Interactive effect of diabetes mellitus and subclinical MRI markers of cerebrovascular disease on cognitive decline and incident dementia: a memory-clinic study.

BACKGROUND: Cognitive impairment is an increasingly recognized comorbidity of diabetes, yet the mechanisms underlying this association remain poorly understood. This knowledge gap has contributed to conflicting findings regarding the impact of diabetes on long-term cognitive outcomes in older adults. The presence of cerebrovascular disease (CeVD) may potentially modify this relationship. However, interactive effect between diabetes and subclinical MRI markers of CeVD on cognitive trajectories and incident dementia remains unexplored. METHODS: A total of 654 participants underwent brain MRI at baseline, from whom 614 with at least one follow-up were selected for longitudinal analysis. Cognitive tests were performed annually up to 5 years. CeVD markers of interest were lacunes, white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), cortical microinfarcts (CMIs), intracranial stenosis (ICS), and cortical infarcts. Blood-based Alzheimer biomarkers, including p-tau181 and p-tau181/Aß42 ratio, were used as indicators of Alzheimer pathology. RESULTS: At baseline, diabetes was associated with lower cognitive performance and higher burden of CeVD, but not p-tau181 or p-tau181/Aß42 ratio. Longitudinally, we found an interactive effect of diabetes and WMHs, rather than an independent effect of diabetes, on cognitive decline and dementia risk. Subgroup analyses showed association of diabetes with cognitive outcomes was stronger in participants with high WMHs load but non-significant in those with low WMHs load. Moreover, these associations remained unchanged after adjusting for blood-based Alzheimer biomarkers. CONCLUSIONS: The effect of diabetes on cognitive decline is contingent upon the presence of WMHs and independent of Alzheimer's pathology. This finding raises the possibility of utilizing WMHs as an imaging biomarker to identify diabetic subgroup at greater risk of developing cognitive impairment. Furthermore, therapeutic interventions targeting WMHs may prevent cognitive deterioration in older adults with diabetes.

Vascular cognitive impairment and dementia: Mechanisms, treatment, and future directions.

Worldwide, around 50 million people live with dementia, and this number is projected to triple by 2050. It has been estimated that 20% of all dementia cases have a predominant cerebrovascular pathology, while perhaps another 20% of vascular diseases contribute to a mixed dementia picture. Therefore, the vascular contribution to dementia affects 20 million people currently and will increase markedly in the next few decades, particularly in lower- and middle-income countries.In this review, we discuss the mechanisms of vascular cognitive impairment (VCI) and review management. VCI refers to the spectrum of cerebrovascular pathologies that contribute to any degree of cognitive impairment, ranging from subjective cognitive decline, to mild cognitive impairment, to dementia. While acute cognitive decline occurring soon after a stroke is the most recognized form of VCI, chronic cerebrovascular disease, in particular cerebral small-vessel disease, can cause insidious cognitive decline in the absence of stroke. Moreover, cerebrovascular disease not only commonly co-occurs with Alzheimer's disease (AD) and increases the probability that AD pathology will result in clinical dementia, but may also contribute etiologically to the development of AD pathologies.Despite its enormous health and economic impact, VCI has been a neglected research area, with few adequately powered trials of therapies, resulting in few proven treatments. Current management of VCI emphasizes prevention and treatment of stroke and vascular risk factors, with most evidence for intensive hypertension control. Reperfusion therapies in acute stroke may attenuate the risk of VCI. Associated behavioral symptoms such as apathy and poststroke emotionalism are common. We also highlight novel treatment strategies that will hopefully lead to new disease course-modifying therapies. Finally, we highlight the importance of including cognitive endpoints in large cardiovascular prevention trials and the need for an increased research focus and funding for this important area.

Risk stratification for cardiovascular disease based on prior coronary artery disease, cerebrovascular disease and type 2 diabetes mellitus.

