Decreased oligodendrocyte nuclear diameter in Alzheimer's disease and lewy body dementia

To better understand the pathogenesis of dementia, it is important to understand histopathologic changes in neurodegenerative diseases because they might highlight key aspects of the degenerative process. In this study, the nuclear diameter of neurons and oligodendrocytes in selected temporal lobe areas were determined in autopsy tissue sections from patients with Alzheimer's disease (AD), Lewy body dementia (LBD) and controls. Our morphometric studies targeted neurons in the CA4 region of the pyramidal cell layer of the hippocampus, neurons in the granular layer of the dentate gyrus and oligodendrocytes in parahippocampal white matter. Mean neuronal nuclear diameters were not different among the studied groups. However, our studies revealed a statistically significant reduction of mean oligodendrocyte nuclear diameter in AD and LBD relative to controls. The reduction of the mean nucleus diameter of oligodendrocytes in LBD was independent of the presence of associated AD pathology in LBD. These findings for the first time identify decreased oligodendrocyte nucleus diameter as a morphologic feature of AD and LBD and may lead to a better understanding of the role of oligodendrocytes in AD and LBD pathogenesis.     

Isoform‐specific upregulation of FynT kinase expression is associated with tauopathy and glial activation in Alzheimer's disease and Lewy body dementias

Cumulative data suggest the involvement of Fyn tyrosine kinase in Alzheimer''s disease (AD). Previously, our group has shown increased immunoreactivities of the FynT isoform in AD neocortex (with no change in the alternatively spliced FynB isoform) which associated with neurofibrillary degeneration and reactive astrogliosis. Since both the aforementioned neuropathological features are also variably found in Lewy Body dementias (LBD), we investigated potential perturbations of Fyn expression in the post‐mortem neocortex of patients with AD, as well as those diagnosed as having one of the two main subgroups of LBD: Parkinson''s disease dementia (PDD) and dementia with Lewy bodies (DLB). We found selective upregulation of FynT expression in AD, PDD, and DLB which also correlated with cognitive impairment. Furthermore, increased FynT expression correlated with hallmark neuropathological lesions, soluble β‐amyloid, and phosphorylated tau, as well as markers of microglia and astrocyte activation. In line with the human post‐mortem studies, cortical FynT expression in aged mice transgenic for human P301S tau was upregulated and further correlated with accumulation of aggregated phosphorylated tau as well as with microglial and astrocytic markers. Our findings provide further evidence for the involvement of FynT in neurodegenerative dementias, likely via effects on tauopathy and neuroinflammation.     

Use-dependent behavioral and neurochemical asymmetry in MPTP mice

Folic acid is believed to play a role in protection from oxidant stress. Low levels of folic acid had been found in serum from patients with Alzheimer disease (AD). Folate concentration was evaluated in sera from 136 patients with cortical dementia [AD, n = 108; frontotemporal dementia (FTD), n = 28], 57 patients with subcortical dementia [Lewy body disease (LBD), n = 9; corticobasal degeneration (CBD), n = 5; progressive supranuclear palsy (PSP), n = 6; Parkinson disease with dementia (PD-Dem), n = 37], and 76 nondemented, healthy age-matched people. Serum folic acid levels were decreased in patients with AD and FTD as compared with either controls or patients with subcortical dementia (3.60 ± 2.22 and 5.37 ± 2.92 μg/L versus 6.87 ± 3.50 μg/L, respectively; P < 0.01). A tendency towards decreased folate concentration was found in LBD and CBD, but not to a significant extent. The highest proportion of folate-deficient patients was found in CBD, FTD and AD (respectively, 60, 48.2 and 46.3% versus 7.9% in controls; P < 0.001). Folate deficiency characterizes FTD as well as AD. These differences observed among different clinical dementing syndromes may be related to neocortical damage.     

