Association of Age-Related Spontaneous Internal Jugular Vein Reflux with Cognitive Impairment and Incident Dementia.

BACKGROUND: It remains unclear whether changes in the venous circulation contribute to cognitive decline. OBJECTIVE: This study aimed to clarify whether the spontaneous jugular vein reflux (JVR) is associated with cognitive impairment and incident dementia. METHODS: Patients with any evidence of cerebral vessel disease on magnetic resonance imaging (MRI) were consecutively enrolled between October 2015 to July 2019. We employed carotid duplex sonography to measure the internal jugular vein (IJV). The subjects were classified into two groups based on the degree of JVR on either side: none, mild (JVR(-) group) and moderate, severe (JVR (+) group) JVR. They underwent both the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment-Japanese (MoCA-J) global tests. Their cognitive status was prospectively assessed until March 2023. RESULTS: 302 patients with an MMSE score ≥24 underwent duplex sonography of the IJV. Among them, 91 had spontaneous JVR on either side. Both MMSE and MoCA-J were significantly lower in patients with JVR (+) group than in the JVR (-) group. After the adjustment for risk factors and MRI findings, intergroup differences in MoCA-J remained significant. Among the cognitive subdomains, median executive function and memory scores were significantly lower in the JVR (+) group than in the JVR (-) group. During the median 5.2-year follow-up, 11 patients with incident dementia were diagnosed. Patients with severe JVR were significantly more likely to be diagnosed with dementia (log-rank test, p = 0.031). CONCLUSIONS: Spontaneous IJV reflux especially severe JVR, was associated with global cognitive function, and potentially with incident dementia.

Association between total cerebral small vessel disease score and cognitive function in patients with vascular risk factors.

Hypertension is the most important risk factor for cerebral small vessel disease (SVD). In this cross-sectional study, we tested the independent association of cerebral SVD burden with global cognitive function and each cognitive domain in patients with vascular risk factors. The Tokyo Women's Medical University Cerebral Vessel Disease (TWMU CVD) registry is an ongoing prospective, observational registry in which patients with any evidence of CVD in magnetic resonance imaging (MRI) and at least one vascular risk factor were consecutively enrolled. For SVD-related findings, we evaluated white matter hyperintensity, lacunar infarction, cerebral microbleeds, enlarged perivascular space, and medial temporal atrophy. We used the total SVD score as the SVD burden. They underwent the Mini-mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) global cognitive tests, and each cognitive domain was evaluated. After excluding patients without MRI T2* images and those with MMSE score <24, we analyzed 648 patients. The total SVD score was significantly associated with MMSE and MoCA-J scores. After adjustment for age, sex, education, risk factors, and medial temporal atrophy, the association between the total SVD score and MoCA-J score remained significant. The total SVD score was independently associated with attention. In conclusion, the total SVD score, cerebral SVD burden, was independently association with global cognitive function and attention. A strategy to reduce SVD burden will have the potential to prevent cognitive decline. A total of 648 patients with any evidence of cerebral small vessel disease (SVD) in MRI and at least one vascular risk factor underwent Mini-mental State Examination (MMSE) and Japanese version of the Montreal Cognitive Assessment (MoCA-J) global cognitive tests. The total SVD scores count the presence of each SVD-related findings (white matter hyperintensity, Lacunar infarction, cerebral microbleeds and enlarged perivascular space), ranging from 0 to 4, as the SVD burden. Total SVD scores were significantly associated with MoCA-J scores (r = -0.203, P < 0.001). After adjustment for age, sex, education, risk factors, and medial temporal atrophy, the association between the total SVD score and global cognitive scores remained significant.

Neuropsychological Profile of Early Cognitive Impairment in Cerebral Small Vessel Disease.

INTRODUCTION: The neuropsychological feature of vascular mild cognitive impairment is a deficit of the frontal-subcortical circuit; however, the features in the early stage are not consistent. In the present study, we aimed to investigate the neuropsychological features of the very early stage of cognitive impairment with cerebral small vessel disease (CSVD) and to elucidate the cognitive differences among CSVD subtypes. METHODS: A comprehensive neuropsychological test battery was applied to nondemented subjects scoring below the cutoff point 26 of the Japanese version of the Montreal Cognitive Assessment. After factor analysis was conducted to identify covert cognitive factors in the battery, correlation analyses were performed between the factors and CSVD subtypes: white matter hyperintensity (WMH), lacunar infarcts (LIs), cerebral microbleeds (CMBs), perivascular spaces, and cortical atrophy. RESULTS: Among the 465 recruited patients, 139 underwent a full neuropsychological test battery. Through factor analysis, the following three factors were extracted: executive function, memory, and attention. Of the CSVD features, total WMH was correlated with executive function and memory, whereas deep WMH was correlated with memory alone. Of the CSVD subtypes, LIs and CMBs were correlated only with executive function. Frontal and posterior atrophy were correlated with memory and attention, whereas medial temporal atrophy was correlated with memory alone. CONCLUSIONS: Executive dysfunction accompanied by subtle impairment of memory and processing speed was the main feature of neuropsychological profiles in the subjects with CSVD, even in the very early stage. Furthermore, each CSVD feature and focal cerebral atrophy are associated with cognitive impairment.

Prolonged central motor conduction time and pyramidal tract degeneration in amyotrophic lateral sclerosis.

