Diagnosis Of Vascular Cognitive Impairment Research Articles

The AHA/ASA and DSM-V diagnostic criteria for vascular cognitive impairment identify cases with predominant vascular pathology.

There are major challenges in determining the etiology of vascular cognitive impairment (VCI) clinically, especially in the presence of mixed pathologies, such as vascular and amyloid. Most recently, two criteria (American Heart Association/American Stroke Association (AHA/ASA) and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V)) have been proposed for the clinical diagnosis of VCI but have not as yet been validated using neuroimaging. This study aims to determine whether the AHA/ASA and DSM-V criteria for VCI can distinguish between cases with predominantly vascular pathology and cases with mixed pathology. A total of 186 subjects were recruited from a cross-sectional memory clinic-based study at the National University Hospital, Singapore. All subjects underwent clinical and neuropsychological assessment, magnetic resonance imaging (MRI) and carbon 11-labeled Pittsburgh Compound B ([11C] PiB) positron emission tomography (PET) scans. Diagnosis of the etiological subtypes of VCI (probable vascular mild cognitive impairment (VaMCI), possible VaMCI, non-VaMCI, probable vascular dementia (VaD), possible VaD, non-VaD) were performed following AHA/ASA and DSM-V criteria. Brain amyloid burden was determined for each subject with standardized uptake value ratio (SUVR) values ⩾1.5 classified as amyloid positive. Using κ statistics, both criteria had excellent agreement for probable VaMCI, probable VaD, and possible VaD (κ = 1.00), and good for possible VaMCI (κ = 0.71). Using the AHA/ASA criteria, the amyloid positivity of probable VaMCI (3.8%) and probable VaD (15%) was significantly lower compared to possible VaMCI (26.7%), non-VaMCI (33.3%), possible VaD (73.3%), and non-VaD (76.2%) (p < 0.001). Similarly, using the DSM-V criteria, the amyloid positivity of probable VaMCI (3.8%) and probable VaD (15%) was significantly lower compared to possible VaMCI (26.3%), non-VaMCI (32.1%), possible VaD (73.3%), and non-VaD (76.2%) (p < 0.001). In both criteria, there was good agreement in differentiating individuals with non-VaD and possible VaD, with significantly higher (p < 0.001) global [11C]-PiB SUVR, from individuals with probable VaMCI and probable VaD, who had predominant vascular pathology. The AHA/ASA and DSM-V criteria for VCI can identify VCI cases with little to no concomitant amyloid pathology, hence supporting the utility of AHA/ASA and DSM-V criteria in diagnosing patients with predominant vascular pathology. Data supporting this study are available from the Memory Aging and Cognition Center, National University of Singapore. Access to the data is subject to approval and a data sharing agreement due to University policy.

Towards inclusive trial design for vascular cognitive impairment in the diverse context of India

AbstractBackgroundThe burden of vascular contribution to cognitive impairment and dementia is substantially higher in low and middle‐income countries like India compared to the high‐income countries (HIC). Nearly 40% of 5.3 million people with dementia are estimated to be due to vascular aetiology. This high burden of vascular cognitive impairment (VCI) is due to a greater prevalence of vascular risk factors such as diabetes, hypertension and stroke as well as low awareness and a wide treatment gap. Lack of validated diagnostic instruments in various regional languages and availability brain imaging pose challenges to diagnosis of VCI. These factors pose unique challenges to reducing the burden of VCI in India. Novel clinical trials are being implemented to risk of progression of VCI, but these efforts are mainly restricted to HIC. The limited availability of evidence for effective treatment and preventive strategies in the context of diverse countries like India are major impediments to effective public health interventions to reduce burden.MethodWe present results from a large cohort of 2000 individuals from multiple centres across the country including individuals at high risk of developing VCI, patients with vascular mild cognitive impairment and vascular dementia. Languages spoken by patients included Kannada, Telugu, Hindi, Malayalam, Urdu, Bengali and English among others. A were illiterate and around 60% were bilingual.ResultsHarmonised cognitive and functional measures adapted to multiple Indian languages and educational variability were used to detect VCI in the diverse population. MRI imaging to detect vascular imaging biomarkers was performed to detect infarcts, cortical atrophy, microbleeds and white matter lesions, for accurate identification of vascular damage and neurodegeneration. Collaborations between multiple centres in a systematic manner are ongoing. Novel public health initiatives with support of policy makers are also being implemented to improve brain health by increasing awareness and reducing risk of stroke and dementia in the community.ConclusionsThese large‐scale efforts towards developing clinical‐trial readiness of VCI cohorts in the community across India will be crucial to fill research evidence gaps and implement clinical trials in India in concurrence with ongoing global efforts.

