Increased plasma levels of BDNF and inflammatory markers in Alzheimer's disease

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. Neurotrophic factors and inflammatory markers may play considerable roles in AD. In this study we measured, through Enzyme-Linked Immunosorbent Assay, the plasma levels of brain derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF) and neuronal growth factor (NGF), as well as tumor necrosis factor-alpha soluble receptors, sTNFR1 and sTNFR2, and soluble intercellular adhesion molecule 1 (sICAM-1), in 50 AD patients, 37 patients with mild cognitive impairment (MCI) and 56 healthy elderly controls. BDNF levels, expressed as median and interquartile range, were higher for AD patients (2545.3, 1497.4–4153.4 pg/ml) compared to controls (1503.8, 802.3–2378.4 pg/ml), P < 0.001. sICAM-1 was also higher in AD patients. sTNFR1 levels were increased in AD when compared to controls and also to MCI. GDNF, NGF and sTNFR2 levels showed no significant differences among the studied groups. The increase in BDNF might reflect a compensatory mechanism against early neurodegeneration and seems to be related to inflammation. sTNFR1 appears to mark not only the inflammatory state but also differentiates between MCI and AD, which may be an additional tool for differentiating degrees of cognitive impairment.     

Decreased Serum Brain-Derived Neurotrophic Factor Levels in Elderly Korean with Dementia

Objective

The primary purpose of this study was to investigate the differences in the serum brain-derived neurotrophic factor (BDNF) level between elderly Korean people over 65 years with and without dementia.

Methods

171 individuals over 65 years were enrolled in this study. Screening for cognitive impairments was carried out using the Mini-Mental Status Examination-Korean version (MMSE-KC). One hundred thirty-two subjects scored below 1.5 standard deviations (SD) of the mean MMSE-KC score, and these were evaluated using the Consortium to Establish a Registry for Alzheimer''s Disease, Korean version (CERAD-K) and the Geriatric Depression Scale (GDS). The Clinical Dementia Rating Scale (CDRS) and the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria were used for further evaluation. Subjects with a CDRS score of 1 or higher were classified as having Alzheimer''s disease (AD), and subjects with a CDRS score of 0.5 were classified as having a mild cognitive impairment (MCI). Subjects with a CDRS score of 0 were classified as having aging-associated cognitive decline (AACD). Serum BDNF levels were analyzed using the enzyme-linked immunosorbent assay (ELISA) method.

Results

The serum BDNF levels were significantly lower in the subjects with MCI and AD compared with the healthy controls (p<0.01). A significant correlation was found between the total MMSE-KC score and serum BDNF level (r=0.295; p<0.01). However, no significant correlation was observed between the severity of MMSE-KC and the total GDS score. A significant difference was found in the total score of GDS between the AACD group and subjects with AD (p<0.05).

Conclusion

This study suggested that BDNF might be involved in the pathophysiology of cognitive decline in elderly people.     

轻度认知功能障碍患者认知损害与血清脑源性神经营养因子水平的相关性

目的 研究轻度认知功能障碍（mild cognitive impairment,MCI）患者认知损害与血清脑源性神经营养因子（brain derived neurotrophic factor,BDNF）水平的关系。 方法 从认知障碍门诊筛选MCI患者30例,正常对照老年人32例,采用酶联免疫吸附法（enzyme linked immunosorbent assay,ELISA）检测MCI患者的血清BDNF水平。 结果 MCI的血清BDNF水平较正常对照组显著升高（P=0.025）,MCI组中血清BDNF与简明精神状态量表（Mini-Mental State Examination Scale,MMSE）中的记忆力（r=-0.494,P=0.009）、语言能力（r=-0.399,P=0.039）呈负相关,与定向力、注意力和计算力、回忆能力无相关性;与临床痴呆量表（Clinical Dementia Rating Scale,CDR）总分呈正相关（r=0.476,P=0.012）;与MMSE总分、全面衰退量表（Global Deterioration Scale,GDS）总分无相关性。 结论 MCI患者的BDNF水平显著升高,提示BDNF可能参与MCI认知损害的病理生理过程     

