scholarly journals The Missing Link in the Pathophysiology of Vascular Cognitive Impairment: Design of the Heart-Brain Study

2017 ◽  
Vol 7 (3) ◽  
pp. 140-152 ◽  
Author(s):  
Astrid M. Hooghiemstra ◽  
Anne Suzanne Bertens ◽  
Anna E. Leeuwis ◽  
Esther E. Bron ◽  
Michiel L. Bots ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Neuropsychological Testing ◽  
Brain Mri ◽  
Vascular Cognitive Impairment ◽  
Imaging Data ◽  
Hemodynamic Changes ◽  
Hemodynamic Status ◽  
The Brain ◽  
Brain Study

Background: Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. Methods: The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz­heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. Results and Conclusions: The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor.

scholarly journals Biomarkers identify the Binswanger type of vascular cognitive impairment

2018 ◽  
Vol 39 (8) ◽  
pp. 1602-1612 ◽  
Author(s):  
Erik Barry Erhardt ◽  
John C Pesko ◽  
Jillian Prestopnik ◽  
Jeffrey Thompson ◽  
Arvind Caprihan ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Magnetic Resonance ◽  
Vascular Disease ◽  
Neuropsychological Testing ◽  
Vascular Cognitive Impairment ◽  
Matrix Metalloproteinase 2 ◽  
Resonance Spectroscopy ◽  
Classification Methods ◽  
Csf Analysis

Binswanger’s disease is a form of subcortical ischemic vascular disease (SIVD-BD) with extensive white matter changes. To test the hypothesis that biomarkers could improve classification of SIVD-BD, we recruited 62 vascular cognitive impairment and dementia (VCID) patients. Multimodal biomarkers were collected at entry into the study based on clinical and neuropsychological testing, multimodal magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis. The patients’ diagnoses were confirmed by long-term follow-up, and they formed a “training set” to test classification methods, including (1) subcortical ischemic vascular disease score (SIVDS), (2) exploratory factor analysis (EFA), (3) logistic regression (LR), and (4) random forest (RF). A subsequently recruited cohort of 43 VCID patients with provisional diagnoses were used as a “test” set to calculate the probability of SIVD-BD based on biomarkers obtained at entry. We found that N-acetylaspartate (NAA) on proton magnetic resonance spectroscopy (1H-MRS) was the best variable for classification, followed by matrix metalloproteinase-2 in CSF and blood–brain barrier permeability on MRI. Both LR and RF performed better in diagnosing SIVD-BD than either EFA or SIVDS. Two-year follow-up of provisional diagnosis patients confirmed the accuracy of statistically derived classifications. We propose that biomarker-based classification methods could diagnose SIVD-BD patients earlier, facilitating clinical trials.

Brain FDG PET for the Etiological Diagnosis of Clinically Uncertain Cognitive Impairment During Delirium in Remission

2020 ◽  
Vol 77 (4) ◽  
pp. 1609-1622
Author(s):  
Franziska Mathies ◽  
Catharina Lange ◽  
Anja Mäurer ◽  
Ivayla Apostolova ◽  
Susanne Klutmann ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Fdg Pet ◽  
False Negative ◽  
Ground Truth ◽  
Etiological Diagnosis ◽  
Geriatric Unit ◽  
Positron Emission ◽  
The Brain ◽  
Hospitalized Geriatric Patients