New horizons in cognitive and functional impairment as a consequence of cerebral small vessel disease.

Cerebral small vessel disease (cSVD) is a frequent finding in imaging of the brain in older adults, especially in the concomitance of cardiovascular disease risk factors. Despite the well-established link between cSVD and (vascular) cognitive impairment (VCI), it remains uncertain how and when these vascular alterations lead to cognitive decline. The extent of acknowledged markers of cSVD is at best modestly associated with the severity of clinical symptoms, but technological advances increasingly allow to identify and quantify the extent and perhaps also the functional impact of cSVD more accurately. This will facilitate a more accurate diagnosis of VCI, against the backdrop of concomitant other neurodegenerative pathology, and help to identify persons with the greatest risk of cognitive and functional deterioration. In this study, we discuss how better assessment of cSVD using refined neuropsychological and comprehensive geriatric assessment as well as modern image analysis techniques may improve diagnosis and possibly the prognosis of VCI. Finally, we discuss new avenues in the treatment of cSVD and outline how these contemporary insights into cSVD can contribute to optimise screening and treatment strategies in older adults with cognitive impairment and multimorbidity.

Vascular cognitive impairment: issues of diagnosis and treatment

Vascular brain diseases are one of the leading causes of death and disability in developed countries. Along with acute disturbance of cerebral circulation, chronic cerebrovascular diseases, which manifest as vascular cognitive impairment (VCI), are of great medical and social importance. VCIs include a wide range of cognitive impairments (CI) ranging from subjective CI to vascular and mixed dementia. The article discusses pathogenetic and clinical variants, approaches to the diagnosis of VCIs, and provides their modern classification. The features of CI, typical for chronic cerebrovascular insufficiency, are described, such as a slowdown in the rate of mental activity and disorders of frontal executive functions in combination with behavioral and emotional disorders. The issues of treatment of VCI are discussed, which should be comprehensive and include correction of the underlying vascular disease, non-drug (regular physical activity, smoking cessation, cognitive training) and drug treatments aimed at improving cognitive functions. The possibilities of modern neuroprotective and symptomatic therapy of CI, including the use of Cellex®, are shown.

Correlations among peripheral blood markers, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events.

Both inflammation and cerebral white matter injury are closely associated with vascular cognitive impairment (VCI). The aim of this study was to analyze the correlation between peripheral serological markers, white matter injury, and cognitive function in patients with non-disabling ischemic cerebrovascular events (NICE); to identify potential biological markers for the diagnosis and prediction of VCI; and to provide a basis for the early diagnosis and intervention of VCI. We collected clinical data, along with demographic and medical history data, from 151 NICE patients. Fasting venous blood samples were collected. Based on the Montreal Cognitive Assessment (MoCA) after admission, we divided the patients into normal cognitive function (NCF) and VCI groups, and then classified them into mild white matter hyperintensity (mWMH) and severe white matter hyperintensity (sWMH) based on Fazekas scores. The differences in serological marker levels were compared between the cognitive function groups and the white matter hyperintensity groups. Binary logistic regression models and receiver operating characteristic curves were used to analyze the diagnostic predictive value of serological markers for VCI in patients with NICE and in the white matter hyperintensity subgroups. Among 151 patients with NICE, 95 were male and 56 were female. Lymphocyte count (OR = 0.405, p = 0.010, 95% CI [0.201, 0.806]), red blood cell count (OR = 0.433, p = 0.010, 95% CI [0.228, 0.821]), and hemoglobin level (OR = 0.979, p = 0.046, 95% CI [0.958, 0.999]) were protective factors for cognitive function in patients with NICE. The sWMH group had a higher age, granulocyte/lymphoid ratio (NLR), and neutrophil percentage but a lower MoCA score, hemoglobin level, and lymphocyte count than the mWMH group. In the mWMH group, lymphocyte count (AUC = 0.713, p = 0.003, 95% CI [0.593, 0.833]) had an acceptable predictive value for the diagnosis of VCI, whereas white blood cell count (AUC = 0.672, p = 0.011, 95% CI [0.545, 0.799]), red blood cell count (AUC = 0.665, p = 0.014, 95% CI [0.545, 0.784]), and hemoglobin level (AUC = 0.634, p = 0.047, 95% CI [0.502, 0.765]) had marginal predictive value for the diagnosis of VCI. In the sWMH group, no significant differences were found in serological markers between the NCF and VCI groups. Lymphocyte count, red blood cell count, and hemoglobin level were independent protective factors for cognitive function in patients with NICE; they can be used as potential biological markers to distinguish VCI in patients with NICE and are applicable to subgroups of patients with mWMH.

