Vascular Mild Cognitive Impairment Patients Research Articles

Exploring cognitive related microstructural alterations in normal appearing white matter and deep grey matter for small vessel disease: A quantitative susceptibility mapping study

Brain microstructural alterations possibly occur in the normal-appearing white matter (NAWM) and grey matter of small vessel disease (SVD) patients, and may contribute to cognitive impairment. The aim of this study was to explore cognitive related microstructural alterations in white matter and deep grey matter nuclei in SVD patients using magnetic resonance (MR) quantitative susceptibility mapping (QSM). 170 SVD patients, including 103 vascular mild cognitive impairment (VaMCI) and 67 no cognitive impairment (NCI), and 21 healthy control (HC) subjects were included, all underwent a whole-brain QSM scanning. Using a white matter and a deep grey matter atlas, subregion-based QSM analysis was conducted to identify and characterize microstructural alterations occurring within white matter and subcortical nuclei. Significantly different susceptibility values were revealed in NAWM and in several specific white matter tracts including anterior limb of internal capsule, corticospinal tract, medial lemniscus, middle frontal blade, superior corona radiata and tapetum among VaMCI, NCI and HC groups. However, no difference was found in white matter hyperintensities between VaMCI and NCI. A trend toward higher susceptibility in the caudate nucleus and globus pallidus of VaMCI patients compared to HC, indicating elevated iron deposition in these areas. Interestingly, some of these QSM parameters were closely correlated with both global and specific cognitive function scores, controlling age, gender and education level. Our study suggested that QSM may serve as a useful imaging tool for monitoring cognitive related microstructural alterations in brain. This is especially meaningful for white matter which previously lacks of attention.

Multimodality neuroimaging in vascular mild cognitive impairment: A narrative review of current evidence.

The vascular mild cognitive impairment (VaMCI) is generally accepted as the premonition stage of vascular dementia (VaD). However, most studies are focused mainly on VaD as a diagnosis in patients, thus neglecting the VaMCI stage. VaMCI stage, though, is easily diagnosed by vascular injuries and represents a high-risk period for the future decline of patients' cognitive functions. The existing studies in China and abroad have found that magnetic resonance imaging technology can provide imaging markers related to the occurrence and development of VaMCI, which is an important tool for detecting the changes in microstructure and function of VaMCI patients. Nevertheless, most of the existing studies evaluate the information of a single modal image. Due to the different imaging principles, the data provided by a single modal image are limited. In contrast, multi-modal magnetic resonance imaging research can provide multiple comprehensive data such as tissue anatomy and function. Here, a narrative review of published articles on multimodality neuroimaging in VaMCI diagnosis was conducted，and the utilization of certain neuroimaging bio-markers in clinical applications was narrated. These markers include evaluation of vascular dysfunction before tissue damages and quantification of the extent of network connectivity disruption. We further provide recommendations for early detection, progress, prompt treatment response of VaMCI, as well as optimization of the personalized treatment plan.

Quantitative morphometric changes in vascular mild cognitive impairment patients: early diagnosis of dementia.

Vascular mild cognitive impairment (VMCI) is an early and reversible stage of dementia. Volume differences in regional gray matter may reveal the development and prognosis of VMCI. This study selected 2 of the most common types of VMCI, namely, periventricular white matter hyperintensities (PWMH, n = 14) and strategic single infarctions (SSI, n = 10), and used the voxel-based morphometry method to quantify their morphological characteristics. Meanwhile, age- and sex-matched healthy volunteers were included (n = 16). All the participants were neuropsychologically tested to characterize their cognitive function and underwent whole-brain magnetic resonance imaging scanning. Our results showed that the volumes of the bilateral temporal lobes and bilateral frontal gray matter were obviously diminished in the PWMH group. The atrophy volume difference was 4,086 voxels in the left temporal lobe, 4,154 voxels in the right temporal lobe, 1,718 voxels in the left frontal lobe, and 1,141 voxels in the right frontal lobe (P ≤ 0.001). Moreover, the characteristics of the gray matter atrophy associated with the PWMH were more similar to those associated with Alzheimer's disease than SSI, which further revealed the susceptibility for escalation from PWMH to dementia. In conclusion, PWMH patients and SSI patients have different morphological characteristics, which explain the different prognoses of VMCI.

