Background/Aims: The metabolic syndrome (MeSy) may be related to Alzheimer’s disease (AD). Our aims were to investigate the association of the MeSy with incident dementia in a multiethnic elderly cohort in the United States. Methods: We conducted cross-sectional and prospective analyses in 2,476 men and women aged 65 years and older and with data available on the MeSy and dementia diagnosis in Northern New York City. MeSy was defined by the National Cholesterol Education Program Adult Treatment Program III and the European Group for the Study of Insulin Resistance criteria. Dementia was diagnosed using standard criteria. Results: No association was found between MeSy and prevalent dementia. After 4.4 years of follow-up, 236 individuals of the 1,833 without prevalent dementia developed dementia. MeSy was not associated with incident dementia. Of the components of the MeSy, diabetes and hyperinsulinemia were associated with an increased risk of incident AD [hazard ratio 1.4 (95% CI 1.0–2.1), and hazard ratio 1.4 (95% CI 0.9–2.7), respectively] and dementia associated with stroke [hazard ratio 1.9 (95% CI 1.1–3.1), and hazard ratio 2.3 (95% CI 1.1–4.7), respectively]. Conclusions: The MeSy was not associated with an increased dementia risk in a multiethnic elderly cohort, but diabetes and hyperinsulinemia were. In the elderly, examining diabetes and hyperinsulinemia separately may be preferable to using the MeSy as a risk factor.
Background The pathogenesis of migraine chronification remains unclear. Functional and structural magnetic resonance imaging studies have shown impaired functional and structural alterations in the brains of patients with chronic migraine. The cerebellum and periaqueductal gray (PAG) play pivotal roles in the neural circuits of pain conduction and analgesia in migraine. However, few neurotransmitter metabolism studies of these migraine-associated regions have been performed. To explore the pathogenesis of migraine chronification, we measured gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the dentate nucleus (DN) and PAG of patients with episodic and chronic migraine and healthy subjects. Methods Using the MEGA-PRESS sequence and a 3-Tesla magnetic resonance scanner (Signa Premier; GE Healthcare, Chicago, IL, USA), we obtained DN and PAG metabolite concentrations from patients with episodic migraine (n = 25), those with chronic migraine (n = 24), and age-matched and sex-matched healthy subjects (n = 16). Patients with chronic migraine were further divided into those with (n = 12) and without (n = 12) medication overuse headache. All scans were performed at the Beijing Tiantan Hospital, Capital Medical University. Results We found that patients with chronic migraine had significantly lower levels of GABA/water (p = 0.011) and GABA/creatine (Cr) (p = 0.026) in the DN and higher levels of Glx/water (p = 0.049) in the PAG than healthy controls. In all patients with migraine, higher GABA levels in the PAG were significantly associated with poorer sleep quality (GABA/water: r = 0.515, p = 0.017, n = 21; GABA/Cr: r = 0.522, p = 0.015, n = 21). Additionally, a lower Glx/Cr ratio in the DN may be associated with more severe migraine disability (r = -0.425, p = 0.055, n = 20), and lower GABA/water (r = -0.424, p = 0.062, n = 20) and Glx/Water (r = -0.452, p = 0.045, n = 20) may be associated with poorer sleep quality. Conclusions Neurochemical levels in the DN and PAG may provide evidence of the pathological mechanisms of migraine chronification. Correlations between migraine characteristics and neurochemical levels revealed the pathological mechanisms of the relevant characteristics.
Background and objective: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the best known and the most common monogenic small vessel disease (SVD). Cognitive impairment is an inevitable feature of CADASIL. Total SVD score and global cortical atrophy (GCA) scale were found to be good predictors of poor cognitive performance in community-dwelling adults. We aimed to estimate the association between the total SVD score, GCA scale and the cognitive performance in patients with CADASIL.Methods: We enrolled 20 genetically confirmed CADASIL patients and 20 controls matched by age, gender, and years of education. All participants underwent cognitive assessments to rate the global cognition and individual domain of executive function, information processing speed, memory, language, and visuospatial function. The total SVD score and GCA scale were rated.Results: The CADASIL group performed worse than the controls on all cognition measures. Neither global cognition nor any separate domain of cognition was significantly different among patients grouped by total SVD score. Negative correlations between the GCA score and cognitive performance were observed. Approximately 40% of the variance was explained by the total GCA score in the domains of executive function, information processing speed, and language. The superficial atrophy score was associated with poor performance in most of the domains of cognition. Adding the superficial atrophy score decreased the prediction power of the deep atrophy score on cognitive impairment alone.Conclusions: The GCA score, not the total SVD score, was significantly associated with poor cognitive performance in patients with CADASIL. Adding the superficial atrophy score attenuated the prediction power of the deep atrophy score on cognitive impairment alone.