Limbic lobe microvacuolation is minimal in Alzheimer's disease in the absence of concurrent Lewy body disease

Microvacuolation is relatively common in the limbic lobe in Lewy body disease (LBD). Similar pathology has also been reported in Alzheimer's disease (AD). Almost all of the studies of microvacuolation in AD, however, antedated the routine application of sensitive immunohistochemical methods to detect Lewy bodies. This raises the possibility that microvacuolation previously reported in AD may have been due to unrecognized LB pathology. To explore this issue, alpha-synuclein immunohistochemistry was used to evaluate a consecutive series of AD as well as cases with mixed AD and LBD (AD/LBD). Independently, the degree of microvacuolation was graded in the entorhinal cortex and the amygdala of the same cases. The results showed that microvacuolation was more common and more severe in AD/LBD than in pure AD cases. In pure AD cases microvacuolation was related to senile plaque density, especially in the amygdala, where many of the neuropil vacuoles were around dense-cored, neuritic plaques. In contrast, in AD/LBD microvacuolation correlated with LB density in the entorhinal cortex and amygdala. These results suggest that microvacuolation has a different pathogenesis in AD and in AD/LBD. Moreover, when prominent microvacuolation is detected in AD, it is imperative to exclude concurrent LBD.     

Efficacy and safety of memantine in Lewy body dementia

Lewy body dementia (LBD) is a progressive brain disease manifest as dementia and parkinsonism, along with psychotic and autonomic disorders. Although studies in recent years have demonstrated the positive effects of cholinesterase inhibitors in LBD, the search for therapeutic agents with other mechanisms of action remains relevant. An open, controlled, 16-week study was performed with the aim of evaluating the efficacy and safety of memantine in patients with clinically diagnosed LBD (criteria of McKeith et al., 1999). The study included 23 patients (mean age 69.2 ± 5.9 years), who were divided into two groups: 14 patients received memantine at a dose of 20 mg/day and nine patients constituted the control group. Efficacy was evaluated using a battery of quantitative neurospychological tests, clinical scales for assessment of fluctuations in mental states, scales for assessment of behavioral and psychotic disorders, and the general clinical impression scale. The results demonstrated that memantine had positive effects on the patients’ general status and cognitive functions (increases on the mini mental state examination by 1.5 points), mainly because of improvements in attention and control functions. There were also reductions in the severity of fluctuations in mental state, aggressivity, lack of spontaneity, and disinhibition. The severity of psychotic and motor disorders did not change significantly. Tolerance of the agent was good, only two patients withdrawing from the study because of episodes of confusion during the dose titration period. Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 108, No. 5, pp. 39–46, May, 2008.     

Cortical rhythms reactivity in AD, LBD and normal subjects: a quantitative MEG study

The present study evaluated the reactivity of cortical rhythms in 15 Alzheimer's disease (AD) patients, 7 Lewy body dementia (LBD) patients and 9 control subjects using a 165 SQUID whole-head MEG system. The absolute power values of the rhythms recorded over different areas over the brain (frontal, parietal, temporal, occipital) were analysed in the 3-47Hz frequency range. The cortical reactivity of the alpha (9-14Hz) and pre-alpha rhythms (7-9Hz) during open and closed eyes conditions differentiated the control group from the patient groups and moderate AD from severe AD and LBD groups, respectively. The cortical reactivity of the slow-band (3-7Hz) obtained by comparing a simple mental task and the rest discriminated the severe AD group from the other groups. In addition, spectral coherence analysis in the alpha band showed that the loss of coherence in AD and LBD patients mainly involved long connections. These results suggest that investigations on rhythms reactivity and spectral coherence might help on the study of the dementias with different etiology.     

Neuropathological correlates of volumetric MRI in autopsy-confirmed Lewy body dementia

The objective of this study was to determine the neuropathological correlates of regional medial temporal lobe volume measures on magnetic resonance imaging (MRI) in subjects with Lewy body dementia (LBD). Twenty-three autopsy-confirmed LBD cases with an MRI scan close to death (mean 1.5 years) were studied. MRI-based volumetric measures were calculated for total intracranial volume, hippocampus, entorhinal cortex, and amygdala. Quantitative neuropathological analysis of plaques, tangles, and Lewy bodies were carried out in the same regions. Spearman's rho was used to examine correlations between MRI volumes and neuropathology measures and linear regression to assess the relationship between neuropathology and MRI volumes. A significant inverse correlation was observed between normalized amygdala volume and percent area of Lewy bodies in the amygdala (r = -0.461, p = 0.035). There were no other significant correlations between regional MRI volume and measures of neuropathology. Lewy body, but not Alzheimer's disease (AD) pathology was associated with reduced amygdala volume in pathologically-verified LBD cases but neither Lewy body nor Alzheimer's disease pathology was associated with volume loss in the hippocampus or entorhinal cortex, suggesting other neuropathological factors account for atrophy in these structures in LBD.     