Background: Positron emission tomography (PET) of the brain with 2-[F-18]-fluoro-2-deoxy-D-glucose (FDG) is widely used for the etiological diagnosis of clinically uncertain cognitive impairment (CUCI). Acute full-blown delirium can cause reversible alterations of FDG uptake that mimic neurodegenerative disease. Objective: This study tested whether delirium in remission affects the performance of FDG PET for differentiation between neurodegenerative and non-neurodegenerative etiology of CUCI. Methods: The study included 88 patients (82.0±5.7 y) with newly detected CUCI during hospitalization in a geriatric unit. Twenty-seven (31%) of the patients were diagnosed with delirium during their current hospital stay, which, however, at time of enrollment was in remission so that delirium was not considered the primary cause of the CUCI. Cases were categorized as neurodegenerative or non-neurodegenerative etiology based on visual inspection of FDG PET. The diagnosis at clinical follow-up after ≥12 months served as ground truth to evaluate the diagnostic performance of FDG PET. Results: FDG PET was categorized as neurodegenerative in 51 (58%) of the patients. Follow-up after 16±3 months was obtained in 68 (77%) of the patients. The clinical follow-up diagnosis confirmed the FDG PET-based categorization in 60 patients (88%, 4 false negative and 4 false positive cases with respect to detection of neurodegeneration). The fraction of correct PET-based categorization did not differ between patients with delirium in remission and patients without delirium (86% versus 89%, p = 0.666). Conclusion: Brain FDG PET is useful for the etiological diagnosis of CUCI in hospitalized geriatric patients, as well as in patients with delirium in remission.

scholarly journals Progression in Vascular Cognitive Impairment: Pathogenesis, Neuroimaging Evaluation, and Treatment

2018 ◽  
Vol 28 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Xin Zhang ◽  
Jiabin Su ◽  
Chao Gao ◽  
Wei Ni ◽  
Xinjie Gao ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Functional Neuroimaging ◽  
Neuropsychological Testing ◽  
Vascular Cognitive Impairment ◽  
Neurological Rehabilitation ◽  
Vessel Occlusion ◽  
Cerebral Vascular Disease ◽  
Clinical Evaluations ◽  
Neurologic Disorders ◽  
Neurological Protection

Vascular cognitive impairment (VCI) defines an entire spectrum of neurologic disorders from mild cognitive impairment to dementia caused by cerebral vascular disease. The pathogenesis of VCI includes ischemic factors (e.g., large vessel occlusion and small vessel dysfunction); hemorrhagic factors (e.g., intracerebral hemorrhage and subarachnoid hemorrhage); and other factors (combined with Alzheimer’s disease). Clinical evaluations of VCI mainly refer to neuropsychological testing and imaging assessments, including structural and functional neuroimaging, with different advantages. At present, the main treatment for VCI focuses on neurological protection, cerebral blood flow reconstruction, and neurological rehabilitation, such as pharmacological treatment, revascularization, and cognitive training. In this review, we discuss the pathogenesis, neuroimaging evaluation, and treatment of VCI.

Manifestation of cognitive impairments after a prior coronavirus infection COVID-19 in a patient with ApoE ε4 genotype

2021 ◽  
Vol 26 (2) ◽  
pp. 25-29
Author(s):  
M. S. Novikova ◽  
V. V. Zakharov ◽  
N. V. Vakhnina
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Small Vessel Disease ◽  
Brain Mri ◽  
Periventricular White Matter ◽  
Everyday Activity ◽  
Apoe Ε4 ◽  
Coronavirus Infection ◽  
Novel Coronavirus

Nowadays, the novel coronavirus infection (COVID-19) pandemic is one of the most important global health problems. There is increasing evidence that COVID-19 affects central and peripheral nervous system as well. The paper presents a clinical case of a 47 old patient with the ApoE ε4 haplotype and family history of Alzheimer’s disease who developed cognitive impairment after acute COVID-19. Before the infection the patient has no cognitive complaints and preserved everyday activity. After novel coronavirus infection, which was observed in mild form, the patient had started to complain on constant excessive forgetfulness. Neuropsychological assessment confirmed the presence of pre-mild cognitive impairment of predominantly single domain amnestic type. However, brain MRI showed only subtle periventricular white matter changes usually attributed to small vessel disease. Memory complaints were observed for 3 months of follow up despite intensive cognitive training, optimization of lifestyle and therapy with choline alphoscerate. Probable links between coronavirus infectious and cognitive impairment manifestation are discussed. There is data that ApoE ε4 haplotype is associated with increase of microglia mediated neuro-inflammation and it can be significant for accelerating of progression of neurodegenerative diseases after COVID-19. Further follow up of the patient is necessary for determination of nosological diagnosis explaining manifested predominantly amnestic type pre-mild cognitive impairment.

