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Lifestyle and vascular risk effects on MRI-based biomarkers of Alzheimer's disease: a cross-sectional study of middle-aged adults from the broader New York City area.
Mosconi, L, Walters, M, Sterling, J, Quinn, C, McHugh, P, Andrews, RE, Matthews, DC, Ganzer, C, Osorio, RS, Isaacson, RS, et al
BMJ open. 2018;8(3):e019362
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Alzheimer’s disease (AD) is the most common form of dementia, affecting nearly 34 million people worldwide. It has been estimated that one in every three cases of AD may be attributable to diet and lifestyle factors. The aim of this study was to investigate the effects of lifestyle and vascular-related risk factors for AD. Researchers studied the brain scans of 116 healthy adults aged 30-60 years. They collected information on factors related to lifestyle, such as diet, physical activity and intellectual enrichment. They also looked at markers for vascular risk such as body mass index (BMI), cholesterol and homocysteine, as well as cognitive function. The researchers found that a Mediterranean-style diet and good insulin sensitivity were both associated with a healthier brain structure. A better score for intellectual enrichment and lower BMI were both associated with better cognition. They concluded that adopting a Mediterranean-style diet and maintaining a healthy weight might reduce the risk of developing AD.
Abstract
OBJECTIVE To investigate the effects of lifestyle and vascular-related risk factors for Alzheimer's disease (AD) on in vivo MRI-based brain atrophy in asymptomatic young to middle-aged adults. DESIGN Cross-sectional, observational. SETTING Broader New York City area. Two research centres affiliated with the Alzheimer's disease Core Center at New York University School of Medicine. PARTICIPANTS We studied 116 cognitively normal healthy research participants aged 30-60 years, who completed a three-dimensional T1-weighted volumetric MRI and had lifestyle (diet, physical activity and intellectual enrichment), vascular risk (overweight, hypertension, insulin resistance, elevated cholesterol and homocysteine) and cognition (memory, executive function, language) data. Estimates of cortical thickness for entorhinal (EC), posterior cingulate, orbitofrontal, inferior and middle temporal cortex were obtained by use of automated segmentation tools. We applied confirmatory factor analysis and structural equation modelling to evaluate the associations between lifestyle, vascular risk, brain and cognition. RESULTS Adherence to a Mediterranean-style diet (MeDi) and insulin sensitivity were both positively associated with MRI-based cortical thickness (diet: βs≥0.26, insulin sensitivity βs≥0.58, P≤0.008). After accounting for vascular risk, EC in turn explained variance in memory (P≤0.001). None of the other lifestyle and vascular risk variables were associated with brain thickness. In addition, the path associations between intellectual enrichment and better cognition were significant (βs≥0.25 P≤0.001), as were those between overweight and lower cognition (βs≥-0.22, P≤0.01). CONCLUSIONS In cognitively normal middle-aged adults, MeDi and insulin sensitivity explained cortical thickness in key brain regions for AD, and EC thickness predicted memory performance in turn. Intellectual activity and overweight were associated with cognitive performance through different pathways. Our findings support further investigation of lifestyle and vascular risk factor modification against brain ageing and AD. More studies with larger samples are needed to replicate these research findings in more diverse, community-based settings.
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The effects of yoga and quiet rest on subjective levels of anxiety and physiological correlates: a 2-way crossover randomized trial.
Albracht-Schulte, K, Robert-McComb, J
BMC complementary and alternative medicine. 2018;18(1):280
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Increased stress and anxiety levels can lead to elevated cardiovascular responses and reduced capacity for stress recovery. Recent studies have found both an acute period of rest and bout of acute aerobic exercise to be effective in reducing stress, suggesting time away from stressors is what alters anxiety levels. Yoga has been reported to improve both physiological and psychological coping response to stressors, however yoga has not been studied in this context. The aim of this randomised, crossover study was to determine the effects of 30 minutes of yoga and seated rest on anxiety measures, namely heart rate variability (HRV), in forty healthy female university students. Participants were randomised to either begin with seated rest or vinyasa yoga, and after each session were shown 90 emotionally stimulating photos. Post-exposure stress and anxiety responses were measured. This study found both rest and yoga were effective for acutely reducing anxiety levels, however these positive effects did not persist after exposure to emotional stimuli. Based on these results, the authors support the theory that time away from stressors is important for reducing anxiety.