Decreased Levels of Circulating Adiponectin in Mild Cognitive Impairment and Alzheimer’s Disease

Adiponectin, an adipocytokine released by the adipose tissue and has important roles in the metabolic regulation and inflammatory control, may play an important roles in the physiopathology of psychiatric and neurodegenerative disorders. The aim of the present work was to evaluate adiponectin serum levels in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) as compared to cognitively healthy elders and to correlate these levels with clinical and cognitive parameters. We further evaluated whether circulating adiponectin levels could predict progression from MCI to Alzheimer’s disease upon follow-up. We recruited 157 subjects (41 with AD, 65 with MCI and 51 elderly controls) in the baseline assessment. Follow-up data were available for 54 subjects with MCI and 43 controls in whom we ascertained the conversion to AD and the progression of cognitive impairment. Adiponectin was assayed by sandwich ELISA. Serum levels of adiponectin were significantly lower in MCI and AD as compared to controls (p < 0.001). After controlling for age, educational level and APOE genotype, adiponectin levels remained significantly reduced in these groups (p < 0.001). Circulating adiponectin levels did not predict cognitive decline in the elderly controls (i.e., progression from normal cognition to MCI) or progression to Alzheimer’s disease in subjects with MCI. We conclude that lower levels of adiponectin were associated with cognitive dysfunction, though it did not predict additional cognitive decline and conversion to dementia in this cohort of elderly subjects. Decreased adiponectin may be a surrogate marker of the pathological process in AD, linking clinical comorbidities, inflammation and cognitive dysfunction.     

Genetic influence of apolipoprotein E4 genotype on hippocampal morphometry: An N = 725 surface‐based Alzheimer's disease neuroimaging initiative study

The apolipoprotein E (APOE) e4 allele is the most prevalent genetic risk factor for Alzheimer's disease (AD). Hippocampal volumes are generally smaller in AD patients carrying the e4 allele compared to e4 noncarriers. Here we examined the effect of APOE e4 on hippocampal morphometry in a large imaging database—the Alzheimer's Disease Neuroimaging Initiative (ADNI). We automatically segmented and constructed hippocampal surfaces from the baseline MR images of 725 subjects with known APOE genotype information including 167 with AD, 354 with mild cognitive impairment (MCI), and 204 normal controls. High‐order correspondences between hippocampal surfaces were enforced across subjects with a novel inverse consistent surface fluid registration method. Multivariate statistics consisting of multivariate tensor‐based morphometry (mTBM) and radial distance were computed for surface deformation analysis. Using Hotelling's T² test, we found significant morphological deformation in APOE e4 carriers relative to noncarriers in the entire cohort as well as in the nondemented (pooled MCI and control) subjects, affecting the left hippocampus more than the right, and this effect was more pronounced in e4 homozygotes than heterozygotes. Our findings are consistent with previous studies that showed e4 carriers exhibit accelerated hippocampal atrophy; we extend these findings to a novel measure of hippocampal morphometry. Hippocampal morphometry has significant potential as an imaging biomarker of early stage AD. Hum Brain Mapp 35:3903–3918, 2014. © 2014 Wiley Periodicals, Inc .     

Association between brain‐derived neurotrophic factor (BDNF) gene polymorphisms and executive function in Japanese patients with Alzheimer's disease