Background and purpose New daily persistent headache (NDPH) and chronic migraine (CM) are two different types of headaches that might involve vascular dysregulation. There is still a lack of clarity about altered brain perfusion in NDPH and CM. This study aimed to investigate the cerebral perfusion variances of NDPH and CM using multi-delay pseudo-continuous arterial spin-labeled magnetic resonance imaging (pCASL-MRI). Methods Fifteen patients with NDPH, 18 patients with CM, and 15 age- and sex-matched healthy controls (HCs) were included. All participants underwent 3D multi-delay pCASL-MRI to obtain cerebral perfusion data, including arrival-time-corrected cerebral blood flow (CBF) and arterial cerebral blood volume (aCBV). The automated anatomical labeling atlas 3 (AAL3) was used to parcellate 170 brain regions. The CBF and aCBV values in each brain region were compared among the three groups. Correlation analyses between cerebral perfusion parameters and clinical variables were performed. Results Compared with HC participants, patients with NDPH were found to have decreased CBF and aCBV values in multiple regions in the right hemisphere, including the right posterior orbital gyrus (OFCpost.R), right middle occipital gyrus (MOG.R), and ventral anterior nucleus of right thalamus (tVA.R), while patients with CM showed increased CBF and aCBV values presenting in the ventral lateral nucleus of left thalamus (tVL.L) and right thalamus (tVL.R) compared with HCs (all p < 0.05). In patients with NDPH, after age and sex adjustment, the increased aCBV values of IFGorb. R were positively correlated with GAD-7 scores; and the increased CBF and aCBV values of tVA.R were positively correlated with disease duration. Conclusion The multi-delay pCASL technique can detect cerebral perfusion variation in patients with NDPH and CM. The cerebral perfusion changes may suggest different variations between NDPH and CM, which might provide hemodynamic evidence of these two types of primary headaches.
Background New daily persistent headache (NPDH) is a rare primary headache that is highly disabling. The pathophysiology of NDPH is still unclear, and we aimed to reveal the underlying mechanism of NDPH through functional magnetic resonance imaging (fMRI) analysis. Methods In this cross-sectional study, thirty patients with NDPH and 30 healthy controls (HCs) were recruited. The blood oxygen level-dependent (BOLD) sequences of all participants were obtained using the GE 3.0 T system. We performed ReHo, ALFF (conventional band: 0.01–0.08 Hz, slow-5: 0.01–0.027 Hz, slow-4: 0.027–0.073 Hz) and seed-based to the whole brain functional connectivity (FC) analysis in the NDPH and HC groups. The sex difference analysis of ReHo, ALFF, and FC values was conducted in the NDPH group. We also conducted Pearson’s correlation analysis between ReHo, ALFF, FC values and clinical characteristics (pain intensity, disease duration, HIT-6, GAD-7, PHQ-9, and PSQI scores). Results Both increased ReHo (PFWE-corr = 0.012) and ALFF values (0.01–0.08 Hz, PFWE-corr = 0.009; 0.027–0.073 Hz, PFWE-corr =0.044) of the left middle occipital gyrus (MOG_L) were found in the NDPH group compared to the HC group. There was no significant difference in FC maps between the two groups. Compared to the HC group, no difference was found in ReHo (p = 0.284), ALFF (p = 0.246), and FC (p = 0.118) z scores of the MOG_L in the NDPH group. There was also no sex difference in ReHo (p = 0.288), ALFF (p = 0.859), or FC z score (p = 0.118) of the MOG_L in patients with NDPH. There was no correlation between ReHo, ALFF, FC z scores and clinical characteristics after Bonferroni correction (p < 0.05/18). Conclusions Patients with NDPH may have abnormal activation of the visual system. Abnormal visual activation may occur mainly in higher frequency band of the classical band. No sex differences in brain activity were found in patients with NDPH.
