Component structure of the Repeatable Battery for the Assessment of Neuropsychological Status in dementia.

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) has been studied relatively extensively in normal samples, and its theoretically derived index scores have been demonstrated to be useful in the assessment of a variety of clinical conditions. However, examinations of the empirical relationships between individual subtests are limited. The intent of the present study was to explore the component structure of the instrument in a sample of 351 individuals with a diagnosed memory disorder, to examine the impact of demographic factors on these empirically derived components, and to explore differences in performance between diagnostic groups. Findings suggested a three-component solution (Memory, Visuomotor Processing, and Verbal Processing). Demographic variables had relatively small, but significant relationships with various component scores. Significant differences were observed between probable Alzheimer's disease and non-Alzheimer's type dementia groups on the memory component score, but not on other component scores or on RBANS index scores.     

Reliability and validity of the Repeatable Battery for the Assessment of Neuropsychological Status in community-dwelling elderly

Introduction

The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) is a widely used screening instrument in neuropsychological assessment and is a brief, individually administered measure. The present study aims to assess the reliability and validity of the Chinese version of the RBANS in community-dwelling elderly.

Material and methods

All subjects come from the community-dwelling elderly in Shanghai, China. They completed a questionnaire concerning demographic information, the mini-mental state examination (MMSE) and the Chinese version of the RBANS. To test for internal consistency, Cronbach''s α was calculated for all six RBANS indices. Correlations between each of the RBANS and MMSE subtests were conducted to measure the concurrent validity. A confirmatory factor analysis (CFA) was conducted to test the construct validity.

Results

The final sample of participants included 236 community-dwelling elderly. The mean total score on the RBANS was 86.02 (±14.19). The RBANS total score showed strong internal consistency (r = 0.806), and the coefficient α value for each of the RBANS scales ranged from 0.142 to 0.727. The total RBANS score was highly correlated with that of the MMSE (r = 0.594, p<0.001), and the RBANS subtests also demonstrated strong correlations with most of the MMSE subtests. The results of the CFA indicated an acceptable fit between the Chinese version of the RBANS and the original.

Conclusions

The Chinese version of the RBANS had relatively good reliability and validity in a community-dwelling elderly sample. It may be a useful screening instrument for conducting cognitive assessments in community-dwelling elderly.     

A meta-analysis of diffusion tensor imaging in mild cognitive impairment and Alzheimer's disease

We reviewed case-control studies of diffusion tensor imaging (DTI) in patients with Alzheimer's dementia (AD) and mild cognitive impairment (MCI), in order to establish the relative severity and location of white matter microstructural changes. EMBASE and MEDLINE were searched using the keywords, ([“diffusion tensor”] and [“Alzheimer*” or “mild cognitive impairment”]), as were reference lists of relevant papers. Forty-one diffusion tensor imaging studies contained data that were suitable for inclusion. Group means and standard deviations for fractional anisotropy and mean diffusivity, or p values from 2-sample tests, were extracted and pooled, using standard methods of meta-analysis and metaregression. Fractional anisotropy was decreased in AD in all regions except parietal white matter and internal capsule, while patients with MCI had lower values in all white matter regions except parietally and occipitally. Mean diffusivity was increased in AD in all regions, and in MCI in all but occipital and frontal regions.     

Daytime sleepiness in mild and moderate Alzheimer's disease and its relationship with cognitive impairment

The increased tendency to fall asleep during the daytime together with increased wakefulness during the night has been demonstrated in patients with advanced Alzheimer's disease (AD). The aim of this study was to assess daytime sleep propensity in a cohort of patients with mild/moderate AD and to correlate it with cognitive impairment. Twenty drug-free AD patients meeting the NINCDS-ADRDA criteria for probable AD were evaluated. According to their Clinical Dementia Rating scores, subjects were classified into mild (CDR1; n=11) and moderate (CDR2; n=9) dementia patients. A group of 12 healthy subjects was taken as controls. The subjects were evaluated by the multiple sleep latency test (MSLT) after their nocturnal sleep pattern had been assessed by a polysomnographic recording throughout the night before. Both groups of AD patients showed a higher level of daytime sleepiness, which was statistically significant for mean daytime sleep latency (MDSL) (controls versus CDR1 and versus CDR2, CDR1 versus CDR2) and for 10:00 and 12:00 hour naps (controls versus CDR1, controls versus CDR2). In the entire group of AD patients, MDSL was significantly related with MMSE, De Renzi's Token test, verbal fluency, verbal digit span, story recall, Raven's Progressive Matrices, Weigl test and Benton's three-dimensional test. These data indicate that an increased sleep propensity during daytime occurs also in patients with mild/moderate AD detected by objective neurophysiological techniques.     