Background: To address the functional roles of genetic polymorphisms of brain‐derived neurotrophic factor (BDNF) in Alzheimer's disease (AD) from a neuropsychological aspect, we used a cross‐sectional study design to investigate the association between novel single nucleotide polymorphisms (SNPs) of the BDNF gene (Val66Met (G196A) and C270T) and the Frontal Assessment Battery (FAB) score, which reflects executive function as a non‐memory cognitive impairment. Methods: One hundred and sixty‐nine outpatients with AD or amnestic mild cognitive impairment (A‐MCI) were recruited to the study and divided into three genotypic groups for each representative BDNF functional polymorphism as follows: (i) Val66Met (G196A): G/G (n= 45), G/A (n= 104), and A/A (n= 20); and (ii) C270T: C/C (n= 160), C/T (n= 9), and T/T (n= 0). Then, age, sex ratio, duration of illness (months), education years, Mini‐Mental State Examination (MMSE) score, behavioral pathology in Alzheimer disease (Behave‐AD) score, Clinical Dementia Rating (CDR) ratio, and total and subtest FAB scores were compared between the genotypic groups for each SNP. Results: Significant differences were found in the total (P < 0.01) and subtest (conflicting instructions and prehension behavior; P < 0.01) FAB scores between the C270T polymorphism groups (C/C and C/T), but not among the G196A polymorphism groups. However, no significant differences in age, sex ratio, duration of illness (months), education years, Behave‐AD score, CDR ratio, or MMSE score (reflecting attention and memory function) were found between the individual polymorphism genotypes (G196A and C270T). Conclusion: Of the known BDNF polymorphisms, the C270T SNP may influence executive dysfunction as a non‐memory cognitive impairment in Japanese patients with AD.     

BDNF serum concentrations show no relationship with diagnostic group or medication status in neurodegenerative disease

Brain-derived neurotrophic factor (BDNF) is a growth factor implicated in neuronal survival. Studies have reported altered BDNF serum concentrations in patients with Alzheimer's disease (AD). However, these studies have been inconsistent. Few studies have investigated BDNF concentrations across multiple neurodegenerative diseases, and no studies have investigated BDNF concentrations in patients with frontotemporal dementia. To examine BDNF concentrations in different neurodegenerative diseases, we measured serum concentrations of BDNF using enzyme-linked immunoassay in subjects with behavioral-variant frontotemporal dementia (bvFTD, n=20), semantic dementia (SemD, n=16), AD (n=34), and mild cognitive impairment (MCI, n=30), as well as healthy older subjects (HS, n=38). BDNF serum concentrations were compared across diagnoses and correlated with cognitive tests and patterns of brain atrophy using voxelbased morphometry. We found small negative correlations between BDNF serum concentrations and some of the cognitive tests assessing learning, information processing speed and cognitive control in complex situations, however, BDNF did not predict disease group membership despite adequate power. These findings suggest that BDNF serum concentration may not be a reliable diagnostic biomarker to distinguish among neurodegenerative diseases.     

The brain-derived neurotrophic factor gene as a possible susceptibility candidate for Alzheimer's disease in a chinese population

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may represent a candidate gene conferring susceptibility to Alzheimer's disease (AD). This is because it has an important role in neuronal survival, and a decreased central level of BDNF is observed in AD. Some previous studies, though not all, have demonstrated that BDNF C270T polymorphisms might be associated with AD susceptibility. We examined the association of the C270T polymorphisms with sporadic AD in a Chinese cohort of 175 AD patients and 189 controls. We also tested BDNF Val66Met-C270T haplotypes for an interaction with the apolipoprotein E upsilon4 (APOE4) allele in AD. The results showed that the frequency of the 66Val allele was significantly lower in AD than controls (p = 0.031), but no significant difference in C270T allele or genotype frequencies was observed between AD cases and controls. Global case-control haplotype analysis showed that there is significant difference in haplotype distribution between both groups (p = 0.033). Stratification of the data according to the APOE status showed that in APOE4 allele bearers there was no significant difference in the frequency of haplotype 66Val-270C between AD and controls (p = 0.125), although there was a significant difference between the two groups in non-APOE4 carriers (p = 0.002). These results suggest that BDNF genetic variation may possibly affect the risk for AD, particularly in subjects who are negative for APOE4.     

