IR for generating DSA-like images and simultaneously reducing various motion artifacts and misregistrations caused by patient body motion, poor breath-holding, bowel and ureter peristalsis, and cardiac pulsation as well as halation artifacts often stemming from the lung field. Free-breath DA with HF can improve body IR workflow and decrease the procedure time by reducing the risk of catheter dislocation and using background structures as anatomical landmarks, demonstrating reduced radiation exposure relative to DSA. Thus, HF should be more widely and effectively utilized for appropriate purposes in body IR. This article illustrates the basic facts and principles of HF in DA, and demonstrates clinical advantages and limitations of this function in body IR.

[A case of bilateral medial medullary and left tegmentum of pontine infarction in whom DSA-MR fusion imaging identified infarct-relevant arteries].

We herein reported a patient with acute ischemic stroke in the bilateral medial medullary and the left tegmentum of the pons who presented with various neurological symptoms. Fusing digital subtraction angiography (DSA) and MRI (DSA-MR fusion imaging) could reveal the infarct-relevant arteries. A 41-year-old male presented with headache, bilateral arm's dysesthesia, quadriplegia, left Horner's syndrome, upbeat nystagmus, internuclear ophthalmoplegia and left peripheral facial paralysis. Diffusion weighted MRI (DWI) revealed the high intensity lesion in the bilateral medial medullary and the left tegmentum of the pons. MRA showed right vertebral artery (VA) occlusion. A high intensity on T1 weighted imaging was shown on the right VA vessel wall. DSA-MR fusion imaging revealed the anterior spinal artery (ASA) occlusion proximal to the infarction. The stenosis was located at the origin of the right VA perforating branch distributing into the infarct lesion. The steno-occlusive lesion of ASA and VA perforating branch due to VA dissection resulted in infarction in the pontomedullary junction and caused various neurological symptoms. DSA-MR fusion imaging would prove the radiological anatomy of infarct-relevant arteries and clarify the etiology of ischemic stroke.

[A case of definite diagnosis of branch atheromatous disease confirmed by digital subtraction angiography-3 tesla magnetic resonance fusion imaging].

We herein experienced one patient with typical branch atheromatous disease (BAD) type infarction. Digital subtraction angiography (DSA) and MRI fusion imaging revealed the relationship between atheromatous plaque and perforating branches. A 66-year-old male presented acute onset of dysarthria, the left side hemiparesis and sensory disturbance. Diffusion-weighted MR imaging (DWI) showed the right pontine acute infarction. We started to treat with dual antiplatelet therapy. However, the left-side hemiparesis was worsening on 4 days after admission. DWI showed infarct growth and plaque imaging revealed the atheromatous plaque in the basilar artery. We fused DSA and MRI T2 weighted imaging (DSA-MR fusion imaging) to illustrate the relationship between the atheromatous plaque and the perforating branches. DSA-MR fusion imaging showed that the paramedian artery and the short circumferential artery ran around and into the pontine infarct lesion. Additionally, one of the paramedian arteries was occluded. Those neuroradiological findings coincided with the pathological concept of BAD. DSA-MR fusion imaging can prove the pathological concept of BAD.

Calmodulin-like skin protein is downregulated in human cerebrospinal fluids of Alzheimer's disease patients with apolipoprotein E4; a pilot study using postmortem samples.

OBJECTIVE: Calmodulin-like skin protein (CLSP) is a secreted peptide that inhibits neuronal cell death, linked to Alzheimer's disease (AD), by binding to the heterotrimeric humanin receptor and activating an intracellular survival pathway. CLSP is only expressed in skin keratinocytes and related epithelial cells, circulates in the blood stream, and passes the blood-cerebrospinal fluid (CSF) barrier. In the current study, we addressed the issues as to whether CLSP functions in the central nervous system and whether the concentration of CLSP is reduced in the CSFs of AD patients. METHODS: Mice were intraperitoneally injected with 5 nmol of recombinant human CLSP. At 1h after the injection, the mice were sacrificed for the analysis of the existence of human CLSP in blood and interstitial fluid (ISF)-containing brain samples. Using postmortem CSF samples, we next determined the concentrations of CLSP in CSFs of human AD and control cases. RESULTS: Intraperitoneally administered recombinant human CLSP circulated in the blood stream and reached the brain interstitial fluid. The concentrations of CLSP in CSFs of human AD and control cases are sufficient to exhibit the CLSP activity. Although the concentrations of CLSP in CSFs were not significantly different between AD and control cases, the concentrations of CLSP are lower in the AD cases with the apolipoprotein E4 genotype than in the AD cases without the apolipoprotein E4 genotype. DISCUSSION: The first result indicates that CLSP enters the central nervous system through the blood-brain barrier. The second result suggests that CLSP functions in the human brains. The third result may exclude the possibility that the downregulation of the CLSP level is involved in the AD pathogenesis. The last result may contribute to the better understanding of the AD pathogenesis from the standpoint of the apolipoprotein E genotype.