Analysis of Factors Affecting Cranial Nerve Function of Patients With Vascular Mild Cognitive Impairment Through Functional Magnetic Resonance Imaging Under Artificial Intelligence Environment.

The study aimed to explore the risk factors of effects of patients with vascular mild cognitive impairment (VaMCI) through functional magnetic resonance imaging (fMRI). In this study, 62 patients were selected from the department of neurology, admitted to Changzhi People's Hospital from October 1, 2018 to February 1, 2020. Patients with VaMCI were defined as the VaMCI group according to Clinical Dementia Rating (CDR), and subjects with normal cognitive function were defined as the normal control (NC) group. All patients underwent fMRI to identify the amplitude low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values, and to analyze their association with VaMCI. The results showed that the VaMCI group had lower scores for Mini-mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and their subitems (visual space and execution, recall, attention and computation, and language ability) than NC group, with statistical differences (P < 0.05). In VaMCI group, the brain regions with increased ALFF values were the left temporal lobe, left parietal lobe, right temporal lobe, right parietal lobe, and posterior cingulate gyrus. Of them, the left parietal lobe and right temporal lobe were negatively correlated with the recall score on MMSE scale (r = −0.216, r = −0.132, P < 0.01). In VaMCI group, the brain regions with decreased ReHo values were the left temporal lobe, occipital lobe, and left middle temporal gyrus. Of them, the left temporal lobe and occipital lobe were positively correlated with MoCA score (r = 0.473, r = 0.848, P < 0.01). In conclusion, VaMCI patients have cognitive impairment and abnormally increased spontaneous brain activity, especially in the left parietal lobe and the right temporal lobe. At rest, VaMCI patients show decreased whole-brain ReHo in the left medial temporal lobe and occipital lobe. Hypertension is a high-risk factor for cognitive impairment in VaMCI patients. The study can provide a theoretical basis for early diagnosis of VaMCI.

Aberrant Amplitude of Low-Frequency Fluctuation and Degree Centrality within the Default Mode Network in Patients with Vascular Mild Cognitive Impairment.

This study aimed to investigate whole-brain spontaneous activities changes in patients with vascular mild cognitive impairment (VaMCI), and to evaluate the relationships between these brain alterations and their neuropsychological assessments. Thirty-one patients with VaMCI and thirty-one healthy controls (HCs) underwent structural MRI and resting-state functional MRI (rs-fMRI) and neuropsychological assessments. The functional alterations were determined by the amplitude of low-frequency fluctuation (ALFF) and degree centrality (DC). The gray matter volume (GMV) changes were analyzed using voxel-based morphometry (VBM). Linear regression analysis was used to evaluate the relationships between the structural and functional changes of brain regions and neuropsychological assessments. The VaMCI group had significantly lower scores in the Montreal Cognitive Assessment (MoCA), and higher scores on the Hamilton Anxiety Rating Scale (HAMA) and Hamilton Depression Rating Scale (HAMD). Compared to the HCs, the VaMCI group exhibited GM atrophy in the right precentral gyrus (PreCG) and right inferior temporal gyrus (ITG). VaMCI patients further exhibited significantly decreased brain activity within the default mode network (DMN), including the bilateral precuneus (PCu), angular gyrus (AG), and medial frontal gyrus (medFG). Linear regression analysis revealed that the decreased ALFF was independently associated with lower MoCA scores, and the GM atrophy was independently associated with higher HAMD scores. The current finding suggested that aberrant spontaneous brain activity in the DMN might subserve as a potential biomarker of VaMCI, which may highlight the underlying mechanism of cognitive decline in cerebral small vessel disease.

Aberrant Brain Regional Homogeneity and Functional Connectivity of Entorhinal Cortex in Vascular Mild Cognitive Impairment: A Resting-State Functional MRI Study.

