Event-Related Functional Magnetic Resonance Imaging Changes during Relational Retrieval in Normal Aging and Amnestic Mild Cognitive Impairment

The earliest cognitive deficits observed in amnestic mild cognitive impairment (aMCI) appear to center on memory tasks that require relational memory (RM), the ability to link or integrate unrelated pieces of information. RM impairments in aMCI likely reflect neural changes in the medial temporal lobe (MTL) and posterior parietal cortex (PPC). We tested the hypothesis that individuals with aMCI, as compared to cognitively normal (CN) controls, would recruit neural regions outside of the MTL and PPC to support relational memory. To this end, we directly compared the neural underpinnings of successful relational retrieval in aMCI and CN groups, using event-related functional magnetic resonance imaging (fMRI), holding constant the stimuli and encoding task. The fMRI data showed that the CN, compared to the aMCI, group activated left precuneus, left angular gyrus, right posterior cingulate, and right parahippocampal cortex during relational retrieval, while the aMCI group, relative to the CN group, activated superior temporal gyrus and supramarginal gyrus for this comparison. Such findings indicate an early shift in the functional neural architecture of relational retrieval in aMCI, and may prove useful in future studies aimed at capitalizing on functionally intact neural regions as targets for treatment and slowing of the disease course. (JINS, 2012, 18, 1-12).     

Quantitative Computed Tomography and Magnetic Resonance Imaging in Aging and Alzheimer's Disease; A Review

In recent aging research, quantitative techniques have been used to overcome limitations of qualitative interpretation of magnetic resonance and computed tomographic imaging. The purpose of this review is to summarize imaging results emphasizing quantitative studies using these two modalities in human aging. Magnetic resonance spectroscopy is viewed as an extension of imaging, and results of in vivo spectroscopic studies are included. Because Alzheimer's disease (AD) is closely related to aging, a discussion of quantitative imaging techniques that may distinguish normal elderly from patients with AD is included.     

帕金森病的功能磁共振成像研究进展

帕金森病（PD）的主要病理改变是黑质多巴胺能神经元变性坏死并引起多巴胺递质减少,通过神经环路可引起包括脑皮质在内广泛的功能及结构改变.功能磁共振成像（fMRI）作为一项功能影像技术能灵敏地检测出这些变化,进而有可能为PD早期诊断提供依据.本文就PD的fMRI研究进展进行综述.     

GABAergic Deafferentation Hypothesis of Brain Aging and Alzheimer’s Disease Revisited

Considering the mechanisms responsible for age- and Alzheimer’s disease (AD)-related neuronal degeneration, little attention was paid to the opposing relationships between the energy-rich phosphates, mainly the availability of the adenosine triphosphate (ATP), and the activity of the glutamic acid decarboxylase (GAD), the rate-limiting enzyme synthesizing the γ-amino butyric acid (GABA). Here, it is postulated that in all neuronal phenotypes the declining ATP-mediated negative control of GABA synthesis gradually declines and results in age- and AD-related increases of GABA synthesis. The Ca²⁺-independent carrier-mediated GABA release interferes with Ca²⁺-dependent exocytotic release of all transmitter-modulators, because the interstitial (ambient) GABA acts on axonal preterminal and terminal varicosities endowed with depolarizing GABA_A-benzodiazepine receptors; this makes GABA the “executor” of virtually all age- and AD-related neurodegenerative processes. Such a role of GABA is diametrically opposite to that in the perinatal phase, when the carrier-mediated GABA release, acting on GABA_A/chloride ionophore receptors, positively controls chemotactic migration of neuronal precursor cells, has trophic actions and initiates synaptogenesis, thereby enabling retrograde axonal transport of target produced factors that trigger differentiation of neuronal phenotypes. However, with advancing age, and prematurely in AD, the declining mitochondrial ATP synthesis unleashes GABA synthesis, and its carrier-mediated release blocks Ca²⁺-dependent exocytotic release of all transmitter-modulators, leading to dystrophy of chronically depolarized axon terminals and block of retrograde transport of target-produced trophins, causing “starvation” and death of neuronal somata. The above scenario is consistent with the following observations: 1) a 10-month daily administration to aging rats of the GABA-chloride ionophore antagonist, pentylenetetrazol, or of the BDZ antagonist, flumazenil (FL), each forestalls the age-related decline in cognitive functions and losses of hippocampal neurons; 2) the brains of aging rats, relative to young animals, and the postmortem brains of AD patients, relative to age-matched controls, show up to twofold increases in GABA synthesis; 3) the aging humans and those showing symptoms of AD, as well as the aging nonhuman primates and rodents—all show in the forebrain dystrophic axonal varicosities, losses of transmitter vesicles, and swollen mitochondria. These markers, currently regarded as the earliest signs of aging and AD, can be reproduced in vitro cell cultures by 1 μM GABA; the development of these markers can be prevented by substituting Cl⁻ with SO₄²⁻; 4) the extrasynaptic GABA suppresses the membrane Na⁺, K⁺-ATPase and ion pumping, while the resulting depolarization of soma-dendrites relieves the “protective” voltage-dependent Mg²⁺ control of the N-methyl-