P3714Cerebral blood flow and cognitive functioning in the heart-brain axis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A E Leeuwis ◽  
A M Hooghiemstra ◽  
E E Bron ◽  
H P Brunner-La Rocca ◽  
L J Kappelle ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cognitive Impairment ◽  
Cognitive Functioning ◽  
Sex Education ◽  
Vascular Cognitive Impairment ◽  
Cognitive Domain ◽  
Cardiovascular Research ◽  
Whole Brain ◽  
Symptomatic Carotid ◽  
Brain Study

Abstract Background Recent studies suggest that cardiovascular disease and dementia are closely related, which led to the concept of a “heart-brain axis”. Dysfunction in any component of the heart-brain axis could be a risk factor for the development of brain damage and consequently to the development of cognitive impairment. In the Heart-Brain study, we focus on vascular cognitive impairment (VCI), symptomatic carotid occlusive disease (COD) and heart failure (HF) as three extreme phenotypes of haemodynamic dysfunction in different components of the heart-brain axis (i.e. heart – carotids – brain). We compared values of cerebral blood flow (CBF), measured with arterial spin labeling (ASL) between patients with HF, COD and VCI and investigated the association between CBF and cognitive functioning. Methods We included 442 participants (129 VCI; 75 COD; 124 HF; and 114 controls) from the Heart-Brain Study (67±9 yrs; 38% F; MMSE 28±2). We used 3T pseudo-continuous ASL to estimate whole-brain and regional partial volume-corrected CBF. Using a standardized neuropsychological assessment, we measured global cognitive functioning and four cognitive domains. Compound z-scores were constructed for each cognitive domain. We investigated associations using linear regression analyses, adjusted for age, sex, education, center and diagnosis. Subsequently, we stratified for diagnosis. Results Whole-brain and regional CBF values were lowest in patients with COD, followed by VCI and HF, compared to controls. Global cognitive functioning was lowest in patients with VCI, followed by COD and HF, compared to controls. Overall, we found hardly any association between whole-brain or regional CBF values and cognitive functioning (standardized beta [stb] = 0.00–0.10, p>0.05). Subsequent stratification for diagnosis showed no association between whole-brain or regional CBF and cognitive functioning in any participant group. Conclusions Our results suggest that reduced CBF is not the major explanatory factor underlying impaired cognitive functioning in patients with disorders along the heart-brain axis. The predisposition of cognitive impairment in these patients is likely to be driven by other (haemodynamic) mechanisms than CBF. Acknowledgement/Funding We acknowledge the support of the Netherlands CardioVascular Research Initiative: the Dutch Heart Foundation (CVON 2012-06 Heart Brain Connection), Du

scholarly journals Disturbance of Intracerebral Fluid Clearance and Blood–Brain Barrier in Vascular Cognitive Impairment

2019 ◽  
Vol 20 (10) ◽  
pp. 2600 ◽  
Author(s):  
Masaki Ueno ◽  
Yoichi Chiba ◽  
Ryuta Murakami ◽  
Koichi Matsumoto ◽  
Ryuji Fujihara ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Blood Brain Barrier ◽  
Brain Function ◽  
Vascular Cognitive Impairment ◽  
Brain Dysfunction ◽  
Brain Parenchyma ◽  
The Other ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Brain

