Effect of 9 - PAHSA on cognitive dysfunction in diabetic mice and its possible mechanism.

Diabetes mellitus (DM) is currently a major global health problem, which is associated with the development of cognitive dysfunction. However, although numerous clinical drugs for hyperglycemia have been used at present, safer and more effective therapeutic intervention strategies for diabetic cognitive impairments are still a huge challenge. Recently, several studies have indicated that a novel class of branched palmitic acid esters of hydroxyl stearic acids (PAHSAs) may have anti-diabetes and anti-inflammatory effects in insulin-resistant mice. Herein, whether the 9-PAHSA that one of the PAHSAs can attenuates DM-associated cognitive impairment in a mouse model of type 2 diabetes has been investigated. Our results showed that 9-PAHSA mildly prevented deficits of spatial working memory in Y-maze test while reversed the preference bias toward novel mice in Social choice test. Furthermore, the effect of REST on cognitive impairment of diabetes was explored for the first time. It was found that the expression of REST in diabetic mice increased, and the expression of target protein BDNF (Brain-derived neurotrophic factor) was decreased. After administration of 9-PAHSA, the situation was reversed. In summary, we conclude that exogenous supplement of 9-PAHSA can improve DM-related cognitive impairment to some extent, and the protective effect may be associated with decreased REST/NRSF (repressor element-1 silencing transcription factor/neuron-restrictive silence factor) and upregulated BDNF expression in frontal cortex.

Blood biomarkers for memory: toward early detection of risk for Alzheimer disease, pharmacogenomics, and repurposed drugs.

Short-term memory dysfunction is a key early feature of Alzheimer's disease (AD). Psychiatric patients may be at higher risk for memory dysfunction and subsequent AD due to the negative effects of stress and depression on the brain. We carried out longitudinal within-subject studies in male and female psychiatric patients to discover blood gene expression biomarkers that track short term memory as measured by the retention measure in the Hopkins Verbal Learning Test. These biomarkers were subsequently prioritized with a convergent functional genomics approach using previous evidence in the field implicating them in AD. The top candidate biomarkers were then tested in an independent cohort for ability to predict state short-term memory, and trait future positive neuropsychological testing for cognitive impairment. The best overall evidence was for a series of new, as well as some previously known genes, which are now newly shown to have functional evidence in humans as blood biomarkers: RAB7A, NPC2, TGFB1, GAP43, ARSB, PER1, GUSB, and MAPT. Additional top blood biomarkers include GSK3B, PTGS2, APOE, BACE1, PSEN1, and TREM2, well known genes implicated in AD by previous brain and genetic studies, in humans and animal models, which serve as reassuring de facto positive controls for our whole-genome gene expression discovery approach. Biological pathway analyses implicate LXR/RXR activation, neuroinflammation, atherosclerosis signaling, and amyloid processing. Co-directionality of expression data provide new mechanistic insights that are consistent with a compensatory/scarring scenario for brain pathological changes. A majority of top biomarkers also have evidence for involvement in other psychiatric disorders, particularly stress, providing a molecular basis for clinical co-morbidity and for stress as an early precipitant/risk factor. Some of them are modulated by existing drugs, such as antidepressants, lithium and omega-3 fatty acids. Other drug and nutraceutical leads were identified through bioinformatic drug repurposing analyses (such as pioglitazone, levonorgestrel, salsolidine, ginkgolide A, and icariin). Our work contributes to the overall pathophysiological understanding of memory disorders and AD. It also opens new avenues for precision medicine- diagnostics (assement of risk) as well as early treatment (pharmacogenomically informed, personalized, and preventive).

Vitamin A deficiency impairs contextual fear memory in rats: Abnormalities in the glucocorticoid pathway.

