Neuropsychiatric symptoms of progressive supranuclear palsy in a dementia clinic

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by supranuclear gaze palsy, postural instability, akinesia and other parkinsonism. Recently, the relationship between PSP and frontotemporal dementia (FTD) has been recognized, which includes clinical, pathological, biochemical and genetic features. However, there have been few studies that directly compared neuropsychiatric symptoms between PSP and FTD. The aim of the present study was to investigate comprehensive psychiatric and behavioural symptoms in PSP and compared them with those in FTD. Methods: Patients with PSP (n = 10) and FTD (n = 13) were selected on the basis of inclusion/exclusion criteria from a consecutive series in the dementia clinic of Kumamoto University Hospital. We assessed their comprehensive neuropsychiatric features by using the Neuropsychiatric Inventory (NPI), the Stereotypy Rating Inventory (SRI) and a specific antisocial behaviour checklist. Results: There were no significant differences in the total NPI and NPI subscale scores between the two groups. Both groups showed quite a similar pattern in the features of neuropsychiatric symptoms: apathy showed the highest score, followed by aberrant motor behaviour and disinhibition. The PSP group was significantly lower in the total SRI and eating and cooking behaviour scores than those in the FTD group. The prevalence of antisocial behaviours in PSP (50%) was equal to those in the FTD group (46%). Conclusions: In a dementia clinic, the neuropsychiatric profile in patients with PSP closely resembled those in the FTD group. The present results suggest that PSP should be considered as not only a movement disorder, but also a disorder with a wide range of neuropsychiatric symptoms.     

Longitudinal cognitive changes in patients with early Parkinson's disease and neuropsychiatric symptoms

Aims

In this study, we aimed to investigate the effect of neuropsychiatric symptoms (NPS) on the rate of cognitive decline for both global cognition and specific cognitive domains in a cohort of patients from the Parkinson's Progression Markers Initiative (PPMI).

Method

Prospectively longitudinal data were obtained from the PPMI cohort. NPS, including depression, anxiety, apathy, psychosis, impulse control disorders (ICDs), and cognition ability, were evaluated by a series of questionnaires. Linear mixed-effects models were used to investigate the relationship between NPS and the rate of cognitive decline. Generalized estimating equations (GEEs) were used to investigate the relationship between NPS and the occurrence of mild cognitive impairment (MCI).

Results

In total, 423 patients with Parkinson's disease (PD) were recruited at baseline and 395, 378, 366, 346, and 315 participants were followed up at 1, 2, 3, 4, and 5 years, respectively. Depression, anxiety, apathy, and psychosis were associated with global cognitive decline. Except for those with ICDs, patients with psychosis, depression, anxiety, and apathy were more likely to meet the criteria for MCI. Patients with depression and anxiety showed a progressive decline in four major cognitive domains. Apathy and ICDs were separately associated with a progressive decline in processing speed-attention and memory, respectively.

Conclusions

Neuropsychiatric symptoms, including psychosis, depression, anxiety, and apathy, could be used to predict future cognitive decline in patients with PD.     

Obsessive-compulsive disorder: a clinical, neuropsychological and positron emission tomography study

The authors compared 16 nondepressed obsessive-compulsive patients (OCS) with 8 normal controls (NC) of similar age for resting-state regional cerebral glucose metabolic rates (rCMRglu) using positron emission tomography with the fluorodeoxyglucose method. OCS were rated for clinical data, and a neuropsychological battery was administered to 14 patients on the day of the scan. Absolute rCMRglu for whole cortex, and normalized prefrontal lateral cortex metabolic rates, were both significantly lower in OCS than in NC. No significant difference between treated (n = 10) and drug-free (n = 6) OCS was found for those variables. OCS were significantly impaired in the neuropsychological tasks assessing memory and attention. The rCMRglu for prefrontal lateral cortex were negatively correlated to Stroop-test subscores. This "frontal-oriented" task assessed the ability of OCS to inhibit immediate but inappropriate responses. These results suggest, in OCS, a modification of the general activating systems of cortical function and a relationship between the lateral prefrontal rCMRglu decrease and a selective attention deficit.     