Biomarkers of oxidative and nitrosative damage in Alzheimer's disease and mild cognitive impairment

Alzheimer's disease (AD) is the most common type of dementia in the elderly. Products of oxidative and nitrosative stress (OS and NS, respectively) accumulate with aging, which is the main risk factor for AD. This provides the basis for the involvement of OS and NS in AD pathogenesis. OS and NS occur in biological systems due to the dysregulation of the redox balance, caused by a deficiency of antioxidants and/or the overproduction of free radicals. Free radical attack against lipids, proteins, sugars and nucleic acids leads to the formation of bioproducts whose detection in fluids and tissues represents the currently available method for assessing oxidative/nitrosative damage. Post-mortem and in-vivo studies have demonstrated an accumulation of products of free radical damage in the central nervous system and in the peripheral tissues of subjects with AD or mild cognitive impairment (MCI). In addition to their individual role, biomarkers for OS and NS in AD are associated with altered bioenergetics and amyloid-beta (Aβ) metabolism. In this review we discuss the main results obtained in the field of biomarkers of oxidative/nitrosative stress in AD and MCI in humans, in addition to their potential role as a tool for diagnosis, prognosis and treatment efficacy in AD.     

Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease

Mild alterations in cognitive function are present in normal aging and severe cognitive alterations are a hallmark of Alzheimer's disease (AD). The cognitive change in AD has been correlated to the characteristic pathologic lesions in the brain, senile plaques (SP) and neurofibrillary tangles. Senile plaques are the most consistent correlative marker in AD. We present preliminary data indicating that abundant SP are found in the brains of nondemented patients dying with or as a result of critical coronary artery disease (cCAD) compared to nonheart disease (non-HD) subjects; 15 of 20 cCAD patients contained SP and only two of 16 non-HD patients contained SP.     

Assessment of ZnT3 and PSD95 protein levels in Lewy body dementias and Alzheimer's disease: association with cognitive impairment

The loss of zinc transporter 3 (ZnT3) has been implicated in age-related cognitive decline in mice, and the protein has been associated with plaques. We investigated the levels of ZnT3 and postsynaptic density protein 95 (PSD95), a marker of the postsynaptic terminal, in people with Parkinson's disease dementia (PDD, n = 31), dementia with Lewy bodies (DLB, n = 44), Alzheimer's disease (AD, n = 16), and controls (n = 24), using semiquantitative western blotting and immunohistochemistry in 3 cortical regions. Standardized cognitive assessments during life and semiquantitative scoring of amyloid β (Aβ), tau, and α-synuclein at postmortem were used to investigate the relationship between ZnT3 and PSD95, cognition and pathology. Associations were observed between ZnT3 and PSD95 levels in prefrontal cortex and cognitive impairment (p = 0.001 and p = 0.002, respectively) and between ZnT3 levels in the parietal cortex and cognitive impairment (p = 0.036). Associations were also seen between ZnT3 levels in cingulate cortex and severity of Aβ (p = 0.003) and tau (p = 0.011) pathologies. DLB and PDD were characterized by significant reductions of PSD95 (p < 0.05) and ZnT3 (p < 0.001) in prefrontal cortex compared with controls and AD. PSD95 levels in the parietal cortex were found to be decreased in AD cases compared with controls (p = 0.02) and PDD (p = 0.005). This study has identified Zn²⁺ modulation as a possible novel target for the treatment of cognitive impairment in DLB and PDD and the potential for synaptic proteins to be used as a biomarker for the differentiation of DLB and PDD from AD.     