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-aspartate (NMDA) channels, thereby enabling Ca²⁺-dependent persistent toxic actions of the excitatory amino acids (EAA); and 5) in whole-cell patch-clamp recording from neurons of aging rats, relative to young rats, the application of 3 μM GABA, causes twofold increases in the whole-cell membrane Cl⁻ conductances and a loss of the physiologically important neuronal ability to desensitize to repeated GABA applications. These age-related alterations in neuronal membrane functions are amplified by 150% in the presence of agonists of BDZ recognition sites located on GABA receptor. The GABA deafferentation hypothesis also accounts for the age- and AD-related degeneration in the forebrain ascending cholinergic, glutamatergic, and the ascending mesencephalic monoaminergic system, despite that the latter, to foster the distribution-utilization of locally produced trophins, evolved syncytium-like connectivities among neuronal somata, axon collaterals, and dendrites, to bidirectionally transport trophins. In such a syncytium, the unmyelinated fine axon collaterals and dendrites are endowed with GABA_A–BDZ receptors whose activation causes a depolarization block, as indicated by recording from unmyelinated axon preterminal and terminal varicosities. The increases of GABA synthesis in the brain stem of aging rats and AD patients result in up to twofold steady GABA elevation, relative to young rats or age-matched human controls, respectively. Thus, GABA and BDZ agonist ligands may block the paracrine-autocrine transport/utilization of trophins. Once initiated, the age- and AD-related deleterious GABA actions may be expected to become a self-reinforcing process, because GABAergic depolarization and dystrophy of axon terminal mitochondria would block ATP production, maximize GAD activity, and GABA synthesis and release. The overview of FL’s unique profile of metabotropic and nootropic actions, apparently contingent on its antagonism of endogenous BDZ ligands, both in humans and animals, suggests that FL has a promising clinical potential.     

Dementia‐related restlessness: relationship to characteristics of persons with dementia and family caregivers

Objective

Dementia‐related restlessness is commonly endorsed by caregivers but not well understood. This study examines differences in characteristics (demographics, cognitive status, physical function, pain, and mood) of persons with dementia whose caregivers endorse restlessness versus those who do not. We also examine the relationship of restlessness to caregiver well‐being including burden, upset with behaviors, mastery, and depressive symptomatology.

Methods

We combined baseline data from three caregiver intervention studies of community‐dwelling persons with dementia who exhibited neuropsychiatric symptoms (n = 569) as measured by the Agitated Behaviors in Dementia Scale. We conducted bivariate correlations and independent t‐tests by using the Agitated Behaviors in Dementia Scale restlessness item.