Vitamin A and its active metabolite, retinoic acid (RA), play a key role in the maintenance of cognitive functions in the adult brain. Depletion of RA using the vitamin A deficiency (VAD) model in Wistar rats leads to spatial memory deficits in relation to elevated intrahippocampal basal corticosterone (CORT) levels and increased hippocampal 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) activity. All of these effects are normalised by vitamin A supplementation. However, it is unknown whether vitamin A status also modulates contextual fear conditioning (CFC) in a glucocorticoid-associated fear memory task dependent on the functional integrity of the hippocampus. In the present study, we investigated the impact of VAD and vitamin A supplementation in adult male rats on fear memory processing, plasma CORT levels, hippocampal retinoid receptors and 11ß-HSD1 expression following a novelty-induced stress. We also examined whether vitamin A supplementation or a single injection of UE2316, a selective 11ß-HSD1 inhibitor, known to modulate local glucocorticoid levels, had any beneficial effects on contextual fear memory and biochemical parameters in VAD rats. We provide evidence that VAD rats exhibit a decreased fear conditioning response during training with a poor contextual fear memory 24 hours later. These VAD-induced cognitive impairments are associated with elevated plasma CORT levels under basal conditions, as well as following a stressful event, with saturated CORT release, altered hippocampal retinoid receptors and 11ß-HSD1 expression. Vitamin A supplementation normalises VAD-induced fear conditioning training deficits and all biochemical effects, although it cannot prevent fear memory deficits. Moreover, a single injection of UE2316 not only impairs contextual fear memory, but also reduces plasma CORT levels, regardless of the vitamin A status and decreases slightly hippocampal 11ß-HSD1 activity in VAD rats following stress. The present study highlights the importance of vitamin A status with respect to modulating fear memory conditioning in relation to plasma CORT levels and hippocampal 11ß-HSD1.

Zinc-Enriched Yeast Improves Learning and Memory Impairments in Zinc-Deficient Rats.

Zinc (Zn) highly concentrates in the brain and plays a key role in memory formation and learning processes. Zn deficiency results in cognitive impairments, memory deficits, alterations of neuropsychological behavior, and motor development. Although Zn-enriched yeast (ZnY) is widely used for dietary fortification and supplementation of Zn, the effect of ZnY on cognition still remains unclear. The purpose of the study was to investigate the effect of ZnY on behavior in Zn-deficient and Zn-sufficient rats. Three-week-old rats were fed low Zn diets for 145 days to establish Zn-deficient rats. ZnY was orally administered to Zn-deficient rats at three dose levels of 1, 2, and 4 mg Zn/kg/day for 55 days. Rat appearance, body weight, plasma and brain Zn, Morris water maze test, and step-through passive avoidance test were observed. Compared to Zn-sufficient rats, body weight gain, plasma zinc level, resident time, and step-through time in Zn-deficient rats were significantly lower. Zn deficiency impaired functions of learning and memory, while ZnY as a plausible therapeutic intervention alleviated the cognitive impairments caused by Zn deficiency.

Bergenia ciliata ameliorates streptozotocin-induced spatial memory deficits through dual cholinesterase inhibition and attenuation of oxidative stress in rats.

Bergenia ciliata (Haw.) Sternb. rhizomes, family Saxifragaceae, are claimed to possess an array of beneficial effects like antioxidant, anti-inflammatory, immunomodulatory, antibacterial and anticancer activities. The plant has also been reported to be used by Nepalese folk to alleviate symptoms related to Parkinson's disease. Oxidative stress is one of the major reasons for cognitive decline observed in sporadic Alzheimer's disease (AD). Bergenia ciliata rhizomes have depicted potent antioxidant properties, but their role in the treatment of Alzheimer's disease is yet unexplored. Therefore, the present study was intended to explore the beneficial effects of methanolic extracts of rhizomes of B. ciliata (BM) in a streptozotocin-induced model of Alzheimer's disease in Wistar rats. Streptozotocin (STZ) was injected intracerebroventricularly (ICV) on day 1 (3 mg/kg, unilaterally) in Wistar rats. BM was thereafter administered (125, 250 and 500 mg/kg b.w./day p.o.), daily for 28 days. Morris water maze and Y maze test were used to evaluate learning and memory in rats on 7th, 14th, 21st and 28th days following initiation of dosing. Terminally, acetylcholinesterase activity, butyrylcholinesterase, and levels of oxidative stress markers were assessed in the serum as well as in brain homogenates of rats. Additionally, histopathological studies were carried out to observe effects in brain tissues at the cellular level. STZ produced significant (p < 0.001) learning and memory impairment, oxidative stress as well as a cholinergic deficit in rats. Whereas, BM treatment at various dose levels was able to significantly and dose-dependently diminish STZ induced behavioral deficits and biochemical anomalies in rats. The observed cognitive improvement following BM administration in STZ injected rats may be accredited to its antioxidant activity and refurbishment of cholinergic functions. The results of the study are indicative of the therapeutic potential of Bergenia ciliata in cognitive disorders such as AD as well as other such neurodegenerative disorders.