AIMS/INTRODUCTION: History of coronary artery disease (CAD), cerebrovascular disease (CeVD), type 2 diabetes and their combined effect on cardiovascular disease are essential for cardiovascular risk management. We investigated the association of prior CAD, prior CeVD, type 2 diabetes and their combination with the risk of cardiovascular disease. MATERIALS AND METHODS: This is a historical cohort study including 342,033 participants (aged 18-72 years) followed up for ≥5 years between 2008 and 2016. Participants were classified into eight groups (with or without prior CAD, prior CeVD and type 2 diabetes). Type 2 Diabetes was defined by fasting plasma glucose and glycated hemoglobin levels, and antidiabetic drug prescription. Prior and subsequent CAD and CeVD were identified according to claims using International Classification of Diseases 10th Revision codes, medical procedures and questionnaires. Cox regression models were used to evaluate the risk of cardiovascular events. RESULTS: The median follow-up period was 6.4 years. The incidence of composite cardiovascular events of CAD and CeVD in the CAD-/CeVD-, CAD+/CeVD-, CAD-/CeVD+ and CAD+/CeVD+ groups were 1.92 and 6.94, 25.14 and 31.98 per 1,000 person-years in non-diabetes participants, and 8.66, 18.04, 39.98 and 60.72 in type 2 diabetes patients, respectively. Hazard ratios of cardiovascular events compared with CAD-/CeVD-/non-diabetes were 1.66 (95% confidence interval 1.55-1.78) in CAD-/CeVD-/type 2 diabetes and 1.84 (1.56-2.18) in CAD+/CeVD-/non-diabetes. CeVD+ was linked to a 4-7-fold increase in the risk of cardiovascular events regardless of CAD+ or type 2 diabetes. CONCLUSIONS: Type 2 diabetes increased the risk of cardiovascular disease as high as a history of CAD, whereas prior CeVD alone increased the risk of future CeVD without additional effects by type 2 diabetes.

Sarcopenia and cognitive impairment in older adults: Long-term prognostic implications based on the National Health and Nutrition Examination Survey (2011-2014).

AIMS: The relationship between sarcopenia and cognitive impairment in older adults remains contentious. This study investigates this association and examines the long-term prognosis for individuals with both conditions. METHODS: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2014, this study focuses on the correlation between sarcopenia and cognitive impairment, as well as the extended prognosis for individuals managing these conditions. RESULTS: The study cohort comprised 2890 participants, with 648 (22.4 %) diagnosed with sarcopenia. Multivariable logistic regression analysis identified a significant association between sarcopenia and an increased risk of cognitive impairment (adjusted odds ratio [aOR]: 1.68, 95 % confidence interval [CI]: 1.30-2.17). Over a median follow-up period of 48 months, 200 individuals (6.9 %) succumbed to cardiovascular and cerebrovascular diseases (CCVDs), including hypertension, congestive heart failure, coronary artery disease, and stroke, as well as Alzheimer's disease (AD). Participants had comorbid conditions such as CCVDs and diabetes mellitus. Kaplan-Meier survival analysis and the Cox proportional hazards model indicated that individuals with both sarcopenia and cognitive impairment had the highest mortality risk from CCVDs and AD (adjusted hazard ratio [aHR]: 2.73, 95 % CI: 1.48-5.02). Individuals with sarcopenia and comorbidities exhibited a higher mortality risk from CCVDs or AD compared to those without sarcopenia but with comorbidities (aHR: 2.71, 95 % CI: 1.37-5.37). CONCLUSION: Sarcopenia is independently associated with cognitive impairment. Older adults with both sarcopenia and cognitive impairment or concurrent comorbidities face increased mortality risks from CCVDs or AD compared to their healthy counterparts.

[Validity and reliability of the Tardieu scale for assessing upper limb spasticity in adults with cerebrovascular disease. Systematic review]. / Validez y fiabilidad de la escala de Tardieu para evaluar la espasticidad en miembro superior en adultos con enfermedad cerebrovascular. Revisión sistemática.