Arterial Spin-Labeling Parameters and Their Associations with Risk Factors, Cerebral Small-Vessel Disease, and Etiologic Subtypes of Cognitive Impairment and Dementia.

Cerebral small-vessel disease may alter cerebral blood flow (CBF) leading to brain changes and, hence, cognitive impairment and dementia. CBF and the spatial coefficient of variation can be measured quantitatively by arterial spin-labeling. We aimed to investigate the associations of demographics, vascular risk factors, location, and severity of cerebral small-vessel disease as well as the etiologic subtypes of cognitive impairment and dementia with CBF and the spatial coefficient of variation. Three hundred ninety patients with a diagnosis of no cognitive impairment, cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia were recruited from the memory clinic. Cerebral microbleeds and lacunes were categorized into strictly lobar, strictly deep, and mixed-location and enlarged perivascular spaces into the centrum semiovale and basal ganglia. Total and region-specific white matter hyperintensity volumes were segmented using FreeSurfer. CBF (n = 333) and the spatial coefficient of variation (n = 390) were analyzed with ExploreASL from 2D-EPI pseudocontinuous arterial spin-labeling images in white matter (WM) and gray matter (GM). To analyze the effect of demographic and vascular risk factors as well as the location and severity of cerebral small-vessel disease markers on arterial spin-labeling parameters, we constructed linear regression models, whereas logistic regression models were used to determine the association between arterial spin-labeling parameters and cognitive impairment no dementia, vascular cognitive impairment no dementia, Alzheimer disease, and vascular dementia. Increasing age, male sex, hypertension, hyperlipidemia, history of heart disease, and smoking were associated with lower CBF and a higher spatial coefficient of variation. Higher numbers of lacunes and cerebral microbleeds were associated with lower CBF and a higher spatial coefficient of variation. Location-specific analysis showed mixed-location lacunes and cerebral microbleeds were associated with lower CBF. Higher total, anterior, and posterior white matter hyperintensity volumes were associated with a higher spatial coefficient of variation. No association was observed between enlarged perivascular spaces and arterial spin-labeling parameters. A higher spatial coefficient of variation was associated with the diagnosis of vascular cognitive impairment no dementia, Alzheimer's disease, and vascular dementia. Reduced CBF and an increased spatial coefficient of variation were associated with cerebral small-vessel disease, and more specifically lacunes, whereas cerebral microbleeds and white matter hyperintensities were associated with WM-CBF and GM spatial coefficient of variation. The spatial coefficient of variation was associated with cognitive impairment and dementia, suggesting that hypoperfusion might be the key underlying mechanism for vascular brain damage.

Diagnosis of vascular cognitive impairment: recommendations of the scientific department of cognitive neurology and aging of the Brazilian Academy of Neurology.

Since the publication of the latest recommendations for the diagnosis and treatment of Vascular Dementia by the Brazilian Academy of Neurology in 2011, significant advances on the terminology and diagnostic criteria have been made. This manuscript is the result of a consensus among experts appointed by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2020-2022). We aimed to update practical recommendations for the identification, classification, and diagnosis of Vascular Cognitive Impairment (VCI). Searches were performed in the MEDLINE, Scopus, Scielo, and LILACS databases. This guideline provides a comprehensive review and then synthesizes the main practical guidelines for the diagnosis of VCI not only for neurologists but also for other professionals involved in the assessment and care of patients with VCI, considering the different levels of health care (primary, secondary and tertiary) in Brazil.

