Vascular Mild Cognitive Impairment Research Articles

Cortical thinning related to periventricular and deep white matter hyperintensities

Previous studies showed that white matter hyperintensities (WMH) are related to cognitive decline in patients with mild cognitive impairment (MCI) or dementia. Moreover, periventricular WMH (periventricular white matter hyperintensities (PWMH)) and deep WMH (deep white matter hyperintensities (DWMH)) may have different effects on cognition. The purpose of this study is to investigate the contributions of PWMH and DWMH to the topography of cortical thinning and to investigate the relationship among WMH, cortical thinning, and cognitive impairments. Participants included 226 patients with Alzheimer's disease or subcortical vascular dementia, and 135 patients with amnestic MCI or subcortical vascular MCI. Cortical thickness was measured using the surface based method. The topography of cortical thinning related to WMH was distributed in the frontal and perisylvian regions, which was similar to that of PWMH. In contrast, there were only small areas of cortical thinning inversely associated with DWMH, which were distributed in medial frontal and lingual gyrus. PWMH, but not DWMH, were associated with the frontal thinning and executive dysfunction; where both PWMH and frontal thinning were independently associated with executive dysfunction. Our results suggest that PWMH are associated with frontal thinning, which is further associated with frontal executive dysfunction.

Patterns of Cognitive Decline and Rates of Conversion to Dementia in Patients with Degenerative and Vascular forms of MCI

According to recent criteria, Mild Cognitive Impairment (MCI) represents a clinical condition with multiple cognitive presentations (amnesic and non amnesic) that can be supported by different types of brain lesions (mainly vascular and atrophic). In order to asses if the cognitive presentation and the rate of progression differ according to the type of brain pathology, two populations of MCI patients, characterized by hippocampal atrophy (n: 39) and vascular subcortical pathology (n: 36) respectively, on the basis of MRI findings, were investigated. Patients underwent an extensive neuropsychological test battery twice (at baseline and at two years follow-up), which is made up of the MMSE and various tests of episodic memory, short-term memory, visual-spatial abilities, executive functions, language, attention, praxis and psychomotor speed. Atrophic and vascular MCI patients showed a remarkably different pattern of impairment at the baseline. The former were significantly more impaired in episodic memory tasks. The latter were more impaired in an action naming task. At the follow up examination, the rate of progression to dementia was higher in atrophic (14/39) than in vascular (5/36) MCI patients. The comparison between neuropsychological scores obtained at the baseline and at the follow-up showed that atrophic MCI patients underwent a severe decline in several cognitive domains, whereas vascular MCI patients showed a significant decline only in those tasks requiring executive abilities. Our results confirm that a selective and severe defect of episodic memory is associated with hippocampal atrophy and that MCI patients with atrophic lesions are more likely to convert to Alzheimer's type dementia while MCI patients with vascular lesions are characterized by a slight decline in executive function over time and by a tendency to develop probable vascular forms of dementia.

Motor intentional disorders in vascular mild cognitive impairment and vascular dementia of subcortical type

Background and Purpose: Damage to the premotor and prefrontal brain regions results in motor intentional disorders (MID) that disrupt initiation, maintenance, and termination of volitional movements. Mild cognitive impairment (MCI) associated with small-vessel disease (subcortical vascular MCI, svMCI) is considered to be a prodromal stage of subcortical vascular dementia (SVaD), as amnestic MCI (aMCI) is regarded as a prodromal stage of Alzheimer’s disease. svMCI is characterized by frontal executive dysfunction and cortical thinning predominantly in the frontal regions. We hypothesized that the performance of svMCI patients on motor intentional tasks would be intermediate between those of healthy controls and SVaD patients, and that svMCI patients who have predominantly frontal injuries would perform worse than would patients with aMCI who have predominantly temporoparietal injuries. Methods: Participants included 27 patients with svMCI, ten cognitively healthy controls, 20 patients with amnestic MCI, and 14 patients with SVaD. The force control capabilities of the index finger were quantified in four phases (initiation, development, maintenance, and termination) using a force dynamometer. The force control test was repeated six times in the patient groups and four times in the control group. Results: Performances among the four groups were as follows: NC=aMCI=svMCI>SVaD for force initiation and termination, NC>aMCI=svMCI>SVaD for force development, and NC=aMCI>svMCI=SVaD for the force maintenance task. Conclusions: In most motor intentional tasks, the severities of MID were greater in patients with SVaD than in patients with svMCI. Of the four motor intentional tasks, the force maintenance task proved sensitive in differentiating aMCI from svMCI. 3 Motor intentional disorders in SVaD and svMCI