Abstract
BACKGROUND Rest or acute exercise can decrease state anxiety, with some evidence showing exercise to prevent laboratory-induced elevations in anxiety. No study has examined whether yoga provides short-term protection against laboratory-induced anxiety. The aim of this study was to examine the effectiveness of an acute YogaFit session on state anxiety and measures of heart rate variability (HRV) to determine whether yoga provides short-term protection against emotional picture stimuli. METHODS A randomized repeated-measures crossover clinical trial was performed. Forty healthy, female college students completed a 30 min session of YogaFit and a time-matched seated rest condition on separate days. After each condition, participants viewed 30 min of emotional picture stimuli. State anxiety, heart rate and time-domain and frequency-domain measures of HRV were assessed baseline, post- condition, and post-exposure to emotional stimuli. Data were analysed using a condition x time (2 × 3) repeated-measures ANOVA. RESULTS Post-hoc comparisons indicate the following: (1) state anxiety significantly decreased from baseline to post-condition for both yoga and rest (p = 0.001) but returned to baseline values following exposure to emotional stimuli (p < 0.001) for both conditions; (2) heart rate decreased post-condition to post-exposure (p = 0.020) and baseline to post-exposure (p = 0.033) for both conditions; (3) time-domain measure of HRV showed a significant increase in HRV between baseline and post-condition (p = 0 .019), post-condition and post-exposure (p = 0 .007), and between baseline and post-exposure (p < 0.001). CONCLUSIONS Both YogaFit and seated rest were effective at acutely reducing state anxiety post-condition, but not at preventing an induced anxiety response post-exposure. Following exposure to the emotionally stimulating pictures, there was a shift from the high frequency-domain to the low frequency-domain and an increase in the time-domain measure of HRV for both the YogaFit and the quiet rest condition. TRIAL REGISTRATION Retrospectively registered 2/16/2018, clinicaltrials.gov, Identifier: NCT03458702 .
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Effect of A Very Low-Calorie Ketogenic Diet on Food and Alcohol Cravings, Physical and Sexual Activity, Sleep Disturbances, and Quality of Life in Obese Patients.
Castro, AI, Gomez-Arbelaez, D, Crujeiras, AB, Granero, R, Aguera, Z, Jimenez-Murcia, S, Sajoux, I, Lopez-Jaramillo, P, Fernandez-Aranda, F, Casanueva, FF
Nutrients. 2018;10(10)
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Obesity is a multi-factorial disorder involving genetic, environmental, metabolic and behavioural factors. Few studies have examined the effect of weight-loss therapy on various psychobiological parameters associated with obesity. Therefore the aim of this 4-month nutritional intervention was to evaluate food and alcohol cravings, physical activity levels, sleep quality, sexual function and quality of life in patients with obesity after following a very low-calorie ketogenic (VLCK) diet. Twenty obese patients were enrolled and participated in psychological questionnaires and anthropometric measurements at four points throughout the intervention: at baseline, maximum ketosis, reduced ketosis and endpoint. A specialist physician and expert dietician closely monitored participants to ensure safety and duration of the ketosis state. This study found that rapid and sustained weight loss induced by a VLCK-diet is associated with better food control and improvements in quality of life in obese subjects. Based on these results, the authors conclude a VLCK-diet is a suitable and valuable treatment option for obese patients.
Abstract
Psychological well-being and hunger and food control are two relevant factors involved in the success of weight-loss therapy in treating obesity. Thus, this study aims to evaluate food and alcohol cravings, physical and sexual activity, sleep, and life quality (QoL) in obese patients following a very low-calorie ketogenic (VLCK) diet, as well as the role of weight lost and ketosis on these parameters. A battery of psychological test was performed in twenty obese patients (12 females, 47.2 ± 10.2 year and BMI of 35.5 ± 4.4) through the course of a 4-month VLCK diet on four subsequent visits: baseline, maximum ketosis, reduced ketosis, and endpoint. Each subject acted as their own control. Relevantly, the dietary-induced changes in body composition (7.7 units of BMI lost, 18 kg of fat mass (1.2 kg of visceral fat mass)) were associated with a statistically significant improvement in food craving scores, physical activity, sleepiness, and female sexual function. Overall, these results also translated in a notable enhancement in QoL of the treated obese patients. Therefore, the rapid and sustained weight and fat mass (FM) loss induced by the VLCK diet is associated with good food control and improvements in the psychological well-being parameters in obese subjects, which could contribute to the long-term success of this therapy.