Results

Nearly 65% (n = 367) of dementia caregivers reported restlessness. There were no significant differences between those with and without (n = 202) reported restlessness concerning functional status (physical or cognitive). However, persons with restlessness had significantly higher pain scores (p < 0.01), were more likely to be on behavioral medications (p < 0.001), and had more neuropsychiatric symptoms as compared with persons without restlessness (M = 11.11, nonrestless; M = 6.61, restless) (p < 0.001). Caregivers of persons with dementia‐related restlessness reported greater burden (p < 0.001), behavioral upset (p < 0.001), depression (p < 0.001), and lower mastery providing care (p < 0.01) compared with caregivers of persons without dementia‐related restlessness.

Conclusions

Restlessness is a common neuropsychiatric symptom that appears to be associated with poorer functioning in persons with dementia and greater distress in their caregivers. Further research is needed to understand the unique contributions of restlessness to care burden and quality of life of persons with dementia, as well as ways to address this distressing symptom. Copyright © 2017 John Wiley & Sons, Ltd.     

轻型缺血性卒中后认知障碍与脑动态功能连接状态改变的功能磁共振成像研究

目的 探索轻型缺血性卒中后有认知障碍（cognitive impairment,CI）患者和无认知障碍（no cognitive impairment,NCI）患者脑动态功能连接（functional connectivity,FC）状态的变化。 方法 选择2014年12月1日-2016年5月31日首都医科大学附属北京天坛医院神经病学中心就诊的 轻型急性缺血性卒中患者为研究对象,对所有患者进行神经心理学评估和多模态MRI检查,分为CI 组（15例）和NCI组（11例）,同时招募年龄、性别均匹配的志愿者作为健康对照（healthy control,HC）组 （29例）。基于静息态功能头颅MRI影像,利用动态功能网络连接方法构建一系列随时间变化的FC网络, 然后通过聚类方法划分为多个具有代表性的动态FC状态（分别为模块化连接状态、强连接状态、局 部连接状态和稀疏连接状态）,比较HC组、CI组与NCI组的FC动态特征（各状态的时间比例、驻留时间 及各状态间的转换次数）差异,并在两个时间点（基线和3个月随访期）探索CI组与NCI组动态FC状态 的变化。 结果 HC组、CI组和NCI组在基线和随访期各连接状态的时间比例差异均无统计学意义。基线CI组 和NCI组在稀疏连接状态的驻留时间比HC组更低,三组差异有统计学意义（P =0.035）,但两两比较 的结果均未通过Bonferroni校正;而在随访期,各连接状态的驻留时间差异均无统计学意义。纵向比 较中,与基线相比,CI组随访期在模块化连接状态的时间比例明显下降（P =0.035）,在稀疏连接状 态的时间比例明显上升（P =0.025）,在模块化连接状态的驻留时间明显降低（P =0.012）;而NCI 组 在两个时间点各连接状态的时间比例和驻留时间差异均无统计学意义。对于转换次数,所有组间的 差异均无统计学意义。 结论 轻型缺血性卒中患者急性期较对照人群有局部连接状态增多而稀疏连接状态减少的趋势, 但差异未达统计学意义;对于有认知障碍的轻型缺血性卒中患者,发病3个月时模块化连接状态和 稀疏连接状态均较急性期显著恢复;动态功能网络能够客观反映大脑功能的变化。     

A Case of Right Cerebellopontine-Angle Lesion: Psychotic Symptoms and Magnetic Resonance Imaging Findings

Here, we report psychotic symptoms together with a right cerebellopontine-angle lesion. A37-year-old female patient presented with a trigeminal Schwannoma occupying the right cerebellopontine angle. Her psychotic symptoms included auditory hallucinations and delusions of persecution. T1- and T2-weighted images on magnetic resonance imaging (MRI) revealed hyperintense and hypointense areas in the right cerebellopontine angle, respectively. The clinical and neuroimaging reviews in this case suggest that sudden onset of psychotic symptoms at a mature age may be associated with a right cerebellopontine-angle lesion and that MRI should be used to evaluate possible organic bases in patients that present with psychosis.