The aim of this study was to investigate changes in regional homogeneity (ReHo) and the functional connectivity of the entorhinal cortex (EC) in vascular mild cognitive impairment (VaMCI) and to evaluate the relationships between such changes and neuropsychological measures in VaMCI individuals. In all, 31 patients with VaMCI and 32 normal controls (NCs) underwent rs-fMRI. Differences in whole-brain ReHo and seed-based bilateral EC functional connectivity (EC-FC) were determined. Pearson's correlation was used to evaluate the relationships between regions with significant group differences and different neuropsychological measures. Vascular mild cognitive impairment (VaMCI) patients had lower scores in Mini-mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) and higher ones in Activity of Daily Living (ADL) (p < 0.05). Vascular mild cognitive impairment (VaMCI) individuals had significantly lower ReHo in the left cerebellum and right lentiform nucleus than NCs (P < 0.05, TFCE FWE correction). Vascular mild cognitive impairment (VaMCI) subjects showed significant decreases in the FC of the right EC in the right inferior frontal gyrus, right middle frontal gyrus, bilateral pre-central gyrus, and right post-central/superior parietal lobules (P < 0.05, TFCE FWE correction). Significant positive correlations were found between ReHo and MoCA scores for the right lentiform nucleus (r = 0.37, P < 0.05). The right post-central/superior parietal lobules showed a significant positive correlation between right EC-FC and MoCA scores (r = 0.37, P < 0.05). Patterns in ReHo and EC-FC changes in VaMCI patients and their correlations with neuropsychological measures may be a pathophysiological foundation of cognitive impairment, which may aid the early diagnosis of VaMCI.

Relevance of brain lesion location for cognition in vascular mild cognitive impairment.

BackgroundVascular mild cognitive impairment (VMCI) is a potentially transitional state between normal aging and vascular dementia. The presence of macroscopic white matter lesions (WML) of moderate or severe extension on brain MRI is the hallmark of the VMCI.ObjectiveTo assess the clinical relevance of the frequency of WML in patients with VMCI independently of total lesion volume (LV).MethodsIn this multicenter study, we included 110 patients with VMCI (age: 74.3 ± 6.6 years; sex: 60 women). Cognitive assessment was performed with the VMCI-Tuscany Neuropsychological Battery, which allowed to identify four VMCI groups: amnestic single (n = 9) and multi-domain (n = 76), non-amnestic single- (n = 10) and multi-domain (n = 15). Distribution and frequency of WML on MRI FLAIR images were evaluated with lesion probability map (LPM). Voxelwise statistics was performed with nonparametric permutation tests, controlling for age, sex, slice thickness, center, magnetic field strength, total LV and head size (p < .01, family-wise error-corrected for multiple comparisons across space).ResultsLPM of the WML had a fairly symmetric and widespread distribution across brain. A higher frequency of WML along association tracts of the WM such as inferior longitudinal fascicle, inferior fronto-occipital fascicle and superior longitudinal fascicle, was correlated with worst cognitive scores at the Trail Making Test Part A and Copy of the Rey–Osterrieth Complex Figure. The non-amnestic groups showed a higher frequency of WML in the anterior cingulum and superior longitudinal fascicle close to the frontal gyrus.ConclusionsOur study showed that in patients with VMCI, independently of total LV, the higher frequency of lesions along association tracts of the WM, which mediate intrahemispheric long-range connectivity, is related with psychomotor speed and constructional praxis. Moreover, a prevalence of lesions in the frontal WM seems to characterize VMCI patients with involvement of non-amnestic domains.

Qualitative Evaluation of the Immediate Copy of the Rey-Osterrieth Complex Figure: Comparison Between Vascular and Degenerative MCI Patients.