阿尔茨海默病与血管性痴呆患者认知功能的比较研究

目的 :评价阿尔茨海默病 (AD)和血管性痴呆 (VD)患者认知功能障碍的异同 ;方法 :用简易智力状态检查表 (MMSE)、韦氏记忆量表 (WMS)、日常生活能力量表 (ADL)对 34例AD患者和 4 9例VD患者的认知功能进行测查 ;结果 :(1)MMSE结果表明AD组在短程记忆得分低于VD组 (P <0 .0 1) ,在语言复述得分高于VD组 (P <0 .0 5 ) ;(2 )WMS结果表明AD组在经历 (P <0 .0 5 )、图形再认 (P <0 .0 5 )、理解记忆 (P <0 .0 5 ) ,定向 (P <0 .0 1)得分显著低于VD组 ;(3)ADL结果显示AD组与VD组无显著差异。结论 :AD组和VD组均有记忆障碍 ,AD组受损更为严重并以记忆注意受损为突出 ,VD组相对较轻并以语言复述受损为突出     

阿尔茨海默病与脑血管病痴呆患者的脑电图比较研究

目的：观察阿尔茨海默病(AD)与脑血管病痴呆的(VD)脑电图(EEC)特点。方法：AD20例，VD18例作脑电图检查，并进行简易智力状态检查(MMSE)评分比较。结果：AD组、VD组EEG示0波增多，6波出现，其中AD组异常率为45％、VD组为72％。结论：VD组较AD组EEG改变更严重。     

Clinicopathologic and genetic features of multiple system atrophy with Lewy body disease

Background: Abnormal aggregates of α‐synuclein are pathologic hallmarks of multiple system atrophy (MSA) and Lewy body disease (LBD). LBD sometimes coexists with MSA, but the impact of co‐pathology, particularly diffuse LBD, on presentation of MSA has not been studied. We aimed to determine the frequency and clinicopathologic features of MSA with LBD (MSA+LBD). Methods: Using hematoxylin & eosin and α‐synuclein‐immunostained slides, we assessed the distribution and severity of LBD in 230 autopsy‐confirmed MSA patients collected from 1998 to 2018. Alzheimer‐type pathology was assessed to assign the likelihood of clinical presentations of dementia with Lewy body (DLB) using the consensus criteria for DLB. We reviewed medical records to characterize clinicopathologic features of MSA+LBD. Genetic risk factors for LBD, including APOE ε4 allele and mutations in GBA, SNCA, LRRK2, and VPS35, were analyzed. Results: LBD was observed in 11 MSA patients (5%); seven were brainstem type, three were transitional type, and one was diffuse type. The latter four had an intermediate or high likelihood of DLB. Three of the four had an antemortem diagnosis of Parkinson’s disease with dementia (PDD) or clinically probable DLB. Two patients had neuronal loss in the substantia nigra, but not in striatal or olivocerebellar systems with widespread glial cytoplasmic inclusions, consistent with minimal change MSA. In these cases, LBD was considered the primary pathology, and MSA was considered coincidental. APOE ε4 allele frequency was not different between MSA+LBD and MSA without LBD. Two of nine MSA+LBD patients had a risk variant of GBA (p.T408M and p.E365K). Conclusions: Although rare, MSA with transitional or diffuse LBD can develop clinical features of PDD or DLB. Minimal change MSA can be interpreted as a coincidental, but distinct, α‐synucleinopathy in a subset of patients with diffuse LBD.     

