Makoto Uchiyama

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.

Pareidolias: complex visual illusions in dementia with Lewy bodies

Patients rarely experience visual hallucinations while being observed by clinicians. Therefore, instruments to detect visual hallucinations directly from patients are needed. Pareidolias, which are complex visual illusions involving ambiguous forms that are perceived as meaningful objects, are analogous to visual hallucinations and have the potential to be a surrogate indicator of visual hallucinations. In this study, we explored the clinical utility of a newly developed instrument for evoking pareidolic illusions, the Pareidolia test, in patients with dementia with Lewy bodies—one of the most common causes of visual hallucinations in the elderly. Thirty-four patients with dementia with Lewy bodies, 34 patients with Alzheimer’s disease and 26 healthy controls were given the Pareidolia test. Patients with dementia with Lewy bodies produced a much greater number of pareidolic illusions compared with those with Alzheimer’s disease or controls. A receiver operating characteristic analysis demonstrated that the number of pareidolias differentiated dementia with Lewy bodies from Alzheimer’s disease with a sensitivity of 100% and a specificity of 88%. Full-length figures and faces of people and animals accounted for >80% of the contents of pareidolias. Pareidolias were observed in patients with dementia with Lewy bodies who had visual hallucinations as well as those who did not have visual hallucinations, suggesting that pareidolias do not reflect visual hallucinations themselves but may reflect susceptibility to visual hallucinations. A sub-analysis of patients with dementia with Lewy bodies who were or were not treated with donepzil demonstrated that the numbers of pareidolias were correlated with visuoperceptual abilities in the former and with indices of hallucinations and delusional misidentifications in the latter. Arousal and attentional deficits mediated by abnormal cholinergic mechanisms and visuoperceptual dysfunctions are likely to contribute to the development of visual hallucinations and pareidolias in dementia with Lewy bodies.

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.

Hallucinators find meaning in noises: pareidolic illusions in dementia with Lewy bodies.

By definition, visual illusions and hallucinations differ in whether the perceived objects exist in reality. A recent study challenged this dichotomy, in which pareidolias, a type of complex visual illusion involving ambiguous forms being perceived as meaningful objects, are very common and phenomenologically similar to visual hallucinations in dementia with Lewy bodies (DLB). We hypothesise that a common psychological mechanism exists between pareidolias and visual hallucinations in DLB that confers meaning upon meaningless visual information. Furthermore, we believe that these two types of visual misperceptions have a common underlying neural mechanism, namely, cholinergic insufficiency. The current study investigated pareidolic illusions using meaningless visual noise stimuli (the noise pareidolia test) in 34 patients with DLB, 34 patients with Alzheimer׳s disease and 28 healthy controls. Fifteen patients with DLB were administered the noise pareidolia test twice, before and after donepezil treatment. Three major findings were discovered: (1) DLB patients saw meaningful illusory images (pareidolias) in meaningless visual stimuli, (2) the number of pareidolic responses correlated with the severity of visual hallucinations, and (3) cholinergic enhancement reduced both the number of pareidolias and the severity of visual hallucinations in patients with DLB. These findings suggest that a common underlying psychological and neural mechanism exists between pareidolias and visual hallucinations in DLB.

Neural Substrates of Cognitive Subtypes in Parkinson's Disease: A 3-Year Longitudinal Study

Background The neuropsychological features and neuropathological progression patterns associated with rapidly evolving cognitive decline or dementia in Parkinsons disease (PD) remain to be elucidated. Methods Fifty-three PD patients without dementia were recruited to participate in a 3-year longitudinal cohort study. The patients were grouped according to the Clinical Dementia Rating (CDR). Group-wise comparisons were made with regard to demographic characteristics, motor symptoms, neuropsychological performances and 18F-fluorodeoxyglucose positron emission tomography. Results Patients who had memory-plus cognitive impairment (patients whose CDR was 0 at baseline and 0.5 in memory and other domains at follow-up, and those whose baseline CDR was 0.5 in memory and other domains) exhibited higher age at onset, visuoperceptual impairment, non-tremor-dominant motor disturbance, rapid symptomatic progression and posterior neocortical hypometabolism. In patients who were cognitively unimpaired and those who had memory-dominant cognitive impairment (patients whose CDR was 0 at baseline and 0.5 only in memory domain at follow-up, and those whose baseline CDR was 0.5 only in memory domain), the posterior neocortex was relatively unaffected until a later stage of the disease. Conclusions These results suggest that visuoperceptual impairment and the early involvement of the posterior neocortex may be risk factors for rapid symptomatic progression and dementia in PD.

Pareidolia in Parkinson's disease without dementia: A positron emission tomography study

BACKGROUND Pareidolia, which is a particular type of complex visual illusion, has been reported to be a phenomenon analogous to visual hallucinations in patients with dementia with Lewy bodies. However, whether pareidolia is observed in Parkinsons disease (PD) or whether there are common underlying mechanisms of these two types of visual misperceptions remains to be elucidated. METHODS A test to evoke pareidolia, the Pareidolia test, was administered to 53 patients with PD without dementia and 24 healthy controls. The regional cerebral metabolic rate of glucose was measured using 18F-fluorodeoxyglucose positron emission tomography in the PD patients. RESULTS PD patients without dementia produced a greater number of pareidolic illusions compared with the controls. Pareidolia was observed in all of the patients having visual hallucinations as well as a subset of those without visual hallucinations. The number of pareidolic illusions was correlated with hypometabolism in the bilateral temporal, parietal and occipital cortices. The index of visual hallucinations was correlated with hypometabolism in the left parietal cortex. A region associated with both pareidolia and visual hallucinations was found in the left parietal lobe. CONCLUSIONS Our study suggests that PD patients without dementia experience pareidolia more frequently than healthy controls and that posterior cortical dysfunction could be a common neural mechanism of pareidolia and visual hallucinations. Pareidolia could represent subclinical hallucinations or a predisposition to visual hallucinations in Lewy body disease.