Diagnóstico do comprometimento cognitivo vascular: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia

ABSTRACT Since the publication of the latest recommendations for the diagnosis and treatment of Vascular Dementia by the Brazilian Academy of Neurology in 2011, significant advances on the terminology and diagnostic criteria have been made. This manuscript is the result of a consensus among experts appointed by the Scientific Department of Cognitive Neurology and Aging of the Brazilian Academy of Neurology (2020-2022). We aimed to update practical recommendations for the identification, classification, and diagnosis of Vascular Cognitive Impairment (VCI). Searches were performed in the MEDLINE, Scopus, Scielo, and LILACS databases. This guideline provides a comprehensive review and then synthesizes the main practical guidelines for the diagnosis of VCI not only for neurologists but also for other professionals involved in the assessment and care of patients with VCI, considering the different levels of health care (primary, secondary and tertiary) in Brazil.

Differential diagnosis of vascular cognitive impairment

Background. Vascular cognitive impairment (VCI), аccording to world statistics, is the second most common cause of cognitive impairment after Alzheimer's disease (AD). Differential diagnosis between the two most common nosological forms of cognitive impairment is not always simple and is based on the clinical characteristic, neuropsychological and neuroradiological features of the disease.&#x0D; Aim. To present a differential diagnosis between VCI and AD using the example of a clinical case of vascular mild cognitive impairment.&#x0D; Materials and methods. A 68-year-old female patient with mild cognitive impairment underwent a neuropsychological testing: the Mini-mental state exam, Frontal assessment battery, the MoCA-test, the Clock-Drawing Test, the 12 Words test, Verbal Association Technique (literal and categorical), The Trail making test (A and B), The digit symbol substitution test, The Boston naming test (40 images), EXIT-25, Beck Depression Scale, Hospital anxiety and depression scale; neuroimaging magnetic resonance imaging in T1, T2, FLAIR, DWI, SWI sequence.&#x0D; Results. On the basis of clinical data, the results of neuropsychological testing and neuroimaging, the differential diagnosis with AD, the patient was diagnosed with vascular mild cognitive impairment. Nootropic therapy (choline alfoscerate) was prescribed and recommendations on risk factors correction were given.&#x0D; Conclusion. The article describes a patient with mild VCI. This case study discusses the main differences between AD and VCI that can be used as a basis for differential diagnosis. The features of cognitive impairments in VCI and AD are described, including the predominance of attention impairment, an executive function disorder in VCI and an impairment of memory progressing according to the Ribots law in AD. Differences in visuospatial skills and language in VCI and AD are discussed. The most reliable neuroradiological signs of cerebrovascular diseases are described.

Association Between Immunoglobulin G N-glycosylation and Vascular Cognitive Impairment in a Sample With Atherosclerosis: A Case-Control Study.

BackgroundAtherosclerosis is considered a crucial component in the pathogenesis of decreased cognitive function, as occurs in vascular cognitive impairment (VCI). Inflammation and the immune response play a significant role in the development of many chronic diseases. Immunoglobulin G (IgG) N-glycosylation has been implicated in the development of a variety of diseases by affecting the anti-inflammatory and proinflammatory responses of IgG. This study aimed to investigate the association between IgG N-glycosylation and VCI in a sample of patients with atherosclerosis through a case-control study.MethodWe recruited a total of 330 patients with atherosclerosis to participate in this case-control study, including 165 VCI patients and 165 sex- and age-matched participants with normal cognitive function. The plasma IgG N-glycans of participants were separated by ultrahigh-performance liquid chromatography. An enzyme-linked immunosorbent assay (ELISA) kit was used to determine the corresponding serum inflammatory factors. Atherosclerosis was diagnosed by carotid ultrasound, and the diagnosis of VCI was based on the “Guidelines for the Diagnosis and Treatment of Vascular Cognitive Impairment in China (2019)”. A multivariate logistic regression model was used to explore the association between IgG N-glycans and VCI. We also analyzed the relationship between IgG N-glycans and the inflammatory state of VCI through canonical correlation analysis (CCA).ResultsThrough the multivariate logistic regression analysis, 8 glycans and 13 derived traits reflecting decreased sialylation and galactosylation and increased bisecting GlcNAc significantly differed between the case and control groups after adjusting for confounding factors (P < 0.05, q < 0.05). Similarly, the differences in TNF-α, IL-6, and IL-10 were statistically significant between the case and control groups after adjusting for the effects of confounding factors (P < 0.05, q < 0.05). The CCA results showed that VCI-related initial N-glycans were significantly correlated with VCI-related inflammatory factors (r = 0.272, P = 0.004). The combined AUC value (AUCcombined = 0.885) of 7 initial glycans and inflammatory factors was higher than their respective values (AUCinitial glycans = 0.818, AUCinflammatory factors = 0.773).ConclusionThe findings indicate that decreased sialylation and galactosylation and increased bisecting GlcNAc reflected by IgG N-glycans might affect the occurrence of VCI in patients with atherosclerosis though promoting the proinflammatory function of IgG. IgG N-glycans may serve as potential biomarkers to distinguish VCI in individuals with atherosclerosis.