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The Effect of a High-Dose Vitamin B Multivitamin Supplement on the Relationship between Brain Metabolism and Blood Biomarkers of Oxidative Stress: A Randomized Control Trial.
Ford, TC, Downey, LA, Simpson, T, McPhee, G, Oliver, C, Stough, C
Nutrients. 2018;10(12)
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A diet rich in vitamins and micronutrients, particularly B vitamins, is essential for body and brain functionality. B vitamin supplementation has been found to reduce depression, enhance mood, lessen anxiety and improve cognition. New neuroimaging techniques have shed light on the relationship between blood and neural biomarkers, connecting diet quality and brain function. The aim of this randomised, placebo-controlled, double-blind trial was to investigate the effect of 6-month high-dose B-vitamin supplementation on neural and blood biomarkers of metabolism in 32 healthy adults. Participants were randomised to consume either B-vitamin supplementation or placebo pills twice a day for six months and underwent blood tests and brain imaging before and after supplementation. This study found supplementation effectively increased vitamin B6 and B12 levels and reduced homocysteine with no changes in folate as compared with placebo. Supplementation promoted neural metabolic pathways and reduced oxidative stress and inflammation. Based on these findings, the authors conclude B-group vitamins are important for maintaining brain health in healthy adults and may play a role in prevention and alleviation of neural disease and disability.
Abstract
A diet rich in B-group vitamins is essential for optimal body and brain function, and insufficient amounts of such vitamins have been associated with higher levels of neural inflammation and oxidative stress, as marked by increased blood plasma homocysteine. Neural biomarkers of oxidative stress quantified through proton magnetic spectroscopy (1H-MRS) are not well understood, and the relationship between such neural and blood biomarkers is seldom studied. The current study addresses this gap by investigating the direct effect of 6-month high-dose B-group vitamin supplementation on neural and blood biomarkers of metabolism. Using a randomized, double-blind, placebo-controlled design, 32 healthy adults (20 female, 12 male) aged 30⁻65 years underwent blood tests (vitamin B6, vitamin B12, folate, and homocysteine levels) and 1H-MRS of the posterior cingulate cortex (PCC) and dorsolateral prefrontal cortex (DLPFC) before and after supplementation. Results confirmed the supplement was effective in increasing vitamin B6 and vitamin B12 levels and reducing homocysteine, whereas there was no change in folate levels. There were significant relationships between vitamin B6 and N-acetylaspartate (NAA), choline, and creatine, as well as between vitamin B12 and creatine (ps < 0.05), whereas NAA in the PCC increased, albeit not significantly (p > 0.05). Together these data provide preliminary evidence for the efficacy of high-dose B-group supplementation in reducing oxidative stress and inflammation through increasing oxidative metabolism. It may also promote myelination, cellular metabolism, and energy storage.
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Limbic-thalamo-cortical projections and reward-related circuitry integrity affects eating behavior: A longitudinal DTI study in adolescents with restrictive eating disorders.
Olivo, G, Wiemerslage, L, Swenne, I, Zhukowsky, C, Salonen-Ros, H, Larsson, EM, Gaudio, S, Brooks, SJ, Schiöth, HB
PloS one. 2017;12(3):e0172129
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This is a highly specialised and technical observational study using brain imaging techniques to investigate longitudinal changes in the brain white matter micro-structure in adolescent patients with restrictive eating disorders (e.g. anorexia nervosa). Twelve patients and twenty-four controls were enrolled into this study. Patients were scanned at diagnosis and after one year of family-based treatment. Brain imaging results were correlated with weight/BMI as well as clinical features of the eating disorder. The observed changes in specific regions of the brain support the hypothesis that neural pathway related to taste processing and reward-related regions are involved, and determine an alteration in food-related cognitive processing in adolescents, leading to restrictive eating behaviour. The observed changes in brain micro-structure appeared to revert after one year of follow-up. This suggests that a prompt intervention might be effective in arresting the disruption of white matter integrity that occurs during the first phases of the eating disorder, and that early treatment is of particular importance in adolescents, as during adolescence processes relating to neuronal structuring and neuroplasticity are at their maximum.
