Apathy and right caudate perfusion in idiopathic normal pressure hydrocephalus: A case-control study.

OBJECTIVES: Apathy is prevalent in patients with idiopathic normal pressure hydrocephalus (iNPH), a treatable disorder resulting from ventricular enlargement. We assessed the relationship between apathy and regional cerebral blood flow (rCBF) in patients with iNPH. METHODS: Before lumbo-peritoneal shunt surgery (LPS), 56 iNPH patients were evaluated on apathy and dysphoria subscales of the Neuropsychiatric inventory (NPI), and were divided into two groups according to NPI apathy score: 15 without apathy (iNPH-APA) and 41 with apathy (iNPH+APA). Among iNPH+APA, 29 patients were evaluated for apathy and dysphoria 3 months after LPS, and were divided into two groups on the basis of the change in NPI apathy score: 13 with improvement (iNPH+ImpAPA) and 16 without improvement in apathy (iNPH-ImpAPA). N-isopropyl-p-iodoamphetamine single photon emission computed tomography using the autoradiography method was performed before and after LPS, and rCBF was calculated in 22 regions of interest in the frontal cortex, basal ganglia, and limbic system. RESULTS: In iNPH+APA, rCBF in the right caudate nuclei before LPS was significantly lower than that in iNPH-APA (P = 0.004; two-sample t test). Between iNPH-ImpAPA and iNPH+ImpAPA, a significant group-by-shunt interaction was observed for rCBF in only the right caudate nuclei (F1, 28  = 11.75, P = 0.002; two-way repeated-measures analysis of variance), with increased rCBF in iNPH+ImpAPA but not in iNPH-ImpAPA. The significant group-by-shunt interaction persisted if change in NPI dysphoria scores was used as a covariate (F1, 27  = 8.33, P = 0.008). CONCLUSIONS: Our findings suggest that right caudate dysfunction might cause apathy in iNPH patients.

Cerebral blood flow and Alzheimer's disease-related biomarkers in cerebrospinal fluid in idiopathic normal pressure hydrocephalus.

AIM: Alzheimer's disease (AD) pathology is highly prevalent in patients with idiopathic normal pressure hydrocephalus (iNPH), and the presence of AD pathology may involve regional cerebral blood flow (rCBF). In this study, we examined the relationship between rCBF and AD-related biomarkers in the cerebrospinal fluid of iNPH patients. METHODS: Patients with iNPH (n = 39) were classified into groups with (iNPH/AD+) (n=15) and without (iNPH/AD-) (n=24) high biomarker probability of AD (i.e. combined low amyloid ß 42 and high total tau in the cerebrospinal fluid). rCBF was quantified in 17 regions of interest by N-isopropyl-p-[123 I]iodoamphetamine single-photon emission computed tomography with the autoradiography method. We compared rCBF between the iNPH/AD- and iNPH/AD+ groups at baseline using a t-test and then compared changes in rCBF after shunt surgery between the groups using a paired t-test and two-way repeated measures ANOVA. RESULTS: At baseline, there were no significant differences in rCBF between the groups in most regions apart from the putamen. After shunt surgery, a significant increase in rCBF in the putamen, amygdala, hippocampus, and parahippocampal gyrus was observed in iNPH/AD- patients. In iNPH/AD+ patients, no significant improvement in rCBF was observed in any region. In repeated measures analysis of variance, a significant group × shunt interaction was observed in the parietal lobe, frontal lobe, posterior cingulate cortex, precuneus, lateral temporal lobe, amygdala, hippocampus, parahippocampal gyrus, and putamen. CONCLUSIONS: Improvement in rCBF after shunt surgery in iNPH/AD+ patients may be poorer than that in iNPH AD- patients.

Changes in brain morphology in patients in the preclinical stage of idiopathic normal pressure hydrocephalus.