Progressive Gray Matter Atrophy in Lacunar Patients with Vascular Mild Cognitive Impairment

Background and Method: We investigated the progression of cognitive and cerebral changes in 30 patients with a first-ever lacunar infarct (LI): 15 with vascular mild cognitive impairment (MCI-V) and 15 without cognitive impairment. All cases were followed up 18 ± 6 months after the stroke and underwent neurological, neuropsychological and MRI assessments at baseline and longitudinally. Results: Differences in the changes in cognitive function over time were observed between the 2 groups, with the MCI-V patients showing slight memory improvements and frontal-lobe-related test impairments from baseline to follow-up evaluations. At baseline, the 2 groups presented similar white matter hyperintensity (WMH) ratings and whole brain gray matter (GM) volumes, and at the follow-up evaluations, both groups had increased WMH lesions and decreased GM volumes; no statistical differences between groups were found. In contrast, a voxel-based morphometry analysis revealed that only MCI-V patients presented clear regional GM volume losses between the first and the second evaluations in cortical (frontal and temporal) and subcortical (pons, cerebellum and caudate) regions. Conclusion: Frontal lobe dysfunction and regional cortical and subcortical GM atrophy best differentiate the clinical course of LI patients with and without cognitive impairment.

Mortality and Institutionalization in Early Survivors of Stroke: The Effects of Cognition, Vascular Mild Cognitive Impairment, and Vascular Dementia

We explored th effects of vascular mild cognitive impairment (VaMCI), vascular dementia (VaD), and other predictors on mortality and institutionalization in early survivors of ischemic stroke without previous dementia who had been admitted to a stroke unit. A total of 202 consecutive consenting eligible ischemic stroke survivors and a matched sample of 97 community controls were followed for up to 10 years. Data for 167 patients who underwent detailed assessment 3-6 months after stroke were analyzed to determine predictors of outcomes. Cumulative mortality rates for patients (and controls) were 27% (4%) for the first 5 years and rose to 83% (10%) by 10 years. Predictors of mortality were older age, any cognitive impairment, less independent function, and less education. Nursing home admission rates were 24% at 5 years and 32% at 10 years for patients and 0 for controls over 8.9 years. Predictors of institutionalization were less independent function and older age. Patients with ischemic stroke who survive the first week have moderate, lower-than-expected mortality rates in the first 5 years that increase thereafter. VaMCI, VaD, and functional decline are predictors of mortality, while functional decline and older age predict institutionalization.

Impaired abstract thinking may discriminate between normal aging and vascular mild cognitive impairment

Cerebrovascular disease (CVD) is associated with cognitive deficits. This cross-sectional study examines differences among healthy elderly controls and patients with vascular mild cognitive impairment (VaMCI) and vascular dementia (VaD) in performances on CAMCOG subscales. Elderly individuals (n=61) were divided into 3 groups, according to cognitive and neuroimaging status: 16 controls, 20 VaMCI and 25 VaD. VaMCI and VaD individuals scored over 4 points on the Hachinski Ischemic Scale. Significant differences in total CAMCOG scores were observed across the three groups (p<0.001). VaD subjects performed worse than those with VaMCI in most CAMCOG subscales (p<0.001). All subscales showed differences between controls and VaD (p<0.001). Performance on abstract thinking showed difference between VaMCI and controls (p<0.001). CAMCOG discriminated controls from VaMCI and VaD. Assessment of abstract thinking may be useful as a screening item for diagnosis of VaMCI.

Vascular cognitive impairment: Current concepts and Indian perspective

Cognitive impairment due to cerebrovascular disease is termed “Vascular Cognitive Impairment” (VCI) and forms a spectrum that includes Vascular Dementia (VaD) and milder forms of cognitive impairment referred to as Vascular Mild Cognitive Impairment (VaMCI). VCI represents a complex neurological disorder that occurs as a result of interaction between vascular risk factors such as hypertension, diabetes, obesity, dyslipidemia, and brain parenchymal changes such as macro and micro infarcts, haemorrhages, white matter changes, and brain atrophy occurring in an ageing brain. Mixed degenerative and vascular pathologies are increasingly being recognised and an interaction between the AD pathology, vascular risk factors, and strokes is now proposed. The high cardiovascular disease burden in India, increasing stroke incidence, and ageing population have contributed to large numbers of patients with VCI in India. Inadequate resources coupled with low awareness make it a problem that needs urgent attention, it is important identify patients at early stages of cognitive impairment, to treat appropriately and prevent progression to frank dementia.