Abstract
Few studies have used diffusion tensor imaging (DTI) to investigate the micro-structural alterations of WM in patients with restrictive eating disorders (rED), and longitudinal data are lacking. Twelve patients with rED were scanned at diagnosis and after one year of family-based treatment, and compared to twenty-four healthy controls (HCs) through DTI analysis. A tract-based spatial statistics procedure was used to investigate diffusivity parameters: fractional anisotropy (FA) and mean, radial and axial diffusivities (MD, RD and AD, respectively). Reduced FA and increased RD were found in patients at baseline in the corpus callosum, corona radiata and posterior thalamic radiation compared with controls. However, no differences were found between follow-up patients and controls, suggesting a partial normalization of the diffusivity parameters. In patients, trends for a negative correlation were found between the baseline FA of the right anterior corona radiata and the Eating Disorder Examination Questionnaire total score, while a positive trend was found between the baseline FA in the splenium of corpus callosum and the weight loss occurred between maximal documented weight and time of admission. A positive trend for correlation was also found between baseline FA in the right anterior corona radiata and the decrease in the Obsessive-Compulsive Inventory Revised total score over time. Our results suggest that the integrity of the limbic-thalamo-cortical projections and the reward-related circuitry are important for cognitive control processes and reward responsiveness in regulating eating behavior.
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Brain atrophy in cognitively impaired elderly: the importance of long-chain ω-3 fatty acids and B vitamin status in a randomized controlled trial.
Jernerén, F, Elshorbagy, AK, Oulhaj, A, Smith, SM, Refsum, H, Smith, AD
The American journal of clinical nutrition. 2015;102(1):215-21
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Mild cognitive impairment (MCI) is a characterised by a decline in cognitive function between normal aging and the development of dementia. While brain atrophy occurs in normal aging, patients with MCI or dementia exhibit much higher rates of atrophy. Results from a recent trial demonstrated that homocysteine-lowering B vitamins resulted in a significant reduction in brain atrophy rates, and links between omega-3 fatty acids and homocysteine have been suggested. The purpose of this study was to investigate whether plasma omega-3 fatty acid concentrations modify the treatment effect of B vitamins on brain atrophy rates among 168 elderly adults with MCI. Participants were randomly assigned to receive placebo or high-dose vitamin B supplementation and both brain scans and plasma concentrations were done at baseline and 2 years. The findings of this study demonstrated that, in patients with high omega-3 plasma concentrations, B vitamin supplementation slowed brain atrophy by 40% compared with those in the placebo group. This indicates that the effect of B vitamin supplementation on brain atrophy rates depend on plasma omega-3 fatty acid concentrations.
Abstract
BACKGROUND Increased brain atrophy rates are common in older people with cognitive impairment, particularly in those who eventually convert to Alzheimer disease. Plasma concentrations of omega-3 (ω-3) fatty acids and homocysteine are associated with the development of brain atrophy and dementia. OBJECTIVE We investigated whether plasma ω-3 fatty acid concentrations (eicosapentaenoic acid and docosahexaenoic acid) modify the treatment effect of homocysteine-lowering B vitamins on brain atrophy rates in a placebo-controlled trial (VITACOG). DESIGN This retrospective analysis included 168 elderly people (≥70 y) with mild cognitive impairment, randomly assigned either to placebo (n = 83) or to daily high-dose B vitamin supplementation (folic acid, 0.8 mg; vitamin B-6, 20 mg; vitamin B-12, 0.5 mg) (n = 85). The subjects underwent cranial magnetic resonance imaging scans at baseline and 2 y later. The effect of the intervention was analyzed according to tertiles of baseline ω-3 fatty acid concentrations. RESULTS There was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined ω-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid) on brain atrophy rates. In subjects with high baseline ω-3 fatty acids (>590 μmol/L), B vitamin treatment slowed the mean atrophy rate by 40.0% compared with placebo (P = 0.023). B vitamin treatment had no significant effect on the rate of atrophy among subjects with low baseline ω-3 fatty acids (<390 μmol/L). High baseline ω-3 fatty acids were associated with a slower rate of brain atrophy in the B vitamin group but not in the placebo group. CONCLUSIONS The beneficial effect of B vitamin treatment on brain atrophy was observed only in subjects with high plasma ω-3 fatty acids. It is also suggested that the beneficial effect of ω-3 fatty acids on brain atrophy may be confined to subjects with good B vitamin status. The results highlight the importance of identifying subgroups likely to benefit in clinical trials. This trial was registered at www.controlled-trials.com as ISRCTN94410159.
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Neurobiologically informed treatment for adults with anorexia nervosa: a novel approach to a chronic disorder.