Vitamin D and Subjective Memory Complaint in Community-Dwelling Older Adults.

BACKGROUND: Older adults with hypovitaminosis D report more often subjective cognitive complaints, especially with regards to memory. This raises prospects that vitamin D may improve older adults' subjective experience of memory disorders. OBJECTIVE: To determine among older community-dwellers whether higher serum 25- hydroxyvitamin D (25OHD) concentrations were associated with fewer memory complaints, while considering different subtypes of memory complaints. METHOD: One hundred eighty Caucasian community-dwellers with memory complaint and no dementia (mean±standard deviation, 71.1±3.4years; 33.3%female) from the French 'EVATEM study' were included in this analysis. Subjective memory complaints regarding memory lapses, problems learning new information, problems finding words, problems calculating and problems concentrating were assessed using a standardized questionnaire. Participants were categorized according to the highest tertile of serum 25OHD (i.e., ≥68nmol/L). Age, gender, body mass index, morbidities burden, use of vitamin D supplements, cognitive performance, mood, serum concentrations of calcium, parathyroid hormone and vitamin B12, creatinine clearance, and season of evaluation were used as potential confounders. RESULTS: Compared to participants with 25OHD<68nmol/L (n=121), those with 25OHD≥68nmol/L had less often problems learning new information (P=0.027). There were no between-group differences for the other memory complaints. The highest 25OHD tertile was cross-sectionally associated with fewer problems learning new information (odds ratio (OR)=0.48, P=0.029), even after adjustment for potential confounders (OR=0.32, P=0.039). CONCLUSION: Higher vitamin D status was associated with reduced problems memorizing new information in older community-dwellers. This novel finding provides a scientific base for vitamin D replacement trials attempting to improve older patients' subjective experience of cognitive decline.

Anserine/Carnosine Supplementation Suppresses the Expression of the Inflammatory Chemokine CCL24 in Peripheral Blood Mononuclear Cells from Elderly People.

Our goal was to determine whether anserine/carnosine supplementation (ACS) suppresses chemokine levels in elderly people. In a double-blind randomized controlled trial, volunteers were assigned to the ACS or placebo group (1:1). Sixty healthy elderly volunteers (active, n = 30; placebo, n = 30) completed the study. The ACS group was administered 1.0 g of anserine/carnosine (3:1) for 3 months. A microarray analysis and subsequent quantitative real-time polymerase chain reaction (qRT-PCR) analysis of peripheral blood mononuclear cells (PBMCs) showed decreased expression of CCL24, an inflammatory chemokine (p < 0.05). Verbal memory, assessed using the Wechsler memory scale-logical memory, was preserved in the ACS group. An age-restricted sub-analysis showed significant verbal memory preservation by ACS in participants who were in their 60s (active, n = 12; placebo, n = 9; p = 0.048) and 70s (active, n = 7; placebo, n = 11; p = 0.017). The suppression of CCL24 expression was greatest in people who were in their 70s (p < 0.01). There was a significant correlation between the preservation of verbal memory and suppression of CCL24 expression in the group that was in the 70s (Poisson correlation, r = 0.46, p < 0.05). These results suggest that ACS may preserve verbal episodic memory, probably owing to CCL24 suppression in the blood, especially in elderly participants.

Gamma-linolenic acid ameliorated glycation-induced memory impairment in rats.