阿尔采木病和血管性痴呆的临床比较

目的　探讨 AD、VD病人的认知障碍及精神病性症状出现率、特点以及 AD组 VD组的不同点。方法　 80例 AD病人、65例 VD病人 ,作 MMSE、HDS、HIS、ALD量表及 WAIS、WMS量表对精神病性症状进行分析。结果　 AD组的WAIS、MMSE、HDS量表分比 VD组低 ,有显著性差异。精神病性症状出现率 AD组 77.5 % ,VD组 84.61 %。两组无显著性差异。但情感脆弱出现率 VD组比 AD组高 ,两组有显著性差异。结论　认知损害是 AD病人的基本症状 ,较 VD病人严重 ,AD、VD的精神病性症状较为常见 ,情感脆弱多见于 VD病人     

Fortress Brain

Neurodegenerative diseases are associated with neuronal inclusions, comprised of protein aggregates. In Alzheimer’s Disease (AD) and Lewy Body Disease (LBD) such lesions are distributed in a hierarchical retrograde transynaptic spatial pattern. This implies a retrograde transynaptic temporal propagation as well. There can be few explanations for this other than infectious agents (prions and viruses). This suggests that AD and LBD (at least) may have infectious origins.     

阿尔采末氏病与多发脑梗塞性痴呆病人认知功能的比较研究

目的：探讨阿尔采末氏病（ＡＤ）和多发脑梗塞性痴呆（ＭＩＤ）病人认知功能的异同。方法：用韦氏成人智力量表和韦氏记忆量表对２１例ＡＤ和１５例ＭＩＤ病人的认知功能进行测查。结果：韦氏智力量表的分析结果表明，ＡＤ组在知识、领悟、算术、相似性、数字广度、词汇和图片排列的量表分以及言语ＩＱ和总ＩＱ显著低于ＭＩＤ组，其余指标差异不显著。ＡＤ组累加、视觉再生、定向、再认、背数的得分以及总量表分和记忆商均明显低于ＭＩＤ组。结论：ＡＤ组和ＭＩＤ组均表现出明显的智能和记忆障碍，ＡＤ组的受损更为严重，以言语理解和记忆注意受损为突出特点，ＭＩＤ组则相对受损较轻，并以操作能力受损为突出特点。     

言语流畅性测验在痴呆识别和鉴别诊断中的应用

目的:评价超市物品言语流畅性测验识别早期痴呆的效力。方法:正常对照242例,阿尔茨海默病276例,血管性痴呆41例,接受MMSE、言语流畅性(VFT)、临床痴呆量表检查。VFT指标有正确总数、串联长度及转换数。结果:不同教育划界分识别轻度AD的敏感度、特异度依次为:0-6年,11,56.5%,72.5%;7-12年,12,75.0%,72.9%;12年 ,13,83.1%,78.4%;对照组言语流畅性成绩与增龄呈负相关、与教育呈正相关;AD组与增龄无关,与教育关联程度明显减低;串联长度对VFT总分贡献高于转换次数;痴呆严重程度相同的VaD患者言语流畅性各项得分均显著低于AD组,类别转换的减少程度(P=0.003)较串联长度(p=0.011)更为明显。结论:超市物品言语流畅性测验识别轻度AD敏感性、特异性高。该测验反映多个认知领域,串联、转换等因子分对痴呆的鉴别诊断具有一定价值。     

阿尔茨海默病、阿尔茨海默病混合型及血管性痴呆患者心理及行为症状的比较

目的 比较阿尔茨海默病(Alzheimer Disease，AD)、AD混合型痴呆(Mixed dementia，MD)、血管性痴呆(Vascular dementia，VD)心理和行为症状(Psychological and behavioral symptoms of dementia，PBSD)的特征。方法 AD、MD及VD患者各30名参加本研究。采用Alzheimer病行为症状评定量表(The Begavioral Pathlolgy in Alzheiner Disease Rating Scale，BEHAVE—AD)、Cohen—Masfield激惹性问卷(The Cohen Mansfield Agitation Inventory，CMAI)评定痴呆患者BPSD。结果 AD患者激惹、焦虑与恐惧发生率较高，VD患者无目的游荡发生率、严重程度较低，MD患者BPSD症状无特异性。结论 AD、VD患者BPSD症状有特异性，MD患者BPSD表现无特异性。     

Boston naming performance distinguishes between Lewy body and Alzheimer''s dementias

