Brain amyloid and cognition in Lewy body diseases

Many patients with PD develop PD with dementia (PDD), a syndrome that overlaps clinically and pathologically with dementia with Lewy bodies (DLB); PDD and DLB differ chiefly in the relative timing of dementia and parkinsonism. Brain amyloid deposition is an early feature of DLB and may account, in part, for its early dementia. We sought to confirm this hypothesis and also to determine whether amyloid accumulation contributes to cognitive impairment and dementia in the broad range of parkinsonian diseases. Twenty-nine cognitively healthy PD, 14 PD subjects with mild cognitive impairment (PD-MCI), 18 with DLB, 12 with PDD, and 85 healthy control subjects (HCS) underwent standardized neurologic and neuropsychological examinations and Pittsburgh compound B (PiB) imaging with PET. Apolipoprotein E (ApoE) genotypes were obtained in many patients. PiB retention was expressed as the distribution volume ratio using a cerebellar tissue reference. PiB retention was significantly higher in DLB than in any of the other diagnostic groups. PiB retention did not differ across PDD, PD-MCI, PD, and HCS. Amyloid burden increased with age and with the presence of the ApoE ε4 allele in all patient groups. Only in the DLB group was amyloid deposition associated with impaired cognition. DLB subjects have higher amyloid burden than subjects with PDD, PD-MCI, PD, or HCS; amyloid deposits are linked to cognitive impairment only in DLB. Early amyloid deposits in DLB relative to PDD may account for their difference in the timing of dementia and parkinsonism.     

Evaluation of arterial stiffness in patients with schizophrenia

The aim of this study was to evaluate arterial stiffness in schizophrenia patients. 28 male patients were included. The intima-media thickness (IMT) of the vessels were taken using high-resolution ultrasonography system. The mean carotid IMT and the mean femoral IMT values of the study group were found to be statistically significantly higher than the values of the control group. As the duration of the disease increased, there was an increase in the carotid IMT, carotid elastic modulus and femoral IMT, whereas there was a decrease in carotid and femoral diastolic wall stress in patients. No statistically significant differences were observed between the groups’ carotid and femoral compliance, distensibility and elastic modulus values. The mean systolic arterial blood pressure in the patient group was determined to be lower than that of the control group. The mean diastolic wall stress values in the carotid and femoral arteries were determined to be lower than those of the control group. There was no relationship between antipsychotic dose, blood pressure and arterial stiffness parameters. Schizophrenia patients are more prone to develop arterial stiffness by atherosclerosis either with the effect of the nature of the disease itself or antipsychotic treatment. But evaluation with more parameters (carotid and femoral compliance, distensibility and elastic modulus) did not indicate any difference from the control group in respect of arterial stiffness. Antipsychotic treatment may play a protective role in terms of arterial stiffness by causing a decrease in systolic arterial pressure and carotid and femoral diastolic wall stress.     

Increased pulse wave velocity in patients with panic disorder: independent vascular influence of panic disorder on arterial stiffness

ObjectiveAcute and chronic mental stress and many psychiatric disorders have been accepted as a cause of cardiovascular disease. Panic disorder, a subtype of anxiety disorder, has been associated with increased risk of fatal myocardial infarction and sudden cardiac death in epidemiological studies. Carotid–femoral pulse wave velocity (CF-PWV) is currently the gold standard measurement of arterial stiffness. CF-PWV is a well-recognized predictor of an adverse cardiovascular outcome with higher predictive value than classical cardiovascular risk factors. The aim of our study is to measure PWV as the surrogate of arterial stiffness and vascular involvement in patients with panic disorder.MethodsForty-two patients with PD, and 30 control participants were included in the study. Patients with hypertension, diabetes mellitus, or the history of any cardiovascular disease were excluded from study.ResultsBaseline characteristics were not significantly different between the two groups, except carotid–femoral pulse wave velocity (PD vs. control; 7.51 ± 2.02 vs. 6.24 ± 1.09 m/s, p = 0.001), heart rate, and smoking status. Additionally, CF-PWV positively correlated with age (r = 0.250, p = 0.034), heart rate (r = 0.284, p = 0.017), systolic and diastolic blood pressure (r = 0.393, p = 0.001 and r = 0.286, p = 0.015, respectively) significantly. However, only the presence of panic disorder was independently related to PWV (βeta: 0.317, p = 0.011) in the multivariate analysis including age, heart rate, smoking status and blood pressure measurements.ConclusionIncreased pulse wave velocity in patients with panic disorder may justify the associated risk as documented in previous studies, and may be useful in identifying the patients with higher risk of future cardiovascular complications.     