The entry of blood-borne macromolecular substances into the brain parenchyma from cerebral vessels is blocked by the blood–brain barrier (BBB) function. Accordingly, increased permeability of the vessels induced by insult noted in patients suffering from vascular dementia likely contributes to the cognitive impairment. On the other hand, blood-borne substances can enter extracellular spaces of the brain via endothelial cells at specific sites without the BBB, and can move to brain parenchyma, such as the hippocampus and periventricular areas, adjacent to specific sites, indicating the contribution of increased permeability of vessels in the specific sites to brain function. It is necessary to consider influx and efflux of interstitial fluid (ISF) and cerebrospinal fluid (CSF) in considering effects of brain transfer of intravascular substances on brain function. Two pathways of ISF and CSF are recently being established. One is the intramural peri-arterial drainage (IPAD) pathway of ISF. The other is the glymphatic system of CSF. Dysfunction of the two pathways could also contribute to brain dysfunction. We review the effects of several kinds of insult on vascular permeability and the failure of fluid clearance on the brain function.

scholarly journals Rapid eye movement sleep behaviour disorder, depression and cognitive impairment. Case study

2000 ◽  
Vol 176 (2) ◽  
pp. 189-192 ◽  
Author(s):  
Nicholas A. Clarke ◽  
Adrian J. Williams ◽  
Michael D. Kopelman
Keyword(s):  
Cognitive Impairment ◽  
Eye Movement ◽  
Rem Sleep ◽  
Neuropsychological Testing ◽  
Brain Mri ◽  
Diagnostic Category ◽  
Rapid Eye Movement ◽  
Behaviour Disorder ◽  
Sleep Behaviour ◽  
Rem Sleep Behaviour Disorder

BackgroundRapid eye movement (REM) sleep behaviour disorder is a relatively new diagnostic category. It has never before been associated with a treatable depressive condition.AimsTo repot on a 74-year-old man with a history of depression and REM sleep behaviour disorder, associated with mild cognitive impairment.MethodAssessment using brain CT, MRI, PET, electroencephalography, neuropsychological testing and nocturnal polysomnography.ResultsDepression was treated with sertraline. Sleep laboratory studies supported a diagnosis of REM sleep behaviour disorder, which was treated with clonazepam. Sleep apnoea, revealed later, was treated with nasal continuous positive airways pressure. Brain MRI showed mild atrophy, but neuropsychological testing indicated no progressive cognitive deterioration.ConclusionsThis case draws attention to REM sleep behaviour disorder and its potential interaction with depression and cognitive impairment, producing symptoms which can be mistaken for early dementia. The diagnosis of REM sleep behaviour disorder is easily missed, and it requires careful history-taking and sleep investigation in all suspected sufferers. Associated neurological, sleep and psychiatric conditions (including depression and cognitive impairment) may confound the diagnosis.

TMS follow-up study in patients with vascular cognitive impairment-no dementia

2013 ◽  
Vol 534 ◽  
pp. 155-159 ◽  
Author(s):  
Rita Bella ◽  
Raffaele Ferri ◽  
Giuseppe Lanza ◽  
Mariagiovanna Cantone ◽  
Manuela Pennisi ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Vascular Cognitive Impairment ◽  
Follow Up Study ◽  
Cognitive Impairment No Dementia

Improving screening for vascular cognitive impairment at three to six months after mild ischemic stroke and transient ischemic attack

2014 ◽  
Vol 26 (5) ◽  
pp. 787-793 ◽  
Author(s):  
YanHong Dong ◽  
Melissa Jane Slavin ◽  
Bernard Poon-Lap Chan ◽  
Narayanaswamy Venketasubramanian ◽  
Vijay Kumar Sharma ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Cognitive Impairment ◽  
Transient Ischemic Attack ◽  
Predictive Value ◽  
Characteristic Curve ◽  
Neuropsychological Testing ◽  
Vascular Cognitive Impairment ◽  
Cognitive Domain ◽  
Speed Test ◽  
Ischemic Attack