CONTEXT: γ-Linolenic acid (GLA) is an important constituent of anti-ageing supplements. OBJECTIVE: The current study investigates the anti-ageing effect of GLA in Sprague-Dawley rats. MATERIALS AND METHODS: GLA (0.1, 0.2, 0.4, 2, 10, 20 and 24 µM) was initially evaluated for its effect on the formation of advanced glycation end products (AGEs) in vitro. For in vivo assessment (1, 5 or 15 mg/kg), the rat model of accelerated ageing was developed using d-fructose (1000 mg/kg (i.p.) plus 10% in drinking water for 40 days). Morris water maze was used to evaluate impairment in learning and memory. The blood of treated animals was used to measure glycosylated haemoglobin (HbA1c) levels. The interaction of GLA with active residues of receptor of AGE (RAGE) was analyzed using AutoDock Vina. RESULTS: Our data showed that GLA inhibited the production of AGEs (IC50 = 1.12 ± 0.05 µM). However, this effect was more significant at lower tested doses. A similar pattern was also observed in in vivo experiments, where the effect of fructose was reversed by GLA only at lowest tested dose of 1 mg/kg. The HbA1c levels also revealed significant reduction at lower doses (1 and 5 mg/kg). The in silico data exhibited promising interaction of GLA with active residues (Try72, Arg77 and Gln67) of RAGE. CONCLUSION: The GLA, at lower doses, possesses therapeutic potential against glycation-induced memory decline.

Pharmacological Evaluation of the Recuperative Effect of Morusin Against Aluminium Trichloride (AlCl3)-Induced Memory Impairment in Rats.

BACKGROUND: Elevation in brain levels of aluminium can be neurotoxic and can cause learning and memory deficiencies. In Chinese medicine, Morus alba is used as a neuroprotective herb. The current study was intended to discover the recuperative effect of morusin against aluminium trichloride (AlCl3)-induced memory impairment in rats along with biochemical mechanism of its protective action. METHODS: Memory deficiency was produced by AlCl3 (100 mg/kg; p.o.) in experimental animals. Learning and memory activity was measured using Morris water maze (MWM) test model. Central cholinergic activity was evaluated through the measurement of brain acetylcholinesterase (AChE) activity. In addition to the above, oxidative stress was determined through assessment of brain thiobarbituric acid-reactive species (TBARS) and glutathione (GSH) levels. RESULTS: AlCl3 administration prompted significant deficiency of learning and memory in rats, as specified by a noticeable reduction in MWM presentation. AlCl3 administration also produced a significant deterioration in brain AChE action and brain oxidative stress (increase in TBARS and decrease in GSH) levels. Treatment with morusin (5.0 and 10.0 mg/kg, dose orally) significantly overturned AlCl3- induced learning and memory shortages along with diminution of AlCl3-induced rise in brain AChE activity and brain oxidative stress levels. CONCLUSION: It may be concluded that morusin exerts a memory-preservative outcome in mental discrepancies of rats feasibly through its various activities.

Effects of in-vitro cultured calculus bovis on learning and memory impairments of hyperlipemia vascular dementia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In-vitro cultured calculus bovis (ICCB) is a quality substitute for natural bezoar which is used for the therapeutic purpose of treating encephalopathy. ICCB has been authorized to use on clinic. The aim of the study is to evaluate the effects and the potential mechanisms of in-vitro cultured calculus bovis (ICCB) on learning and memory impairments of hyperlipemia vascular dementia (HVD) rats. MATERIALS AND METHODS: The HVD model was established by permanent occlusion of bilateral common carotid arteries based on hyperlipemia rats. Learning and memory abilities were evaluated by morris water maze test and shuttle box test. Ultraviolet-visible spectrophotometry (UV-vis) was employed to determine the SOD, MDA and NO in cerebral tissue, as well as the TG in serum. HE staining and toluidine blue staining were employed to evaluate cone cells damage in hippocampus CA1. An immunohistochemistry was used to measure the Bax and Bcl-2 expressions in cerebral tissue. RESULTS: Compared with control group, the abilities of spatial learning and memory and conditional memory were decreased significantly in HVD group (P<0.01, P<0.05). MDA content in cerebral tissue was remarkably increased while the SOD activity and NO content were both decreased (P<0.01). TG content in serum was increased remarkably (P<0.01). And the cone cells in hippocampus CA1 were damaged obviously. Compared with HVD group, ICCB treatment improved the abilities of learning and memory, elevated the SOD activity (P<0.01, P<0.05), reduced the MDA content (P<0.01) as well as the TG content in serum (P<0.01), increased the NO content (P<0.01), improved the damaged cone cells in hippocampus CA1, increased the number of cones cells (P<0.01), decreased the Bax expression, and increased the Bcl-2 expression (P<0.01). CONCLUSION: ICCB could improve the abilities of learning and memory in HVD rats. It might be related to anti-oxidative, regulation of Bax and Bcl-2 expressions, and the alleviation of cone cells damage.