Although naming impairment is common among persons with dementia, little is known about how specific error types on naming tasks may differ between dementias. Recent research has suggested that persons with dementia with Lewy bodies (DLB) have more visuospatial/visuoperceptual dysfunction than those with Alzheimer's disease (AD), which may impact their ability to correctly perceive and name objects. Our retrospective study evaluated the presence and frequency of error types among patients with DLB and AD on the Boston Naming Test (BNT). Errors on the BNT were classified into five types (i.e., visuoperceptual, semantic, phonemic, no response, and other), and performance was compared among 31 probable DLB patients and 31 probable AD patients matched for age, gender, education, and overall dementia severity. AD patients' overall performance on the BNT was significantly worse than DLB patients (p<.05). In terms of error types, DLB patients made significantly more visuoperceptual errors (p<.05) while AD patients made significantly more semantic errors (p<.001). Logistic regression revealed that the number of visuoperceptual and semantic errors significantly predicted group membership (p<.005), with an accuracy of up to 85%. Results suggest that error analysis of BNT responses may be useful in distinguishing between patients with DLB and AD.     

Alzheimer病与脑血管性痴呆的P300比较研究

目的:探讨P_(300)对Alzheimer病(AD)和脑血管性痴呆(VD)的诊断和辅助鉴别价值。方法:应用美国Nicolet Spirit脑电生理仪以及“听觉oddball'’为诱发模式,检测了25例AD患者、24例VD患者和22名正常老年人(NC)的P_(300)°结果与NC相比,AD组和VD组P_(300)均有多指标多区域变异,且为同一方向即潜伏期延迟和波幅下降,但变异程度AD组更趋明显。与VD组相比,AD组在Cz区域,靶P_2、N_2潜伏期上延迟,靶P_2波幅下降,AD组在P_Z和F_z区域有类似的表现。在靶潜伏期延迟上,AD组的P_3(在Pz区域)和VD组的N2(在Fz区域),均与其认知功能评定(MMSE评分)相关。结论P_(300)对临床诊断AD病和VD患者有一定价值。P300可以辅助评定痴呆认知功能损害程度。分析P_(300)的不同成分可能对鉴别AD和VD类型有意义。     

Elevated brain scyllo-inositol concentrations in patients with Alzheimer's disease

in vivo (1)H MRS reveals reduced N-acetylaspartate (NAA) and elevated myo-inositol (mI) in patients with mild Alzheimer's disease (AD) and patients with amnestic mild cognitive impairment (MCI). We are unaware of studies that have documented abnormal scyllo-inositol (sI) levels in patients with AD or patients with MCI, although a previous MRS study in older adults has indicated that sI is a peak of interest to measure in AD. Fifteen patients with mild AD, 26 patients with amnestic MCI, and 19 healthy older adults were recruited to this study. All underwent (1)H MRS of the posterior cingulate gyrus of the brain using a 3 T MRI scanner. Increases in the sI/creatine (Cr) ratio were observed in patients with mild AD (P < 0.05). The mI/Cr ratio was raised in patients with mild AD (P < 0.01) and MCI (P < 0.05). Reduced NAA/Cr was detected in patients with mild AD (P < 0.05). The sI/Cr ratio correlated negatively (r = -0.60, P < 0.05) with a measure of clock drawing in patients with mild AD, indicating that impaired cognitive ability in AD is associated with higher concentrations of sI/Cr. In vivo measurement of sI/Cr in the posterior cingulate gyrus of patients with mild AD revealed increases compared with cognitively healthy older adults. Further research on the mechanisms of sI increase in AD is needed. Future studies on the longitudinal course of sI/Cr in MCI and AD appear warranted.     

CSF somatostatin in Alzheimer's disease

Studies have previously demonstrated low somatostatin levels in autopsy cortical tissue from Alzheimer's disease (AD) patients and low somatostatin levels in CSF obtained from subjects with dementia. We evaluated levels of this peptide in 21 non-depressed subjects, 10 with AD, 2 with Parkinson's disease (PD), and 9 with other neurological conditions. The AD patients had significantly lower mean CSF somatostatin than the "other" neurological patients (14.6 +/- 1.5 S.E.M. versus 26.7 +/- 3.2 pg/ml, p less than 0.005). A demented PD subject had a level in the range of the AD group, while the non-demented PD patient had a value above this range. Thus, all 11 patients with AD or PD dementia, analogous disorders, had levels below 21.8 mg/ml, while 7 of the 10 remaining patients had values above 21.8 pg/ml. Age did not explain this finding.