The pathology of REM sleep behavior disorder with comorbid Lewy body dementia

A patient with REM sleep behavior disorder who subsequently developed probable Lewy body dementia is now reported to have a definite pathologic diagnosis of Lewy body dementia. Examination of brain revealed Lewy bodies as well as marked neuronal loss in brainstem monoaminergic nuclei-particularly locus coeruleus and substantia nigra-that inhibit cholinergic neurons in the pedunculopontine nucleus mediating atonia during REM sleep.     

Attention and cognition in patients with obsessive-compulsive disorder

Although a dysfunctional prefrontal-striatal system is presupposed in obsessive-compulsive disorder (OCD), this is not sustained by neuropsychological studies. The aim of this study was twofold: (i) to investigate the cognitive deficits in patients with OCD compared to matched healthy controls; and (ii) to relate cognitive performance to clinical characteristics in patients with OCD. In this study, 39 patients with primary OCD according to Diagnostic and Statistical Manual, fourth edition criteria were compared to 26 healthy control subjects on a battery measuring verbal memory and executive functioning. Patients with OCD showed slowed learning on the verbal memory task and made more errors on the Wisconsin Card Sorting Test. Errors were failures to maintain set, which were related to severity of OCD symptomatology. The results show that patients with OCD have cognitive deficits. The authors hypothesize that these deficits may be interpreted by attentional deficits caused by a dysfunctional anterior cingulate cortex.     

Serum levels of coenzyme Q in patients with Lewy body disease

Summary. The purpose of the present study was to compare serum levels of coenzyme Q₁₀ (CoQ₁₀) and the coenzyme Q₁₀ cholesterol (CoQ₁₀/cholesterol) ratio in 18 patients with Lewy body disease (LBD) with 20 matched controls. The mean serum coenzyme Q10 levels in patients with LBD were significantly reduced with respect to control group, however, no differences were found in CoQ₁₀/cholesterol ratio between LBD patients and control group. There was no correlation among CoQ₁₀ and CoQ₁₀/cholesterol ratio with age, age of onset, body mass index, duration of the disease or scores of the Mini Mental State Examination, UPDRS and Hoehn and Yahr stage. These results suggest the involvement of this enzimatic system in the pathogenic mechanism of LBD. Received September 3, 2001; accepted December 20, 2001 Published online July 26, 2002     

Metabolic impairment of brain metabolism in patients with Lewy body dementia

A reliable assessment of dementia is essential for a differentiated treatment. Recent studies have demonstrated a poor accuracy of clinical criteria for diagnosis of Lewy body dementia. Diffuse Lewy body disease (LBD) is the second most common cause of senile degenerative dementia and is characterized histologically by the occurrence of Lewy bodies in allocortical, neocortical and subcortical structures. Seven male patients (mean age 81 years) with clinically suspected diffuse LBD were investigated with 18F-fluorodeoxyglucose (FDG)-PET using a Siemens ECAT-ART PET-scanner. The 18F-FDG-PET showed a diffuse glucose hypometabolism in the entire cerebral cortex with relative sparing of the primary sensory-motor cortex in all patients. This diffuse metabolic impairment in the entire cortex with relative sparing of central region seems to be a typical pattern for LBD, distinct from Alzheimer's disease.     

Association of Sult4A1 SNPs with psychopathology and cognition in patients with schizophrenia or schizoaffective disorder

A number of genes located on chromosome 22q11-13, including catechol-O-methyltransferase (COMT), are potential schizophrenia susceptibility genes. Recently, the sulfotransferase-4A1 (Sult4A1) locus within chromosome 22q13 was reported to be linked to schizophrenia in a family TDT study. Sult4A1 is related to metabolism of monoamines, particularly dopamine and norepinephrine, both of which have been implicated in the pathophysiology of the psychopathology and cognitive dysfunction components of schizophrenia. An available, prospectively collected data base was interrogated to determine how three Sult4A1 SNPs: rs138060, rs138097, and rs138110, previously shown to be associated with schizophrenia might be associated with psychopathology, cognition, and quality of life in a sample of 86 Caucasian patients with schizophrenia or schizoaffective disorder. The majority of patients met criteria for treatment resistant schizophrenia and had been drug-free for one week or longer at the time of evaluation. The major findings were: 1) patients heterozygous (T/G) for rs138060 had significantly worse Brief Psychiatric Rating Scale (BPRS) Total and anxiety/depression sub-scale scores, and higher Scale for the Assessment of Positive Symptoms (SAPS) Total scores than G/G homozygous patients; and 2) patients heterozygous (A/G) for rs138097 demonstrated significantly worse performance on neuropsychological testing, specifically on tests of executive function and working memory, compared to patients homozygous for the G and A alleles. RS138110 was unrelated to psychopathology and cognition. These results provide the first evidence of how genetic variation in Sult4A1 may be related to clinical symptoms and cognitive function in schizophrenia, and permit future studies to attempt to replicate these potentially important findings.     