Geriatric problems correlated with cognitive decline using a screening test named "Dr. SUPERMAN" for comprehensive geriatric assessment in elderly inpatients.

AIM: We have recently developed and validated a screening test for comprehensive geriatric assessment (CGA). We investigated the prevalence of geriatric problems in elderly inpatients using CGA, and determined the relationship between geriatric problems and cognitive decline. METHODS: We enrolled consecutive elderly inpatients aged >65 years who were admitted to all of the hospital departments at Tokyo Medical University Hospital, Tokyo, Japan, between July and December 2013. We investigated the prevalence of specific geriatric problems or situations in elderly inpatients using a screening test for CGA named "Dr. SUPERMAN." We examined 3969 elderly inpatients (2211 men and 1758 women; mean age 75.5 ± 6.7 years) using CGA. Inpatients were divided into three groups by age, namely, 65-74 years, 75-84 years and ≥85 years. Inpatients were divided into the two groups of "internal medicine" and "other departments." RESULTS: Geriatric problems were more frequently found in patients who were aged ≥85 years and admitted to "internal medicine" departments. Furthermore, multiple regression analysis found cognitive decline significantly correlated with ADL decline, age, poor medication adherence, upper and lower extremity function disorder, visual/auditory disorder, and urinary disorder. In particular, cognitive decline strongly correlated with a decline in activities of daily living. CONCLUSIONS: CGA should be considered for the treatment of elderly inpatients, particularly those with cognitive decline and admitted to "internal medicine" departments. Geriatr Gerontol Int 2017; 17: 1252-1256.

Differences in peripheral oxidative stress markers in Alzheimer's disease, vascular dementia and mixed dementia patients.

AIMS: We determined whether the possible roles of oxidative stress differ in the pathophysiology and cognitive decline of Alzheimer's disease (AD), vascular dementia (VaD) and mixed Alzheimer's/vascular dementia (MD). METHODS: We measured the levels of diacron reactive oxygen metabolite (dROM), reflecting the amount of organic hydroperoxides, and biological anti-oxidant potential (BAP), measuring the ferric reducing ability of blood plasma, in 72 patients with AD, 27 with VaD, 24 with MD and 53 non-demented outpatients (control group). In addition, endogenous plasma anti-oxidants, such as albumin, total bilirubin and uric acid, were compared among the groups. All participants with VaD and MD showed extensive white matter hyperintensity, in addition to multiple lacunes. RESULTS: The dROM levels were significantly higher in the AD and MD groups than in the control group. The BAP levels were significantly lower in the MD group than in the control, AD and VaD groups. The AD group showed significantly lower levels of bilirubin and uric acid than the control group. The MD group showed a significantly lower level of albumin than the control and AD groups, and a significantly lower level of bilirubin than the control group. The Mini-Mental State examination scores correlated significantly with dROM levels and BAP/dROM ratios in the AD group. CONCLUSIONS: An imbalance in pro-oxidant and anti-oxidant defenses is apparently involved in the pathophysiology of the AD and MD groups. The extent of oxidative stress damage might differ in subtypes of dementia by being greater in the MD group than in other types of dementia. Synergic effects of the degenerative element of AD and white matter lesions might be associated with oxidative stress damage in the MD group.

Comprehensive geriatric assessment in elderly patients with dementia.

