A prospective multicenter validation study of a machine learning algorithm classifier on quantitative electroencephalogram for differentiating between dementia with Lewy bodies and Alzheimer's dementia.

BACKGROUND AND PURPOSE: An early and accurate diagnosis of Dementia with Lewy bodies (DLB) is critical because treatments and prognosis of DLB are different from Alzheimer's disease (AD). This study was carried out in Japan to validate an Electroencephalography (EEG)-derived machine learning algorithm for discriminating DLB from AD which developed based on a database of EEG records from two different European countries. METHODS: In a prospective multicenter study, patients with probable DLB or with probable AD were enrolled in a 1:1 ratio. A continuous EEG segment of 150 seconds was recorded, and the EEG data was processed using MC-004, the EEG-based machine learning algorithm, with all clinical information blinded except for age and gender. RESULTS: Eighteen patients with probable DLB and 21 patients with probable AD were the included for the analysis. The performance of MC-004 differentiating probable DLB from probable AD was 72.2% (95% CI 46.5-90.3%) for sensitivity, 85.7% (63.7-97.0%) for specificity, and 79.5% (63.5-90.7%) for accuracy. When limiting to subjects taking ≤5 mg donepezil, the sensitivity was 83.3% (95% CI 51.6-97.9), the specificity 89.5% (66.9-98.7), and the accuracy 87.1% (70.2-96.4). CONCLUSIONS: MC-004, the EEG-based machine learning algorithm, was able to discriminate between DLB and AD with fairly high accuracy. MC-004 is a promising biomarker for DLB, and has the potential to improve the detection of DLB in a diagnostic process.

Descriptive, injunctive, or the synergy of both? Experimenting normative information on behavioral changes under the COVID-19 pandemic.

Backgrounds: The effectiveness of citizens' behavioral changes to prevent the spread of SARS-CoV-2, such as avoiding large social events, relies on science communication from policymakers and collective action among peer citizens. Extant studies recognize the potential effects of information stimuli on citizens' behavioral changes, including what epidemiological experts request (injunctive information) and what surrounding people behave (descriptive information). Yet, they have insufficiently assessed the co-occurrence and possible interaction of multiple information stimuli. Methods: 1,819 Japanese citizens aged 18 or over were recruited for an experimental survey during March 1-3, 2021 and asked their views on a hypothetical wedding attendance in Japan while being exposed to randomly assigned normative information stimuli. Their willingness to attend a wedding asked before and after the intervention was measured. Infection risk perception was also asked as a mediating variable. Results: Findings suggest the constant supremacy of descriptive information and no synergistic effects in the interaction of multiple information stimuli. We also report that the effects of injunctive and descriptive information vary according to participants' risk perception, age, and trust in experts. Conclusion: Our experimental test enables a systematic assessment of multiple normative information and confirms the primacy of descriptive information as the main driver of behavioral change. Communication by medical experts has limitations but is still effective in specific categories of the population.

Relationship between decreased cerebral blood flow and amnesia after microsurgery for anterior communicating artery aneurysm.

OBJECTIVE: Postoperative amnesia after surgery for anterior communicating artery aneurysm might be associated with the damage of the basal forebrain. Our purpose was to verify whether decreased regional cerebral blood flow (rCBF) in basal forebrain could be related to the degree of postoperative amnesia. METHODS: Regional voxel rCBF data analyzed using three-dimensional stereotactic surface projection on 123I-IMP-SPECT were compared between ten patients with postoperative amnesia and 13 normal subjects. The Severity (average Z score of the voxels with a Z score that exceeds a threshold value of 2) was calculated. The cerebral lobes with rCBF exhibiting Severity > 2 in all patients were identified. In these lobes, we then examined whether there was a gyrus exhibiting Severity that was negatively related to memory quotients (MQs). RESULTS: In the right subcallosal gyrus, there was a significant negative correlation between Severity and visual MQ (ρ= - 0.884, p = 0.0007) or general MQ (ρ =- 0.853, p = 0.0017). In the right anterior cingulate gyrus, there was a significant negative correlation between Severity and verbal MQ (ρ = - 0.769, p = 0.0092). In the right rectal gyrus, there was a significant negative correlation between Severity and general MQ (ρ = - 0.811, p = 0.0044). No significant correlations were found between Severity in other brain regions and verbal, visual, or general MQ. CONCLUSIONS: The decreased rCBF in the subcallosal gyrus included in the basal forebrain, anterior cingulate gyrus, and the rectal gyrus in the right hemisphere was related to postoperative amnesia.

[Medial Temporal Lobe Amnesia].