不同认知功能障碍程度阿尔茨海默病患者海马、内嗅皮层体积变化及其与MMSE评分的关系

目的 探讨不同认知功能障碍程度的患者阿尔兹海默病（AD）海马、内嗅皮层体积的变化,及其与简易精神状态检查表（MMSE）评分的相关性。方法 横断面研究。纳入2017年9月—2021年9月联保部队第九六〇医院淄博院区86例AD患者临床和影像学资料,其中男54例、女32例,年龄55~87（73.9±8.1）岁。根据临床痴呆评定量表（CDR）评分将86例患者分为3组,其中36例CDR评分0.5分患者为轻度认知障碍（MCI）组,21例1分患者为轻度AD组,29例2~3分患者为中重度AD组。患者均应用MRI测量双侧海马体积、内嗅皮层体积,采用MMSE评分评估患者认知功能。观察指标：（1）比较3组患者性别、年龄、受教育年限等临床基线资料,以及MMSE评分;（2）比较3组患者海马体积和内嗅皮层体积;（3）分析AD患者MMSE评分与海马、内嗅皮层体积的相关性。结果 （1）3组患者性别、年龄、受教育年限等临床基线资料比较差异均无统计学意义（P值均>0.05）。MCI组、轻度AD组、中重度AD组患者MMSE评分依次降低,差异有统计学意义（F=113.29,P<0.001）。（2）MCI组、轻度AD组、中重度AD组左右侧海马体积MRI测量值分别为（3.24±0.32）cm³和（3.22±0.31）cm³、（2.72±0.53）cm³和（2.84±0.56）cm³、（2.31±0.55）cm³和（2.46±0.54）cm³,左右侧内嗅皮层体积分别为（1.42±0.26）cm³和（1.39±0.27）cm³、（1.28±0.24）cm³和（1.24±0.25）cm³、（1.04±0.31）cm³和（1.06±0.34）cm³。3组患者左右侧海马体积、内嗅皮层体积MRI测量值比较,均为MCI组>轻度AD组>中重度AD组,差异均有统计学意义（P值均<0.05）。（3）86例AD患者MMSE评分10~27（20.9±5.2）分,与左右两侧海马体积、内嗅皮层体积MRI测量值均呈正相关（r=0.82、0.81、0.73、0.72,P值均<0.001）。结论 随着认知功能障碍程度的加重,AD患者海马、内嗅皮层体积MRI测量值逐渐减小,且MMSE评分与海马、内嗅皮层体积存在相关性。     

肉苁蓉总苷对阿尔茨海默病模型大鼠学习认知功能和氧化应激的影响*

目的：探讨肉苁蓉总苷（ GCs）对阿尔茨海默病（AD）模型大鼠学习认知功能的影响及其作用机制。方法： 双侧脑室注射Aβ1-42 制备AD大鼠模型,连续给予模型大鼠不同剂量的GCs 腹腔注射20 d,Morris 水迷宫检测各 组大鼠空间学习记忆能力,尼氏染色观察海马CA1区细胞形态并计数正常锥体细胞;免疫组织化学测定脑组织突 触素（ SYN）含量、酶联免疫吸附试验测定血清超氧化物歧化酶（ SOD）和谷胱甘肽过氧化物酶（ GSH-Px）活 性、丙二醛（ MDA）的含量。结果：GCs 可明显缩短逃避潜伏期与上台前路程,明显增加目标象限时间百分比 与穿越平台次数;GCs 能提高海马CA1区锥体细胞的存活率,明显增加SYN蛋白的表达和提高SOD、GSH-Px 活 性,降低MDA的活性。结论：GCs 改善AD学习认知障碍的机制可能是通过减少自由基堆积、清除体内过多的 过氧化物,进而提高突触可塑性来改善学习认知功能。     

Measurements of medial temporal lobe atrophy for prediction of Alzheimer's disease in subjects with mild cognitive impairment