Sex, apolipoprotein E epsilon 4 status, and hippocampal volume in mild cognitive impairment

BACKGROUND: Subjects with mild cognitive impairment (MCI) have been shown to have reduced hippocampal volumes relative to normal elderly control subjects. The presence of the apolipoprotein E epsilon4 (APOE*E4) allele has been associated with greater hippocampal atrophy in women than in men with Alzheimer disease. This relationship has not been demonstrated in MCI. OBJECTIVE: To examine the relationship between APOE genotype and hippocampal volume in men and women with MCI. DESIGN: This study evaluated MCI in 193 subjects (86 women and 107 men) participating in a multicenter clinical trial, all of whom underwent magnetic resonance imaging at their baseline visit. We evaluated the association among the number of APOE*E4 alleles, memory performance, and hippocampal volume in men and women with tests of means and multiple linear regressions. RESULTS: Compared with MCI subjects with no APOE*E4 alleles, women with 1 or 2 APOE*E4 alleles were found to have significantly reduced hippocampal volume, whereas men only showed a significant reduction in hippocampal volume when carrying 2 APOE*E4 alleles. Worsening of performance on a delayed word recall task (Alzheimer's Disease Assessment Scale cognitive subscale) showed an identical pattern in association with APOE*E4 allele dose and sex. Furthermore, when controlling for memory performance on delayed word recall, the APOE*E4 effect on hippocampal volumes was attenuated in men, but remained significant in women. CONCLUSION: The APOE*E4 genotype status appears to have a greater deleterious effect on gross hippocampal pathology and memory performance in women than in men.     

Reduced hippocampal volumes in healthy carriers of brain-derived neurotrophic factor Val66Met polymorphism: Meta-analysis

Abstract

Objectives. Converging evidence suggests that the brain-derived neurotrophic factor (BDNF) gene Val66Met polymorphism affects brain structure. Yet the majority of studies have shown no effect of this polymorphism on hippocampal volumes, perhaps due to small effect size. Methods. We performed a meta-analysis of studies investigating the association between Val66Met BDNF polymorphism and hippocampal volumes in healthy subjects by combining standardized differences between means (SDM) from individual studies using random effect models. Results. Data from 399 healthy subjects (255 Val-BDNF homozygotes and 144 carriers of at least one Met-BDNF allele) in seven studies were meta-analysed. Both the left and right hippocampi were significantly larger in Val-BDNF homozygotes than in carriers of at least one Met-BDNF allele (SDM = 0.41, 95% Confidence Interval = 0.20; 0.62, z = 3.86, P = 0.0001; SDM = 0.41; 95% Confidence Interval = 0.20; 0.61, z = 3.81, P = 0.0001, respectively), with no evidence of publication bias. Conclusions. Healthy carriers of BDNF gene Val66Met polymorphism show bilateral hippocampal volume reduction. The effect size was small, but the same direction of effect was seen in all meta-analyzed studies. The association with the BDNF gene Val66Met polymorphism makes hippocampal volume a potential candidate for an endophenotype of disorders presenting with reduced hippocampal volumes.     

Mild cognitive impairment with subcortical vascular features: clinical characteristics and outcome

Objectives: To identify non-demented individuals with cognitive impairment due to a cerebrovascular etiology among those coming to observation of a memory clinic and to describe their clinical features and outcome. Methods: Patients were enrolled in a prospective study on early cognitive impairment carried out in a Memory Clinic. Mild cognitive impairment of the vascular type (MCI-V) was defined based on modified criteria for subcortical vascular dementia (SVD) by Erkinjuntti and colleagues. Twenty-nine patients with MCI-V (age 78 ± 7, Mini Mental State Exam (MMSE) 24 ± 3) were compared with 14 with mild cognitive impairment of degenerative etiology (MCI) based on the Mayo Clinic criteria (age 72 ± 9, MMSE 25 ± 2), and to 21 patients with frank SVD (age 80 ± 6, MMSE 21 ± 3). Patients were followed over time for 32 ± 8 months. Results: MCI-V patients had a neuropsychological profile characterized by poor performance on frontal tests (Wisconsin card sorting and word fluency) and neurological features of parkinsonism without tremor (impairment of balance and gait). Of those followed for at least 40 months, 50 % of patients with MCI-V and SVD had died, while all MCI patients were still alive (P = 0.03). Of those alive, 68 % of the MCI-V, 52 % of the SVD, and 17 % of the MCI patients had reached one of the following outcomes at 40 months: nursing home placement, functional loss, and cognitive deterioration (P = 0.02). Conclusions: Patients with MCI-V have a distinctive clinical picture and can be identified in a clinical setting. Because of the high frequency of adverse outcomes, very early preventive measures need to be devised. Received: 27 July 2001, Received in revised form: 22 February 2002, Accepted: 22 April 2002 Correspondence to Giovanni B. Frisoni, MD     

