vitamin-k-semiquinone-radical and Cognition-Disorders

Epidemiological studies and basic research suggest a protective effect of long-chain omega-3 polyunsaturated fatty acids, antioxidants and B vitamins against brain aging. However, most randomized controlled trial (RCTs) with nutritional supplements have yielded disappointing effects on cognition so far. This paper suggests some original directions for future research to better support a role of nutrition in brain aging. The role of other nutrients such as docosapentaenoic acid and fat-soluble vitamins D and K should be investigated. A more holistic approach of nutrition is necessary, encompassing potential synergies between nutrients as found in a balanced diet. Potential beneficiaries of a nutritional supplementation should be better targeted, according to their dietary, cognitive and maybe genetic characteristics. Innovative RCTs should be implemented to assess the impact of nutrition for the prevention or treatment of cognitive decline in older persons, using intermediate biomarkers of disease progression and mechanisms of action of nutrients as outcomes.

Topics: Aged; Aging; Antioxidants; Brain; Cognition; Cognition Disorders; Dietary Supplements; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Feeding Behavior; Humans; Nutritional Status; Randomized Controlled Trials as Topic; Vitamin B Complex; Vitamin D; Vitamin K

The human gastrointestinal tract harbors trillions of bacteria, most of which are commensal and have adapted over time to the milieu of the human colon. Their many metabolic interactions with each other, and with the human host, influence human nutrition and metabolism in diverse ways. Our understanding of these influences has come through breakthroughs in the molecular profiling of the phylogeny and the metabolic capacities of the microbiota. The gut microbiota produce a variety of nutrients including short-chain fatty acids, B vitamins, and vitamin K. Because of their ability to interact with receptors on epithelial cells and subepithelial cells, the microbiota also release a number of cellular factors that influence human metabolism. Thus, they have potential roles in the pathogenesis of metabolic syndrome, diabetes, non-alcoholic fatty liver disease, and cognition, which extend well beyond their traditional contribution to nutrition. This review explores the roles of the gut microbiota in human nutrition and metabolism, and the putative mechanisms underlying these effects.

Topics: Animals; Bacterial Physiological Phenomena; Carbohydrate Metabolism; Cognition Disorders; Diabetes Mellitus; Energy Metabolism; Epithelial Cells; Fatty Acids, Volatile; Fatty Liver; Fermentation; Food; Gastrointestinal Tract; Humans; Intestinal Absorption; Lipid Metabolism; Metabolic Syndrome; Mice; Minerals; Non-alcoholic Fatty Liver Disease; Nutritional Physiological Phenomena; Obesity; Proteins; Vitamin B Complex; Vitamin K

Topics: Biological Availability; Bone and Bones; Cognition Disorders; Humans; Osteoporosis; Oxidative Stress; Vitamin K; Vitamins