Background: The mechanism of obesity paradox in stroke is not clear. This study aimed to investigate whether uric acid (UA) contributes to obesity-stroke outcome paradox.Material and Methods: The study cohort consisted of 1,984 IS patients recruited in the ACROSS-China study. Serum UA and BMI were measured at admission. Low and high BMI groups were defined by the threshold of 24, and low and high UA by the age- and sex-specific median. Poor outcomes were defined as modified Rankin scale score ≥3 in 1 year after onset.Results: UA was significantly and positively correlated with BMI. Lower levels of UA and BMI were significantly associated with higher risk of poor outcomes. Incidence of the poor outcome was 34.5, 29.4, 27.7, and 23.5% in the BMI/UA groups of low/low, high/low, low/high and high/high, respectively, with p = 0.001 for trend. The association between low UA and poor outcome was significant in lower BMI groups (odds ratio = 1.36, p = 0.006 in quartile 1 and 1.28, p = 0.021 in quartile 2), but the odds ratios were not significant in the BMI quartile 3 and 4 groups, with p = 0.038 for trend. The adverse effect of lower UA was significant in males, but not in females, with p = 0.006 for sex difference.Conclusions: These findings suggest that low UA and low BMI have a joint effect on poor outcomes in IS patients. Across BMI categories, uric acid is differentially associated with functional outcome after stroke. This effect of low UA in the low BMI groups may be one of the mechanisms underlying the obesity-stroke paradox of the outcome in IS patients.
The white matter disease spectrum is associated with many genetic diseases, including AARS2, CADASIL, ALD, and others. In this study, to determine the novel alanyl-tRNA synthetase 2 mutation implicated in white matter disease, several families with an autosomal recessive inheritance pattern of white matter disease were analyzed by whole-exome sequencing. Variants were prioritized according to their rarity and pathogenic variants in genes already known to be associated with leukodystrophies and were confirmed by Sanger sequencing using standard protocols. We identified 5 rare variants (c.452T>C chr6:44279256 p.M151T, c.1871G>A chr6:44272054 p.W624X, c.802A>G chr6:44278128 p.M268V, c.1703-1704del chr6:-44272430-44272431 p.Q568fs, and c.179C>A chr6-44280882 p.P60H) with varying expression in 4 independent Chinese families with leukodystrophy. These single nucleotide variants (SNVs), or deletion mutations, each induced a frameshift, causing a missense mutation in alanyl-tRNA synthetase 2. These findings suggested that all mutations might contribute to the development of leukodystrophy in the examined family members. Combined with previous findings, our data confirmed that the novel mutations are located in leukodystrophy-related risk genes. We also summarized all the alanyl-tRNA synthetase 2 mutations related to the onset of leukodystrophies in adults.
Objective: To explore gamma-aminobutyric acid (GABA) and glutamate/glutamine (Glx) levels in the right thalamus of patients with episodic migraine (EM) and chronic migraine (CM) and their effects on the chronification of migraine.Background: Migraine affects approximately 1 billion people worldwide, with 2.5%-3% of people with EM progressing to CM each year. Magnetic resonance spectroscopy studies have revealed altered GABA and Glx levels in the thalamus of patients with migraine without aura, but these neurometabolic concentrations are underexplored in the thalamus of patients with CM. Methods:In this cross-sectional study, patients with EM and CM were recruited.Mescher-Garwood point resolved spectroscopy sequence was used to acquire neurotransmitter concentrations in the right thalamus of patients with EM and CM and matched healthy controls (HCs).Results: A total of 26 patients (EM, n = 11; CM, n = 15) and 16 age-and sex-matched HCs were included in the analysis. There were significantly lower GABA+/Water levels in the right thalamus of the CM group (mean ± standard deviation: 2.27 ± 0.4 [institutional units]) than that of the HC group (2.74 ± 0.4) (p = 0.026; mean difference [MD] = −0.5 [i.u.]), and lower Glx/Cr levels in the EM group (mean ± SD: 0.11 ± < 0.1) than in the HCs (0.13 ± < 0.1) and CM group (0.13 ± < 0.1) (p = 0.023, MD < −0.1, and p = 0.034, MD < −0.1, respectively). The GABA+/Glx ratio was lower in the CM group (mean ± SD: 0.38 ± 0.1) compared to the EM group (0.47 ± 0.1)
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