INTRODUCTION: The increase in the number of people with upper limb spasticity as a sequela of cerebrovascular disease, which negatively impacts their autonomy, functional independence and participation, and affects their quality of life, calls for the application of precise and objective instruments for its measurement and evaluation. OBJECTIVE: To assess the validity and reliability of the Tardieu scale in the evaluation of upper extremity spasticity in adults with cerebrovascular disease. MATERIALS AND METHODS: The search strategy was implemented in eight databases; the systematic review protocol was registered beforehand in INPLASY (with registration no. 2023110076). The evidence was synthesised in three phases: a tabular presentation of results, an evaluation of the quality of the articles, and a narrative synthesis of the findings. RESULTS: Only three of the 33 articles identified fulfilled the variables that enable the validity and reliability of the Tardieu scale to be established. The measurements of angles and velocities R1, R2 and R2-R1 were analysed. Student's t-test to assess the reliability between the measurements of R1 and R2; and angles R2 and R2-R1 showed statistical significance, which confirmed the reliability of the scale. CONCLUSIONS: The Tardieu scale proved robust. It is important to note that the sample size, the time of evolution of the disease and the age of the patients may influence the results of the scale.

TITLE: Validez y fiabilidad de la escala de Tardieu para evaluar la espasticidad en miembro superior en adultos con enfermedad cerebrovascular. Revisión sistemática.Introducción. El incremento en el número de personas con espasticidad en los miembros superiores como secuela de una enfermedad cerebrovascular, que impacta negativamente en la autonomía, la independencia funcional y la participación, y afecta a la calidad de vida de las personas, demanda la aplicación de herramientas clínicas precisas y objetivas para su medición y evaluación. Objetivo. Evaluar la validez y la fiabilidad de la escala de Tardieu en la evaluación de la espasticidad en las extremidades superiores de adultos con enfermedad cerebrovascular. Materiales y métodos. La estrategia de búsqueda se implementó en ocho bases de datos; el protocolo de revisión sistemática se registró previamente en INPLASY (registro n.o 2023110076). La síntesis de la evidencia se llevó a cabo en tres fases: presentación tabular de resultados, evaluación de la calidad de los artículos y síntesis narrativa de los hallazgos. Resultados. De los 33 artículos identificados, sólo tres cumplieron con las variables que permiten establecer la validez y la fiabilidad de la escala de Tardieu. Se analizaron las medidas de los ángulos y velocidades R1, R2 y R2-R1. La prueba de la t de Student para evaluar la fiabilidad entre las medidas de R1 y R2; los ángulos R2 y R2-R1 mostraron significancia estadística, lo que confirmó la confiabilidad de la escala. Conclusiones. La escala de Tardieu demostró robustez. Es importante considerar que el tamaño de la muestra, el tiempo de evolución de la enfermedad y la edad de los pacientes pueden influir en los resultados de la escala.

A cohort study of the effects of social support on cerebral cardiovascular disease in subjects with metabolic syndrome.

INTRODUCTION: Previous studies have extensively examined the relationship between social support and various health outcomes. However, little is known about the distinct longitudinal associations between perceived social support and the development of cardiovascular events in patients with metabolic syndrome. In this cohort study, we investigated whether the levels of perceived social support in patients with metabolic syndrome were associated with an increased risk of cerebrovascular and cardiovascular events. METHODS: The level of social support was assessed using the Medical Outcomes Study-Social Support Survey (MOS-SSS) in 2,721 individuals living in Wonju and Pyeongchang, South Korea. The presence of metabolic syndrome was determined by physical measurements and blood tests, and the occurrence of cerebral cardiovascular disease in relation to the presence of metabolic syndrome and the level of social support was analyzed using Cox proportional-hazards models. RESULTS: The median follow-up period was 2,345 days (2,192-2,618). Overall, in the group with metabolic syndrome and low social support, low social support was associated with an increased risk of later cerebral cardiovascular events; in this group, the hazard ratio after adjusting for confounding variables was 1.97 times (95% confidence interval, 1.01-3.85) higher than that in the group without metabolic syndrome and low social support. CONCLUSION: This study shows, for the first time, that the level of social support is a risk factor for preventing cerebral cardiovascular disease in patients with metabolic syndrome and suggests that social support status should be incorporated into multifactorial risk assessment and intervention procedures to prevent metabolic syndrome and cerebral cardiovascular disease.