Glucose metabolism and rate constants in Alzheimer''s disease examined with dynamic positron emission tomography scan

Glucose metabolic rate constants in patients with Alzheimer's disease were analyzed using dynamic positron emission tomography with [18-F] fluoro-2-deoxyglucose (FDG). The cerebral metabolic rate of glucose (CMRG) was calculated using obtained rate constants, as well as the autoradiographic method. The half-life and distribution volume of FDG between the blood and the brain tissue were also calculated from obtained metabolic rate constants. The most severely affected metabolic step was the phosphorylation of glucose in the parietotemporal regions. The distribution volume of FDG showed no remarkable deviation from normal controls, while the half-life of FDG was found to be longer in the parietal and temporal regions. The CMRG from rate constants and that from the autoradiographic method showed no remarkable differences.     

Neural correlates of tinnitus duration and Distress: A positron emission tomography study

Cerebral ¹⁸F‐deoxyglucose positron emission tomography (FDG‐PET) has shown altered auditory pathway activity in tinnitus. However, the corresponding studies involved only small samples and analyses were restricted to the auditory cortex in most studies. Evidence is growing that also limbic, frontal, and parietal areas are involved in the pathophysiology of chronic tinnitus. These regions are considered to mediate perceptual, attentional, and emotional processes. Thus, the aim of the present study was the systematic evaluation of metabolic brain activity in a large sample of tinnitus patients. Ninety one patients with chronic tinnitus underwent FDG‐PET. The effects of tinnitus severity (assessed by a tinnitus questionnaire score), duration and laterality were evaluated with statistical parametric mapping (SPM) in whole brain analyses. In addition, region of interest analyses were performed for primary auditory areas. Tinnitus duration correlated positively with brain metabolism in right inferior frontal, right ventro‐medial prefrontal, and right posterior cingulate cortex. Tinnitus distress correlated positively with activation of left and right posterior inferior temporal gyrus as well as left and right posterior parahippocampal–hippocampal interface. Region of interest analysis demonstrated an overactivation of left in contrast to right Heschl's gyrus independently from tinnitus laterality and anatomical hemispheric differences. Tinnitus duration and distress were associated with areas involved in attentional and emotional processing. This is in line with recent findings indicating the relevance of higher order areas in the pathophysiology of tinnitus. Earlier results of asymmetric activation of the auditory cortices in tinnitus were confirmed, i.e., left‐sided overactivation was found independently from tinnitus laterality. Hum Brain Mapp, 2013. © 2011 Wiley Periodicals, Inc.     

In vivo evaluation of striatal dopamine reuptake sites using 11C-nomifensine and positron emission tomography

In vitro nomifensine demonstrates high affinity and specificity for dopamine reuptake sites in the brain. In the present study 11C-nomifensine was administered i.v. in trace amounts (10-50 micrograms) to ketamine anaesthetized Rhesus monkeys (6-10 kg b.w.) and the time-course of radioactivity within different brain regions was measured by positron emission tomography (PET). Six base-line experiments lasting for 60-80 min were performed. The procedure was repeated after pretreatment with nomifensine (2-6 mg/kg i.v.), another reuptake inhibitor, mazindol (0.3 mg/kg i.v.), desipramine (0.5 mg/kg i.v) or spiperone (0.3 mg/kg i.v.) before the administration of a second 11C-nomifensine dose. The highest radioactivity uptake was found in the dopamine innervated striatum and the lowest in a region containing the cerebellum, known to be almost devoid of dopaminergic neurons. The difference between striatal and cerebellar uptake of 11C-nomifensine derived radioactivity was markedly reduced after nomifensine and mazindol but not after desipramine and spiperone. These results indicate that in vivo the striatal uptake of 11C-nomifensine, as measured with PET, involves specific binding with the dopamine reuptake sites. In the first human applications of 11C-nomifensine and PET in a healthy volunteer, the regional uptake of radioactivity was similar to that in base-line experiments with Rhesus monkeys. In the healthy subject the striatal/cerebellar ratio was 1.6, 50 min after the injection of 11C-nomifensine. In a hemi-parkinsonian patient this ratio was 1.1 contralaterally and 1.3 ipsilaterally to the affected side. 11C-nomifensine and PET seems to be an auspicious method to measure the striatal dopaminergic nerve terminals of man in vivo.     

