Amitriptyline improves cognitive and neuronal function in a rat model that mimics dementia with lewy bodies.

Dementia with Lewy bodies (DLB), a highly prevalent neurodegenerative disorder, causes motor and cognitive deficits. The main pathophysiologies of DLB are glutamate excitotoxicity and accumulation of Lewy bodies comprising α-synuclein (α-syn) and ß-amyloid (Aß). Amitriptyline (AMI) promotes expression of glutamate transporter-1 and glutamate reuptake. In this study, we measured the effects of AMI on behavioral and neuronal function in a DLB rat model. We used rivastigmine (RIVA) as a positive control. To establish the DLB rat model, male Wistar rats were stereotaxically injected with recombinant adenoassociated viral vector with the SNCA gene (10 µg/10 µL) and Aß (5 µg/2.5 µL) into the left ventricle and prefrontal cortex, respectively. AMI (10 mg/kg/day, i.p.), RIVA (2 mg/kg/day, i.p.), or saline was injected intraperitoneally after surgery. From the 29th day, behavioral tests were performed to evaluate the motor and cognitive functions of the rats. Immunohistochemical staining was used to assess neuronal changes. We measured the α-syn level, number of newborn cells, and neuronal density in the hippocampus and in the nigrostriatal dopaminergic system. The DLB group exhibited deficit in object recognition. Both the AMI and RIVA treatments reversed these deficits. Histologically, the DLB rats exhibited cell loss in the substantia nigra pars compacta and in the hippocampal CA1 area. AMI reduced this cell loss, but RIVA did not. In addition, the DLB rats exhibited a lower number of newborn cells and higher α-syn levels in the dentate gyrus (DG). AMI did not affect α-syn accumulation but recovered neurogenesis in the DG of the rats, whereas RIVA reversed the α-syn accumulation but did not affect neurogenesis in the rats. We suggest that AMI may have potential for use in the treatment of DLB.

[Relationship between microalbuminuria and cognition in primary hypertension patients].

OBJECTIVE: To study the relationship between microalbuminuria and cognitive impairment in primary hypertensive patients. METHODS: A total of 200 hypertensive patients were included in this study. Blood pressure, body height and weight, total cholesterol, triglyceride, fasting plasma glucose, 2 hour-postprandial blood sugar, insulin level and urine protein were measured. Microalbuminuria and urine creatinine were determined in patients without proteinuria. The risk stratification of hypertension was evaluated. The cognitive function and calculate scores were tested by the Mini Mental State Examination (MMSE) and patients were divided into two groups: > 24-scores were classified as normal cognition group, < or = 24-scores as impaired cognition group. RESULTS: Among the 200 hypertensive patients, proteinuria was detected in 25 patients. There was no significant difference in the cognitive function between patients with and without proteinuria (P > 0.05). There were significant differences on age, educational level, occupation, smoking, history of coronary heart disease, history of cerebrovascular disease, the risk stratification of hypertension, microalbuminuria/creatinine ratio, postprandial insulin level, cholesterol and diastolic blood pressure between normal cognition function group and impaired cognition function group (all P < 0.05). Multivariate logistic regression analysis showed that microalbuminuria, educational level and the risk stratification of hypertension were significantly correlated to cognition impairment (all P < 0.05). CONCLUSIONS: Educational level, the risk stratification of hypertension and microalbuminuria are associated with cognitive impairment in this patient cohort.