Hypochondriasis as an early manifestation of dementia with Lewy bodies: an autopsied case report.

Discrepancies between clinical and pathological diagnoses of dementia with Lewy bodies (DLB) may occur because the full disease progression remains unclear, especially during the early stage. Herein, we report the case of a 78-year-old Japanese man with hypochondriasis who had autopsy-confirmed limbic-type DLB pathology. He exhibited no core clinical features of DLB. We attempted to identify the clinicopathological correlations in the early stages of DLB. At the age of 77, he became hypochondriacal and exhibited progressive cognitive decline after the death of his wife. He was concerned about his poor physical condition, but hospital examinations did not identify any overtly abnormal findings. At 78 years of age, he consulted a neurologist with complaints of facial numbness and irritability. Neurological examination revealed no overt abnormality, and he scored 21 points on the Mini-Mental State Examination. Magnetic resonance imaging of the brain showed mild bilateral ventricular enlargement. The patient was clinically diagnosed as having possible Alzheimer's disease. Approximately 1 month after his consult, he died of acute pneumonia in a psychiatric hospital to which he had been admitted for severe aggressive behaviour. He exhibited no core clinical features pointing towards a clinical diagnosis of DLB. Neuropathological investigation revealed limbic-type Lewy body disease with concurrent minimum Alzheimer-type pathology, which corresponds to high-likelihood DLB pathology based on the Third Consortium DLB pathological criteria. The patient had minimum nigral degeneration, which is consistent with the absence of parkinsonism. This autopsied case suggests that some DLB patients exhibit hypochondriasis in the early stage of the disease, even if they lack the core clinical features of DLB.

Autopsy-confirmed hippocampal-sparing Alzheimer's disease with delusional jealousy as initial manifestation.

Alzheimer's disease (AD) is clinically characterized by gradual onset over years with worsening of cognition. The initial and most prominent cognitive deficit is commonly memory dysfunction. However, a subset of AD cases has less hippocampal atrophy than would be expected relative to the predominance of cortical atrophy. These hippocampal-sparing cases have distinctive clinical features, including the presence of focal cortical clinical syndromes. Given that previous studies have indicated that severe hippocampal atrophy corresponds to prominent loss of episodic memory, it is likely that memory impairment is initially absent in hippocampal-sparing AD cases. Here, we report on a patient with an 8-year history of delusional jealousy with insidious onset who was clinically diagnosed as possible AD and pathologically confirmed to have AD with relatively preserved neurons in the hippocampus. This patient had delusional jealousy with a long pre-dementia stage, which initially was characterized by lack of memory impairment. Head magnetic resonance imaging findings showed preserved hippocampal volume with bilateral enlarged ventricles and mild-to-moderate cortical atrophy. Head single-photon emission computed tomography revealed severely decreased regional cerebral blood flow in the right temporal lobe. The resolution of the delusion was attributed to pharmacotherapy by an acetylcholinesterase inhibitor, suggesting that the occurrence of delusional jealousy was due to the disease process of AD. Although the neural basis of delusional jealousy remains unclear, this hippocampal-sparing AD case may be classified as an atypical presentation of AD.

Aberrant brain dynamics in individuals with clinical high risk of psychosis.

Background: Resting-state network (RSN) functional connectivity analyses have profoundly influenced our understanding of the pathophysiology of psychoses and their clinical high risk (CHR) states. However, conventional RSN analyses address the static nature of large-scale brain networks. In contrast, novel methodological approaches aim to assess the momentum state and temporal dynamics of brain network interactions. Methods: Fifty CHR individuals and 33 healthy controls (HC) completed a resting-state functional MRI scan. We performed an Energy Landscape analysis, a data-driven method using the pairwise maximum entropy model, to describe large-scale brain network dynamics such as duration and frequency of, and transition between, different brain states. We compared those measures between CHR and HC, and examined the association between neuropsychological measures and neural dynamics in CHR. Results: Our main finding is a significantly increased duration, frequency, and higher transition rates to an infrequent brain state with coactivation of the salience, limbic, default mode and somatomotor RSNs in CHR as compared to HC. Transition of brain dynamics from this brain state was significantly correlated with processing speed in CHR. Conclusion: In CHR, temporal brain dynamics are attracted to an infrequent brain state, reflecting more frequent and longer occurrence of aberrant interactions of default mode, salience, and limbic networks. Concurrently, more frequent and longer occurrence of the brain state is associated with core cognitive dysfunctions, predictors of future onset of full-blown psychosis.