Cortical Thinning in Vascular Mild Cognitive Impairment and Vascular Dementia of Subcortical Type

Amnestic mild cognitive impairment (MCI) is known to be a preclinical stage of Alzheimer's disease (AD). Similarly, MCI associated with small-vessel disease (svMCI), might be a forme froste of subcortical vascular dementia (SVaD). Patterns of cortical thinning in addition to the ischemia rating on MRI may further elucidate the clinical characteristics and pathogenesis of SVaD and svMCI. We tried to determine if svMCI differs from SVaD in the distribution of cortical atrophy, which may help understand the hierarchy between svMCI and SVaD and possibly also how svMCI evolves into SVaD. Twenty patients with SVaD, 34 patients with svMCI, 115 patients with AD, and 96 individuals with normal-cognition (NC) were imaged with magnetic resonance imaging (MRI) including 3-dimensional volumetric images for cortical thickness analysis across the entire brain. Compared to NC, svMCI patients showed cortical thinning in inferior frontal and orbitofrontal gyri, anterior cingulate, insula, superior temporal gyrus, and lingual gyrus, while cortical thinning in SVaD patients involved all these areas plus dorsolateral prefrontal and temporal cortices. Our findings suggest the presence of hierarchy between svMCI and SVaD, and that the cognitive decline from svMCI to SVaD is associated with lesions in dorsolateral prefrontal and temporal cortices.

Quality of life in patients with vascular mild cognitive impairment

Objective: Vascular cognitive impairment (VCI) is an entity associated with vascular damage of the brain resulted in cognitive dysfunction of a wide spectrum from mild cognitive impairment to vascular dementia. The quality of life (QL) of patients with VCI is poorly understood especially in patients with mild VCI. The aim of the study was to estimate medical factors influencing on QL of the patients with mild VCI.

Quality of life in patients with vascular mild cognitive impairment

Objective. Vascular cognitive impairment (VCI) is an entity associated with vascular damage of the brain resulting in cognitive dysfunction of a wide spectrum from mild cognitive impairment to vascular dementia. The quality of life (QL) of patients with VCI is poorly understood especially in patients with mild VCI. The aim of the study was to estimate medical factors influencing QL of patients with mild VCI.

Cognitive assessment batteries for patients with mild vascular cognitive impairment

Background and aims: To develop a comprehensive and a screening neuropsychological battery for mild vascular cognitive impairment (mVCI).

Correlation of Regional White Matter Hyperintensities with Cognitive Deficiency in Vascular Mild Cognitive Impairment and Dementia of Subcortical Type

Correlation of Regional White Matter Hyperintensities with Cognitive Deficiency in Vascular Mild Cognitive Impairment and Dementia of Subcortical Type

Subcortical Vascular versus Amnestic Mild Cognitive Impairment: Comparison of Cerebral Glucose Metabolism

Most studies on mild cognitive impairment (MCI) have been focused on amnestic MCI (aMCI) that is the preclinical stage of Alzheimer's disease (AD). In contrast, only a few studies have involved patients in the preclinical stages of subcortical vascular dementia (subcortical vascular MCI, svMCI). We tried to compare the overall glucose metabolism in patients with svMCI with that of patients with aMCI. We compared the regional metabolic patterns shown on 18 F-FDG (fluro deoxy glucose) positron emission tomography (PET) images from 18 patients with svMCI with those from 25 aMCI patients matched for age, sex, education, and mini-mental state examination (MMSE) score and with those from 35 healthy subjects using a voxel-wise analysis. SPM 2 was used for statistical analysis. Relative to normal controls, the hypometabolic regions in the aMCI patients were in the bilateral parahippocampal, bilateral posterior cingulate, left superior temporal gyri, left inferior parietal lobule, and right inferior frontal gyrus while those in the svMCI patients were located in the thalamus, insula, superior temporal gyrus, anterior cingulate gyrus, cingulum, right basal ganglia, cerebellum, and brainstem. A direct comparison of glucose metabolism between svMCI and aMCI showed that the glucose hypometabolism in patients with svMCI was more severe in the thalamus, brainstem, and cerebellum. Our study suggested that svMCI was distinct from aMCI in terms of neuropsychological and PET findings, which may explain their clinical manifestations.