AIM: We have recently developed and validated a screening test for comprehensive geriatric assessment (CGA) named "Dr. SUPERMAN". We compared the results obtained by the CGA of patients with Alzheimer's disease (AD), vascular dementia (VaD) and dementia with Lewy bodies (DLB), and determined the relationship between functional deficits and clinical characteristics in each type of dementia. METHODS: We used Dr. SUPERMAN to examine patients with AD (24 men and 53 women, mean age 83.0 ± 5.1 years), VaD (10 men and 12 women, mean age 80.4 ± 5.0 years) and DLB (28 men and 20 women, mean age 81.2 ± 5.5 years). RESULTS: Patients with DLB or VaD had functional deficits more frequently than those with AD in many fields. Significant correlations between functional impairments and clinical characteristics, such as age, sex and Mini-Mental State Examination scores, in the non-AD group (including DLB and VaD) were found in more extensive fields than those in the AD group. CONCLUSIONS: Patients with dementia, particularly DLB, have several geriatric problems. Correlations between functional deficits and clinical characteristics differ between the AD group and the non-AD group. Non-AD patients of older age who are male and have advanced dementia are more likely have several functional deficits. In addition to age and severity of dementia, the type of dementia should be considered in the treatments and interventions of elderly patients with dementia.

Longitudinal study of regional cerebral blood flow in elderly patients with idiopathic rapid eye movement sleep behavior disorder.

AIM: Single photon emission computed tomography (SPECT) studies showed that regional cerebral blood flow (rCBF) abnormalities in idiopathic rapid eye movement (REM) sleep behavior disorder (iRBD) are similar to those seen in Parkinson's disease (PD) and dementia with Lewy bodies (DLB). The aim of the present study was to assess the longitudinal rCBF changes in patients with iRBD using repeated SPECT. METHODS: Nine patients with iRBD (7 men and 2 women; mean age 71.1 ± 3.2 years) underwent baseline and follow-up SPECT studies (a mean interval of 22.8 ± 9.2 months). RESULTS: A decrease in rCBF was found in bilateral parietotemporal and occipital areas at the first and second SPECT. Compared with the first SPECT, the second SPECT showed a decreased rCBF in the medial portions of the parietooccipital lobe with a significant decrease in rCBF of the right posterior cingulate. None of the patients showed any neurological deficits, including extrapyramidal and cerebellar signs, visual hallucinations, and neuropsychological impairments during the study. CONCLUSION: These findings suggest that longitudinal measurements of rCBF can show the presence of progressing neurodegenerative process in iRBD. Longitudinal SPECT study can be used to monitor the progression of degenerative process in patients with iRBD, even though there were no evolving neurological and neuropsychiatric impairments.

[Age-related changes of sensory system].

Pathological processes usually superimpose on physiological aging even in the sensory system including visual, hearing, olfactory, taste and somatosensory functions. Representative changes of age-related changes are presbyopia, cataracts, and presbyacusis. Reduced sense of smell is seen in normal aging, but the prominent reduction detected by the odor stick identification test is noticed especially in early stage of Alzheimer or Parkinson disease. Reduced sense of taste is well-known especially in salty sense, while the changes of sweet, bitter, and sour tastes are different among individuals. Finally, deep sensation of vibration and proprioception is decreased with age as well as superficial sensation (touch, temperature, pain). As a result, impaired sensory system could induce deterioration of the activities of daily living and quality of life in the elderly.

[Establishment of a short-form screening test for malnutrition in a newly developed comprehensive geriatric assessment initiative named 'Dr. SUPERMAN'].

AIM: Assessment of the nutritional state is important in comprehensive geriatric assessment (CGA). Several standardized screening tests for malnutrition are available such as the Mini-Nutritional Assessment (MNA) and MNA-Short Form (MNA-SF). However, it takes more than 10 minutes to perform the MNA-SF alone. We have developed a CGA initiative named 'Dr. SUPERMAN', which is designed to accomplish CGA within 10 minutes. In this study, we evaluated a short-form screening test for malnutrition preceding the MNA. METHODS: The MNA-SF, which consists of 6 items (A-F), was administered to 163 elderly outpatients (mean age: 83.4 years, 80 men) with various diseases. Using the results of the MNA-SF score (normal ≥ 12 and abnormal ≤ 11) as a gold standard, the sensitivity, specificity, and positive predictive values (PPVs) of each item were calculated and the best combination of 2 items for identifying malnutrition among the elderly outpatients was selected. According to the combination of 2 items (item B: weight loss during the last 3 months; item F: body mass index (BMI)/calf circumference (CC) in cm), they were divided into 2 groups: the normal control (NC) group (neither items B nor F) and the malnutrition/at risk (MN) group (either items B or D, or both). Findings of the clinical feature, anthropometric measurement, and nutritional biomarker between the 2 groups were examined to clarify the characteristics of each. RESULTS: The MNA-SF score was distributed as follows: 3-7 in 12 cases, 8-11 in 68 cases, and 12-14 in 83 cases. Based on the MNA-SF score, the combination of items B and F revealed the highest sensitivity (91.3%), specificity (63.9%), and PPV (70.9%), resulting in 103 cases in the MN group and 60 cases in the NC group. A high frequency of anorexia, living alone, hypoprealbuminemia, lymphocytopenia, and dehydration was observed in the MN group, whereas a high frequency of leg edema was observed in the NC group. Cases showing a positive wall-occiput test, which compelled the alternation of CC with BMI, accounted for 24% of all cases. CONCLUSIONS: The combination of 'weight loss during the last 3 months' and initial BMI ≥ 23/CC <31 cm along with a positive wall-occiput test was a useful and valuable SF screening test for malnutrition in elderly outpatients.