Fish Oil Supplementation Increases Event-Related Posterior Cingulate Activation in Older Adults with Subjective Memory Impairment.

OBJECTIVES: To determine the effects of long-chain omega-3 (LCn-3) fatty acids found in fish oil, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on cortical blood oxygen level-dependent (BOLD) activity during a working memory task in older adults with subjective memory impairment. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Academic medical center. PARTICIPANTS: Healthy older adults (62-80 years) with subjective memory impairment, but not meeting criteria for mild cognitive impairment or dementia. INTERVENTION: Fish oil (EPA+DHA: 2.4 g/d, n=11) or placebo (corn oil, n=10) for 24 weeks. MEASUREMENTS: Cortical BOLD response patterns during performance of a sequential letter n-back working memory task were determined at baseline and week 24 by functional magnetic resonance imaging (fMRI). RESULTS: At 24 weeks erythrocyte membrane EPA+DHA composition increased significantly from baseline in participants receiving fish oil (+31%, p ≤ 0.0001) but not placebo (-17%, p=0.06). Multivariate modeling of fMRI data identified a significant interaction among treatment, visit, and memory loading in the right cingulate (BA 23/24), and in the right sensorimotor area (BA 3/4). In the fish oil group, BOLD increases at 24 weeks were observed in the right posterior cingulate and left superior frontal regions during memory loading. A region-of-interest analysis indicated that the baseline to endpoint change in posterior cingulate cortex BOLD activity signal was significantly greater in the fish oil group compared with the placebo group during the 1-back (p=0.0003) and 2-back (p=0.0005) conditions. Among all participants, the change in erythrocyte EPA+DHA during the intervention was associated with performance in the 2-back working memory task (p = 0.01), and with cingulate BOLD signal during the 1-back (p = 0.005) with a trend during the 2-back (p = 0.09). Further, cingulate BOLD activity was related to performance in the 2-back condition. CONCLUSION: Dietary fish oil supplementation increases red blood cell omega-3 content, working memory performance, and BOLD signal in the posterior cingulate cortex during greater working memory load in older adults with subjective memory impairment suggesting enhanced neuronal response to working memory challenge.

Effects of Curculigoside on Memory Impairment and Bone Loss via Anti-Oxidative Character in APP/PS1 Mutated Transgenic Mice.

Alzheimer's disease (AD) and osteoporosis are two closely related multifactorial progressively degenerative diseases that predominantly affect aged people. These two diseases share many common risk factors, including old age, being female, smoking, excessive drinking, low estrogen, and vitamin D3 levels. Additionally, oxidative damage and the dysfunction of the antioxidant system play important roles in the pathogenesis of osteoporosis and AD. Aß not only leads to impaired memory but also plays a crucial role in the demineralization process of bone tissues of older people and women with menopause. Curculigoside can promote calcium deposition and increase the levels of ALP and Runx2 in osteoblasts under oxidative stress via anti-oxidative character. Therefore, we investigated the effects of CUR on the spatial learning and memory by the Morris water maze and brain immunohistochemistry, and bone microstructure and material properties of femurs by micro-computed tomography and mechanical testing in APP/PS1 mutated transgenic mice. Oral administration of CUR can significantly enhance learning performance and ameliorate bone loss in APP/PS1 mutated transgenic mice, and the mechanism may be related to its antioxidant effect. Based on these results, CUR has real potential as a new natural resource for developing medicines or dietary supplements for the prevention and treatment of the two closely linked multifactorial progressive degenerative disorders, AD and osteoporosis.

Low-level prenatal lead exposure alters auditory recognition memory in 2-month-old infants: an event-related potentials (ERPs) study.