The role of apolipoprotein E polymorphisms in levodopa-induced dyskinesia

Molchadski I, Korczyn AD, Cohen OS, Katzav A, Nitzan Z, Chapman J, Hassin‐Baer S. The role of apolipoprotein E polymorphisms in levodopa‐induced dyskinesia.
Acta Neurol Scand: 2011: 123: 117–121.
© 2010 John Wiley & Sons A/S. Objectives – To determine the relationship between apolipoprotein E (APOE) polymorphisms to the time to appearance of levodopa‐induced dyskinesia (LID) in patients with Parkinson’s disease. Methods – The APOE genotype of 155 consecutive patients treated with levodopa was determined and its effect on the time of onset of LID was examined using Cox regression model, controlling for gender, age of disease onset, time to initiation of levodopa treatment and history of smoking. Results – Two patients were homozygous for the APOE ε2 allele, 7 had ε2/ε3, 1 had ε2/ε4, 130 had ε3/ε3, 12 had ε3/ε4 and 3 had ε4/ε4; LID appeared in 57.4% of the patients, appearing 4.1 ± 3.5 years after the initiation of levodopa treatment. The survival curve for LID was not affected by the APOE genotype (P = 0.34). Conclusion – APOE polymorphisms were found not to be associated with either the occurrence or the time to development of LID.     

Markers of Alzheimer's disease in a population attending a memory clinic

BackgroundNew marker-based criteria for the diagnosis of Alzheimer's disease (AD) were recently proposed. We describe their operational translation in 144 consecutive patients referred to our Memory Clinic.MethodsVisual ratings of hippocampal atrophy and of cortical glucose hypometabolism in magnetic resonance imaging and positron emission tomography, and concentrations of total tau and Aβ1-42 in cerebrospinal fluid were assessed in 12 patients with subjective memory complaints (SMCs) (Mini-Mental State Examination [MMSE] score, 28.0 ± 1.1 [mean ± SD]), 37 with mild cognitive impairment (MCI) (MMSE, 25.1 ± 3.6), 55 with AD (MMSE, 21.1 ± 3.5), and 40 with non-AD dementia (MMSE, 21.6 ± 5.5).ResultsThe sensitivity for AD of each individual biomarker was higher (65% to 87%) than for MCI (18% to 50%). Each biomarker's specificity for SMC and non-AD dementias was good to moderate (83% and 53%). Positivity for at least one marker increased the probability 38 times of belonging to the AD group (P < 0.0001).ConclusionThe new diagnostic criteria can be operationalized in clinical routines, but longitudinal studies of MCI patients will need to assess the criteria's prognostic value.     