Brain perfusion SPECT with an automated quantitative tool can identify prodromal Alzheimer's disease among patients with mild cognitive impairment

To improve diagnosis of early Alzheimer's disease (AD), i.e., prodromal AD, by an automated quantitative tool combining brain perfusion single-photon emission computed tomography (SPECT) images and memory tests scores in order to be applied in clinical practice. In this prospective, longitudinal, multi-centric study, a baseline (99m)Tc-ECD perfusion SPECT was performed in 83 patients with memory complaint and mild cognitive impairment (MCI). After a 3-year follow-up, 11 patients progressed to Alzheimer's disease (MCI-AD group), and 72 patients remained stable (MCI-S group), including 1 patient who developed mild vascular cognitive impairment. After comparison between the MCI-S and MCI-AD groups with a voxel-based approach, region masks were extracted from the statistically significant clusters and used alone or in combination with Free and Cued Selective Reminding Test (FCSRT) scores for the subject's categorization using linear discriminant analysis. Results were validated using the leave-one-out cross-validation method. Right parietal and hippocampal perfusion was significantly (p<0.05, corrected) decreased in the MCI-AD group as compared to the MCI-S group. The patients' classification in the MCI group using the mean activity in right and left parietal cortex and hippocampus yielded a sensitivity, specificity, and accuracy of 82%, 90%, and 89%, respectively. Combination of SPECT results and FCSRT free recall scores increased specificity to 93%. The combination of an automated quantitative tool for brain perfusion SPECT images and memory test scores was able to distinguish, in a group of amnestic MCI, patients at an early stage of AD from patients with stable MCI.

Relationships between 24-Hour Blood Pressures, Subcortical Ischemic Lesions, and Cognitive Impairment

Background and PurposeThe most important treatment for subcortical vascular dementia (SVaD) is controlling the blood pressure (BP). However, the few studies that have investigated the relationships between diurnal BP rhythm and subcortical ischemic vascular cognitive impairment have produced inconclusive results. In the study presented here, the 24-hour BP values of three groups of subjects-patients with subcortical vascular mild cognitive impairment (SvMCI), patients with SVaD, and normal controls-were compared using working criteria and 24-hour ambulatory BP (ABP) monitoring.MethodsThe subjects (42 patients with SVaD, 37 patients with SvMCI, and 30 controls) were selected according to the study's inclusion/exclusion criteria. All subjects underwent brain magnetic resonance (MR) imaging and MR angiography, detailed neuropsychological testing, and 24-hour ABP monitoring.ResultsThe prevalence of nondippers differed markedly between the control group and both the SVaD and SvMCI groups. Loss of nocturnal dipping was significantly associated with SVaD [odds ratio (OR), 4.827; 95% confidence interval (CI), 1.07-12.05].ConclusionsIt was found that SVaD is associated with loss of nocturnal BP dipping combined with increased pulse pressure and systolic BP (SBP) variability. Correction of these factors could therefore be important in the prevention of SVaD, independent of measures used to reduce BP.

Differences in Neuropsychiatric Symptoms according to Mild Cognitive Impairment Subtypes in the Community

Background/Aims: Mild cognitive impairment (MCI) has been subtyped according to its cognitive features and its likely etiology. We aimed to investigate the neuropsychiatric features of the MCI using the Neuropsychiatric Inventory and compare them according to subtypes. Methods: MCI patients were classified according to cognitive features (e.g. amnestic vs. nonamnestic MCI), likely etiology (e.g. vascular vs. nonvascular MCI) and functional status (e.g. MCI-I vs. MCI-II). The percentage of subjects exhibiting each of the 12 behaviors in the Neuropsychiatric Inventory was compared among the groups using a χ² test. Results: There were 382 subjects in the MCI group. In terms of each neuropsychiatric symptom, there were no differences in frequency between the MCI groups subtyped according to cognitive features or likely etiology. However, a significantly higher frequency of delusion, aggression, irritability and eating behavior was observed in the MCI-II group in comparison to the MCI-I group. Conclusion: The differences in neuropsychiatric symptoms were distinctive between the MCI groups subtyped according to functional status.