Counting-backward test for executive function in idiopathic normal pressure hydrocephalus.

The aim of this study was to develop and validate a bedside test for executive function in patients with idiopathic normal pressure hydrocephalus (INPH).

The Pareidolia Test: A Simple Neuropsychological Test Measuring Visual Hallucination-Like Illusions

Background Visual hallucinations are a core clinical feature of dementia with Lewy bodies (DLB), and this symptom is important in the differential diagnosis and prediction of treatment response. The pareidolia test is a tool that evokes visual hallucination-like illusions, and these illusions may be a surrogate marker of visual hallucinations in DLB. We created a simplified version of the pareidolia test and examined its validity and reliability to establish the clinical utility of this test. Methods The pareidolia test was administered to 52 patients with DLB, 52 patients with Alzheimer’s disease (AD) and 20 healthy controls (HCs). We assessed the test-retest/inter-rater reliability using the intra-class correlation coefficient (ICC) and the concurrent validity using the Neuropsychiatric Inventory (NPI) hallucinations score as a reference. A receiver operating characteristic (ROC) analysis was used to evaluate the sensitivity and specificity of the pareidolia test to differentiate DLB from AD and HCs. Results The pareidolia test required approximately 15 minutes to administer, exhibited good test-retest/inter-rater reliability (ICC of 0.82), and moderately correlated with the NPI hallucinations score (rs = 0.42). Using an optimal cut-off score set according to the ROC analysis, and the pareidolia test differentiated DLB from AD with a sensitivity of 81% and a specificity of 92%. Conclusions Our study suggests that the simplified version of the pareidolia test is a valid and reliable surrogate marker of visual hallucinations in DLB.

Deconstructing psychosis and misperception symptoms in Parkinson’s disease

Objective Patients with Lewy body disease develop a variety of psychotic and misperception symptoms, including visual hallucinations and delusions, as well as ‘minor hallucinations’, that is, a sense of presence, passage hallucinations and visual illusions. Although these symptoms have been suggested to have common underlying mechanisms, the commonalities and differences among them have not been systematically investigated at the neural level. Methods Sixty-seven patients with Parkinson’s disease underwent neuropsychological and behavioural assessments, volumetric MRI and 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). A factor analysis was performed to discover correlations among psychotic and misperception symptoms, other behavioural symptoms and neuropsychological performances. Partial least-squares correlation analysis was used to investigate the relationship between these symptoms and the joint features of MRI and FDG-PET. Results A sense of presence, passage hallucinations and visual illusions constituted a single behavioural factor (minor hallucinations/illusions). Visual hallucinations formed another behavioural factor along with delusions, depression and fluctuating cognition (psychosis/dysphoria). Three distinct brain–behaviour correlation patterns were identified: (1) posterior cortical atrophy/hypometabolism associated with minor hallucinations/illusions and visuospatial impairment; (2) upper brainstem and thalamic atrophy/hypometabolism associated with psychosis/dysphoria and (3) frontal cortical atrophy/hypometabolism associated with non-visual cognition. No significant differences in neuroimaging findings were identified between patients who had minor hallucinations/illusions alone and patients who also had visual hallucinations. Conclusions Our findings suggest that combined damage to the upper brainstem/thalamus and the posterior neocortex underlies both minor hallucinations/illusions and visual hallucinations and that the former pathology is more associated with visual hallucinations/frank psychosis and the latter is more associated with minor hallucinations/illusions.

Defining visual illusions in Parkinson's disease: Kinetopsia and object misidentification illusions

OBJECTIVE To identify the phenomenological features and neural correlates of visual illusions in Parkinsons disease (PD). METHODS Ninety-three patients with PD were assessed via questionnaires regarding visual illusions and behavioral symptoms, and neuropsychological tests, motor assessments and 18-F fluorodeoxyglucose-positron emission tomography (FDG-PET) were performed. The relationship between visual illusions or hallucinations and regional cerebral glucose metabolism was investigated using partial least squares (PLS) correlation and conventional mass-univariate analyses. RESULTS Kinetopsia, in which stationary objects are perceived as being in motion, and object misidentification illusions, in which objects are misperceived as different objects, were the most common types of visual illusions. Kinetopsia and object misidentification illusions were identified in 24 patients (25.8%) and 17 patients (18.3%), respectively. Eleven patients with kinetopsia and 9 patients with object misidentification illusions had visual hallucinations. Kinetopsia and visual hallucinations were associated with hypometabolism in the temporo-parietal cortices, whereas object misidentification illusions were associated with hypometabolism in the early visual cortex, as well as the temporo-parietal cortices. CONCLUSIONS Our findings suggest that kinetopsia and object misidentification illusions are the most common types of visual illusions in PD. Despite the phenomenological diversity of visual illusions and hallucinations in PD, all of these symptoms are associated with dysfunction of the temporo-parietal cortices, which support visual spatial processing, rather than dysfunction of the ventral temporo-occipital cortices, which supports visual object recognition.