Knatz, S, Wierenga, CE, Murray, SB, Hill, L, Kaye, WH
Dialogues in clinical neuroscience. 2015;17(2):229-36
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Anorexia nervosa (NA) is a serious disorder that can have significant medical and psychological impairment. The magnitude of its impact and risk to long-term health means the development of an effective treatment protocol is of critical importance. Advances in brain imaging have led to an improved understanding of the disease. Studies suggest that AN individuals tend to have specific personality traits related to neural circuit functions that can maintain the disorder. These include perfectionism, anxiety, inflexibility and harm avoidance. Imaging data suggests that anticipated anxiety may contribute to food restriction. Treatment is moving from focusing on symptoms to the psychopathology and physiology underpinning the disorder. The Neurobiologically Enhanced With Family Eating Disorder Trait Response Treatment (NEW FED TR) was developed on the basis of neurobiology and AN specific etiology. It is delivered to AN patients and their carers (friends, family, spouse, siblings) and targets their cognitions and eating behaviours.
Abstract
Anorexia nervosa (AN) is a severe and debilitating disorder with significant medical and psychological sequelae. To date, there are no effective treatments for adults, resulting in high rates of chronicity, morbidity, and mortality. Recent advances in brain imaging research have led to an improved understanding of etiology and specific neurobiological mechanisms underlying symptoms. Despite this, there are no treatments focused on targeting symptoms using this empirically supported mechanistic understanding of the illness. Updated treatment approaches focused on targeting neurobiological mechanisms underlying core AN symptomatology are necessary to improve treatment out-comes for this population. Neurobiologically Enhanced With Family Eating Disorder Trait Response Treatment (NEW FED TR) is a neurobiologically informed treatment targeting key temperament constructs associated with the illness through the delivery of psychoeducation and skills training to patients and nominated carers. La anorexia nerviosa (AN) es un trastorno grave y debilitante con importantes secuelas médicas y psicológicas. A la fecha no existen tratamientos efectivos para adultos, lo que lleva a altas frecuencias de cronicidad, morbilidad y mortalidad. Avances recientes en la investigación imaginológica han conducido a un progreso en la comprensión de la etiología y de los mecanismos neurobiológicos específicos de los síntomas subyacentes. A pesar de esto, no existen tratamientos enfocados en los síntomas blanco que utilicen esta comprensión mecanicista con un sus-tento empírico de la enfermedad. Para mejorar los resultados terapéuticos para esta población es necesario que las aproximaciones terapéuticas actuales se enfoquen en los mecanismos neurobiológicos blanco a la base de la sintomatología central de la AN. El NEW FED TR (Neuro-biologically Enhanced With Family Eating Disorder Trait Response Treatment) es un tratamiento neurobiológicamente informado que apunta a constructos temperamentales clave asociados con la enfermedad a través de la entrega de psicoeducación y entrenamiento en herramientas para pacientes y cuidadores designados. L'anorexie mentale est une maladie sévère et invalidante aux séquelles médicales et psychologiques importantes. À ce jour, il n'existe pas de traitement efficace chez l'adulte ; les taux de chronicité, morbidité et mortalité sont donc élevés. Des avancées récentes de la recherche en imagerie cérébrale ont permis de mieux comprendre l'étiologie et les mécanismes neurobiologiques spécifiques à l'origine des symptômes. Mais malgré cela, aucun traitement ciblant les symptômes et fondé sur cette compréhension mécanistique de la maladie sur des bases empiriques n'a vu le jour. Améliorer les résultats des traitements pour cette population nécessite d'actualiser ceux qui ciblent les mécanismes neurobiologiques au coeur de l'anorexie mentale. Le NEW FED TR (Neurobiologically Enhanced With Family Eating Disorder Trait Response Treatment) est un programme thérapeutique neurobiologique ciblant les concepts de personnalité clés associés à la maladie en faisant bénéficier les patients et les soignants désignés de mesures psychoéducatives et d'acquisition de compétences.
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Zinc supplementation in the treatment of anorexia nervosa.