Impact of Brain MRI Markers on Major and Mild Vascular Cognitive Impairment in CADASIL

Background: Cognitive impairment is the second most common clinical manifestation in cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, understanding of cognitive impairment in CADASIL has been hampered by lack of consensus on diagnosis of vascular cognitive impairment (VCI). We used vascular impairment of cognition classification consensus study principles (VICCCS-1) and protocols (VICCCS-2) to assess the cognitive impairment in CADASIL. We also evaluated the impact of MRI markers on major and mild VCI in CADASIL.Methods: We prospectively recruited 64 patients who underwent standardized brain MRI and detailed neuropsychological test. MRI analysis included number of lacunes, number of cerebral microbleeds (CMB), normalized volume of white-matter hyperintensities (nWMH), and brain parenchymal fraction (BPF). BPF has been used to measure brain atrophy. The patients were divided into three groups: those with normal cognition (CADASIL-NC, n=14), those with mild VCI (CADASIL-mild VCI, n=38), and those with major VCI (CADASIL-major VCI, n=11).Results: The three groups differed according to age, with the major VCI group being older. The major VCI group had more lacunes, more CMB, more extensive white matter lesions and lower BPF than NC group. There were no significant differences between NC and mild VCI groups in BPF. BPF and age were the independent predictors of major VCI. There was a tendency that women were at higher risk for mild VCI, though it did not reach statistical significance. Women were older than men, but had lower number of lacunes in mild VCI.Conclusions: These findings suggest that brain atrophy and age are the main predictors of major VCI in CADASIL.

Evaluation of Vascular Cognitive Impairment Using the ICMR-Neuro Cognitive Tool Box (ICMR-NCTB) in a Stroke Cohort from India.

Vascular cognitive impairment (VCI) presents with a spectrum of cognitive impairment due to stroke and poses a huge socioeconomic burden especially in low middle-income countries. There is a critical need for early recognition and identification of VCI patients. Therefore, we developed and validated culturally appropriate neuropsychological instruments, the ICMR-Neuro Cognitive Tool-Box (ICMR-NCTB) and Montreal Cognitive Assessment (MoCA) to diagnose vascular MCI and dementia in the Indian context. A total of 181 participants: 59 normal cognition, 25 stroke with normal cognition, 46 vascular MCI (VaMCI) and 51 vascular dementia (VaD) were recruited for the study. The ICMR-NCTB and MoCA were administered to patients with VCI and major cognitive domains were evaluated. The ICMR-NCTB was found to have good internal reliability in VaMCI and VaD. The sensitivity of the ICMR-NCTB to detect VaMCI and VaD ranged from 70.8% to 72.9% and 75.9% to 79.7%, respectively, and the specificity for VaMCI and VaD ranged from 84.8% to 86.1% and 82.5% to 85.2%, respectively. The MoCA had excellent sensitivity and specificity to detect VaMCI and VaD at ideal cut-off scores. The ICMR-NCTB is a valid neuropsychological toolbox that can be used for comprehensive cognitive assessment and diagnosis of VCI in India. In addition, the Indian version of MoCA is more adept as a screening instrument to detect VCI due to its high sensitivity. The ICMR-NCTB will aid in early detection and management of many patients, thereby reducing the burden of vascular MCI and dementia in India.