Insights into REM sleep behavior disorder pathophysiology in brainstem-predominant Lewy body disease

BACKGROUND AND PURPOSE: Rapid eye movement (REM) sleep behavior disorder (RBD) is a parasomnia reflecting changes in the brain, but which specific neuronal networks are involved in human RBD pathogenesis has not yet been determined. To date, only one case of idiopathic RBD has undergone autopsy, in which "incidental Lewy body disease" was found. Due to the severe neuronal loss and gliosis in the substantia nigra (SN) and locus ceruleus (LC) in this case, degeneration of brainstem monoaminergic neurons was postulated as the underlying substrate for RBD. Additional cases of idiopathic RBD with neuropathologic examination may help clarify which key brainstem structures are involved. PATIENT AND METHODS: Case report with neuropathologic analysis. RESULTS: A man with polysomnographically proven RBD (onset age 57 years), but no other neurologic signs or symptoms, underwent neuropathologic examination upon his death at age 72. Histopathologic analysis showed Lewy body disease, but no significant neuronal loss or gliosis was present in the SN or LC. CONCLUSIONS: This case represents another example of Lewy body disease associated with RBD. The minimal degenerative changes in the SN and LC call into question the role of these nuclei in RBD, at least in our case. We suggest additional cases of idiopathic RBD undergo neuropathologic analyses to better delineate the neurologic substrate of this intriguing parasomnia.     

抑郁症首次发病患者认知功能的研究

目的探讨抑郁症首次发病(以下简称首发)患者的认知功能特点及其影响因素。方法采用韦氏成人智力量表、韦氏记忆量表、威斯康星卡片分类测验(WCST)分别评定116例首发抑郁症患者(抑郁症组)和41名健康人(对照组)的认知状况,采用汉密尔顿抑郁量表(24项,HAMD)评定病情严重程度。对影响神经心理学测验成绩的临床症状进行逐步多元回归分析。结果(1)抑郁症组的长时记忆[(35.28±7.27)分]、短时记忆[(51.32±13.41)分]、记忆商数[(89.46±17.84)]、语言智商数[(110.96±13.72)]、操作智商数[101.90±15.98)]、智商数[(107.41±15.78)]均明显低于对照组[长时记忆(44.05±5.06)分,短时记忆(71.41±8.51)分,记忆商数(121.90±11.26),语言智商数(117.49±10.99),操作智商数(117.24±10.54),智商数[(118.98±10.95)],差异均有统计学意义(均P<0.01)。抑郁症组的WCST总测验数[(74.70±27.96)个]、持续错误数[(26.07±15.31)个]、随机错误数[(24.46±17.54)个]均明显高于对照组[WCST总测验数(60.15±23.05)个,持续错误数(17.56±11.44)个,随机错误数(17.73±14.27)个],差异有统计学意义(P<0.01或<0.05)。抑郁症组长时记忆成绩、短时记忆成绩和记忆商数低于对照组2个标准差。(2)逐步多元回归分析显示,抑郁症患者的长时记忆成绩及记忆商数与绝望感因子分均呈负相关(均P=0.00),短时记忆成绩和即刻记忆成绩与阻滞因子分均呈负相关(均P=0.00),语言智商与焦虑/躯体化因子分呈负相关(P=0.01),操作智商及智商与HAMD总分均呈负相关(均P=0.01),WCST总测验数和持续错误数与HAMD总分均呈正相关(P=0.01,P=0.02),随机错误数与阻滞因子分呈正相关(P=0.02)。结论首发抑郁症患者急性期的记忆、语言智商、操作智商和执行功能明显减退,临床症状严重程度影响认知功能的改变。     

Serum heart-fatty acid binding protein levels in patients with Lewy body disease

OBJECTIVE: In order to examine a possible role of serum heart-fatty acid binding protein (H-FABP) in patients with Lewy body disease, we measured serum levels of H-FABP in patients with dementia with Lewy bodies (DLB), Parkinson's disease (PD), and Alzheimer's disease (AD). METHODS: Serum levels of H-FABP were measured using a solid-phase enzyme-linked immunoassay. Iodine-123 metaiodobenzylguanidine ((123)I-MIBG) cardiac scintigraphy was performed on each patient and the heart to mediastinum (H/M) ratio was calculated. Receiver operating characteristic (ROC) analysis was used to calculate the optimal cutoff values of the H-FABP between DLB and AD patients. Independent predictive variables for serum H-FABP levels were analyzed using multivariate regression analysis. RESULTS: Serum levels of H-FABP were significantly higher in DLB patients and PD patients than in AD patients. H/M ratios of the DLB and PD patients were significantly lower than those of AD patients. The diagnostic value of the serum H-FABP levels between AD and DLB patients was inferior to that of the delayed H/M ratio of (123)I-MIBG cardiac scintigraphy. Multivariate regression analysis revealed that the delayed H/M ratio predicted serum H-FABP levels in the PD patients. CONCLUSIONS: Examination of serum H-FABP levels did not allow discrimination between DLB and AD patients. Cardiac sympathetic nerve dysfunction may be associated with elevation of serum H-FABP in Lewy body disease patients.     