BACKGROUND: Specific ventriculomegaly features, including tight high-convexity and medial subarachnoid spaces, are found on magnetic resonance images in patients with idiopathic normal pressure hydrocephalus (iNPH). However, some healthy elderly individuals with no typical triad symptoms of iNPH also exhibit specific magnetic resonance image features of iNPH. Therefore, this study quantitatively clarified the brain morphology of suspected iNPH patients with no objective triad symptoms (iNPH-NOS). METHODS: We recruited patients with suspected iNPH and divided them into two groups based on their iNPH grading scale scores: the iNPH-NOS group and the iNPH with apparent objective triad symptoms (iNPH-AOS) group. Data for normal controls (NC) were taken from the database used in our previous study. We compared the relative volumes of ventricle systems (VS), Sylvian fissures (SF), and sulci at high convexity and the midline (SHM), adjusted by the intracranial volume, of the iNPH-NOS, iNPH-AOS, and NC groups. Additionally, we compared the relative volumes of VS, SF, and SHM in iNPH-NOS patients between their first visit and follow-up 1 year later. RESULTS: Fifteen iNPH-NOS patients and 45 iNPH-AOS patients were recruited, and 24 NCs were found in the database. The relative volumes of VS and SF were significantly smaller than in NCs than in the iNPH-NOS and iNPH-AOS groups, and the relative volume of SHM was significantly larger in NCs. The relative volume of SHM was significantly larger in the iNPH-NOS group than in the iNPH-AOS group, but there were no significant differences in the relative volumes of VS and SF between these groups. In the iNPH-NOS group, the relative volumes of VS and SF were significantly smaller at the first visit than 1 year later, whereas the relative volume of SHM was significantly larger. In 6 of 15 iNPH-NOS patients, objective symptoms appeared during the observation period. CONCLUSIONS: Our results indicate that iNPH-NOS patients were in the transitional stage between normal and iNPH-AOS, both morphologically and clinically.

Advantages of different care services for reducing neuropsychiatric symptoms in dementia patients.

BACKGROUND: It is assumed that care services effectively reduce behavioural and psychological symptoms of dementia (BPSD). However, it is unclear which care services are effective for reducing specific BPSD. The aim of this study was to clarify which care services were recognized by care specialists as being effective for reducing each of 11 BPSD. METHODS: We sent unsigned questionnaires to care specialists in Japan. The questionnaires asked specialists to choose from 12 kinds of care services the most, second-most, and third-most effective service for reducing each of 11 BPSD. The most effective service was scored as 3 points, the second-most was 2 points, and the third-most was 1 point. Specialists were also asked to describe why they chose each service. The 12 kinds of care services were categorized into four categories: (i) home-visit; (ii) outpatient; (iii) short-stay; and (iv) facility. Total scores for each category were analyzed using a two-way anova. The reasons care specialists chose each service were analyzed using morphological analysis, and representative reasons were extracted. RESULTS: A total of 103 questionnaires were returned. Of the four service categories, outpatient services yielded the highest score for reducing apathy (P < 0.001) due to the effectiveness of participating in recreation and receiving stimulation. Facility services yielded the highest score for reducing aberrant motor behaviour (P < 0.001). Short-stay services yielded the lowest score for reducing depression (P < 0.001). For eight other kinds of BPSD, there were no significant differences between home-visit and facility services or between outpatient and facility services. CONCLUSIONS: Care specialists reported that effective care services for reducing BPSD differed among types of BPSD. In-home care services might be effective at reducing many BPSD except for aberrant motor behaviour, suggesting that greater use of in-home care services might enable people with BPSD to live in their homes for longer.

Alpha event-related synchronization after eye closing differs in Alzheimer's disease and dementia with Lewy bodies: a magnetoencephalography study.

BACKGROUND: The electroencephalography (EEG) abnormalities found in patients with dementia with Lewy bodies (DLB) are conflicting. In this study, we used magnetoencephalography, which has higher spatial resolution than electroencephalography, to explore neurophysiological features of DLB that may aid in the differential diagnosis. METHODS: Six patients with DLB, 11 patients with Alzheimer's disease, and 11 age-matched normal subjects were recruited. We investigated alterations in the ratio of event-related synchronization (ERS) in the alpha band after eye-closing. RESULTS: Although the averaged ratio change of alpha ERS after eye-closing appeared predominantly in the posterior brain regions in all study groups, DLB patients had the weakest ratio change of alpha ERS. In particular, DLB patients exhibited a significantly reduced ratio change of alpha ERS in the bilateral inferior temporal gyrus, right occipital pole, and left parieto-occipital cortex compared to Alzheimer's disease patients or normal controls. CONCLUSION: Our findings indicated that a reduced ratio change of alpha ERS in the posterior brain regions elicited by eye-closing is a brain electromagnetic feature of DLB.

Characteristics of behavioral symptoms in right-sided predominant semantic dementia and their impact on caregiver burden: a cross-sectional study.