Our aim was to compare the predictive accuracy of 4 different medial temporal lobe measurements for Alzheimer's disease (AD) in subjects with mild cognitive impairment (MCI). Manual hippocampal measurement, automated atlas-based hippocampal measurement, a visual rating scale (MTA-score), and lateral ventricle measurement were compared. Predictive accuracy for AD 2 years after baseline was assessed by receiver operating characteristics analyses with area under the curve as outcome. Annual cognitive decline was assessed by slope analyses up to 5 years after baseline. Correlations with biomarkers in cerebrospinal fluid (CSF) were investigated. Subjects with MCI were selected from the Development of Screening Guidelines and Clinical Criteria for Predementia AD (DESCRIPA) multicenter study (n = 156) and the single-center VU medical center (n = 172). At follow-up, area under the curve was highest for automated atlas-based hippocampal measurement (0.71) and manual hippocampal measurement (0.71), and lower for MTA-score (0.65) and lateral ventricle (0.60). Slope analysis yielded similar results. Hippocampal measurements correlated with CSF total tau and phosphorylated tau, not with beta-amyloid 1–42. MTA-score and lateral ventricle volume correlated with CSF beta-amyloid 1–42. We can conclude that volumetric hippocampal measurements are the best predictors of AD conversion in subjects with MCI.     

Animal models in the study of Alzheimer's disease and Parkinson's disease: A historical perspective

Alzheimer's disease and Parkinson's disease are two of the most prevalent and disa-bling neurodegenerative diseases globally. Both are proteinopathic conditions and while occasionally inherited, are largely sporadic in nature. Although the advances in our understanding of the two have been significant, they are far from complete and neither diagnosis nor the current practices in treatment and rehabilitation is ad-equately helpful. Animal models have historically found application as testing beds for novel therapeutics and continue to be valuable aids in pharmacological research. This review chronicles the development of those models in the context of Alzheimer's and Parkinson's disease, and highlights the shifting paradigms in studying two human- specific conditions in non- human organisms.     

Immunoglobulins, cognitive status and duration of illness in alzheimer''s disease

Immunologic changes have been reported in the dementing illnesses of mid and late life. The results of two studies of drug-free males meeting research diagnostic criteria for primary neuronal degeneration of the Alzheimer's type suggest that serum IgG levels decrease with the progression of dementia. Serum IgG levels were inversely correlated with duration of illness and the levels of psychiatric symptomatology. Performance on the mini-mental status examination was positively associated with serum IgG concentrations.     

Immunoglobulins, cognitive status and duration of illness in alzheimer's disease

Immunologic changes have been reported in the dementing illnesses of mid and late life. The results of two studies of drug-free males meeting research diagnostic criteria for primary neuronal degeneration of the Alzheimer's type suggest that serum IgG levels decrease with the progression of dementia. Serum IgG levels were inversely correlated with duration of illness and the levels of psychiatric symptomatology. Performance on the mini-mental status examination was positively associated with serum IgG concentrations.     

The role of premorbid personality and cognitive factors in awareness of illness,memory, and behavioural functioning in Alzheimer's disease

Introduction. Research has suggested an association between personality factors and awareness in patients with dementia, yet valid measurement of premorbid personality is problematic. The present study aimed to better reveal the relationship between premorbid personality and awareness by using improved methodology. Moreover, the study aims to contrast the strength of the relationship of premorbid personality and awareness with that of cognitive factors.

Methods. Awareness of illness, symptoms, mnemonic and behavioural impairments, and treatment compliance were measured in 27 patients with mild-to-moderate Alzheimer's disease (AD) diagnosed by standard criteria for probable AD. Participant premorbid personality was measured using average retrospective Neuroticism-Extroversion-Openness Inventory (NEO-FFI) scores from two informants. Correlations were performed to investigate the relationship between awareness and personality dimensions, as well as measures of cognitive style, neuropsychological function, mood, carer burden, and sociodemographic factors.

Results. There was little relationship between awareness and personality scores, but modest associations between awareness and mood, age, and age of onset of first symptoms. Awareness of memory was related to memory functioning. Increased carer burden was associated with lack of awareness of cognitive-behavioural deficits but there were only few and weak associations between awareness and measures of cognitive functioning.

Conclusions. There was little support for an association between previous personality and awareness in dementia. However, increased carer burden was associated specifically with lack of awareness of cognitive-behavioural deficits not deficits in ADL, whereas lower awareness of ADL and not cognitive-behavioural deficits was associated with age. Awareness of memory appeared to be a metamemory capacity. Mood and age rather than personality and cognition are stronger predictors of awareness in early Alzheimer's disease.     