Triglyceride-glucose index as a potential predictor of major adverse cardiovascular and cerebrovascular events in patients with coronary heart disease complicated with depression.

Background: Triglyceride-glucose (TyG) index is a surrogate marker of insulin resistance and metabolic abnormalities, which is closely related to the prognosis of a variety of diseases. Patients with both CHD and depression have a higher risk of major adverse cardiovascular and cerebrovascular events (MACCE) and worse outcome. TyG index may be able to predict the adverse prognosis of this special population. Methods: The retrospective cohort study involved 596 patients with both CHD and depression between June 2013 and December 2023. The primary outcome endpoint was the occurrence of MACCE, including all-cause death, stroke, MI and emergent coronary revascularization. The receiver operating characteristic (ROC) curve, Cox regression analysis, Kaplan-Meier survival analysis, and restricted cubic spline (RCS) analysis were used to assess the correlation between TyG index and MACCE risk of in patients with CHD complicated with depression. Results: With a median follow-up of 31 (15-62) months, MACCE occurred in 281(47.15%) patients. The area under the ROC curve of TyG index predicting the risk of MACCE was 0.765(0.726-0.804) (P<0.01). Patients in the high TyG index group(69.73%) had a significantly higher risk of developing MACCE than those in the low TyG index group(23.63%) (P<0.01). The multifactorial RCS model showed a nonlinear correlation (nonlinear P<0.01, overall P<0.01), with a critical value of 8.80 for the TyG index to predict the occurrence of MACCE. The TyG index was able to further improve the predictive accuracy of MACCE. Conclusions: TyG index is a potential predictor of the risk of MACCE in patients with CHD complicated with depression.

Characteristics and treatment of midlife-onset epilepsy: A 24-year single-center, retrospective study.

OBJECTIVE: This study aimed to analyze the clinical characteristics, etiology, and treatment of midlife-onset epilepsy in a real-world setting at a single center in China. METHODS: The clinical data of patients who attended the epilepsy clinic of the Department of Neurology, First Medical Center of Chinese PLA General Hospital from February 1999 to March 2023 were retrospectively analyzed. The clinical characteristics, etiology, and risk factors for midlife-onset epilepsy over the past 24 years were analyzed. RESULTS: Of the 969 patients with onset at 45-64 years of age, 914 were diagnosed with epilepsy with at least two unprovoked seizures 24 h apart. Of those, 99.7% (911) were of focal origin. The median duration from the initial seizure to follow-up treatment was 2 months (interquartile range [IQR]: 1.0-6.0 months). Before commencing treatment, 30.2% (207/683) of patients experienced more than two seizures. A structural etiology was found in 66.3% (606/914) of patients. Cerebrovascular disease (CVD) and traumatic brain injury (TBI) accounted for 19.9% (182/914) and 16.6% (152/914) of the cases, respectively. Logistic regression analysis showed that patients with abnormal imaging (odds ratio [OR] 2.04; 95% confidence interval [CI] 1.25-3.32; p = .004), focal seizures (OR 2.98; 95%CI 1.82-4.87; p < .001), and seizure clusters (OR 2.40; 95%CI 1.21-4.73; p = .01) had poor drug responses. Treatment outcomes were generally better in patients with epilepsy after CVD (OR .49; 95%CI .28-.85; p = .01). Treatment initiation after two seizures (OR .70; 95%CI .42-1.15; p = .16) or 6 months after the first seizure (OR 1.17; 95%CI .66-2.09; p = .58) did not result in poor drug effectiveness. SIGNIFICANCE: Midlife-onset epilepsy is typically of focal etiology, with CVD being the most common cause, and tends to respond well to medication. The median duration from the initial seizure to follow-up treatment was 2 months. Over 30% of patients experienced more than two seizures before commencing treatment, but this did not affect subsequent outcomes.