Fluorodeoxyglucose F18 positron emission tomography in a case of slowly progressive pure alexia

We describe a 71-year-old patient with slowly progressive pure alexia in which analysis of her fluorodeoxyglucose FDG-PET scan revealed an area of focal hypometabolism in the visual word form area. She presented with difficulty reading. Examination revealed pure alexia with preservation of other cognitive domains. Brain MRI revealed only slight atrophy. A Fluorodeoxyglucose F18 positron emission tomography scan revealed hypometabolism in the occipital cortex bilaterally, left greater than right, with normal metabolism elsewhere in the brain. This case highlights the utility of FDG-PET scan in evaluating focal neurodegenerative conditions before clear atrophy can be seen on MRI.     

轻度认知障碍^18F-FDG PET显像的研究进展

轻度认知障碍(MCI)的病理改变与早期或临床前期阿尔茨海默病(AD)相似,MCI患者已经成为预测AD是否发生、有效延缓或早期干预治疗AD的最适群体,FDG PET脑功能显像可反映局部脑内葡萄糖代谢率,为MCI的病理学研究及临床诊断提供一种新的可靠工具.正确认识MCI与正常脑老化、AD脑葡萄糖代谢的不同、FDG PET图像特征及影响因素、对于预测病程及早期干预治疗、检测治疗效果、预防AD的发生及提高老年人生活质量有着重要的意义.     

Antipsychotic drug use and associations with neuropsychiatric symptoms in persons with impaired cognition: a cross-sectional study

Background: Neuropsychiatric symptoms (NPS) in cognitive disorders impair quality of life, increase caregiver stress, and may lead to earlier institutionalization and death. The objective of this study was to investigate the use of antipsychotics among persons with cognitive impairment in home care and residential care, and its associations with NPS and personal characteristics.

Methods: Data were collected in the South Savo Hospital District area with 105 000 inhabitants, where 66 of 68 institutions providing long-term residential care and 20 of 21 municipal home care producers joined the study. Nurses recorded the current use of drugs, the activities of daily living (ADL), prevalence of diagnosed dementia, and assessed the cognitive status and the prevalence of recent NPS based on the item list of the Neuropsychiatric Inventory (NPI).

Results: The study population was 1909 persons with cognitive impairment, and 1188 of them lived in residential care. Antipsychotics were used by 563 (29.5%) persons in the whole study population. In residential care 448 (37.7%) used antipsychotics and the corresponding figure in home care was 115 (15.9%). In the multivariate analysis, the antipsychotic use was associated with living in residential care, benzodiazepine use, and with NPS symptoms agitation/aggression (OR =1.70, 95% CI =1.16–2.48), disinhibition (OR =2.33, 95% CI =1.31–4.15), hallucinations (OR =2.77, 95% CI =1.69–4.55), and delusions (OR =1.71, 95% CI =1.01–2.91).

Conclusions: Antipsychotic use was common among persons with cognitive impairment. The results suggest that antipsychotics are commonly used to treat hyperactivity and psychotic symptoms, especially in residential care.     

Receptor binding and selectivity of three 11C-labelled dopamine receptor antagonists in the brain of Rhesus monkeys studied with positron emission tomography

ABSTRACT— The regional distribution of 3 11C-labelled dopamine receptor antagonists, N-methyl spiperone, raclopride and clozapine, in the brain of Rhesus monkeys was studied by positron emission tomography (PET). The measured radioactivities in the striatal area were similar for the 3 antagonists, although the highest selectivity as compared to cerebellum was found for 11C-raclopride 60 min after administration. The selectivity of the radiotracers for the serotonin and D₂-dopamine receptors was evaluated after pretreatment of the monkeys with serotonin and dopamine receptor antagonists. 11C-N-methylspiperone and 11C-clozapine both bound to serotonin receptors in the frontal cortex and to D₂-dopamine receptors in the striatal area. Raclopride was selectively bound to the D₂-dopamine receptors. The radioactivities measured in the striatal area with cerebellum as reference were fitted to a 3-compartment model which made possible evaluation of receptor binding characteristics. The rate proportional to the association rate constant for the receptor, k_on and number of receptors, B_max, varied from 0.02–0.07 min^-1 between the studied radiolabelled drugs, whereas the apparent dissociation rate was highest for clozapine. This means that clozapine had the lowest affinity for the receptors in the striatum, assuming that the B_max values are identical. The observed difference in selective receptor binding and binding characteristics of the 3 tracers may have an influence both on the clinical efficacy and side effects of the studied dopamine receptor antagonists.