The medial temporal lobe was identified as an important neural structure in human memory by the advent of patient H.M., who suffered from severe amnesia caused by bilateral medial temporal lobectomy. Dozens of neuropsychological study of H.M. led to the classification of human memory into declarative and non-declarative memory, as well as short-term and long-term memory. The medial temporal lobe subserves declarative memory and long-term memory. It also plays an important role especially in the process of memory consolidation. The psychological and neurological mechanisms of the consolidation process can be investigated through the study of retrograde amnesia and epileptic amnesia.

Subcallosal and Heubner artery infarcts following surgical repair of an anterior communicating artery aneurysm: a causal relationship with postoperative amnesia and long-term outcome.

Since the 1950s, amnesia or memory impairment has been repeatedly reported in patients following surgical repair of anterior communicating artery (ACoA) aneurysms. Postoperative infarctions following surgical repair of ACoA aneurysms are classified as involvement of the subcallosal artery (the largest unpaired perforator of the ACoA), the recurrent artery of Heubner (RAH), or a combination of both. Postoperative amnesia can seriously affect the patient's quality of life, thus prompting physicians to discuss the symptomatology of the three infarction patterns. We made the following speculations regarding the causal relationship between the infarction pattern and postoperative amnesia. First, postoperative amnesia is most likely caused by an infarction in the territory of the subcallosal artery, particularly in the column of the fornix, a constituent of the Papez neuronal circuit. Second, infarction in the RAH territory alone is unlikely to cause significant amnesia. Third, infarcted foci in the RAH territory, when associated with a subcallosal artery infarction, can cause considerable frontal dysfunction due to impaired frontostriatal circuits in patients with postoperative amnesia, with resultant worsening of the long-term outcome or quality of life.

A change in brain white matter after shunt surgery in idiopathic normal pressure hydrocephalus: a tract-based spatial statistics study.

BACKGROUND: The aim of this study was to elucidate changes in cerebral white matter after shunt surgery in idiopathic normal pressure hydrocephalus (INPH) using diffusion tensor imaging (DTI). METHODS: Twenty-eight consecutive INPH patients whose symptoms were followed for 1 year after shunt placement and 10 healthy control (HC) subjects were enrolled. Twenty of the initial 28 INPH patients were shunt-responsive (SR) and the other 8 patients were non-responsive (SNR). The cerebral white matter integrity was detected by assessing fractional anisotropy (FA) and mean diffusivity (MD). The mean hemispheric DTI indices and the ventricular sizes were calculated, and a map of these DTI indices was created for each subject. The DTI maps were analysed to compare preshunt INPH with HC and preshunt INPH with 1 year after shunt placement in each INPH group, using tract-based spatial statistics. We restricted analyses to the left hemisphere because of shunt valve artefacts. RESULTS: The ventricles became significantly smaller after shunt placement both in the SR and SNR groups. In addition, there was a significant interaction between clinical improvement after shunt and decrease in ventricular size. Although the hemispheric DTI indices were not significantly changed after shunt placement, there was a significant interaction between clinical improvement and increase in hemispheric MD. Compared with the HC group, FA in the corpus callosum and in the subcortical white matter of the convexity and the occipital cortex was significantly lower in SR at baseline, whereas MD in the periventricular and peri-Sylvian white matter was significantly higher in the SR group. Compared with the pre-operative images, the post-operative FA was only decreased in the corona radiata and only in the SR group. There were no significant regions in which DTI indices were altered after shunt placement in the SNR group. CONCLUSIONS: Brain white matter regions in which FA was decreased after shunt placement were in the corona radiata between the lateral ventricles and the Sylvian fissures. This finding was observed only in shunt-responsive INPH patients and might reflect the plasticity of the brain for mechanical pressure changes from the cerebrospinal fluid system.

Amyloid deposits and response to shunt surgery in idiopathic normal-pressure hydrocephalus.

OBJECTIVES: In previous studies, patients with idiopathic normal-pressure hydrocephalus (iNPH) occasionally showed Alzheimer's pathology in frontal lobe cortical biopsy during cerebrospinal fluid shunt surgery or intracranial pressure monitoring. In clinical practice, the differential diagnosis of iNPH from Alzheimer's disease (AD) can be problematic, particularly because some iNPH cases exhibit AD comorbidity. In this study, we evaluated amyloid deposition in the brains of patients with iNPH before shunt surgery, and investigated the association between brain amyloid deposits and clinical improvement following the surgery. MATERIALS & METHODS: Amyloid imaging was performed in patients with iNPH or AD and also in healthy control subjects by using positron emission tomography (PET) and a radiolabeled pharmaceutical compound, (11)C-BF227. Using the cerebellar hemispheres as reference regions, the standard uptake value ratio (SUVR) of the neocortex was estimated and used as an index for amyloid deposition. In patients with iNPH, clinical symptoms were assessed before shunt surgery and 3 months after surgery. RESULTS: Five of the 10 patients with iNPH had neocortical SUVRs that were as high as those of AD subjects, whereas the SUVRs of the 5 patients were as low as those of healthy controls. A significant inverse correlation between neocortical SUVRs and cognitive improvements after shunt surgery was observed in iNPH. CONCLUSIONS: The amount of amyloid deposits ranges widely in the brains of patients with iNPH and is associated with the degree of cognitive improvement after shunt surgery.