Cellular and extracellular white matter alterations indicate conversion to psychosis among individuals at clinical high-risk for psychosis.

OBJECTIVES: It is important to find biomarkers associated with transition to illness in individuals at clinical high-risk for psychosis (CHR). Here, we use free-water imaging, an advanced diffusion MRI technique, to identify white matter alterations in the brains of CHR subjects who subsequently develop psychosis (CHR-P) compared to those who do not (CHR-NP). METHODS: Twenty-four healthy controls (HC) and 30 CHR individuals, 8 of whom converted to schizophrenia after a mean follow-up of 15.16 months, received baseline MRI scans. Maps of fractional anisotropy (FA), FA of cellular tissue (FAT), and extracellular free-water (FW) were extracted using tract-based spatial statistics after which voxel-wise non-parametric group statistics and correlations with symptom severity were performed. RESULTS: There were no significant differences between HCs and the combined CHR group. However, prior to conversion, CHR-P showed widespread lower FA compared to CHR-NP (pFWE < 0.05). FA changes in CHR-P were associated with significantly lower FAT and higher FW, compared to CHR-NP. Positive symptoms correlated significantly with diffusion parameters in similar regions as those discriminating CHR-P from CHR-NP. CONCLUSIONS: Our study suggests that cellular (FAT) and extracellular (FW) white matter alterations are associated with positive symptom severity and indicate an elevated illness risk among CHR individuals.

Increased functional connectivity in a population at risk of developing Parkinson's disease.

BACKGROUND: While the concept of prodromal Parkinson's disease (PD) is well established, reliable markers for the diagnosis of this disease stage are still lacking. We investigated the functional connectivity of the putamina in a resting-state functional MRI analysis in persons with at least two prodromal factors for PD, which is considered a high risk for PD (HRPD) group, in comparison to PD patients and controls. METHODS: We included 16 PD patients, 20 healthy controls and 20 HRPD subjects. Resting state echo planar images and anatomical T1-weighted images were acquired with a Siemens Prisma 3 T scanner. The computation of correlation maps of the left and the right putamen to the rest of the brain was done in a voxel-wise approach using the REST toolbox. Finally, group differences in the correlation maps were compared on voxel-level and summarized in cluster z-statistics. RESULTS: Compared to both PD patients and healthy controls, the HRPD group showed higher functional connectivity of both putamina to brain regions involved in execution of motion and coordination (cerebellum, vermis, pre- and postcentral gyrus, supplementary motor area) as well as the planning of movement (precuneus, cuneus, superior medial frontal lobe). CONCLUSIONS: Higher functional connectivity of the putamina of HRPD subjects to other brain regions involved in motor execution and planning may indicate a compensatory mechanism. Follow-up evaluation and independent longitudinal studies should test whether our results reflect a dynamic process associated with a prodromal PD state.

Assessing self-reported clinical high risk symptoms: The psychometric properties of the polish version of the prodromal questionnaire-brief and a proposal for an alternative approach to scoring.