[A role of cerebrovascular diseases in the progression of multiple sclerosis]. / Rol' tserebrovaskulyarnykh zabolevanii v progressirovanii rasseyannogo skleroza.

OBJECTIVE: To identify the association between cerebrovascular diseases (CVD) and multiple sclerosis (MS) among patients over 50 years old in two independent populations of Moscow and Tyumen. MATERIAL AND METHODS: The study included 94 patients with MS in combination with CVD (main group) and 90 age-and sex-matched patients with MS without a vascular history (comparison group). An analysis of parameters such as disease duration, EDSS at different time points, disease progression index, duration of first remission in each population separately and in both populations together was carried out. RESULTS: The presence of CVD in patients with MS was associated with the presence of other diseases that are associated with an increased risk of developing cerebrovascular pathology. In the main group, there was a statistically significant decrease in the duration of the first remission and an increase in the disease progression index. In addition, other diseases and syndromes were identified in the main group that, in combination with CVD in patients with MS, could lead to a worsening of the course of MS. These included arterial hypertension, diabetes mellitus, obesity, dyslipidemia, chronic venous insufficiency, and regular use of proton pump inhibitors. CONCLUSION: Comorbid vascular pathology can affect the severity of MS from the very beginning of the disease. It can lead to a shorter duration of the first remission and a higher disease progression index, increasing the degree of disability. The combination of autoimmune-inflammatory, demyelinating, and vascular processes can worsen the prognosis for MS.

[Cognitive impairment in cerebrovascular diseases]. / Kognitivnye narusheniya pri sosudistykh zabolevaniyakh golovnogo mozga.

Cognitive impairment, which is highly prevalent, especially among older people, leads to a decrease in the quality of life of patients, impairment of daily activities, and an increased risk of dementia and mortality. Currently, much attention is paid to mild cognitive impairment. The article discusses diagnostic criteria and possible clinical variants of this syndrome. Given the high rate of progression of mild cognitive impairment to dementia, it is necessary to identify risk groups and carry out therapeutic preventive measures. Correction of potentially modifiable risk factors is considered as a promising direction of therapy. Sufficient physical and mental activity, proper diet, normalization of sleep, visual acuity and hearing are necessary. Preventing stroke and controlling vascular risk factors may reduce the risk of mild cognitive impairment progressing to dementia.

Epidemiology and Comorbidities of Vestibular Disorders: Preliminary Findings of the AVOCADO Study.

INTRODUCTION: Studies on incidence and prevalence of vestibular disorders tend to focus on small pockets of patients recruited from specialized clinics and often exclude measures of vestibular function. The objectives of the study were to characterize patients with common vestibular disorders, estimate the prevalence of common vestibular disorders, and ascertain whether patients with vestibular disorders experience increased risks of falls and morbidity. MATERIALS AND METHODS: This retrospective cohort study includes both inpatient and outpatient routine clinical care data culled from a nationally representative, population-based sample. Patients were included if their record in the TriNetX Diamond Cohort comprised at least one vestibular function test or vestibular diagnosis. The main outcome measures were diagnosis with a vestibular disorder, a fall, or a common medical comorbidity (e.g., diabetes, cerebrovascular disease). RESULTS: The cohort includes n = 4,575,724 patients, of which 55% (n = 2,497,136) had a minimum of one vestibular diagnosis. Patients with vestibular diagnoses were 61.3 ± 16.6 years old (mean ± standard deviation), 67% women, 28% White race (69% unknown race), and 30% of non-Hispanic or Latino ethnicity (66% unknown ethnicity). The prevalence of vestibular disorders was estimated at 2.98% (95% confidence interval [CI]: 2.98-2.98%). Patients with vestibular diagnoses experienced a significantly greater odds of falls (odds ratio [OR] = 1.04; 95% CI: 1.02-1.05), cerebrovascular disease (OR = 1.42; 95% CI: 1.40-1.43), ischemic heart disease (OR = 1.17; 95% CI: 1.16-1.19), and diabetes (OR = 1.14; 95% CI: 1.13-1.15), among others. DISCUSSION: Vestibular disorders affect an estimated 3% of the U.S. population, after weighting. Patients with these disorders are at greater risk for many common, consequential medical conditions.