The incidence of atrial fibrillation (AF) and of thromboembolic complications increases along with age. This is also the case for cognitive function disturbances; therefore their occurrence in patients (pts) with AF may hamper control of anticoagulant therapy and maintenance of therapeutic INR values. The aim of the study was to evaluate the effect of cognitive function disturbances on implementation and monitoring of the treatment with oral vitamin K antagonists (VKA) in patients with AF. The relationship between the level of cognitive function disturbances and the severity of experienced AF symptoms was defined.. The analysis included a group of 93 pts (41 males, 52 females, mean age: 76.8) with a diagnosis of AF and with indications for anticoagulation treatment with VKAs (CHA2DS2VASc > or = 2, HAS-BLED < 3), referred to the Clinic of Internal Diseases and Clinical Pharmacology of the Medical University of Lodz. In a group of pts (n = 46) treated chronically with VKAs, mean INR values at admission to the hospital were calculated and the number of results falling within the therapeutic range of 2-3, by the severity of cognitive disturbances, was analyzed. Cognitive abilities were assessed with the Mini Mental State Examination Scale (MMSE) (MMSE-Mini-mental state examination). The EHRA (European Heart Rhythm Association) classification was used to assess AF-related complaints.. The 93 studied subjects were divided into 3 groups: group I with normal cognitive function (MMSE = 24-27) - n = 35; group II with disturbances of cognitive function without dementia (MMSE = 24-26) - n = 35 and group III with dementia (MMSE < 24) - n = 23.66% of pts with normal MMSE result were referred to the hospital because AF-related symptoms and in the group of patients with MMSE < 24 these symptoms were the cause of hospitalization in 23% of pts. Despite the fact that all patients had indications for VKAs, this treatment was not started in 40%, 51.4% and 65% of pts in group I, II and III, respectively. At admission to the hospital, therapeutic level INR values were found only in 34.8% of AF pts. 49% of pts were treated with VKAs in total. In group II, a high percentage of patients (43%) treated with aspirin was found in spite of high thromboembolic risk and no contraindications to VKAs. About 23% of pts with a normal MMSE result and 14% of pts in group II experienced AF-related symptoms preventing them from normal functioning and performing daily activities (EHRA IV). Nobody in group III reported severe AF-related symptoms.. Along with the advancing age, there is an increase of the incidence of persistent and fixed atrial fibrillation, of the risk of thromboembolic complications and of the severity of cognitive function disturbances. Treatment with oral vitamin K antagonists was implemented much less frequently among patients with atrial fibrillation and cognitive function disturbances, as compared to the patients with normal cognitive function. The MMSE test should be routinely performed in patients with atrial fibrillation to monitor the efficacy and safety of the treatment with oral vitamin K antagonists properly. In patients with disturbances of cognitive function, significantly lower reportability of AF-related complaints was shown, as compared to individuals without these disturbances. Patients with normal MMSE result were referred to the hospital because AF-related symptoms, in the group of patients with MMSE < 23 the main reason for hospitalization was the severity of the symptoms heart failure. ECG should be a routine test performed in elderly patients with cognitive function disturbances or with dementia to detect atrial fibrillation.

Topics: Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cognition Disorders; Comorbidity; Dementia; Drug Monitoring; Drug Utilization; Electrocardiography; Female; Humans; Incidence; Male; Middle Aged; Thromboembolism; Vitamin K

Vitamin K participates in brain physiology. This study aimed to determine whether using vitamin K antagonists (VKAs), which interfere with the vitamin K cycle, were (i) cross-sectionally associated with altered cognitive performance, and (ii) independent predictors of cognitive changes in older adults over 24 months. Information was collected on the use of VKAs (i.e., warfarin, acenocoumarol, and fluindione) among 378 geriatric outpatients (mean, 82.3 ± 5.6 years; 60.1% female). Global cognitive performance and executive functions were assessed with Mini-Mental State Examination (MMSE) and Frontal Assessment Battery (FAB) scores, respectively, at baseline and after 12 and 24 months of follow-up. Age, gender, body mass index, mean arterial pressure, disability, gait speed, comorbidities, atrial fibrillation, stroke, carotid artery stenosis, leukoaraiosis grade on computed tomography (CT) scan, psychoactive drugs, antidementia drugs, blood-thinning drugs (i.e., anticoagulants other than VKAs, antiplatelet medications), serum creatinine levels, and vitamin B12 concentrations were considered as potential confounders. Using VKAs was associated with lower (i.e., worse) FAB score at baseline (adjusted β = -2.1,

Topics: Age Factors; Aged; Aged, 80 and over; Anticoagulants; Cognition; Cognition Disorders; Cognitive Aging; Cross-Sectional Studies; Executive Function; Female; Geriatric Assessment; Humans; Male; Mental Status and Dementia Tests; Prospective Studies; Risk Factors; Time Factors; Vitamin K

A growing body of evidence supports a beneficial role for vitamin K in brain and cognition, notably in studies where animals are rendered vitamin K deficient by warfarin, a potent vitamin K antagonist (VKA). Given VKAs are commonly used oral anticoagulants in older persons, we investigated the relationship between VKA therapy and cognitive performances over 10 years in participants of the Three-City study.. The Three-City cohort included 7,133 nondemented community dwellers, aged 65 years or older at baseline. Exposures to VKAs and platelet aggregation inhibitors, another antithrombotic agent, were determined at baseline. Participants underwent cognitive assessment at baseline and every 2 years over 10 years. Associations were analyzed with mixed linear models adjusting for many covariates including VKA and platelet aggregation inhibitor indications.. About 239 (3.4%) and 1,192 (16.7%) of the participants were treated with VKAs and platelet aggregation inhibitors at baseline, respectively. VKA treatment was significantly associated with worse performances on Benton Visual Retention Test assessing visual memory (adjusted mean difference -0.29; p = .02 in multivariate models) and Isaacs Set Test assessing verbal fluency (adjusted mean difference -1.37; p = .0009) at baseline. Treatment with VKAs was not associated with global cognitive functioning on the Mini Mental State Examination, neither with rate of subsequent decline in scores on all three cognitive tests. No associations were found between platelet aggregation inhibitors and cognitive performances or rate of decline.. These findings do not indicate a long-term detrimental effect of VKAs on cognition, but the risk-benefit balance of VKA treatment still deserves further research.