The immediate copy of the Rey-Osterrieth Complex Figure (ROCF) is considered a visuo-spatial test. However, reproducing this complex structure possibly involves also executive functions, such as planning and organizational strategies. In a previous study, we found a high rate of impaired performances in this test in a sample of subcortical vascular mild cognitive impairment patients. Executive functions contribution in the immediate copy of the ROCF can be assessed with the Boston Qualitative Scoring System (BQSS). We aimed at examining whether BQSS executive scores of ROCF immediate copy: (1) differ between vascular (v-MCI) and degenerative MCI (d-MCI) patients; (2) can at least partly explain the high rate of abnormal ROCF immediate copy performances in v-MCI patients. Thirty d-MCI patients (age 75.2 ± 4.4) and 27 v-MCI (age 73.2 ± 6.9) were enrolled. The performances of patients were scored using the BQSS executive scores (Fragmentation, Planning, Organization, Perseveration) during the accomplishment of ROCF immediate copy. Comparing d-MCI and v-MCI performances, d-MCI patients scored worse on ROCF delayed recall (9.9 ± 4.7 vs. 13.4 ± 5.9, p = .020) and MMSE (23.9 ± 2.6 vs. 27.8 ± 2.3, p = .001) while v-MCI patients had more frequently impaired performances in ROCF immediate copy (40% vs. 81%, p = .001) and showed worse scores on Fragmentation (2.4 ± 0.9 vs. 1.8 ± 1.3, p = .035), Planning (2.4 ± 0.8 vs. 1.8 ± 1, p = .039), Organization (4.8 ± 1.3 vs. 3.6 ± 2.1, p = .017), and Perseveration (3.5 ± 0.8 vs. 2.9 ± 1.2, p = .048). The performance of v-MCI patients in ROCF immediate copy seemed to be more affected by executive dysfunction than the performance obtained by d-MCI. When analyzing ROCF performances, a qualitative approach allows to evaluate patients' strategies during the reproduction, and thus to discriminate between executive and visuo-constructional abilities.

A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis.

ABSTRACT.Background.Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder.Objective:This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach.Methods:Medline, Web of Knowledge and PsycINFO were searched, using the terms: “vascular mild cognitive impairment” OR “vascular cognitive impairment no dementia” OR “vascular mild neurocognitive disorder” AND “dysexecutive” OR “executive function”. Meta-analyses were conducted for each of the selected tests, using random-effect models.Results:Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls.Conclusion:A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.

Cerebral gray matter volume reduction in subcortical vascular mild cognitive impairment patients and subcortical vascular dementia patients, and its relation with cognitive deficits.

IntroductionSubcortical vascular mild cognitive impairment (svMCI) is the predementia stage of subcortical vascular dementia (SVaD). The aim of this research is to explore and compare cerebral gray matter (GM) volume reduction in svMCI patients and SVaD patients, and to investigate the relationship between cerebral GM volume reduction and cognitive deficits.MethodsThirty one svMCI patients, 29 SVaD patients, and 31 healthy controls were recruited in our research. They conducted neuropsychological tests and brain structural magnetic resonance imaging (MRI) examination. To detect cerebral GM volume reduction in svMCI patients and SVaD patients, we used statistical parametric mapping 8‐voxel‐based morphometry 8 (SPM8‐VBM8) method to analyze MRI data. To detect the relationship between cerebral GM volume reduction and cognitive deficits, multiple linear regression analysis was used.ResultsCompared with healthy controls, svMCI patients showed cerebral GM volume reduction in hippocampus and parahippocampal gyrus, insula and superior temporal gyrus. Compared with healthy controls, SVaD patients exhibited more atrophy which encompasses all of these areas plus anterior and middle cingulate, inferior temporal gyrus, orbitofrontal cortex, and superior frontal gyrus. In svMCI patients, cerebral GM volume reduction correlated with memory loss, attention dysfunction, and language dysfunction; in SVaD patients, besides those cognitive deficits, cerebral GM volume reduction correlated with more cognitive impairments, including executive dysfunction, neuropsychiatric symptom, and depression.ConclusionsOur findings prove that both svMCI patients and SVaD patients exhibit cerebral GM volume reduction and there may exist a hierarchy between svMCI and SVaD, and cerebral GM volume reduction in both svMCI patients and SVaD patients correlates with cognitive deficits, which can help us understand the mechanism of cognitive impairments in svMCI patients and SVaD patients, and diagnose SVaD at its early stage.

