Impact of Increased Hemoglobin on Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Studies of the impact of increased hemoglobin on spontaneous intracerebral hemorrhage (ICH) are limited. The present study aimed to explore the effect of increased hemoglobin on ICH. METHODS: A retrospective single-center study using medical records from a database processed by univariate and multivariate analyses was performed in the People's Hospital of Tibet Autonomous Region in Lhasa, Tibet, China. RESULTS: The mean hemoglobin level in 211 patients with ICH was 165.03 ± 34.12 g/l, and a median hematoma volume was 18.5 ml. Eighty-eight (41.7%) patients had large hematomas (supratentorial hematoma ≥ 30 ml; infratentorial hematoma ≥ 10 ml). No differences in ICH risk factors between the groups with different hemoglobin levels were detected. Increased hemoglobin was independently associated with large hematomas [odds ratio (OR) 1.013, P = 0.023]. Increased hemoglobin was independently associated with ICH with subarachnoid hemorrhage (OR 1.014, P = 0.016), which was more pronounced in men (OR 1.027, P = 0.002). Increased hemoglobin was independently associated with basal ganglia hemorrhage and lobar hemorrhage in men (OR 0.986, P = 0.022; OR 1.013, P = 0.044, respectively) but not in women (P > 0.1). CONCLUSIONS: Increased hemoglobin was independently associated with large hemorrhage volume. Increased hemoglobin was independently associated with lobar hemorrhage in men and ICH with subarachnoid hemorrhage, which was more pronounced in men. Additional studies are needed to confirm our findings and explore potential mechanisms.

Case Report/Case Series: Rare case of anti-LGI1 limbic encephalitis with rapidly progressive dementia, psychiatric symptoms, and frequently seizures: A case report.

RATIONALE: Anti leucine-rich glioma inactivated 1 (LGI1) limbic encephalitis (LE) is rare autoimmune encephalitis, characterized by acute or subacute cognitive impairment, faciobrachial dystonic seizures, mental disorders, and refractory hyponatremia. As a type of treatable rapidly progressive dementia with a good prognosis, early, and accurate diagnosis is essential. We present a case of anti-LGI1 LE who was initially misdiagnosed with Alzheimer disease because his clinical manifestations were similar to Alzheimer disease. PATIENT CONCERNS: A male patient presenting with rapidly progressive dementia, faciobrachial dystonic seizures, psychiatric disturbance, and refractory hyponatremia was admitted. The scores of Mini-Mental State Examination, Montreal Cognitive Assessment, and Neuropsychiatric Inventory were 19/30, 16/30, and 91/144, respectively. Brain magnetic resonance images indicated moderate atrophy of the hippocampus and abnormally hyperintensities in the left medial temporal and hippocampus. DIAGNOSIS: The patient was diagnosed with anti-LGI1 LE based on the presence of LGI-1 antibodies in the cerebrospinal fluid and serum and clinical manifestations. INTERVENTIONS: Patient was treated with glucocorticoid against LGI1, antiepileptic drug, cholinesterase inhibitors, and other adjuvant therapy. OUTCOMES: The patient showed marked improvement on immunotherapy. Clinical symptoms were disappeared and the LGI-1 antibodies in cerebrospinal fluid and serum were both negative at the time of discharge. CONCLUSIONS: Recognition of the specific symptoms and LGI-1 antibody test will be helpful for the early diagnosis, prompt immunotherapy, and good prognosis. This case raises the awareness that rapidly progressive dementia with frequent seizures could be caused by immunoreactions.

The etiological effect of a new low-frequency ESR1 variant on Mild Cognitive Impairment and Alzheimer's Disease: a population-based study.

Latent genetic variations of cholesterol metabolism-related genes in late-onset Alzheimer's disease, especially, as well as in mild cognitive impairment pathogenesis are still to be studied extensively. Thus, we performed the targeted-sequencing of 12 nuclear receptor genes plus APOE which were involved in cholesterol content modulation to screen susceptible genetic variants and focused on a new risk variant ESR1 rs9340803 at 6q25.1 for both late-onset Alzheimer's disease (OR=3.30[1.84~4.22], p<0.001) and mild cognitive impairment (OR=3.08[1.75~3.89], p<0.001). This low-frequency variant was validated in three independent cohorts totaling 854 late-onset Alzheimer's disease cases, 1059 mild cognitive impairment cases and 1254 controls from nine provinces of China mainland. Preliminary functional study on it revealed decreased ESR1 expression in vitro. Besides, we detected higher serum Aß1-40 concentration in participants carrying this variant (p=0.038) and lower plasma total cholesterol level in this variant carriers with late-onset Alzheimer's disease (p=0.009). In summary, we identified a susceptible variant which might contribute to developing mild cognitive impairment at earlier stage and Alzheimer's Disease later. Our study would provide new insight into the disease causation of late-onset Alzheimer's disease and could be exploited therapeutically.

Age-related formaldehyde interferes with DNA methyltransferase function, causing memory loss in Alzheimer's disease.

Hippocampus-related topographic amnesia is the most common symptom of memory disorders in Alzheimer's disease (AD) patients. Recent studies have revealed that experience-mediated DNA methylation, which is regulated by enzymes with DNA methyltransferase (DNMT) activity, is required for the formation of recent memory as well as the maintenance of remote memory. Notably, overexpression of DNMT3a in the hippocampus can reverse spatial memory deficits in aged mice. However, a decline in global DNA methylation was found in the autopsied hippocampi of patients with AD. Exactly, what endogenous factors that affect DNA methylation still remain to be elucidated. Here, we report a marked increase in endogenous formaldehyde levels is associated with a decline in global DNA methylation in the autopsied hippocampus from AD patients. In vitro and in vivo results show that formaldehyde in excess of normal physiological levels reduced global DNA methylation by interfering DNMTs. Interestingly, intrahippocampal injection of excess formaldehyde before spatial learning in healthy adult rats can mimic the learning difficulty of early stage of AD. Moreover, injection of excess formaldehyde after spatial learning can mimic the loss of remote spatial memory observed in late stage of AD. These findings suggest that aging-associated formaldehyde contributes to topographic amnesia in AD patients.

High manganese, a risk for Alzheimer's disease: high manganese induces amyloid-ß related cognitive impairment.

Excess manganese (Mn) in brain can be neurotoxic, implicated in several neurodegenerative disorders such as sporadic Alzheimer's disease (AD). However, little is known about the altered metal environment including elevated Mn in the progressive cognitive impairment of AD. Indeed, whether high Mn is associated with AD risk remains elusive. In the study, we recruited 40 Chinese elders with different cognitive statuses and investigated concentrations of Mn in whole blood and plasma amyloid-ß (Aß) peptides. Surprisingly, there were significant correlations of Mn with Mini-Mental State Examination score and Clinical Dementia Rating Scale score. In addition, plasma Aß peptides increased with elevated Mn. Further studies both in vitro and in vivo demonstrated dose-related neurotoxicity and increase of Aß by Mn treatment, which was probably caused by disrupted Aß degradation. These data suggested that high Mn may be involved in the progress of AD as an essential pathogenic factor.