Utility of Different MR Modalities in Mild Cognitive Impairment and Its Use as a Predictor of Conversion to Probable Dementia

Mild cognitive impairment has been regarded as a pre-Alzheimer condition, but some patients do not develop dementia. The authors' objective was to determine whether findings from a combined use of H1 magnetic resonance spectroscopy (MRS), perfusion imaging (PI), and diffusion-weighted imaging (DWI) would predict conversion from amnesic mild cognitive impairment to dementia and to compare the diagnostic accuracy in discriminating patients with probable Alzheimer disease (AD), mixed dementia (MD), Lewy body dementia (LBD), pre-Alzheimer disease mild cognitive impairment (MCI), vascular MCI (VaMCI), and anxious or depression patients with cognitive impairment (DeMCI). A longitudinal cohort of 119 consecutive and incident subjects (73 women, 46 men; age 70+/-9.5 years) who fulfilled the criteria of amnesic MCI was followed for a mean period of 29 months. At baseline, a neuropsychological examination and standard blood test were performed, and different areas were examined by proton MRS, PI, and DWI. Among the group of patients considered to have AD, we also included patients with MD because these patients have a neurodegenerative component. After the follow-up period, 54 patients were considered as converted to dementia (49 with AD; 5 with LBD), 28 patients as MCI, 22 patients as DeMCI, and 15 patients as VaMCI. We found that N-acetylaspartate (NAA)/creatine (Cr) ratios in posterior cingulated gyri (PCG) predict the conversion to probable AD with a sensitivity of 82% and specificity of 72%, and NAA/Cr ratios in the left occipital cortex (LOC) had a sensitivity of 78% and specificity of 69%. When we used spectroscopy in the PCG and LOC to differentiate the types of MCI and dementias, we found significance differences in NAA/Cr, NAA/myoinositol (mI), NAA/choline (Cho), mI/NAA, and Cho/Cr ratios. The apparent diffusion coefficient (ADC) values in the right hippocampus showed differences in patients with LBD and DeMCI (P=.003), LBD with MCI (P=0.48), and LBD and VaMCI (P=.009). NAA/Cr ratios in PCG and LOC can predict the conversion from MCI to dementia with high sensitivity and specificity. MRS can differentiate AD from MCI, but cannot differentiate the types of MCI. DWI in the right hippocampus presents higher values of ADC in LBD and allows differentiating it from MCI.

Difference of the hippocampal and white matter microalterations in MCI patients according to the severity of subcortical vascular changes: Neuropsychological correlates of diffusion tensor imaging

Objectives Most imaging studies of mild cognitive impairment (MCI) have focused on gray matter alterations, although many MCI patients demonstrate subcortical vascular changes. We investigated the changes of the hippocampal area and various white matter areas in MCI patients with using diffusion tensor imaging (DTI), according to the severity of subcortical vascular changes, and we then correlated the DTI findings with the neuropsychological results. Patients and methods Among the 40 MCI patients, the 21 non-vascular MCI (nvMCI) and 19 vascular MCI (vMCI) patients were subdivided according to Erkinjuntti's imaging criteria. The mean diffusivity (MD) and fractional anisotropy (FA) were compared in the bilateral temporal, frontal, parietal and occipital white matter regions, as well as in the bilateral hippocampi, centrum semiovale, and the midline genu and splenum of the corpus callosum among the nvMCI and vMCI patients and the 17 controls. The neuropsychological findings were also compared between the subgroups. Results All the MCI patients showed decreased FA and increased MD in all the regions except the occipital areas. In the parietal regions and centrum semiovale, the vMCI patients had a greater FA decrease than the nvMCI patients and controls. In the hippocampi, the FA was lowest in the nvMCI patients. The memory function in the nvMCI patients was more impaired than that in the vMCI patients. The vMCI patients showed impairment of the visuospatial and frontal executive functions. Conclusion We were able to correlate the microstructural alterations with the neuropsychological findings in the MCI subgroups.

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.

Prevention of CIND by physical activity: Different impact on VCI-ND compared with MCI

Cognitive impairment that does not meet the criteria for dementia ("Cognitive Impairment, No Dementia" -- CIND) is a heterogeneous category with an increased risk of dementia. While greater physical activity is generally associated with a lower odds of both dementia and CIND, whether this effect applies across subgroups is not known. To investigate the association between physical activity and the risk of vascular CIND (VCI-ND) or mild cognitive impairment (MCI). In the Canadian Study of Health and Aging community-dwelling cohort, of 4683 people who were not impaired at baseline, 3945 remained without cognitive impairment at 5 years, 454 were diagnosed with CIND, and 284 with dementia. Incident CIND and VCI-ND (n=163) and MCI (n=100) subtypes were investigated in relation to baseline physical activity, stratified by sex. In women, moderate-high exercise was associated with a lower odds of CIND (OR=0.62, 95% CI=0.46-0.84) and VCI-ND (0.34, 0.18-0.63) relative to low exercise. There was no association for men or for MCI. Exercise appears to reduce the risk of VCI-ND in women. Whether the lack of an effect of exercise on the odds of MCI reflects that 'prevented AD' is indistinguishable from MCI is an intriguing possibility that merits further study.