Electrophysiological methods to detect the degeneration of the upper motor neuron system have not been fully established in patients with amyotrophic lateral sclerosis (ALS). This may be partly because the parallel demonstration of electrophysiology and a corresponding pathological abnormality is insufficient, and because a substantial number of patients with ALS do not exhibit upper motor neuron degeneration. Recently, we encountered 2 patients with ALS who had been examined for abnormal central motor conduction time (CMCT) using transcranial magnetic stimulation within a 20-day period prior to their death. Autopsy revealed that 1 patient had marked pyramidal degeneration with prolonged CMCT; in contrast, the other patient had no obvious pyramidal degeneration and showed normal CMCT. Both the patients with contrasting clinicopathological differences contributed to the identification that the prolongation of CMCT was possibly linked to the degeneration of the corticospinal tract. This report indicates that CMCT is useful for predicting the severity of upper motor neuron degeneration in patients with ALS.

Effects of Pemafibrate in Patients with Stroke and Hypertriglyceridemia: Baseline Cerebral Artery Diseases and 3-Month Laboratory Outcomes.

AIMS: The role of hypertriglyceridemia in stroke is poorly understood. The Pemafibrate for Prevention of Atherosclerotic Diseases in Stroke (PPAR Stroke) study was designed to assess the effects of a novel selective peroxisome proliferator-activated receptor alpha modulator, pemafibrate, on vascular outcomes in stroke patients with hypertriglyceridemia. METHODS: This was a prospective single-arm study including 74 patients (mean age, 64.1 years; male 75.7%) with stroke and hypertriglyceridemia (defined as fasting serum triglycerides levels of ≥ 150 mg/dL) who were treated with pemafibrate at 0.2 mg or 0.1 mg/day. The present report assessed the association of hypertriglyceridemia with cerebral large and small vessel diseases at baseline and changes in laboratory parameters after a three-month pemafibrate therapy. RESULTS: Patients with triglycerides levels of ≥ 227 mg/dL (higher than the median) more often presented with intracranial artery atherosclerotic stenosis than those with triglycerides levels of 150-227 mg/dL (44.4% vs. 21.6%, p=0.037). On the other hand, no differences were found in the prevalence of extracranial artery atherosclerosis and cerebral small vessel diseases. Mean triglycerides levels were significantly reduced from 285 mg/dL at baseline to 175 mg/dL at 3 months (p＜0.001). High-density lipoprotein cholesterol levels increased from 48 mg/dL to 53 mg/dL (p＜0.001). In addition, significant reductions in alanine aminotransferase, γ-glutamyl transpeptidase, and interleukin-6 levels were observed (p＜0.001, p=0.002, and p=0.044, respectively). CONCLUSIONS: Higher triglycerides levels are associated with intracranial artery atherosclerosis. Pemafibrate showed pleiotropic effects not only in ameliorating atherogenic dyslipidemia but also in the reduction of the levels of inflammatory markers and hepatobiliary enzymes.

Recurrent Stroke Incidence and Etiology in Patients with Embolic Stroke of Undetermined Source and Other Stroke Subtypes.

AIMS: This study aimed at clarifying the incidence of recurrent stroke and its etiology in patients with embolic stroke of undetermined source (ESUS) and other stroke subtypes in both the acute and chronic periods. METHODS: A total of 645 patients who were admitted with acute ischemic stroke (IS) between March 2015 and August 2019 were enrolled. Among them, 511 patients with ESUS, cardioembolism (CE), large artery atherosclerosis (LAA), or small vessel disease (SVD) were analyzed in this study. After discharge, 391 patients who visited the outpatient clinic were followed up until August 2020. The outcome was stroke recurrence. RESULTS: In the acute admission, recurrence rates were 7.6%, 8.1%, 18.8%, and 2.2% in patients with ESUS, CE, LAA, and SVD, respectively, and there were significant differences between the groups. The subtype of recurrence was almost identical to that of the index stroke. In the outpatient clinic, the annual recurrence rates were 4.4%, 4.3%, 6.0%, and 2.9% in ESUS, CE, LAA, and SVD, respectively, and no difference was observed. Subtypes of recurrence in outpatients with ESUS included ESUS, intracerebral hemorrhage (ICH), and SVD. Patients with ESUS and SVD had a higher risk of ICH during follow-up. CONCLUSIONS: Although the risk of recurrence was comparable between patients with ESUS and CE and intermediate between patients with LAA and SVD, in the acute admission unit, the risk in outpatients was similar among all subtypes. ESUS was the most recurrent stroke subtype in outpatients with ESUS. The risk of hemorrhagic stroke was significant in patients with SVD and ESUS.

[MRI arterial spin labeling is useful for diagnosing recovery from nonconvulsive status epilepticus with sustained periodic discharges].

A 75-year-old man with a history of temporal lobe epilepsy (treated with levetiracetam) was transferred to our hospital because of loss of consciousness. At admission, he was drowsy and exhibited myoclonus on the left side of face. We established a diagnosis of status epilepticus and started treatment with levetiracetam, fosphenytoin, and midazolam. FLAIR and DWI showed hyperintensity in the right cerebral cortex. Electroencephalography (EEG) showed lateralized periodic discharges (LPDs) at the right hemisphere, indicative of non-convulsive status epilepticus (NCSE). He regained consciousness after treatment with anti-epileptic drugs but showed persistent LPDs in EEG. MRI arterial spin labeling (ASL) showed normal perfusion in the right hemisphere; therefore, he was deemed to have recovered from status epilepticus and transferred to the rehabilitation hospital. MRI ASL is useful for diagnosing recovery from NCSE irrespective of sustained periodic discharges on EEG.