Conservation of species,volume, and belief in patients with Alzheimer's disease: The issue of domain specificity and conceptual impairment

Two studies investigated whether patients with Alzheimer's disease (AD) suffer high-level and category-specific impairment in the conceptual domain of living things. In Experiment 1, AD patients and healthy young and healthy elderly controls took part in three tasks: the conservation of species, volume, and belief. All 3 tasks required tracking an object's identity in the face of irrelevant but salient transformations. Healthy young and elderly controls performed at or near ceiling on all tasks. AD patients were at or near ceiling on the volume and belief tasks, but only about half succeeded on the species task. Experiment 2 demonstrated that the results were not due to simple task demands. AD patients' failure to conserve species indicates that they are impaired in their theoretical understanding of living things, and their success on the volume and belief tasks suggests that the impairment is domain-specific. Two hypotheses are put forward to explain the phenomenon: The first, a category-specific account, holds that the intuitive theory of biology undergoes pervasive degradation; the second, a hybrid domain-general/domain-specific account, holds that impairment to domain-general processes such as executive function interacts with core cognition, the primitive elements that are the foundation of domain-specific knowledge.     

Changes in the levels of plasma soluble fractalkine in patients with mild cognitive impairment and Alzheimer's disease

Soluble fractalkine plays a distinctive role in the inflammatory processes of the nervous system; however, the role of soluble fractalkine in Alzheimer's disease (AD) has not yet been investigated. In the present study, we evaluated the levels of plasma soluble fractalkine in patients with mild cognitive impairment (MCI), patients with AD and healthy controls. We also investigated the changes in the levels of plasma soluble fractalkine in patients with AD. A total of 102 patients with cognitive impairment, including 51 patients with MCI, 51 patients with AD, and 57 healthy control subjects, were enrolled in this study. The Mini-Mental Status Examination (MMSE) was used to evaluate the severity of cognitive impairment in patients with MCI and AD. The levels of plasma soluble fractalkine were measured using a specific enzyme-linked immunosorbent assay. There were significant group differences in the levels of plasma soluble fractalkine between the MCI, AD, and control groups. Post hoc analyses revealed significant differences between the MCI and control groups, the AD and control groups, and the MCI and AD groups. The level of plasma soluble fractalkine was significantly greater in the patients with mild to moderate AD than in the patients with severe AD. In addition, there was a positive correlation between MMSE score and plasma soluble fractalkine level in the patients with AD. This study provides preliminary evidence that soluble fractalkine is involved in the pathogenesis of AD.     

Five out of 16 plasma signaling proteins are enhanced in plasma of patients with mild cognitive impairment and Alzheimer's disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with characteristic neuropathological changes of the brain. Great efforts have been undertaken to determine the progression of the disease and to monitor therapeutic interventions. Especially, the analysis of blood plasma had yielded incongruent results. Recently, Ray et al. (Nat. Med. 13, 2007, 1359f) identified changes of 18 signaling proteins leading to an accuracy of 90% in the diagnosis of AD. The aim of the present study was to examine 16 of these signaling proteins by quantitative Searchlight multiplex ELISA in order to determine their sensitivity and specificity in our plasma samples from AD, mild cognitive impairment (MCI), depression with and without cognitive impairment and healthy subjects. Quantitative analysis revealed an increased concentration in Biocoll isolated plasma of 5 out of these 16 proteins in MCI and AD patients compared to healthy subjects: EGF, GDNF and MIP1δ (in AD), MIP4 (in MCI) and RANTES (in MCI and AD). ROC analysis predicted a sensitivity of 65-75% and a specificity of 52-63% when comparing healthy controls versus MCI or AD. Depression without any significant cognitive deficits did not cause any significant changes. Depressed patients with significant cognitive impairment were not different from MCI patients. In conclusion, we detected a number of altered proteins that may be related to a disease specific pathophysiology. However, the overall expression pattern of plasma proteins could not be established as a biomarker to differentiate MCI from AD or from depression.