[Impairment of attention and executive functions in chronic cerebrovascular disease and Alzheimer's disease]. / Narushenie vnimaniya i upravlyayushchikh funktsii pri sosudistykh kognitivnykh narusheniyakh i bolezni Al'tsgeimera.

OBJECTIVE: To establish specific features of executive functions (EF) impairment and attention in vascular cognitive impairment (VCI) and Alzheimer's disease (AD). MATERIAL AND METHODS: Eighty people (over the age of 50) diagnosed with cerebrovascular disease (CVD) and AD, as well as 29 healthy volunteers (control group), were examined. The following neuropsychological methods were used to study the quantitative and qualitative characteristics of cognitive impairments: Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), EXIT-25, Frontal Assessment Battery (FAB), Clock Drawing Test, «12 Words¼ test, verbal associations (literal and categorical) method, Trail Making Test A and B, Symbol-Digit Modalities Test (SDMT), Stroop Test, and Benton Visual Retention Test. Mandatory inclusion criteria in the study included having a completed magnetic resonance imaging (MRI) of the brain (in T1, T2, FLAIR, DWI, SWI modes) within 1 year before enrollment in one of the groups. RESULTS: No significant differences in age, sex, and level of education were found between the groups. Groups AD and CVD were also comparable in the severity of cognitive impairment overall. Attention and working memory deficits were observed in both CVD and AD, with slightly more pronounced deficits in the AD group. Qualitative analysis of individual components of working memory revealed that both CVD and AD groups had comparable cognitive control impairment compared to the control group, while AD was characterized by a more significant decrease in intellectual flexibility compared to CVD. Sustained attention was equally impaired among patients in the CVD and AD groups, with a significant difference from the control group (p<0.05). In terms of memory, it was found that auditory-verbal memory and semantic memory were significantly more affected in AD, while visual memory was impaired in both conditions. CONCLUSION: Attention and EF impairments are not specific to the «subcortical¼ type of cognitive disorders. Already in the early stages, AD is characterized by a significant impairment of attention and EF, and such a component of EF as intellectual flexibility suffers at the onset of AD to a greater extent than in VCI. Memory impairments are not specific to AD; already at the onset of VCI, visual memory impairment comparable to AD is noted. The obtained data can be used for early neuropsychological diagnosis and differential diagnosis of dementing cerebral diseases.

Developmental priming of early cerebrovascular ageing: Implications across a lifetime.

INTRODUCTION: Neurological conditions such as Alzheimer's disease and stroke represent a substantial health burden to the world's ageing population. Cerebrovascular dysfunction is a key contributor to these conditions, affecting an individual's risk profile, age of onset, and severity of neurological disease. Recent data shows that early-life events, such as maternal health during pregnancy, birth weight and exposure to environmental toxins can 'prime' the vascular system for later changes. With age, blood vessels can become less flexible and more prone to damage. This can lead to reduced blood flow to the brain, which is associated with cognitive decline and an increased risk of stroke and other cerebrovascular diseases. These in turn increase the risk of vascular dementia and Alzheimer's disease. OBJECTIVES: We aim to explore how early life factors influence cerebrovascular health, ageing and disease. METHODS: We have reviewed recently published literature from epidemiological studies, clinical cases and basic research which explore mechanisms that contribute to cerebrovascular and blood-brain barrier dysfunction, with a particularly focus on those that assess contribution of early-life events or vascular priming to subsequent injury. RESULTS: Perinatal events have been linked to acute cerebrovascular dysfunction and long-term structural reorganisation. Systemic disease throughout the lifetime that produce inflammatory or oxidative stress may further sensitise the cerebrovasculature to disease and contribute to neurodegeneration. CONCLUSIONS: By identifying these early-life determinants and understanding their mechanisms, scientists aim to develop strategies for preventing or mitigating cerebrovascular ageing-related issues.