Role of White Matter Hyperintensities and Related Risk Factors in Vascular Cognitive Impairment: A Review.

White matter hyperintensities (WMHs) of presumed vascular origin are one of the imaging markers of cerebral small-vessel disease, which is prevalent in older individuals and closely associated with the occurrence and development of cognitive impairment. The heterogeneous nature of the imaging manifestations of WMHs creates difficulties for early detection and diagnosis of vascular cognitive impairment (VCI) associated with WMHs. Because the underlying pathological processes and biomarkers of WMHs and their development in cognitive impairment remain uncertain, progress in prevention and treatment is lagging. For this reason, this paper reviews the status of research on the features of WMHs related to VCI, as well as mediators associated with both WMHs and VCI, and summarizes potential treatment strategies for the prevention and intervention in WMHs associated with VCI.

Diagnostic accuracy of brief cognitive screening tools to diagnose vascular cognitive impairment in Peru.

To evaluate the diagnostic accuracy of three brief cognitive screening (BCS) tools, Peruvian version of Addenbrooke's Cognitive Examination (ACE-Pe), of INECO Frontal Screening (IFS-Pe) and of the Mini-Mental State Examination (MMSE-Pe), for the diagnosis of vascular cognitive impairment (VCI) and its non-dementia stages (VCI-ND) and vascular dementia (VD) in patients with cerebral stroke in Lima-Peru. A cohort analysis to evaluate the diagnostic accuracy of three BCS for VCI. Two hundred and four patients were evaluated: 61% Non-VCI, 30% VCI-ND and 9% VD. To discriminate patients with VCI from controls, the area under the curve (AUC) of ACE-Pe, IFS-Pe and MMs-Pe were 0.99 (95% confidence interval [CI] 0.98-0.99), 0.99 (95%CI 0.98-0.99) and 0.87 (95%CI 0.82-0.92), respectively. Of the three BCS, the IFS-Pe presented a larger AUC to discriminate VCI-ND from VD (AUC=0.98 [95%CI 0.95-1]) compared to ACE-Pe (AUC=0.84 [95%CI 0.74-0.95]) and MMSE-Pe (0.92 [95%CI 0.86-0.99]). The IFS-Pe presented a higher sensitivity (S), specificity (Sp), and positive (+LR) and negative likelihood ratios (-LR) (S=96.72%, Sp=89.47%, +LR=9.1 and -LR=0.03) than ACE-Pe (S=96.72%, Sp=63.16%, +LR=2.62 and -LR=0.05) and MMSE-Pe (S=90.16%, Sp=78.95%, +LR=4.28 and -LR=0.12). In the multiple regression analysis, the IFS-Pe was not affected by age, sex or years of schooling. The IFS-Pe has the best diagnostic accuracy for detecting VCI and discriminating between pre-dementia (VCI-ND) and dementia (VD) stages.

Evaluation and Treatment of Vascular Cognitive Impairment by Transcranial Magnetic Stimulation.

The exact relationship between cognitive functioning, cortical excitability, and synaptic plasticity in dementia is not completely understood. Vascular cognitive impairment (VCI) is deemed to be the most common cognitive disorder in the elderly since it encompasses any degree of vascular-based cognitive decline. In different cognitive disorders, including VCI, transcranial magnetic stimulation (TMS) can be exploited as a noninvasive tool able to evaluate in vivo the cortical excitability, the propension to undergo neural plastic phenomena, and the underlying transmission pathways. Overall, TMS in VCI revealed enhanced cortical excitability and synaptic plasticity that seem to correlate with the disease process and progression. In some patients, such plasticity may be considered as an adaptive response to disease progression, thus allowing the preservation of motor programming and execution. Recent findings also point out the possibility to employ TMS to predict cognitive deterioration in the so-called “brains at risk” for dementia, which may be those patients who benefit more of disease-modifying drugs and rehabilitative or neuromodulatory approaches, such as those based on repetitive TMS (rTMS). Finally, TMS can be exploited to select the responders to specific drugs in the attempt to maximize the response and to restore maladaptive plasticity. While no single TMS index owns enough specificity, a panel of TMS-derived measures can support VCI diagnosis and identify early markers of progression into dementia. This work reviews all TMS and rTMS studies on VCI. The aim is to evaluate how cortical excitability, plasticity, and connectivity interact in the pathophysiology of the impairment and to provide a translational perspective towards novel treatments of these patients. Current pitfalls and limitations of both studies and techniques are also discussed, together with possible solutions and future research agenda.