Design of a comprehensive Alzheimer’s disease clinic and research center in Spain to meet critical patient and family needs

ObjectivesAlzheimer's disease (AD) affects people worldwide, and the prevalence is increasing as the population ages. There is an international effort to understand the biology of AD to develop primary and secondary prevention strategies, and to develop effective therapeutic interventions for individuals who are already symptomatic. One of the critically important pieces of all national plans to address AD is the call for the development of service models to deliver quality, effective care based on the best evidence available.MethodsWe describe one type of care model developed by the Fundacio ACE, Institut Catala de Neurociencies Aplicades (Fundacio ACE, Barcelona, Spain) that integrates diagnosis, therapy, follow-up care, daycare, and a day hospital, and does so in the context of an active clinical research and educational program.ResultsThere were 13,048 individuals newly evaluated and diagnosed in Fundacio ACE between 1996 and 2011. Of these, 6132 had AD (47.0%), 3871 had mild cognitive impairment (MCI) (29.7%), and 1958 had no cognitive impairment (15.0%). Follow-up information is available on 4735 (47.3%) AD and MCI patients, and these data indicate that MCI develops into dementia at a rate of 222.6/1000 person-years. Apolipoprotein E (APOE) genotyping was available in 22.4% of the patients. The ε4 allele occurred in 45.7% of the AD patients, in 37.8% of the MCI subjects, and in 31.6% of those without cognitive impairment.ConclusionsFundació ACE can serve as a model system that can be adapted to other settings within their specific cultural, governmental, and legal constraints.     

Serum brain-derived neurotrophic factor levels as a novel biological marker for the activities of psychiatric symptoms in systemic lupus erythematosus

Abstract

Objectives. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious but potentially treatable disease. However, biological markers such as IgG index or IL-6 do not always reflect the severity of the psychotic symptoms of NPSLE. We hypothesized that serum BDNF levels may be a biological marker for reflecting the severity of the psychiatric symptoms of NPSLE. Methods. The participants enrolled in this study were 28 healthy volunteers and 54 Japanese SLE inpatients at the University Hospital of Occupational and Environmental Health, all of whom fulfilled the criteria for the classification of SLE. SLE patients were divided into the three groups: NPSLE with psychiatric symptoms including an acute confusional state, anxiety disorder, cognitive dysfunction, mood disorder, and psychosis (NP group); NPSLE without psychiatric symptoms (NN group); and SLE without neuropsychiatric symptoms (S group). The serum BDNF levels were measured by ELISA. Results. Serum BDNF levels were significantly increased in the NP group (mean ± SE = 37.0 ± 5.46 ng/ml) compared with those in the other three groups (NN group; mean ± SE=9.1 ± 2.44 ng/ml, P < 0.0001, S group; mean ± SE=10.4 ± 2.51 ng/ml, P < 0.0001, healthy control; mean ± SE= 11.44 ± 0.69, P < 0.0001). Subsequently, serum BDNF levels were decreased in parallel with the improvement of psychiatric symptoms in the NP group. Conclusion. These results suggest that serum BDNF is a biological marker for the severity of psychiatric symptoms in NPSLE patients.     

Cholesterol in mild cognitive impairment and Alzheimer’s disease in a birth cohort over 14 years

Animal epidemiological and clinical studies suggest that cholesterol is a risk factor for Alzheimer’s disease (AD). Nevertheless, the relation of cholesterol to mild cognitive impairment (MCI), influence of APOE genotype and its changes in lifespan is controversial. We investigated the potential impact of plasma total cholesterol (TC) on development of MCI and AD in the interdisciplinary longitudinal study on adult development and aging, a representative birth cohort (born 1930–1932), examined in 1993/1994 (VT1), 1997/1998 (VT2), and 2005/2007 (VT3). Of 500 participants at baseline, 381 survived and were examined at VT3. After exclusion of participants with lifetime prevalence of major psychiatric diseases or mild cognitive disorder due to a medical condition, 222 participants were included in the analysis. At VT3, 82 participants had MCI, 22 participants had AD, and 118 were in good health. Participants with MCI and AD at VT3 evidenced higher TC levels at VT1 than those who were healthy. Higher TC levels at baseline were associated with an increased risk for cognitive disorders at VT3 (highest vs. lowest quartile: OR 2.64, 95 % CI 1.12–6.23, p < 0.05). Over the 14 year follow-up, TC levels declined in those with MCI and AD, but remained stable in those who remained healthy. These findings were not modified by APOE genotype or use of cholesterol-lowering medications. Our findings demonstrate that higher TC levels are observed long before the clinical manifestation of MCI and AD in patients without psychiatric or somatic comorbidities and are independent of APOE genotype.     