Protective effects of APOE e2 against disease progression in subcortical vascular mild cognitive impairment patients: A three-year longitudinal study

Although the association between apolipoprotein E (APOE) genotype and disease progression is well characterized in patients with Alzheimer’s disease, such a relationship is unknown in patients with subcortical vascular cognitive impairment. We evaluated whether APOE genotype is associated with disease progression in subcortical vascular mild cognitive impairment (svMCI) patients. We prospectively recruited 72 svMCI patients (19 APOE4 carriers, 42 APOE3 homozygotes, and 11 APOE2 carriers). Patients were annually followed-up with brain MRI and neuropsychological tests for three years and underwent a second Pittsburgh compound B (PiB)-PET at a mean interval of 32.3 months. Amyloid-ß burden was quantified by PiB standardized uptake value ratio (SUVR), and the amount of small vessel disease was quantified by number of lacune and small vessel disease score on MRI. We also measured cortical thickness. During the three years of follow-up, compared to the APOE3 homozygotes, there was less increase in PiB SUVR among APOE2 carriers (p = 0.023), while the APOE genotype did not show significant effects on small vessel disease progression. APOE2 carriers also showed less cortical thinning (p = 0.023) and a slower rate of cognitive decline (p = 0.009) compared to those with APOE3 homozygotes. Our findings suggest that, in svMCI patients, APOE2 has protective effects against amyloid-ß accumulation, cortical thinning, and cognitive decline.

Regional Gray Matter Atrophy in Vascular Mild Cognitive Impairment

The aim of this study was to explore the neuroanatomical bases of vascular mild cognitive impairment (VaMCI) with respect to attention/executive function, memory, language, and visuospatial function. We used voxel-based morphometric analysis to identify brain regions that significantly differed in terms of gray matter volumes (GMVs) between 43 patients with VaMCI and 55 healthy controls. Then, we compared the individual GMVs of the selected regions with the neuropsychological profiles of the VaMCI patients. The delayed recall component of the Rey-Osterrieth Complex Figure Test (CFT) (74.4%), the Symbol Digit Modalities Test (74.4%), the Boston Naming Test (51.2%), and the CFT-copy (81.4%) shared the highest incidence of impairment in the 4 cognitive domains, respectively. Compared with controls, patients with VaMCI exhibited significantly reduced GMVs. This effect was mainly present in the frontal regions, including the bilateral dorsolateral prefrontal cortex (DLPFC), the orbital portion of the superior frontal gyrus (SFG), and the left supplemental motor area, and was also observed in the bilateral posterior cingulated cortex (PCC). GMVs were significantly correlated with performance in the Trail Making Test, part B, in the bilateral DLPFC and PCC, the clock drawing test in the right orbital portion of the SFG, and CFT-delayed recall in the right PCC. These results, from the perspective of brain morphology, uniquely explored the specific cerebral structural changes of VaMCI, thus providing a deeper understanding of the pathophysiology of the disease.

Evidence-based medical research on diagnostic criteria and screening technique of vascular mild cognitive impairment

Background Vascular mild cognitive impairment (VaMCI) is the prodromal syndrome of vascular dementia (VaD) and key target for drug treatment. There is controversy over the diagnostic criteria and screening tools of VaMCI, which affects its clinical diagnosis. This paper aims to explore the clinical features, diagnostic criteria and screening technique of VaMCI. Methods Taking "vascular mild cognitive impairment OR vascular cognitive impairment no dementia" as retrieval terms, search in PubMed database from January 1997 to March 2015 and screen relevant literatures concerning VaMCI. According to Guidance for the Preparation of Neurological Management Guidelines revised by European Federation of Neurological Societies (EFNS) in 2004, evidence grading was performed on literatures. Results A total of 32 literatures in English were selected according to inclusion and exclusion criteria, including 3 guidelines and consensus and 29 clinical studies. Seven literatures (2 on Level Ⅰ, 5 on Level Ⅱ) studied on neuropsychological features in VaMCI patients and found reduced processing speed and executive function impairment were main features. Two literatures reported the diagnostic criteria of VaMCI, including VaMCI criteria published by American Heart Association (AHA)/American Stroke Association (ASA) in 2011 and "Diagnostic Criteria for Vascular Cognitive Disorders" published by International Society for Vascular Behavioral and Cognitive Disorders (VASCOG) in 2014. Fifteen literatures (4 on LevelⅠ, 11 on Level Ⅱ) described the diagnostic criteria of VaMCI used in clinical research, from which 6 operational diagnostic items were extracted. Fourteen literatures (4 on Level Ⅰ, 10 on Level Ⅱ) described neuropsychological assessment tools for VaMCI screening, and found the 5-minute protocol recommended by National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) was being good consistency with other neuropsychological assessment tools. Conclusions The neuropsychological features of VaMCI have guiding significance for diagnosis. VASCOG diagnostic criteria for VaMCI is practical in clinical practice, and 5-minute protocol is suitable for clinical rapid screening of VaMCI. DOI: 10.3969/j.issn.1672-6731.2015.07.007

Post-stroke memory impairment among patients with vascular mild cognitive impairment.