[Screening test for overactive bladder in a newly developed comprehensive geriatric assessment initiative].

PURPOSE: Lower urinary tract symptoms, particularly in overactive bladder (OAB), are frequently observed among elderly patients. The impact of OAB on their quality of life is so strong that the assessment of OAB is necessary in comprehensive geriatric assessment (CGA). As CGA takes time to complete, we established a convenient instrument consisting of 2 questions on OAB and assessed its utility. METHOD: We recruited 123 elderly patients with various diseases (mean age: 83.2 years, 63 men), in whom 2 questions on nocturia (Q1) and urinary incontinence at night (Q2) were asked. Thereafter, overactive bladder symptom scores (OABSS) were obtained to diagnose OAB based on the OAB criteria. Statistical analyses for Q1 and Q2 were performed using the OABSS criterion as a gold standard. To elucidate the clinical characteristics of the elderly patients, they were divided into 2 groups on the basis of the presence or absence of nocturia: nocturia (+) and nocturia (-) groups. The nocturia (+) group was subdivided into 2 subgroups: with or without incontinence. RESULTS: Nocturia (Q1) was observed in 82 elderly patients and urinary incontinence (Q2) in 23, whereas OAB was diagnosed in 22. The sensitivity, specificity, and positive predictive value (PPV) of Q1 (Q1+Q2) were 100% (68.2%), 40.6% (92.1%), and 26.8% (65.2%), respectively. The nocturia (+) group patients were characterized as predominantly composed of men with cerebrovascular disease, disturbed activities of daily living, interrupted sleep, delayed wake-up time, and treatment with diuretics. Furthermore, Parkinson disease, depressive state, sedentary life style, and treatment without diuretics were frequently observed in patients in the incontinence (+) subgroup. CONCLUSION: A low PPV with a high sensitivity of Q1 was improved by using Q1+Q2, where both Q1 and Q2 enable better assessment of OAB resulting in being a useful screening test for OAB.

[Leg edema detected on comprehensive geriatric assessment for elderly outpatients and its associated risk factors].

AIM: Leg edema, observed on comprehensive geriatric assessment (CGA) of 142 elderly outpatients with a variety of chronic diseases, was studied clinically to clarify its incidence and its associated risk factors. METHODS: The severity of pitting edema was assessed at 3 points, namely, the pretibial edge, medial malleolus, and the dorsum of the foot. On palpation, edema was graded as 0 to 3 for each point on one leg, the sum of which was used as the edema score. According to the edema score, subjects were divided into 3 groups; the moderate to severe (MS) group, the slight to mild (SM) group, and the group without pitting edema. The MS group was defined as having an edema score of 4 or more or edema of grade 2 or more, while the SM group was defined as having an edema score of 2 to 3 points without edema of grade 2 or more. The status of underlying disease, vascular risks, varicose veins, medications, daily activity, nutrition, total protein (TP), albumin, brain natriuretic peptide (BNP), and the estimated glomerular filtration rate (eGFR) were compared among the 3 groups. RESULTS: There were 36 subjects in the MS group and 19 subjects in the SM group. Diabetes, atrial fibrillation, varicose veins, and polypharmacy were more frequent in the MS group than in the control group. Sedentary life style, house-bound, and gait trouble were significantly more frequent in the MS and SM groups. There were no significant differences in the scores of the Mini-Nutritional Assessment Short Form among the groups, although both the body weight and calf circumference in the MS group were significantly greater than those in the group without pitting edema. Low serum TP, albumin and eGFR were seen in the MS group as well as high BNP levels. Multiple regression analysis revealed diabetes, varicose veins, sedentarism, and hypoalbuminemia as risk factors associated with leg edema (R(2)=0.365, p<0.0001). CONCLUSION: Leg edema was frequent in the elderly outpatients and was associated strongly with diabetes, varicose veins, sedentarism, and hypoalbuminemia. These findings suggest that advising against a sedentary life style could help the resolution of edema, and also indicates the clinical usefulness of CGA. Furthermore, leg edema should be seriously considered along with nutritional assessment because edema could influence various anthropometric parameters.