SHORT COMMUNICATION: Apolipoprotein E genotype and Cognition in Bipolar Disorder

Apolipoprotein E (APOE) has been extensively studied as a risk factor for sporadic and late onset Alzheimer's Disease (AD). APOE allele*3, the most frequent variant, is not associated to cognitive dysfunction (CD) or to increased AD risk. Differently, the *4 allele is a well‐established risk factor for CD, while the *2 allele is associated with survival and longevity. CD is an important feature of Bipolar Disorder (BD) and recent data suggest that CD may be one of its endophenotypes, although controversial results exist. The aim of this research is to study the association of APOE genotype (APOE) and neurocognitive function in a sample of drug free young BD‐type I patients. Sample consisted of 25 symptomatic BD (type I) patients (age 18–35 years old). They were submitted to an extensive neuropsychological evaluation and genotyped for APOE. Subjects with allele*2 presented better cognitive performance. The presence of allele*4 was associated with worse performance in a few executive tasks. APOE*3*3 was associated with overall severe dysfunction on cognitive performance. In young individuals with nontreated BD‐type I, APOE may predict cognitive performance. Further and larger studies on APOE and cognition in BD are required to clarify whether APOE is a BD cognitive endophenotype.     

脑小血管病所致认知功能障碍与血清脑源性神经营养因子水平的相关性

目的 分析脑小血管病（cerebral small vessel diseases,CSVD）所致认知功能障碍与脑源性神经营养 因子（brain derived neurotrophic factor,BDNF）水平的相关性。 方法 前瞻性纳入2019年4月-2020年4月连续就诊于新乡医学院第一附属医院的CSVD患者为研究 对象。根据MMSE评分将其分为认知功能正常组（27～30分）、轻度认知功能障碍组（21～26分）及中 度认知功能障碍组（10～20分）,比较三组基线资料及血清BDNF水平,分析BDNF水平与认知功能的 相关性。 结果 最终纳入60例CSVD患者,平均年龄60.6±10.5岁,男性38例（63.3%）;其中认知功能正常组 21例（35.0%）、轻度认知功能障碍组24例（40.0%）、中度认知功能障碍组15例（25.0%）。三组间年 龄、受教育年限、BDNF水平差异均有统计学意义。Pearson相关性分析结果显示,血清BDNF水平、受 教育年限与MMSE评分呈正相关（r =0.499,P =0.043;r＝0.516,P＜0.001）,年龄与MMSE评分呈负相 关（r =-0.577,P＜0.001）。 结论 CSVD所致认知功能障碍与血清BDNF水平存在相关性,即血清BDNF水平越低,认知功能损害 程度越重。     

Gender-specificities in Alzheimer's disease and mild cognitive impairment

Background Amnestic Mild Cognitive Impairment (MCI) is a condition with an increased risk for developing Alzheimer's disease (AD). Presently, gender differences are neglected in the assessment of MCI and AD. Methods We examined verbal and visuospatial episodic memory in 143 subjects diagnosed as healthy controls (HC; N = 48, Mini-Mental State Examination (MMSE) 29.2 ± 1.0 (mean ± standard deviation)), MCI (N = 43,MMSE 28.5 ± 1.4), and AD (N = 49, MMSE 25.1 ± 2.2). Findings Female HC and MCI subjects performed better on verbal episodic memory tasks than males. In contrast, visuospatial episodic memory was better in male than female AD patients. Conclusions We interpret the results in light of a genderspecific cognitive reserve and conclude that the gender-specificity of neuropsychological performance needs to be accounted for in clinical diagnosis of Alzheimer’s disease.