Keiko Nomura

Neuropsychiatric Symptoms in Patients with Idiopathic Normal Pressure Hydrocephalus

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

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

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

Classification of delusions in Alzheimer's disease and their neural correlates

Background:u2002 Previous findings on neural correlates of delusion in Alzheimers disease (AD) have been inconsistent because of methodological issues, such as treating multiple delusions as a single entity. In this retrospective study, we classified AD delusions and investigated their neural correlates by using single‐photon emission computed tomography data.

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

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

Association between Milder Brain Deformation before a Shunt Operation and Improvement in Cognition and Gait in Idiopathic Normal Pressure Hydrocephalus

We investigated the association between the degree of deformation of the brain before shunt operation and improvement of gait and cognitive impairment after shunt operation in 16 patients with idiopathic normal pressure hydrocephalus (iNPH). We evaluated gait and cognitive impairment and measured the cerebrospinal fluid volume in the ventricles/sylvian fissure (vVS) and the subarachnoid space at high convexity/midline areas (vHCM) using MR images with voxel-based morphometry before and 3 months after shunt operation. We used the ratio of vVS to vHCM (vVS/vHCM) as an index of the severity of brain deformation. After shunt operation, improvements were observed in gait, as shown by the Timed Up and Go (TUG) test and 10-meter reciprocating walking test (WT), and in cognitive function, as shown by the Mini-Mental State Examination, Alzheimer Disease Assessment Scale, Frontal Assessment battery (FAB), and Trail Making test A (TMT-A). The vVS/vHCM ratio was negatively correlated with improvement of the FAB, TMT-A and TUG. Preoperative vVS/vHCM was not significantly correlated with preoperative clinical assessments. The rate of change of vVS/vHCM was positively correlated with improvement in the WT. The improvements of gait and cognitive function were larger in iNPH patients with milder deformation of the brain before shunt operation.

Possible roles of the dominant uncinate fasciculus in naming objects: A case report of intraoperative electrical stimulation on a patient with a brain tumour

How the dominant uncinate fasciculus (UF) contributes to naming performance is uncertain. In this case report, a patient with an astrocytoma near the dominant UF was given a picture-naming task during intraoperative electrical stimulation in order to resect as much tumourous tissues as possible without impairing the dominant UF function. Here we report that the stimulations with the picture-naming task also provided some insights into how the dominant UF contributes to naming performance. The stimulation induced naming difficulty, verbal paraphasia, and recurrent and continuous perseveration. Moreover, just after producing the incorrect responses, the patient displayed continuous perseveration even though the stimulation had ended. The left UF connects to the inferior frontal lobe, which is necessary for word production, so that the naming difficulty appears to be the result of disrupted word production caused by electrical stimulation of the dominant UF. The verbal paraphasia appears to be due to the failure to select the correct word from semantic memory and the failure to suppress the incorrect word. The left UF is associated with working memory, which plays an important role in recurrent perseveration. The continuous perseveration appears to be due to disturbances in word production and a failure to inhibit an appropriate response. These findings in this case suggest that the dominant UF has multiple roles in the naming of objects.

EEG and Neuronal Activity Topography analysis can predict effectiveness of shunt operation in idiopathic normal pressure hydrocephalus patients