Cognitive profile of idiopathic normal pressure hydrocephalus.

BACKGROUND/AIMS: Frontal lobe dysfunction is believed to be a primary cognitive symptom in idiopathic normal pressure hydrocephalus (iNPH); however, the neuropsychology of this disorder remains to be fully investigated. The objective of this study was to delineate a comprehensive profile of cognitive dysfunction in iNPH and evaluate the effects of cerebrospinal fluid (CSF) shunt surgery on cognitive dysfunction. METHODS: A total of 32 iNPH patients underwent neuropsychological testing of memory, attention, language, executive function, and visuoperceptual and visuospatial abilities. Of these 32 patients, 26 were reevaluated approximately 1 year following CSF shunt surgery. The same battery of tests was performed on 32 patients with Alzheimer's disease (AD) and 30 healthy elderly controls. RESULTS: The iNPH patients displayed baseline deficits in attention, executive function, memory, and visuoperceptual and visuospatial functions. Impairments of attention, executive function, and visuoperceptual and visuospatial abilities in iNPH patients were more severe than in those with AD, whereas the degree of memory impairment was comparable to that in AD patients. A significant improvement in executive function was observed following shunt surgery. CONCLUSION: Patients with iNPH are impaired in various aspects of cognition involving both 'frontal' executive functions and 'posterior cortical' functions. Shunt treatment can ameliorate executive dysfunction.

White matter involvement in idiopathic normal pressure hydrocephalus: a voxel-based diffusion tensor imaging study.

The aim of this study was to characterise the white matter damage involved in idiopathic normal pressure hydrocephalus (INPH) using diffusion tensor imaging (DTI) and the relationship between this damage and clinical presentation. Twenty patients with INPH, 20 patients with Alzheimer's disease and 20 patients with idiopathic Parkinson's disease (as disease control groups) were enrolled in this study. Mean diffusivity (MD) and fractional anisotropy (FA) were determined using DTI, and these measures were analysed to compare the INPH group with the control groups and with certain clinical correlates. On average, the supratentorial white matter presented higher MD and lower FA in the INPH group than in the control groups. In the INPH group, the mean hemispheric FA correlated with some of the clinical measures, whereas the mean hemispheric MD did not. On a voxel-based statistical map, white matter involvement with high MD was localised to the periventricular regions, and white matter involvement with low FA was localised to the corpus callosum and the subcortical regions. The total scores on the Frontal Assessment Battery were correlated with the FA in the frontal and parietal subcortical white matter, and an index of gait disturbance was correlated with the FA in the anterior limb of the left internal capsule and under the left supplementary motor area. DTI revealed the presence of white matter involvement in INPH. Whereas white matter regions with high MD were not related to symptom manifestation, those with low FA were related to motor and cognitive dysfunction in INPH.

False item recognition in patients with Alzheimer's disease.

Recent evidence suggests that patients with Alzheimer's disease (AD), as compared with normal individuals, exhibit increased false recognition by stimulus repetition in the Deese-Roediger-McDermott (DRM) task or associative recognition memory tasks, probably due to impaired recollection-based monitoring. However, because of possible alternative explanations for the findings of these previous studies, the evidence for impaired recollection-based monitoring in AD patients remains inconclusive. In this study, we employed stimulus repetition in old/new recognition judgments of single-item picture memory without a factor of association between the stimuli and examined whether AD patients showed increased false item recognition as compared with healthy controls. AD patients and healthy controls studied single-item pictures presented either once or three times. They were later asked to make an old/new recognition judgment in response to (a) Same pictures, pictures identical to those seen at encoding, (b) Similar lures, novel pictures similar to but not identical to those seen at encoding, and (c) Dissimilar lures, novel pictures not similar to those seen at encoding. For Same pictures, repeated presentation of stimuli increased the proportion of "old" responses in both groups. For Similar lures, repeated presentation of stimuli increased the rate of "old" responses in AD patients but not in control subjects. The results of the present study clearly demonstrated elevated false recognition by stimulus repetition in single-item recognition in AD patients. The present findings strongly support the view that AD patients are impaired in their ability to use item-specific recollection in order to avoid false recognition.