The Application of rs-fMRI in Vascular Cognitive Impairment.

The incidence of vascular cognitive impairment (VCI) has been increasing for years and has become a major disabling factor in middle-aged and elderly populations. The pathogenesis of VCI is unclear, and there are no standard diagnostic criteria. Resting-state functional magnetic resonance imaging (rs-fMRI) can be used to detect spontaneous brain functional activity in a resting state, which facilitates in-depth investigation of the pathogenesis of VCI and provides an objective reference for early diagnosis, differential diagnosis, and prognostic evaluation. This article mainly reviews the principle and analysis of rs-fMRI data, as well as the progress of its application for VCI diagnosis.

Correlations of serum cystatin C level and gene polymorphism with vascular cognitive impairment after acute cerebral infarction.

The aim of this study was to explore the possible correlations of serum cystatin C level and cystatin C gene (CST3) polymorphism with vascular cognitive impairment in patients who had acute cerebral infarction. A total of 152 patients with acute cerebral infarction were recruited in this case-control study. Patients were divided into vascular cognitive impairment (VCI) group (n = 71) and cognitive impairment no dementia (CIND) group (n = 81). The serum concentrations of cystatin C were measured with immunoturbidimetric assay while the gene polymorphisms of CST3 were determined by technique polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In the VCI group, serum cystatin C level was significantly higher than that in the control group. The frequency of the B allele was found to be higher in the VCI group as compared with that of the CIND group (18.5% vs 7.7%, p = 0.006). In logistic regression analysis, significant associations of VCI with high serum cystatin C level (OR 3.837 (1.176-12.520), p = 0.026) and CST3 B allele (OR 2.038 (1.048-3.963), p = 0.036) were also found. A high cystatin C level and CST3 B allele confer risks for VCI after acute cerebral infarction. It is probable that measurement of the serum cystatin C level and detection of CST3 gene polymorphism would aid in the early diagnosis of VCI, but further studies are warranted.

Symptomatic Treatment of Vascular Cognitive Impairment (STREAM-VCI): Protocol for a Cross-Over Trial.

BackgroundPeople with vascular cognitive impairment (VCI) constitute a clinically heterogeneous group, but previous symptomatic drug trials in VCI did not take this clinical heterogeneity into account. Executive dysfunction and memory impairment are the cognitive domains that are most frequently impaired in VCI, and these impairments are likely to reflect vascular damage to specific neurotransmitter systems, which opens the possibility for targeted symptomatic treatment directed at specific neurotransmitters.ObjectiveHere we describe the design of the “Symptomatic Treatment of Vascular Cognitive Impairment” (STREAM-VCI) trial. In this proof-of-concept study, we investigate whether people with VCI with executive dysfunction due to vascular damage to the monoaminergic neurotransmitter system differentially respond to a monoaminergic challenge, whereas people with VCI with memory dysfunction associated with vascular damage to the cholinergic system will in turn respond to a cholinergic challenge.MethodsThe STREAM-VCI is a single center, double blind, three-way cross-over trial among 30 people with VCI, in which subjects received a single dose of galantamine, methylphenidate, or placebo on separate occasions. The most important inclusion criteria were a diagnosis of VCI with a Mini-Mental State Examination score of ≥16 and a Clinical Dementia Rating of 0.5-1.0. For each person, the challenges consisted of a single 16 mg dose of galantamine, 10 mg of methylphenidate, and placebo, in random order on three separate visits. Change in performance in executive functioning and memory was assessed directly after the challenge using standardized neuropsychological tests. We will correlate a positive response to the cholinergic and monoaminergic treatment with differences in structural and functional connectivity at baseline using structural magnetic resonance imaging (MRI), diffusion tension MRI, and resting-state functional MRI.ResultsThe protocol of this study is approved by the Medical Ethics Committee of VU University Medical Center and the competent authority. The first participant was enrolled in April 2014. In September 2017, enrolment for the study was completed. We expect to publish the results in 2018.ConclusionsSTREAM-VCI is the first study to investigate the association of a response to a cholinergic and monoaminergic treatment with structural and functional connectivity of the monoaminergic and/or cholinergic systems on MRI. We aim to predict on an individual basis which individuals show a positive response to a cholinergic and/or monoaminergic challenge in people with VCI. This may be instrumental in moving in the direction of individually-tailored pharmacological interventions based on MRI measures in people with VCI.Trial RegistrationClinicalTrials.gov NCT02098824; https://clinicaltrials.gov/ct2/show/NCT02098824 (Archived by WebCite at http://www.webcitation.org/6xhO7Ya1q)