Subgroups of Alzheimer's disease associated with diabetes mellitus based on brain imaging.

BACKGROUND/AIMS: We attempted to define possible subgroups of Alzheimer's disease (AD) associated with diabetes mellitus (DM) based on brain imaging. METHODS: We classified 175 patients with clinically diagnosed AD and type 2 DM into 4 subgroups on the basis of the presence or absence of cerebrovascular disease (CVD) on MRI (CVD or no CVD) and posterior cerebral hypoperfusion on SPECT (AD pattern or no AD pattern). Differences in the clinical characteristics among the subgroups were examined. RESULTS: The subgroup showing neither a CVD pattern nor an AD pattern had significantly older age, higher hemoglobin A1c level, longer duration of diabetes, higher frequency of insulin therapy, lower frequency of apolipoprotein E4 carriers, less severe medial temporal lobe atrophy, more impaired attention, less impaired word recall, and slower progression of cognitive impairment than the subgroup showing an AD pattern. We found no characteristic features of other subgroups. CONCLUSION: The clinical features of subjects with AD associated with DM may differ depending on brain imaging patterns. Among them, there may be a dementia subgroup with characteristics predominantly associated with DM-related metabolic abnormalities.

Preoperative prediction of macrophage infiltration by 3-D tomographic ultrasound in endoarterectomized carotid plaques in elderly patients.

AIM: Assessment of plaque characteristics is important for the optimal treatment of carotid stenosis, particularly in elderly patients. Macrophage infiltration is reported to be involved in carotid plaque instability. However, immunohistochemical assessment of the detailed localization of macrophage infiltration in carotid plaques remains limited. We attempted to elucidate this using 3-D ultrasonography (3D-US). We compared findings of the detailed localization of macrophage infiltration with findings from the newly developed tomographic ultrasound imaging (TUI). METHODS: We obtained specimens of carotid arteries from 18 patients undergoing carotid endarterectomy (CEA), and investigated the localization of macrophages and vascular smooth muscle cells. Their localization obtained from 11 patients was compared with their preoperative TUI findings. RESULTS: We classified the localization of macrophage infiltration into four types: (i) focal infiltration in the thick fibrous cap (12 cases); (ii) subendothelial zonal infiltration (2 cases); (iii) peripheral infiltration around the lipid core (8 cases); and (iv) local infiltration near the shoulder of the fibrous cap (2 cases). Among them, preoperative TUI was available in 11 CEA cases for histological comparison. We identified two sites of focal macrophage infiltration that corresponded to local echogenic lesions without an acoustic shadow on TUI. The proliferation of smooth muscle cells failed to show an apparent echogenicity. CONCLUSIONS: TUI could not only evaluate the morphological features, but also showed the two types of focal macrophage infiltration relevant to plaque instability as an echogenic focus. TUI carried out by 3D-US is an easily applicable and non-invasive method that is considered useful for evaluating carotid plaques in elderly patients.

Rate of progression of Alzheimer's disease in younger versus older patients: a longitudinal single photon emission computed tomography study.

AIM: Although several researchers have examined the effect of age on disease progression in patients with Alzheimer's disease (AD), the results are controversial. We investigated the effect of age on the rate of progression of cognitive impairment and on regional cerebral blood flow (rCBF) deficits using longitudinal single photon emission computed tomography (SPECT) studies. METHODS: We divided 75 patients with AD who were followed up for 24-90 months into the younger AD group (n=32, age at initial examination ≤ 75 years) and the older AD group (n=43, age at initial examination >75 years). We assessed changes in Mini-Mental State Examination (MMSE) scores and rCBF between initial and final examinations. RESULTS: The change in the annual MMSE score was greater in the younger AD group than in the older AD group. The mean annual MMSE score changes correlated significantly with age at the initial examination. The initial and follow-up SPECT studies showed more severe and extensive rCBF deficits in the younger AD group than in the older AD group. CONCLUSION: Our longitudinal SPECT study showed that the rate of progression of cognitive impairment and the rCBF deficits were higher in younger patients with AD than in older patients with AD. Therefore, age is an important factor to consider, not only in the diagnosis, but also in the treatment and prognosis of patients with AD.