BACKGROUND: This study aimed to clarify the neuropsychiatric symptoms of right-sided predominant semantic dementia (SD-R) by comparing them with those of behavioral variant frontotemporal dementia (bvFTD), left-sided predominant SD (SD-L), and Alzheimer's disease (AD). This study also aimed to identify clinical factors related to caregiver burden for bvFTD, SD-R, and SD-L. METHODS: The neuropsychiatric symptoms of 28 patients with bvFTD, 14 patients with SD-R, 24 patients with SD-L, and 43 patients with AD were evaluated using the Neuropsychiatric Inventory (NPI) and the Stereotypy Rating Inventory (SRI). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Dementia severity was assessed using the Clinical Dementia Rating. Activities of daily living were assessed using the Lawton Instrument Activities of Daily Living (IADL) scale and the Physical Self-Maintenance Scale. We compared the NPI and SRI scores among the four groups using the Kruskal-Wallis test. In addition, clinical factors related to caregiver burden, represented by the Japanese version of the Zarit Burden Interview (J-ZBI), were analyzed using multiple regression analysis in the bvFTD, SD-R, and SD-L groups. RESULTS: The NPI total score and the NPI subscale scores of apathy and disinhibition were significantly higher in the bvFTD group than in the SD-L and AD groups. The SD-R group scores were closer to those of the bvFTD group than the SD-L group. The SRI total score and SRI subscale scores for eating and cooking and speaking were significantly higher in the bvFTD, SD-R, and SD-L groups than in the AD group. The NPI total score was significantly associated with the J-ZBI score in the bvFTD group. The NPI total score and Lawton IADL scale score were independently associated with the J-ZBI score in the SD-R group. Furthermore, the NPI total score and MMSE score were independently associated with the J-ZBI score in the SD-L group. CONCLUSIONS: SD-R seemed to be a similar condition to bvFTD rather than SD-L regarding behavioral symptoms. Our results suggest that each frontotemporal dementia subgroup requires different approaches to reduce the caregiver burden.

Clinical profiles of people with dementia exhibiting with neuropsychiatric symptoms admitted to mental hospitals: A multicenter prospective survey in Japan.

AIMS: Patients with severe behavioral and psychological symptoms of dementia (BPSD) are often admitted to mental hospitals, while, inpatient care could also lead to prolonged hospital stay. The present study aims to survey clinical profiles of patients who required inpatient treatment for BPSD, and then establish the criteria for introducing inpatient treatment through assessment by certified psychiatrists. METHODS: We performed a prospective survey about clinical characteristics of people with dementia who required treatment of BPSD at 12 mental medical institutions. All patients were assessed by certified psychiatrists to determine the optimal treatment settings: outpatient or inpatient. The multivariate logistic regression analysis was performed to specify factors contributed to the judgement of clinicians. Subsequently, the receiver operating characteristic curve analysis was conducted to explore a score derived from the Neuropsychiatric Inventory to divide patients into outpatient or inpatient groups. RESULTS: The present study included 386 patients, of which 242 were admitted to mental hospitals. BPSD were classified into four domains, and aggressive BPSD was significantly associated with assessment for inpatient treatment; the adjusted odds ratio was approximately 2 regardless of dementia severity. Furthermore, the composite score of agitation, irritability and aberrant behavior showed the highest area under the curve value (=0.706), which differentiated inpatients from outpatients with a sensitivity of 76% and a specificity of 54%. CONCLUSIONS: Aggressive BPSD was the risk factor for inpatient treatment. The composite score of the Neuropsychiatric Inventory subdomain-related aggressive BPSD could be a screening tool to introduce inpatient treatment for BPSD. Geriatr Gerontol Int 2021; 21: 825-829.

EEG Resting-State Networks Responsible for Gait Disturbance Features in Idiopathic Normal Pressure Hydrocephalus.

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric disease characterized by gait disturbance, cognitive dysfunction, and urinary incontinence that affects a large population of elderly people. These symptoms, especially gait disturbance, can potentially be improved by cerebrospinal fluid (CSF) drainage, which is more effective if performed at an early stage of the disease. However, the neurophysiological mechanisms of these symptoms and their recovery by CSF drainage are poorly understood. In this study, using exact low-resolution brain electromagnetic tomography-independent component analysis (eLORETA-ICA) with electroencephalography (EEG) data, we assessed activities of five EEG resting-state networks (EEG-RSNs) in 58 iNPH patients before and after drainage of CSF by lumbar puncture (CSF tapping). In addition, we assessed correlations of changes in these five EEG-RSNs activities with CSF tapping-induced changes in iNPH symptoms. The results reveal that compared with 80 healthy controls, iNPH patients had significantly decreased activities in the occipital alpha rhythm, visual perception network, and self-referential network before CSF tapping. Furthermore, CSF tapping-induced changes in occipital alpha activity correlated with changes in postural sway and frontal lobe function. Changes in visual perception network activity correlated with changes in gait speed. In addition, changes in memory perception network activity correlated with changes in Parkinsonian gait features. These results indicate a recruitment of cognitive networks in gait control, and involvement of the occipital alpha activity in cognitive dysfunction in iNPH patients. Based on these findings, eLORETA-ICA with EEG data can be considered a noninvasive, useful tool for detection of EEG-RSN activities and for understanding the neurophysiological mechanisms underlying this disease.