Idiopathic normal pressure hydrocephalus (iNPH) is a neuropsychiatric syndrome characterized by gait disturbance, cognitive impairment and urinary incontinence that affect elderly individuals. These symptoms can potentially be reversed by cerebrospinal fluid (CSF) drainage or shunt operation. Prior to shunt operation, drainage of a small amount of CSF or “CSF tapping” is usually performed to ascertain the effect of the operation. Unfortunately, conventional neuroimaging methods such as single photon emission computed tomography (SPECT) and functional magnetic resonance imaging (fMRI), as well as electroencephalogram (EEG) power analysis seem to have failed to detect the effect of CSF tapping on brain function. In this work, we propose the use of Neuronal Activity Topography (NAT) analysis, which calculates normalized power variance (NPV) of EEG waves, to detect cortical functional changes induced by CSF tapping in iNPH. Based on clinical improvement by CSF tapping and shunt operation, we classified 24 iNPH patients into responders (N = 11) and nonresponders (N = 13), and performed both EEG power analysis and NAT analysis. We also assessed correlations between changes in NPV and changes in functional scores on gait and cognition scales before and after CSF tapping. NAT analysis showed that after CSF tapping there was a significant decrease in alpha NPV at the medial frontal cortex (FC) (Fz) in responders, while nonresponders exhibited an increase in alpha NPV at the right dorsolateral prefrontal cortex (DLPFC) (F8). Furthermore, we found correlations between cortical functional changes and clinical symptoms. In particular, delta and alpha NPV changes in the left-dorsal FC (F3) correlated with changes in gait status, while alpha and beta NPV changes in the right anterior prefrontal cortex (PFC) (Fp2) and left DLPFC (F7) as well as alpha NPV changes in the medial FC (Fz) correlated with changes in gait velocity. In addition, alpha NPV changes in the right DLPFC (F8) correlated with changes in WMS-R Mental Control scores in iNPH patients. An additional analysis combining the changes in values of alpha NPV over the left-dorsal FC (∆alpha-F3-NPV) and the medial FC (∆alpha-Fz-NPV) induced by CSF tapping (cut-off value of ∆alpha-F3-NPV + ∆alpha-Fz-NPV = 0), could correctly identified “shunt responders” and “shunt nonresponders” with a positive predictive value of 100% (10/10) and a negative predictive value of 66% (2/3). In contrast, EEG power spectral analysis showed no function related changes in cortical activity at the frontal cortex before and after CSF tapping. These results indicate that the clinical changes in gait and response suppression induced by CSF tapping in iNPH patients manifest as NPV changes, particularly in the alpha band, rather than as EEG power changes. Our findings suggest that NAT analysis can detect CSF tapping-induced functional changes in cortical activity, in a way that no other neuroimaging methods have been able to do so far, and can predict clinical response to shunt operation in patients with iNPH.

Reversibility of brain morphology after shunt operations and preoperative clinical symptoms in patients with idiopathic normal pressure hydrocephalus.

Brain deformations might prevent clinical symptoms from worsening in patients with idiopathic normal pressure hydrocephalus (iNPH). We investigated the relationship between reversibility of brain morphology after shunt operations and preoperative clinical symptoms in iNPH patients.

Effects of donepezil on sleep disturbances in patients with dementia with Lewy bodies: An open-label study with actigraphy

We investigated whether donepezil, a cholinesterase inhibitor, can be used to treat sleep disturbances in patients with dementia with Lewy bodies (DLB). Sleep disturbances were evaluated with the sleep disturbances item of the Neuropsychiatric inventory (NPI) and an actigraph in 16 DLB patients and 24 normal elderly control (NC) subjects. The presence/absence of nine kinds of sleep symptoms, such as dream enactment, were also evaluated in the DLB patients. The DLB patients were then given 5mg/day donepezil for 14 weeks and evaluated again. Eight of the 16 DLB patients had some sleep disturbances before taking donepezil. The actigraphy data indicated that average activity count per minute in sleep (AAC), which reflects body activity at night, was significantly higher and total sleep time was significantly longer in DLB patients than in NC subjects. The NPI sleep disturbances score significantly improved and the number of DLB patients who had sleep disturbances decreased after taking donepezil. The actigraphy results indicate that the sum of all wake epochs within the sleep period, which reflects the degree of fragmented sleep, and the AAC decreased in the DLB patients after donepezil treatment. These results indicate that donepezil treatment reduced sleep disturbances in DLB patients.

Electrical stimulation of the parahippocampal gyrus for prediction of posthippocampectomy verbal memory decline

OBJECTIVE Epilepsy surgery is of known benefit for drug-resistant temporal lobe epilepsy (TLE); however, a certain number of patients suffer significant decline in verbal memory after hippocampectomy. To prevent this disabling complication, a reliable test for predicting postoperative memory decline is greatly desired. Therefore, the authors assessed the value of electrical stimulation of the parahippocampal gyrus (PHG) as a provocation test of verbal memory decline after hippocampectomy on the dominant side. METHODS Eleven right-handed, Japanese-speaking patients with medically intractable left TLE participated in the study. Before surgery, they underwent provocative testing via electrical stimulation of the left PHG during a verbal encoding task. Their pre- and posthippocampectomy memory function was evaluated according to the Wechsler Memory Scale-Revised (WMS-R) and/or Mini-Mental State Examination (MMSE) before and 6 months after surgery. The relationship between postsurgical memory decline and results of the provocative test was evaluated. RESULTS Left hippocampectomy was performed in 7 of the 11 patients. In 3 patients with a positive provocative recognition test, verbal memory function, as assessed by the WMS-R, decreased after hippocampectomy, whereas in 4 patients with a negative provocative recognition test, verbal memory function, as assessed by the WMS-R or MMSE, was preserved. CONCLUSIONS Results of the present study suggest that electrical stimulation of the PHG is a reliable provocative test to predict posthippocampectomy verbal memory decline.