路易体痴呆的诊断

目的 探讨路易体痴呆(dementia with Lewy body，DLB)的早期诊断。方法 根据病理确诊的1例DLB患者和3例临床诊断DLB患者的症状、体征和影像学变化，分析DLB的临床特征。结果 4例息者都有以下特点：(1)波动性进行性痴呆；(2)生动的视幻觉；(3)锥体外系症状；(4)对神经安定剂敏感。结论 根据以上特点，生前诊断DLB是可能的，对疑诊DLB的患者应慎用神经安定剂和抗胆碱能类药物。     

Probabilistic reasoning in patients with body dysmorphic disorder

Background and Objectives

Many patients with body dysmorphic disorder (BDD) have poor insight into their condition. Indeed, their conviction in their ugliness is often delusional. Perhaps the most robust information-processing abnormality associated with delusions is a jumping to conclusions (JTC) reasoning bias such that delusional individuals request significantly less information before making a decision relative to healthy controls. We investigated whether patients with BDD (n = 20) demonstrate a JTC reasoning style relative to patients with OCD (n = 20) and healthy controls (n = 20).

Methods

Participants completed a clinician-rated measure of delusionality and two tests of probabilistic reasoning: the beads task and the survey task.

Results

Patients with BDD did exhibit higher delusionality than the patients with OCD. They did not, however, exhibit a JTC reasoning bias relative to the patients with OCD or the healthy controls. Patients with poor insight BDD requested significantly less information before making a decision than did patients with fair insight BDD.

Limitations

The clinical groups were characterized by multiple comorbidities and concomitant medications. The BDD group had relatively good insight as compared to other studies examining delusionality in BDD.

Conclusions

Taken together, our results suggest that although a JTC reasoning bias was not present in all patients with BDD, a modest JTC reasoning bias may be present among patients with poor insight BDD. Future studies could provide additional information on this hypothesis.     

Cortical and amygdalar Lewy body burden in Parkinson's disease patients with visual hallucinations

Visual hallucinations (VH) are among the most common non-motor complications of Parkinson's disease (PD). A few studies on their etiopathogenesis have suggested involvement of cortical and amygdalar areas. In order to investigate the possible association between extranigral Lewy Body (LB) distribution across cortical and amygdalar regions and the presence of VH in PD brain donors, we conducted a clinico-pathological comparison of 10 PD patients with VH vs 10 closely matched PD patients without VH. The LB burden was significantly higher across the amygdala and the frontal, temporal and parietal cortical areas in patients with VH. Although our results suggest significant extranigral involvement, the precise etiopathologic mechanisms responsible for the development of VH need further clarification.     

Association between male gender and cortical Lewy body pathology in large autopsy series

Sex-linked factors may alter risk for neurodegenerative diseases. Definitive diagnoses are not established until autopsy, so neuropathological studies are critical. There have not been reported gender-related differences in neocortical Lewy bodies (LBs) using large multi-center autopsy series. We evaluated the associations between gender and pathologically characterized neurodegenerative diseases. Cases with Alzheimer’s disease (AD), neocortical LBs, AD + neocortical LBs, or neither pathology were evaluated as separate groups. Results were corrected for possible confounders including age at death, smoking history, and education. The settings were the University of Kentucky Alzheimer’s Disease Center and the National Alzheimer’s Coordinating Center (NACC) Registry autopsy series; 3,830 subjects met inclusion criteria. Patients with neocortical (“diffuse”) or intermediate (“limbic”) LB pathologies tended to be male (male:female odds ratios ~2.9 with 95% CI 2.02–4.18). The preponderance of males dying with neocortical LB pathology was seen consistently across age groups and was not due to the potential confounders evaluated. By contrast, individuals dying with AD pathology were more likely to be female if dying over 80 (male:female odds ratio 0.66, 95% CI 0.50–0.88), but that tendency was not seen in individuals dying with AD pathology prior to age 80. Increased understanding of the male predominance in neocortical LB pathology may help guide clinicians, because males are more likely to be “undercalled” for neocortical LBs clinically, and females are more likely to be “overcalled” (P < 0.05 for both). Males are far more likely than females to die with neocortical LB pathology. This phenomenon may help guide medical practice including clinical trial study design.