Is the midbrain involved in the manifestation of gait disturbance in idiopathic normal-pressure hydrocephalus?

Gait disturbance is the most common symptom in idiopathic normal-pressure hydrocephalus (iNPH). However, its pathophysiology in iNPH has not been clarified. Some researchers have hypothesized that the mesencephalic locomotor region, which is a functionally defined area in the brainstem playing an important role in locomotion, is involved in the development of gait disturbance in iNPH. The purpose of the study was to investigate whether the midbrain is involved in the manifestation of gait disturbance in iNPH. Twenty-one iNPH patients who showed clinical improvements after shunt surgery were studied. Brain magnetic resonance imaging (MRI) was performed and clinical symptoms were assessed before and 1 year after surgery. Gait disturbance was assessed by the Timed Up and Go test and gait subcategory of the iNPH Grading Scale, a validated assessment tool for iNPH symptoms. Anteroposterior, left-to-right diameter and cross-sectional areas of the midbrain were measured at the inferior collicular level of axial images in MRI. The diameters and cross-sectional area of the midbrain at baseline did not show significant correlation with gait assessments at baseline (Spearman's correlation). The midbrain measurement did not show significant difference between the baseline and postoperative values (paired t test), and its change rates did not show significant correlation with the change (rates) of the gait assessments. In this study there were no findings to suggest involvement of the midbrain in the manifestation of gait disturbance in iNPH. The hypothesis that the mesencephalic locomotor region is involved in the manifestation of gait disturbance in iNPH needs to be reconsidered.

Changes in the volumes of the brain and cerebrospinal fluid spaces after shunt surgery in idiopathic normal-pressure hydrocephalus.

OBJECTIVES: To investigate volumetric changes of the brain and cerebrospinal fluid (CSF) spaces after shunt surgery in shunt-responsive idiopathic normal-pressure hydrocephalus (iNPH), and correlations between the changes and postoperative clinical improvements. METHODS: Twenty-one patients with shunt-responsive iNPH were studied. Magnetic resonance imaging (MRI) of the brain was performed before and 1year after surgery, and clinical symptoms were assessed by the iNPH Grading Scale, a validated assessment tool of the triad of iNPH, the Modified Rankin Scale, the Timed Up and Go Test, and neuropsychological tests including the Mini-Mental State Examination. The volumes of the left cerebral hemisphere, infratentorial brain, ventricles, and suprasylvian and infrasylvian subarachnoid CSF spaces were measured using an MRI-based volumetric technique. RESULTS: The volumes of the cerebral hemisphere and infratentorial brain did not change significantly after shunt surgery (p=0.231, 0.109, respectively). The volumes of the ventricles and infrasylvian subarachnoid CSF spaces were significantly decreased (p<0.0001, <0.05, respectively), with a mean change rate of -26.1% and -4.5%, respectively. The volumes of the suprasylvian subarachnoid CSF spaces increased significantly (p<0.0001), with a mean change rate of 43.5%. The decrease in ventricular volumes was significantly correlated with clinical improvement.

Memory repression: brain mechanisms underlying dissociative amnesia.

Dissociative amnesia usually follows a stressful event and cannot be attributable to explicit brain damage. It is thought to reflect a reversible deficit in memory retrieval probably due to memory repression. However, the neural mechanisms underlying this condition are not clear. We used fMRI to investigate neural activity associated with memory retrieval in two patients with dissociative amnesia. For each patient, three categories of face photographs and three categories of people's names corresponding to the photographs were prepared: those of "recognizable" high school friends who were acquainted with and recognizable to the patients, those of "unrecognizable" colleagues who were actually acquainted with but unrecognizable to the patients due to their memory impairments, and "control" distracters who were unacquainted with the patients. During fMRI, the patients were visually presented with these stimuli and asked to indicate whether they were personally acquainted with them. In the comparison of the unrecognizable condition with the recognizable condition, we found increased activity in the pFC and decreased activity in the hippocampus in both patients. After treatment for retrograde amnesia, the altered pattern of brain activation disappeared in one patient whose retrograde memories were recovered, whereas it remained unchanged in the other patient whose retrograde memories were not recovered. Our findings provide direct evidence that memory repression in dissociative amnesia is associated with an altered pattern of neural activity, and they suggest the possibility that the pFC has an important role in inhibiting the activity of the hippocampus in memory repression.