This study used event-related potentials (ERPs) to assess effects of low-level prenatal lead exposure on auditory recognition memory in 2-month-old infants. Infants were divided into four groups according to cord-blood lead concentration: (1) <2.00 µ g/dL, (2) 2.00-2.99 µ g/dL, (3) 3.0-3.7 µ g/dL, and (4) ≥3.7 µ g/dL. The first group showed the normally expected differences in P2, P750, and late slow wave (LSW) amplitudes elicited by mothers' and strangers' voices. These differences were not observed for one or more ERP components in the other groups. Thus, there was electrophysiological evidence of poorer auditory recognition memory at 2 months with cord-blood lead ≥2.00 µ g/dL.

Vitamin D and long-term memory in multiple sclerosis.

BACKGROUND AND OBJECTIVE: Memory disturbance is a frequent cognitive complaint by patients with multiple sclerosis (MS). Recent dementia research suggests a beneficial role for vitamin D in long-term memory functioning. While data suggest ameliorative effects of vitamin D for the physical impairments of MS, it is unknown whether vitamin D can benefit the cognitive sequelae. We examined the relationship between serum levels of vitamin D and performance on verbal and nonverbal tests of long-term memory in patients with MS. METHODS: A sample of 35 adults with relapsing-remitting MS completed cognitive testing and a vitamin D serum (25[OH]D) assay. Memory assessment used clinically established neuropsychological tests with multiple testing formats to determine whether vitamin D level was associated with memory during conditions of varying retrieval demands. Intellectual functioning and mood were also assessed to control for potential confounds. RESULTS: Vitamin D level was positively associated with performance on immediate and delayed recall trials of the Rey Complex Figure Test, effects that held after controlling for intelligence and disease duration. Vitamin D level was not associated with mood, intelligence, or verbal memory performance on the California Verbal Learning Test, Second Edition. CONCLUSIONS: Higher vitamin D level was associated with better nonverbal long-term memory performance in MS, particularly in conditions when no aid was given to help retrieval. These results supplement the literature on the neuroprotective effects of vitamin D and suggest that vitamin D is a worthwhile adjunct treatment for MS.

Ethylbenzene-induced hearing loss, neurobehavioral function, and neurotransmitter alterations in petrochemical workers.

OBJECTIVE: To estimate hearing loss, neurobehavioral function, and neurotransmitter alteration induced by ethylbenzene in petrochemical workers. METHODS: From two petrochemical plants, 246 and 307 workers exposed to both ethylbenzene and noise were recruited-290 workers exposed to noise only from a power station plant and 327 office personnel as control group, respectively. Hearing and neurobehavioral functions were evaluated. Serum neurotransmitters were also determined. RESULTS: The prevalence of hearing loss was much higher in petrochemical groups than that in power station and control groups (P < 0.05). Compared with the control group, scores of neurobehavioral function reflecting learning and memory were decreased in petrochemical workers (P < 0.05), as well as acetylcholinesterase activity. Negative correlation was shown between neurobehavioral function and acetylcholinesterase. CONCLUSIONS: Ethylbenzene exposure might be associated with hearing loss, neurobehavioral function impairment, and imbalance of neurotransmitters.

Effects of manganese from a commercial multi-trace element supplement in a population sample of Canadian patients on long-term parenteral nutrition.

BACKGROUND: Long-term parenteral nutrition (PN) can be associated with micronutrient deficiency or toxicity depending on supplementation. Recently, hypermanganesemia and potential neurological toxicity were reported. The aim of this study was to assess the effect of manganese supplementation in a sample of patients on long-term PN receiving manganese (Mn) as part of a multi-trace element (TE) supplement. METHODS: A convenience sample of 16 patients underwent clinical and blood biochemical measurements as well as magnetic resonance imaging (MRI) of the brain. Descriptive statistics were performed. RESULTS: The mean daily Mn supplementation was 7.28 ± 0.97 µmol/d (400 ± 53 µg/d), which was within the American Medical Association Nutrition Advisory Group guidelines of 2.73-14.56 µmol/d (150-800 µg/d) but exceeded the American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.) 2002 recommendations of 1.09-1.82 µmol/d (60-100 µg/d). The mean whole blood Mn level was 1.38 ± 0.29 times the upper limit of normal (ULN), and 8 of 14 patients with blood measurements had Mn levels above ULN. On MRI, 81% of patients had high signals on T1-weighted images assumed to be Mn deposits in their basal ganglia. Two patients with positive MRI (15%) had a clinical diagnosis of Parkinson disease. Multiple neuropsychiatric complaints were reported, including depression (66%), lack of concentration (42%), memory disturbances (17%), and gait instability (8%). CONCLUSION: These results suggest that Mn status is elevated in these patients. Manganese supplementation should be used with caution in patients receiving long-term PN, and attention should be paid to the Mn content of multi-TE supplements.