Topics: Aged; Anticoagulants; Antithrombins; Cognition Disorders; Female; France; Geriatric Assessment; Humans; Longitudinal Studies; Male; Neuropsychological Tests; Platelet Aggregation Inhibitors; Prospective Studies; Risk Factors; Vitamin K

Increased dietary intake of vitamin K, a fat-soluble nutrient involved in brain health and function, has been associated with better cognitive performance in older adults. Our objective was to determine whether the dietary vitamin K intake was associated with the presence and severity of subjective memory complaint among older adults.. Observational, cross-sectional cohort study.. One hundred sixty older adults taking no vitamin K antagonist were included. The daily dietary vitamin K intake was assessed using a 50-item food frequency questionnaire. The subjective memory complaint was assessed at the same time using the Memory Complaint Questionnaire (MAC-Q; score 0-30, best). Serious subjective memory complaint was defined as MAC-Q score ≤15. Age, gender, body mass index, education level, number of comorbidities, history of stroke, objective cognitive disorders, functional autonomy, mood, serum concentrations of vitamin B12, TSH, albumin, and estimated glomerular filtration rate were used as potential confounders.. Compared to participants without serious subjective memory complaint, those with serious subjective memory complaint (n=110) had a lower mean dietary vitamin K intake (298.0±191.8μg/day versus 393.8±215.2μg/day, P=0.005). Increased log dietary vitamin K intake was positively associated with the MAC-Q score used as a quantitative variable (fully adjusted β=0.79, P=0.031), and inversely with serious subjective memory complaint (fully adjusted OR=0.34, P=0.017).. Increased dietary vitamin K intake was associated with fewer and less severe subjective memory complaint in older adults taking no vitamin K antagonists. These findings provide epidemiological data supporting future vitamin K replacement trials.

Topics: Aged; Aged, 80 and over; Cognition Disorders; Cohort Studies; Cross-Sectional Studies; Diet; Female; Humans; Male; Memory; Surveys and Questionnaires; Vitamin K

Vitamin K is involved in brain physiology, suggesting that its deficiency induces cognitive decline. Our objective was to determine whether using vitamin K antagonists (VKAs) was associated with cognitive impairment among geriatric patients.. Two hundred sixty-seven older patients (mean, 83.4 ± 8.1 years; 56.9% female) were categorized according to cognitive impairment (ie, Mini-Mental State Examination ≤ 25). The regular use of VKAs was sought by questioning the patients, relatives, and family physicians. Age, gender, body mass index, comorbidity burden, mood and executive functioning, history of atrial fibrillation, ischemic stroke, intracranial hemorrhage and transient ischemic attack, use of other anticoagulants and antiplatelet medications, and severe renal failure were used as potential confounders.. Compared with participants without cognitive impairment (n = 70), those with Mini-Mental State Examination ≤ 25 used more frequently VKAs (p = .038). The risk of cognitive impairment was 15% higher with VKAs, specifically with fluindione. Using VKAs was independently associated with cognitive impairment (fully adjusted odds ratio = 17.4 [95% CI: 1.4-224.2], p = .028).. We found more frequent cognitive impairment associated with the use of VKAs, specifically fluindione, among geriatric patients.