BACKGROUND: Psychotic-like experiences (PLEs) might occur in the general population as low-risk individual differences or prodromal features, requiring quick detection and early intervention. The aims of this study were to conduct a mini-systematic review of the prognostic abilities of the Prodromal Questionnaire-Brief (PQ-B), describe the PLEs distribution for the first time in a Polish population, assess PQ-B reliability and propose an innovative scoring approach based on cluster analysis. METHODS: Five hundred and twenty eight (334 female) adult volunteers underwent screening with the PQ-B, 49% also underwent the early psychosis screening test PRIME, to verify the tests' psychometric properties, to compare the prognostic accuracy of the PQ-B to the more restrictive PRIME, and to the detected types of possible diagnosis in the general population. RESULTS: Almost 70% of respondents met the prognostic criteria of the PQ-B while only 30.6% met the PRIME criteria. Both tests proved reliable (α > .835) and valid (rho >.710; P < .001). A cluster analysis identified three different sub-groups detected with the PQ-B: healthy individuals without PLE; healthy with low-distressing PLEs; and possibly prodromal subjects reporting less frequent but more distressing PLEs and no worries about their own mental state. Also in systematic reviews, authors of different adaptations have observed that the PQ-B has too low specificity and postulated the need for higher cut-offs. CONCLUSION: Study provides evidence of good reliability and sensitivity of the PQ-B in assessing PLEs among the general population, but emphasizes that straightforward quantitative scoring criteria are still unclear. A more qualitative approach might be useful for differentiating true prodromal subjects from clinically low-risk individual differences.

EEG-Informed fMRI Reveals a Disturbed Gamma-Band-Specific Network in Subjects at High Risk for Psychosis.

OBJECTIVES: Abnormalities of oscillatory gamma activity are supposed to reflect a core pathophysiological mechanism underlying cognitive disturbances in schizophrenia. The auditory evoked gamma-band response (aeGBR) is known to be reduced across all stages of the disease. The present study aimed to elucidate alterations of an aeGBR-specific network mediated by gamma oscillations in the high-risk state of psychosis (HRP) by means of functional magnetic resonance imaging (fMRI) informed by electroencephalography (EEG). METHODS: EEG and fMRI were simultaneously recorded from 27 HRP individuals and 26 healthy controls (HC) during performance of a cognitively demanding auditory reaction task. We used single trial coupling of the aeGBR with the corresponding blood oxygen level depending response (EEG-informed fMRI). RESULTS: A gamma-band-specific network was significantly lower active in HRP subjects compared with HC (random effects analysis, P < .01, Bonferroni-corrected for multiple comparisons) accompanied by a worse task performance. This network involved the bilateral auditory cortices, the thalamus and frontal brain regions including the anterior cingulate cortex, as well as the bilateral dorsolateral prefrontal cortex. CONCLUSIONS: For the first time we report a reduced activation of an aeGBR-specific network in HRP subjects brought forward by EEG-informed fMRI. Because the HRP reflects the clinical risk for conversion to psychotic disorders including schizophrenia and the aeGBR has repeatedly been shown to be altered in patients with schizophrenia the results of our study point towards a potential applicability of aeGBR disturbances as a marker for the prediction of transition of HRP subjects to schizophrenia.

A follow up study of non-demented patients with primary visual cortical hypometabolism: prodromal dementia with Lewy bodies.

We previously reported non-demented patients with glucose hypometabolism in the primary visual cortex (PVC), which is the preferentially affected region in patients with dementia with Lewy bodies (DLB). It remains unknown, however, whether these patients represent a prodromal DLB state. Eleven non-demented patients who attended our memory clinic for more than three years (mean follow-up period: 44 ± 5 months) were examined. All the patients had glucose hypometabolism in the PVC on [(18)F]-fluoro-d-glucose (FDG) positron emission tomography (PET) scans at baseline. Four patients, including one with a clinical history of occipital bleeding, exhibited no core or suggestive features of DLB. Seven patients reported recurrent nocturnal dream-enactment behavior, which is consistent with probable rapid eye movement (REM) sleep behavior disorder (RBD). The condition of the patient with occipital bleeding was stable, which is consistent with an underlying non-neurodegenerative disorder. Of the remaining 10 patients, 5 had stable cognitive conditions (non-converters) and 5 exhibited progression to dementia (converters). The clinical diagnoses of 4 patients with probable RBD were changed to probable DLB. Despite no differences in psychological profiles at baseline between non-converters and converters, the initial pattern of cortical metabolism differed: converters had lower glucose hypometabolism in the parietal and the lateral occipital cortex compared to non-converters. The metabolic reduction in the PVC is present in patients with prodromal DLB. Moreover, the spatial profiles of reduced glucose metabolism at baseline could help to define the distinct prognostic subgroup that has a greater risk of conversion to DLB.