CSF cystatin C and diffusion tensor imaging parameters as biomarkers of upper motor neuron degeneration in amyotrophic lateral sclerosis.

OBJECTIVES: The establishment of biomarkers for amyotrophic lateral sclerosis (ALS) will be useful for early diagnosis and may provide evidence about pathogenesis. To elucidate whether high-field magnetic resonance (MR) findings and multimodal analysis of cerebrospinal fluid (CSF) levels of cystatin C could be indicators of upper motor neuron (UMN) involvement in ALS. PATIENTS AND METHODS: Patients with ALS (n = 20), multiple sclerosis (n = 15), immune mediated chronic polyneuropathy (n = 17), and acute polyneuropathy (n = 12) were included in this retrospective study. Clinical indices including UMN signs were assessed, and 3.0-Tesla diffusion tensor imaging and MR spectroscopy were performed in patients with ALS. CSF levels of cystatin C were measured using enzyme-linked immunosorbent assay. RESULTS: MR findings indicated that decreased anisotropy, increased diffusion, and increased myo-inositol/creatine ratio were also significantly correlated with UMN involvement in patients with ALS. The CSF cystatin C levels were significantly lower in patients with ALS than in the other three groups. The reduction of CSF cystatin C levels was significantly correlated with clinical UMN involvement (r = -0.505, p =  0.023). CONCLUSIONS: Reduced cystatin C in CSF can reflect UMN involvement as shown in high-field MR of ALS, potentially providing a new biomarker for UMN degeneration in ALS.

Neural Basis of Apathy in Patients with Amnestic Mild Cognitive Impairment.

BACKGROUND: Although apathy is associated with damage to the frontal and temporal lobes in Alzheimer's disease (AD), the crucial regions for apathy in patients with amnestic mild cognitive impairment (aMCI) are unknown. OBJECTIVE: To identify brain regions associated with apathy in aMCI patients. METHODS: The subjects of this study were 98 aMCI patients who were entered in our dementia registry between March 1, 2009 and April 30, 2015 and who satisfied our criteria for aMCI. The association between the apathy score of the Neuropsychiatric Inventory and regional gray matter volume was analyzed using voxel-based morphometry. The association between apathy score and regional cerebral blood flow (rCBF) measured with single photon emission computed tomography (SPECT) was analyzed using Statistical Parametric Mapping. RESULTS: The aMCI patients were classified into aMCI with and without "SPECT images suggestive of AD" (aMCI-AD+ and aMCI-AD-, respectively) based on the Z-score summation analysis method. In aMCI-AD+ (n = 31), apathy was significantly and negatively correlated with gray matter volume in the right caudate nucleus and with rCBF in five regions (left posterior-medial frontal lobe, right superior frontal lobe, bilateral culmen-fusiform gyri, and left occipital lobe). In aMCI-AD-(n = 67), apathy was significantly and negatively correlated with gray matter volumes in five regions but it was not correlated with rCBF in any regions. CONCLUSION: In patients with a high probability of being in the aMCI stage of AD, apathy was associated with atrophy of the right caudate nucleus and hypoperfusion in the frontal, temporal and occipital lobes.

Association between high biomarker probability of Alzheimer's disease and improvement of clinical outcomes after shunt surgery in patients with idiopathic normal pressure hydrocephalus.

We examined the effect of the pathology of Alzheimer's disease (AD) on improvement of clinical symptoms after shunt surgery in patients with idiopathic normal pressure hydrocephalus (iNPH). Forty-four iNPH patients were classified into 18 patients with (iNPH/AD+) and 26 patients without (iNPH/AD-) combination with low amyloid ß42 and high total tau in cerebrospinal fluid (CSF). We compared improvements after lumbo-peritoneal shunt surgery (LPS) between the two groups in Timed Up & Go Test, 10-m reciprocating walking test, Digit Symbol Substitution Test, attention test, delayed recall test, Mini-Mental State Examination, iNPH grading scale, Neuropsychiatric Inventory, Zarit Burden Interview, and other evaluations. Three months after LPS, gait, urination, overall cognition, psychomotor speed, attention, and neuropsychiatric symptoms significantly improved in both groups, but the improvement in delayed recall and reduction of caregiver burden were significantly greater in iNPH/AD- than iNPH/AD+. In addition, improvement in delayed recall score after LPS was significantly and negatively correlated with the probability of AD as judged by amyloid ß42 and total tau levels in CSF. Three months after LPS, almost all of the triad symptoms decreased in iNPH patients with and without AD pathology but memory improved only in iNPH patients without AD pathology.