Vitamin D status and scholastic achievement in middle age childhood.

Non-classical effects of vitamin D are not surprising in that many tissues, including neurons, possess vitamin D receptors. Thirty school aged children with delayed scholastic achievement and 15 normal ones were enrolled in the current study to identify the serum 25-hydroxy vitamin D [25(OH) D] status in school aged children in relation to their scholastic achievement. Besides estimation of serum 25(OH) D levels, neuro-developmental assessment was done using the Wechsler Intelligence Scale for Children (WISC) and the Benton's Visual Retention Test (BVRT). Serum 25(OH) D was significantly lower in children with delayed scholastic achievement. Picture completion scores were significantly lower in children with deficient and inadequate serum 25(OH) D. There were positive correlations between serum 25(OH) D level and values of WISC. Regarding BVRT results, good memory was associated with adequate serum 25(OH) D. In conclusion, serum 25(OH) D is deficient in children with delayed scholastic achievement causing affection of memory and learning process. Larger scale studies using learning assessment tools are thus recommended to further prove this point and search the impact of vitamin D supplementation on the school achievement in this age group.

Plasma long-chain omega-3 fatty acids and atrophy of the medial temporal lobe.

OBJECTIVE: The long-chain ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are potential candidates for interventions to delay Alzheimer disease (AD), but evidence from clinical studies is mixed. We aimed at determining whether plasma levels of EPA or DHA predict atrophy of medial temporal lobe (MTL) gray matter regions in older subjects. METHODS: A total of 281 community dwellers from the Three-City Study, aged 65 years or older, had plasma fatty acid measurements at baseline and underwent MRI examinations at baseline and at 4 years. We studied the association between plasma EPA and DHA and MTL gray matter volume change at 4 years. RESULTS: Higher plasma EPA, but not DHA, was associated with lower gray matter atrophy of the right hippocampal/parahippocampal area and of the right amygdala (p < 0.05, familywise error corrected). Based on a mean right amygdala volume loss of 6.0 mm(3)/y (0.6%), a 1 SD higher plasma EPA (+0.64% of total plasma fatty acids) at baseline was related to a 1.3 mm(3) smaller gray matter loss per year in the right amygdala. Higher atrophy of the right amygdala was associated with greater 4-year decline in semantic memory performances and more depressive symptoms. CONCLUSION: The amygdala, which develops neuropathology in the early stage of AD and is involved in the pathogenesis of depression, may be an important brain structure involved in the association between EPA and cognitive decline and depressive symptoms.

Memory improvements in elderly women following 16 weeks treatment with a combined multivitamin, mineral and herbal supplement: A randomized controlled trial.

RATIONALE: There is potential for multivitamin supplementation to improve cognition in the elderly. This randomized, double-blind, placebo-controlled trial was conducted to investigate the effects of 16 weeks multivitamin supplementation (Swisse Women's 50+ Ultivite ®) on cognition in elderly women. METHODS: Participants in this study were 56 community dwelling, elderly women, with subjective complaints of memory loss. Cognition was assessed using a computerized battery of memory and attention tasks designed to be sensitive to age-related declines to fluid intelligence, and a measure of verbal recall. Biochemical measures of selected nutrients, homocysteine, markers of inflammation, oxidative stress, and blood safety parameters were also collected. All cognitive and haematological parameters were assessed at baseline and 16 weeks post-treatment. RESULTS: The multivitamin improved speed of response on a measure of spatial working memory, however benefits to other cognitive processes were not observed. Multivitamin supplementation decreased levels of homocysteine and increased levels of vitamin B(6) and B(12), with a trend for vitamin E to increase. There were no hepatotoxic effects of the multivitamin formula indicating this supplement was safe for everyday usage in the elderly. CONCLUSION: Sixteen weeks ssupplementation with a combined multivitamin, mineral and herbal formula may benefit working memory in elderly women at risk of cognitive decline.