Abstract WP158: Supervised, Self Administered Tablet Based Cognitive Assessment in Neurodegenerative Disorders

Introduction: The diagnosis of vascular cognitive impairment relies on bedside tools to quantify the degree of disease burden. Given the critical importance of implementing early interventions, it is becoming increasingly important to investigate more sensitive and easily administered tools for accurately characterizing these deficits. Hypothesis: The current study aims to evaluate the effectiveness of using Miro, a tablet-based mobile application, developed by The Cognitive Healthcare Company, designed to measure the same cognitive domains as traditional pencil-and-paper tests but (1) require less administration time; (2) provide reliable scoring; (3) offer greater ease of use; and (4) capture and analyze informative data, like speech, fine motor function and eye movements, that are not typically used in clinical settings. Methods: Subjects were recruited from the Stroke and Cognitive Disorders Clinic. Subjects were randomized to undergo pencil-and-paper or iPad testing first. The battery of tests in each medium take roughly 60 minutes to complete. In this ongoing study, there will be 3 total participant visits over one year, to evaluate rate of decline or improvement in each medium. Results: 11 subjects have been enrolled in the study thus far. These subjects have a mean age of 64.6 ± 9.48 and years of education 16.3 ± 2.61.There were strong Spearman rho correlations between pencil and paper testing and iPad testing on digit span forwards (0.848, p &lt; 0.002), digit span backwards (0.946, p &lt; 0.001), symbol digit coding (0.936, p &lt; 0.001), Trails A and B (0.794, p &lt; 0.006). When asked to rate their preference on a 7-point Likert scale (1=iPad based, 4=no preference, 7=paper based), subjects reported a mean score of 3.36 (SD 1.55), demonstrating a slight but not statistically significant preference for iPad. Technicians uniformly found the iPad app easier to administer and less time-consuming for them. Conclusions: Given the growing population of individuals with vascular cognitive impairment, it is crucial to test whether this accessible, cost-effective, mobile testing modality can be effectively utilized to assess change in cognitive function after stroke. Our preliminary results indicate that iPad based interventions area promising means to meet this goal.

Progress toward standardized diagnosis of vascular cognitive impairment: Guidelines from the Vascular Impairment of Cognition Classification Consensus Study

IntroductionProgress in understanding and management of vascular cognitive impairment (VCI) has been hampered by lack of consensus on diagnosis, reflecting the use of multiple different assessment protocols. A large multinational group of clinicians and researchers participated in a two-phase Vascular Impairment of Cognition Classification Consensus Study (VICCCS) to agree on principles (VICCCS-1) and protocols (VICCCS-2) for diagnosis of VCI. We present VICCCS-2. MethodsWe used VICCCS-1 principles and published diagnostic guidelines as points of reference for an online Delphi survey aimed at achieving consensus on clinical diagnosis of VCI. ResultsSix survey rounds comprising 65–79 participants agreed guidelines for diagnosis of VICCCS-revised mild and major forms of VCI and endorsed the National Institute of Neurological Disorders–Canadian Stroke Network neuropsychological assessment protocols and recommendations for imaging. DiscussionThe VICCCS-2 suggests standardized use of the National Institute of Neurological Disorders–Canadian Stroke Network recommendations on neuropsychological and imaging assessment for diagnosis of VCI so as to promote research collaboration.