ABSTRACTBackground:The Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) were compared with and without the addition of a brief processing speed test, the symbol digit modalities test (SDMT), for vascular cognitive impairment (VCI) screening at three to six months after stroke.Methods:Patients with ischemic stroke and transient ischemic attack were assessed with MoCA and MMSE, as well as a formal neuropsychological battery three to six months after stroke. VCI was defined by impairment in any cognitive domain on neuropsychological testing. The area under the receiver operating characteristic curve (AUC) was used to compare test discriminatory ability.Results:One hundred and eighty-nine patients out of 327 (58%) had VCI, of whom 180 (95%) had vascular mild cognitive impairment (VaMCI), and nine (5%) had dementia. The overall AUCs of the MoCA and MMSE scores and performance at their respective cut-off points were equivalent in detecting VCI (AUCs: 0.87 (95% CI 0.83–0.91) vs. 0.84 (95% CI 0.80–0.88), p = 0.13; cut-offs: MoCA (≤23) vs. MMSE (≤26), sensitivity: 0.78 vs. 0.71; specificity: 0.80 vs. 0.82; positive predictive value: 0.84 vs. 0.84; negative predictive value: 0.72 vs. 0.67; and correctly classified 78.6% vs. 75.5%; p = 0.42). The AUCs of MMSE and MoCA were improved significantly by the SDMT (AUCs: MMSE+SDMT 0.90 (95% CI 0.87–0.93), p <0.001; MoCA+SDMT 0.91 (95% CI 0.88–0.94), p < 0.02).Conclusions:The MoCA and MMSE are equivalent and moderately sensitive, and can be supplemented with the SDMT to improve their accuracy in VCI screening.

scholarly journals Distinct amyloid and tau PET signatures are associated with diverging clinical and imaging trajectories in patients with amnestic syndrome of the hippocampal type

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Julien Lagarde ◽  
Pauline Olivieri ◽  
Matteo Tonietto ◽  
Philippe Gervais ◽  
Claude Comtat ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Medial Temporal Lobe ◽  
Neuropsychological Testing ◽  
Brain Mri ◽  
Similar Degree ◽  
Age Related ◽  
Amnestic Syndrome ◽  
Tau Pet ◽  
Tau Pet Imaging

AbstractWe aimed to investigate the amyloid and tau PET imaging signatures of patients with amnestic syndrome of the hippocampal type (ASHT) and study their clinical and imaging progression according to their initial PET imaging status. Thirty-six patients with a progressive ASHT and 30 controls underwent a complete neuropsychological assessment, 3 T brain MRI, [11C]-PiB and [18F]-Flortaucipir PET imaging. Subjects were clinically followed-up annually over 2 years, with a second 3 T MRI (n = 27 ASHT patients, n = 28 controls) and tau-PET (n = 20 ASHT patients) at the last visit. At baseline, in accordance with the recent biological definition of Alzheimer’s disease (AD), the AD PET signature was defined as the combination of (i) positive cortical amyloid load, and (ii) increased tau tracer binding in the entorhinal cortices and at least one of the following regions: amygdala, parahippocampal gyri, fusiform gyri. Patients who did not meet these criteria were considered to have a non-AD pathology (SNAP). Twenty-one patients were classified as AD and 15 as SNAP. We found a circumscribed tau tracer retention in the entorhinal cortices and/or amygdala in 5 amyloid-negative SNAP patients. At baseline, the SNAP patients were older and had lower ApoE ε4 allele frequency than the AD patients, but both groups did not differ regarding the neuropsychological testing and medial temporal lobe atrophy. During the 2-year follow-up, the episodic memory and language decline, as well as the temporo-parietal atrophy progression, were more pronounced in the AD sub-group, while the SNAP patients had a more pronounced progression of atrophy in the frontal lobes. Longitudinal tau tracer binding increased in AD patients but remained stable in SNAP patients. At baseline, distinct amyloid and tau PET signatures differentiated early AD and SNAP patients despite identical cognitive profiles characterized by an isolated ASHT and a similar degree of medial temporal atrophy. During the longitudinal follow-up, AD and SNAP patients diverged regarding clinical and imaging progression. Among SNAP patients, tau PET imaging could detect a tauopathy restricted to the medial temporal lobes, which was possibly explained by primary age-related tauopathy.

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