Brazilian Association of Nutrology
Revista da Associacao Medica Brasileira (1992). 2013;59(4):321-4
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Anorexia nervosa (AN) is a disorder characterised by significant weight loss, restrictive diets, a search for thinness and a distortion of body image. Zinc is a key micronutrient that plays essential roles in the body including in gene transcription regulation and enzyme reactions. There is a similarity between symptoms of zinc deficiency and AN; namely weight loss, changes in appetite and sexual dysfunction. This review aims to provide healthcare professionals with insight into the nutritional recommendations for zinc in patients with AN. The review suggests that there are clinical studies demonstrating a strong association between AN and low levels of serum zinc and low levels of urinary zinc suggesting a micronutrient deficiency in these individuals. The severity of zinc deficiency is associated with greater weight deficits and longer AN duration. It is also associated with higher levels of anxiety and depression in AN individuals. Zinc is key in smell and taste perception and the brain regions associated with interpreting eating as pleasurable. Reduced food intake and practices like purging and low-zinc diets may exacerbate any low levels and impair zinc absorption. A controlled study showed that oral supplementation resulted in a higher rate of body mass index (BMI) increase and an improvement in neurotransmitters. The review recommends: 1. Check serum levels of zinc in AN patients as it may be low. Zinc status may contribute to eating behaviour including gaining pleasure from eating, smell and taste. 2. Zinc supplementation of 15mg/daily for preventative purposes and 15-20mg/daily if zinc deficiency is identified after testing. The review recommends supplementation for a minimum of 2 months.
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Effectiveness and safety of citicoline in mild vascular cognitive impairment: the IDEALE study.
Cotroneo, AM, Castagna, A, Putignano, S, Lacava, R, Fantò, F, Monteleone, F, Rocca, F, Malara, A, Gareri, P
Clinical interventions in aging. 2013;8:131-7
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The number of people aged 65 years and over with mild vascular cognitive impairment is continuing to increase. Vascular disease can reduce cerebral perfusion, causing oxidative stress and neurodegeneration. Citicoline [pharmaceutical] inhibits apoptosis associated with cerebral ischemia and in several models of neurodegeneration has been able to potentiate neuroplasticity. The aim of this study was to assess the effectiveness and safety of oral citicoline in elderly people with mild vascular cognitive impairment. A total of 349 patients were included in the study who were assigned to open-label treatment with oral citicoline 500 mg twice a day in a fasting state or to no treatment (controls). Results show that citicoline is effective and safe in the treatment of mild vascular cognitive impairment. The treated group showed improvement in MMSE (Mini-Mental State Examination) scores, with an increase of 0.5 points shown over the course of the study. Authors conclude that further studies are required in order to confirm the findings of this study, and to further assess the efficacy and safety of long-term administration of a dietary supplement such as Cytidine-5′-diphosphate choline.
Abstract
BACKGROUND The studio di intervento nel decadimento vascolare lieve (IDEALE study) was an open multicenter Italian study, the aim of which was to assess the effectiveness and safety of oral citicoline in elderly people with mild vascular cognitive impairment. METHODS The study was performed in 349 patients. The active or citicoline group was composed of 265 patients and included 122 men and 143 women of mean age 79.9 ± 7.8 years selected from six Italian regions. Inclusion criteria were age ≥ 65 years, Mini-Mental State Examination (MMSE) score ≥ 21, subjective memory complaints but no evidence of deficits on MMSE, and evidence of vascular lesions on neuroradiology. Those with probable Alzheimer's disease were excluded. The control group consisted of 84 patients, including 36 men and 48 women of mean age 78.9 ± 7.01 (range 67-90) years. Patients included in the study underwent brain computed tomography or magnetic resonance imaging, and plasma dosage of vitamin B12, folate, and thyroid hormones. Functional dependence was investigated by scores on the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales, mood was assessed by the Geriatric Depression Scale (GDS), and behavioral disorders using the Neuropsychiatric Inventory scale. Comorbidity was assessed using the Cumulative Illness Rating Scale. An assessment was made at baseline (T0), after 3 months (T1), and after 9 months (T2, ie, 6 months after T1). The main outcomes were an improvement in MMSE, ADL, and IADL scores in the study group compared with the control group. Side effects were also investigated. The study group was administered oral citicoline 500 mg twice a day throughout the study. RESULTS MMSE scores remained unchanged over time (22.4 ± 4 at T0; 22.7 ± 4 at T1; 22.9 ± 4 at T2), whereas a significant difference was found between the study and control groups, both in T1 and in T2. No differences were found in ADL and IADL scores between the two groups. A slight but not statistically significant difference was found in GDS score between the study and control groups (P = 0.06). No adverse events were recorded. CONCLUSION In this study, citicoline was effective and well tolerated in patients with mild vascular cognitive impairment. Citicoline activates biosynthesis of phospholipids in neuronal membranes, increases brain metabolism as well as norepinephrine and dopamine levels in the central nervous system, and has neuroprotective effects during hypoxia and ischemia. Therefore, citicoline may be recommended for patients with mild vascular cognitive impairment.