Topics: Aged; Aged, 80 and over; Aging; Anticoagulants; Atrial Fibrillation; Cognition Disorders; Cross-Sectional Studies; Female; Humans; Male; Mental Status Schedule; Phenindione; Pilot Projects; Risk Factors; Stroke; Vitamin K

Topics: Aged; Antifibrinolytic Agents; Atrophy; Biological Availability; Cognition Disorders; Female; Hippocampus; Humans; Intelligence Tests; Magnetic Resonance Imaging; Male; Neuroimaging; Sphingolipids; Statistics as Topic; Vitamin K; Vitamin K Deficiency

The aim of this study was to examine the association between dephospho-uncarboxylated matrix Gla protein (dp-ucMGP), an indicator of vitamin K status, and cognitive decline, and the modifying role of 25(OH)D.. Longitudinal study with six years follow-up.. Community based.. 599 participants of the Longitudinal Aging Study Amsterdam (aged 55-65 years).. Information processing speed and a composite Z-score by combining three domains of cognition reflecting general cognitive functioning.. Generalized estimating equations (GEE) showed no significant associations between dp-ucMGP and decline in general cognitive functioning. Vitamin D modified the association between dp-ucMGP and speed of information processing (p<0.05). In the group with a 25(OH)D concentration > 50 nmol/l, the highest tertile of dp-ucMGP (>406 pmol/l), which corresponds to lower vitamin K levels, was associated with 1.5 higher score on information processing speed (p=0.023) as compared to the lowest tertile of dp-ucMGP.. In contrast to our hypothesis, a suboptimal vitamin K was not associated with cognitive decline in middle-aged adults.

Topics: Calcium-Binding Proteins; Cognition; Cognition Disorders; Extracellular Matrix Proteins; Female; Humans; Longitudinal Studies; Male; Matrix Gla Protein; Middle Aged; Nutritional Status; Vitamin D; Vitamin K; Vitamin K Deficiency; Vitamins

Nowadays, anticoagulant therapy belongs to the most commonly used forms of pharmacotherapy in modern medicine. The most important representatives of anticoagulants are heparins (unfractionated heparin and low-molecular-weight heparin) and coumarin derivatives (vitamin K antagonists--VKA). Next to the many advantages of traditional oral anticoagulants may also have disadvantages. In Poland most often used two VKA: acenocoumarol and warfarin. The aim of the work is the analysis of the causes of the occurrence of bleeding disorders and symptoms of overdose VKA in patients to be hospitalized. In the years 2012 to 2014 were hospitalized 62 patients with overdose VKA (40 women and 22 men). The average age of patients was 75.3 years) and clotting disturbances and/or bleeding. At the time of the admission in all patients a significant increase in the value of the INR was stated, in 22 patients INR result was " no clot detected", on the remaining value of the INR were in the range of 7 to 13.1. On 51 patients observed different severe symptoms of bleeding (hematuria, bleeding from mucous membranes of the nose or gums ecchymoses on the extremities, bleeding from the gastrointestinal tract--as in 5 patients has led to significant anemia and transfusion of concentrated red blood cells. Up on 33 patients kidney function disorder were found--exacerbated chronic renal failure and urinary tract infection. 8 diagnosed inflammatory changes in the airways. On 13 patients, it was found a significant degree of neuropsychiatric disorders (dementia, cognitive impairment), which made impossible the understanding the sense of treatment and cooperation with the patient. In 6 patients the symptoms of overdose were probably dependent on the interaction with the congestants at the same time (change the preparation of anticoagulant, NSAIDs, antibiotics). In 2 cases, the overdose was a suicide attempt in nature. In addition to the above mentioned disorders, on two of those patients diagnosed with a malignant disease. Two patients died, the other has been improving and anticoagulant therapy with VKA was continued, in 4 VKA were changed to low-molecular-weight heparin, and on 4 commissioned new generation anticoagulant (rivaroxaban).

Topics: Acenocoumarol; Aged; Aged, 80 and over; Anticoagulants; Cognition Disorders; Dementia; Drug Interactions; Drug Overdose; Female; Humans; Male; Neoplasms; Poland; Suicide, Attempted; Vitamin K; Warfarin

Presentation of three controversial drugs with unequal value and of new anticoagulation strategies. The renewal of interest in oral anticoagulants is striking; it is the consequence of the better measure of the hypocoagulability and a diminution of the risk of haemorrhage. Also as striking, is the extension of the preventive and curative indications of the low molecular weight heparins.

Topics: Aged; Anticoagulants; Cholinesterase Inhibitors; Circadian Rhythm; Cognition Disorders; Heroin Dependence; Humans; Melatonin; Methadone; Narcotics; Tacrine; Vitamin K