Serum vitamin D in patients with mild cognitive impairment and Alzheimer's disease

Objectives: To determine the relevance of Mini-Mental State Examination (MMSE), serum 25-hydroxyvitamin D (25(OH)D3), and 1,25(OH)2D3 concentrations to mild cognitive impairment (MCI) and various stages of Alzheimer's disease (AD). Materials and Methods: The study included 230 participants (>74 years) allocated to three main groups: 1-healthy subjects (HS, n = 61), 2-patients with MCI (n = 61), and 3- patients with Alzheimer's disease (AD) subdivided into three stages: mild (n = 41), moderate (n = 35), and severe AD (n = 32). The cognitive status was evaluated using MMSE. Serum 25 (OH)D3 (ng/ml) and 1,25(OH)2D3 concentrations (pg/ml) were determined by competitive radioimmunoassay. Results: MMSE scores and 25(OH)D3 were decreased in MCI and all stages of the AD in both genders. MMSE variability was due to gender in HS (11%) and to 25(OH)D3 in MCI (15%) and AD (26%). ROC analysis revealed an outstanding property of MMSE in diagnosis of MCI (AUC, 0.906; CI 95%, 0.847–0.965; sensitivity 82%; specificity, 98%) and AD (AUC, 0.997; CI 95%, 0.992–1; sensitivity, 100%; specificity, 98%). 25(OH)D3 exhibited good property in MCI (AUC, 0.765; CI 95%, 0.681–0.849; sensitivity, 90%; specificity, 54%) and an excellent property in diagnosis of AD (AUC, 0.843; CI 95%, 0.782–0.904; sensitivity, 97%; specificity, 79%). Logistic analyses revealed that, in MCI, MMSE could predict (or classify correctly) with 97.6% accuracy (Wald, 15.22, β, −0.162; SE, 0.554; OR = 0.115:0.039–0.341; p =.0001), whereas 25(OH)D3 with 80% accuracy (Wald, 41,013; β, −0.213; SE, 0.033; OR = 0.808: 0.757–863; p =.0001). 25(OH)D3 was the only significant predictor for the severe AD and contributed to MMSE variability. Age and gender were significant predictors only in the moderate AD. In patients with MCI, 25(OH)D3 and 1,25(OH)2D3 were correlated men, but in case of the AD, they were correlated in women. Conclusions: MMSE and serum 25(OH)D3 concentrations could be useful biomarkers for prediction and diagnosis of MCI and various stages of the AD. The results support the utility of vitamin D supplementation in AD therapy regimen. © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc

Effect of nilvadipine on memory impairment and hippocampal malondialdehyde in rats with 4-vessel occlusion ischemia

Purpose: Nilvadipine is a dihydropyridine-type calcium channel blocker with emanating neuroprotective properties in various models of neuronal diseases. This study aimed at investigating the prophylactic effect of nilvadipine on memory impairment and hippocampal malodialdehyde (MDA) levels in global brain ischemia model induced by 4-vessel occlusion ischemia (4-VO) in rat. Materials and methods: The 4-VO ischemia was induced in Wistar rats by occluding the vertebral arteries permanently by cauterization. The common carotid arteries were twice occluded bilaterally for 10 minute at 60 minute interval. One week after 4-VO the memory was evaluated measuring the correct and error choices in 8-armed radial maze. The ischemiareperfusion- induced damage was evaluated measuring level of MDA in the hippocampus using thiobarbituric acid method. The study involved three groups: sham, ischemia-control and ischemia nilvadipin. Nilvadipine (3.2 mg/kg/day) was administerd for 7 days prior to 4-VO Results: The 4-VO impaired memory performance by decreasing the correct choices (long termreference memory) and increasing the error choices (short term-working memory) (p<0,001). Nilvadipine improved the performance by increasing the correct choices (p<0.002) and decreasing the error choices (p<0.05). Nilvadipine decreased (p<0.001) the elevated MDA induced by 4-VO. Conclusion: The prophylactic treatment with nilvadipine improved memory impairment and reduced the elevated hippocampal MDA induced by 4-VO. The prophylactic use of nilvadipine could be beneficial for inhibiting the ischemia related memory impairment in risky patients

Effects of 8-residue β sheet breaker peptides on aged Aβ40-induced memory impairment and Aβ40 expression in rat brain and serum following intraamygdaloid injection.

Amyloidβ-protein (Aβ) assembly into toxic fibrillar structures is seminal in development of senile plaques, the pathological hallmark of Alzheimer's disease. Blocking this process could have a therapeutic value. β-sheet breaker peptides (βSBP) decrease Aβ fibrillogenesis and neurotoxicity by preventing or dissolving misfolded Aβ aggregates. The present study investigated the effects of βSBPs on Aβ40-related neuropathology, memory impairment in 8-armed radial maze and expression of Aβ40 in brain and serum. Aβ40 was injected into amygdaloid nucleus followed 8 days later by octapeptideβSBPs 15-22, 16-23 and 17-24. Aβ40 was detected not only in amygdala, but also in serum. Aβ40 induced cellular changes in amygdala and additionally in hippocampus. Aβ40 decreased correct choices, whereas increased errors (both number of arms revisited and total number of revisits) and latency of completing the maze test. The βSBPs decreased Aβ40-induced pathological changes, memory impairment and Aβ40 expression in serum. The βSBP15-22 distinctively decreased the total errors on day 14. The present results show that octapeptide βSBPs corrected Aβ40-induced memory impairment, and support investigation of βSBPs as a promising treatment of diseases characterized by neurodegeneration and memory impairment such as Alzheimer's disease

Role of dopaminergic system in core part of nucleus accumbens in hyperlocomotion and rearing induced by MK-801 in rats: A behavioral and in vivo microdialysis study

We investigated modification of the MK-801 effect on motor activity and extracellular amines concentration by 6-hydroxydopamine (6-OHDA)-induced lesion of core nucleus accumbens (cACC) of rats. In vivo microdialysis-HPLC showed that the concentrations (fmol/μl) of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and serotonin were 0.738±0.135, 155.34±41.01 and 0.334±0.024, respectively, in the cACC of intact rats. The DOPAC/DA ratio was 264.24±94.01. Unilateral lesion of the cACC with 6-OHDA (8 μg/μl) substantially reduced DA (-93%) and DOPAC (-97%) in desipramine (30 mg/kg, i.p.)-pretreated rats (6-OHDA+DMI rats) as compared to the 65% reduction rate of both amines in saline-pretreated rats (6-OHDA+saline rats). Moreover, DOPAC was reduced by 72% in 6-OHDA+DMI rats. MK-801 increased DOPAC (426-467%) and DOPAC/DA ratio (180-230%) in intact rats. On the other hand, MK-801 increased DA by 154% and 505% in 6-OHDA+saline and 6-OHDA+DMI rats, respectively. 6-OHDA reduced the effect of MK-801 on DOPAC and DOPAC/DA ratio. In the behevioral studies, MK-801 (0.01 - 0.3 mg/kg, i.p.) increased locomotor activity and rearing of intact rats. Bilateral 6-OHDA+DMI mesion of the cACC caused greater reduction in the effect of MK-801 (0.1 mg/kg) than that of the shell nucleus accumbens. These results suggest that increased extracellular DOPAC concentration (but not DA) and DOPAC/DA ratio in the cACC plays an important role in MK-801-hyperactivity