BackgroundThe American Stroke Association/American Heart Association recommended the criteria for diagnosis of vascular cognitive impairment and memory impairment (MI) is a feature in the classification of vascular mild cognitive impairment (VaMCI). VaMCI patients with MI may differ in terms of infarct location or demographic features, so we evaluated the clinical characteristics associated with MI in patients with VaMCI.MethodsA prospective multicenter study enrolled 353 acute ischemic stroke patients who underwent evaluation using the Korean Vascular Cognitive Impairment Harmonization Standard Neuropsychological Protocol at three months after onset. The association between MI and demographic features, stroke risk factors, and infarct location was assessed.ResultsVaMCI was diagnosed in 141 patients, and 58 (41.1%) exhibited MI. Proportions of men and of left side infarcts were higher in VaMCI with MI than those without (75.9 vs. 57.8%, P = 0.03, 66.7 vs. 47%, P = 0.02). Multiple logistic analyses revealed that male sex (odds ratio [OR] 3.07, 95% confidence interval [95% CI] 1.12-8.42), left-side infarcts (OR 3.14, 95% CI 1.37-7.20), and basal ganglia/internal capsule infarcts (OR 4.53, 95% CI 1.55-13.22) were associated with MI after adjusting other demographic variables, vascular risk factors, and subtypes of stroke.ConclusionsMI is associated with sex and infarct location in VaMCI patients.

Profile of Cognitive Complaints in Vascular Mild Cognitive Impairment and Mild Cognitive Impairment

Objective. Vascular mild cognitive impairment (VaMCI) is differentiated from mild cognitive impairment (MCI) by the presence of vascular events such as stroke or small vessel disease. Typically, MCI and VaMCI patients present with subjective complaints regarding cognition; however, little is known about the specific nature of these complaints. We aimed to create a profile of subjective cognitive complaints in MCI and VaMCI patients with similar levels of objective cognitive performance. Methods. Twenty MCI and twenty VaMCI patients were recruited from a Memory Disorders Clinic in Toronto. Subjective cognitive complaints were assessed and categorized using the Neuropsychological Impairment Scale. Results. MCI and VaMCI patients achieved similar scores on measures of objective cognitive function (P > 0.100). However, the VaMCI group had more subjective complaints than the MCI group (P = 0.050), particularly in the critical items, cognitive efficiency, memory, and verbal learning domains of the Neuropsychological Impairment Scale. Conclusions. Our findings support the idea that VaMCI and MCI differ in their clinical profiles, independent of neuroimaging. VaMCI patients have significantly more subjective cognitive complaints and may be exhibiting particular deficits in memory, verbal learning, and cognitive efficiency. Our findings promote the need for further research into VaMCI-specific cognitive deficits.

Increased plasma levels of heat shock protein 70 in patients with vascular mild cognitive impairment

Heat shock proteins (Hsps) have been regarded as cytoprotectants that protect brain cells from damage encountered following cerebral ischemia or during the progression of neurodegenerative diseases. In this study, we assessed the plasma Hsp70 and Hsp27 levels in not cognitively impaired (NCI) subjects and in patients with mild cognitive impairment (MCI), vascular mild cognitive impairment (VMCI), and probable Alzheimer's disease (AD). Comparison of the plasma Hsp70 and Hsp27 levels of the 4 groups revealed that only the plasma Hsp70 level of VMCI patients (14.11 ng/ml) was significantly higher than that of NCI subjects (11.32 ng/ml), MCI patients (10.16 ng/ml), and patients with probable AD (10.16 ng/ml) after adjustment of age, sex, and education (F=4.231, d.f.=3, p=0.008). Furthermore, there was no difference in plasma Hsp27 levels among the 4 groups. These findings suggest that the plasma Hsp70 level may be related to vascular factors or inflammation.