Headache due to Vascular Disorders.

Headache and cerebrovascular disease (CVD) are inextricably linked. Although in some cases headache complicating CVD may be little more than a symptomatic afterthought, in other cases, early recognition of headache's role in the CVD process is critical to effective management. In other words, headaches secondary to CVD span a spectrum, and in this article, we will review that spectrum.

Accelerated decline in motor suppression in patients with cerebrovascular disorders: A kinetic analysis using the square-tracing task.

BACKGROUND: Patients with cerebrovascular disorders (CVDs) tend to exhibit impulsive behaviour without controlling their movements, leading to difficulty in performing activities of daily living and an increased risk of accidents. This hastiness, termed 'pacing impairment', has been studied but is not fully understood. OBJECTIVE: To experimentally examine the kinetic features of pacing impairment by focusing on changes in speed and investigating neuropsychological substrates. METHODS: We instructed 53 inpatients with CVDs, 20 orthopaedic inpatients, and 20 healthy participants to trace a 200 mm-sided square as slowly as possible for 120 seconds. We measured the tracing length and mean acceleration and examined the relationship between these measurements, neuropsychological symptoms, and lesion sites. RESULTS: Gradual acceleration in drawing, i.e., decline in motor suppression, was observed more frequently in the CVD group than in the control groups. Excessive acceleration was associated with unilateral spatial neglect, frontal lobe signs, and attention disorders but not with motor impersistence. Additionally, the incidence of excessive acceleration did not differ between left and right hemisphere lesion subgroups and was not associated with any specific lesion site. CONCLUSION: Pacing impairment can manifest as general or holistic deficits in attentional function widely distributed throughout the cerebral hemispheres.

Amyloid ß oligomer induces cerebral vasculopathy via pericyte-mediated endothelial dysfunction.

BACKGROUND: Although abnormal accumulation of amyloid beta (Aß) protein is thought to be the main cause of Alzheimer's disease (AD), emerging evidence suggests a pivotal vascular contribution to AD. Aberrant amyloid ß induces neurovascular dysfunction, leading to changes in the morphology and function of the microvasculature. However, little is known about the underlying mechanisms between Aß deposition and vascular injuries. Recent studies have revealed that pericytes play a substantial role in the vasculopathy of AD. Additional research is imperative to attain a more comprehensive understanding. METHODS: Two-photon microscopy and laser speckle imaging were used to examine cerebrovascular dysfunction. Aß oligomer stereotactic injection model was established to explain the relationship between Aß and vasculopathy. Immunofluorescence staining, western blot, and real-time PCR were applied to detect the morphological and molecular alternations of pericytes. Primary cultured pericytes and bEnd.3 cells were employed to explore the underlying mechanisms. RESULTS: Vasculopathy including BBB damage, hypoperfusion, and low vessel density were found in the cortex of 8 to 10-month-old 5xFAD mice. A similar phenomenon accompanied by pericyte degeneration appeared in an Aß-injected model, suggesting a direct relationship between Aß and vascular dysfunction. Pericytes showed impaired features including low PDGFRß expression and increased pro-inflammatory chemokines secretion under the administration of Aß in vitro, of which supernatant cultured with bEND.3 cells led to significant endothelial dysfunction characterized by TJ protein deficiency. CONCLUSIONS: Our results provide new insights into the pathogenic mechanism underlying Aß-induced vasculopathy. Targeting pericyte therapies are promising to ameliorate vascular dysfunction in AD.