Background: Measurement of plasma total homocysteine has become common as new methods have been introduced. A wide range of disorders are associated with increased concentrations of total homocysteine. The purpose of this review is to provide an international expert opinion on the practical aspects of total homocysteine determinations in clinical practice and in the research setting and on the relevance of total homocysteine measurements as diagnostic or screening tests in several target populations. Methods: Published data available on Medline were used as the basis for the recommendations. Drafts of the recommendations were critically discussed at meetings over a period of 3 years. Outcome: This review is divided into two sections: (a) determination of homocysteine (methods and their performance, sample collection and handling, biological determinants, reference intervals, within-person variability, and methionine loading test); and (b) risk assessment and disease diagnosis (homocystinuria, folate and cobalamin deficiencies, cardiovascular disease, renal failure, psychiatric disorders and cognitive impairment, pregnancy complications and birth defects, and screening of elderly and newborns). Each of these subsections concludes with a separate series of recommendations to assist the clinician and the research scientist in making informed decisions. The review concludes with a list of unresolved questions.

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Facts and Recommendations about Total Homocysteine Determinations: An Expert Opinion

Nutrient reference values for Australia and New Zealand: Including recommended dietary intakes

Cholinesterase Inhibitors in Alzheimer's Disease

The purpose of this guideline is to present evidence-based and consensus-based recommendations for the prevention and treatment of postoperative delirium. The cornerstones of the guideline are the preoperative identification and handling of patients at risk, adequate intraoperative care, postoperative detection of delirium and management of delirious patients. The scope of this guideline is not to cover ICU delirium. Considering that many medical disciplines are involved in the treatment of surgical patients, a team-based approach should be implemented into daily practice. This guideline is aimed to promote knowledge and education in the preoperative, intraoperative and postoperative setting not only among anaesthesiologists but also among all other healthcare professionals involved in the care of surgical patients.

European Society of Anaesthesiology evidence-based and consensus-based guideline on postoperative delirium

Among polyunsaturated omega-3 fatty acids, ALA (alpha-linolenic acid) provided the first coherent multidisciplinary experimental demonstration of the effect of diet (one of its major macronutrient) on the structure, the biochemistry, the physiology and thus the function of the brain. In fact, DHA (docosahexaenoic acid) is one for the major building structures of membrane phospholipids of brain and absolute necessary of neuronal function. It was first demonstrated that the differentiation and functioning of cultured brain cells requires not only ALA, but also the very long polyunsaturated omega-3 (DHA) and omega-6 carbon chains. Then, it was found that ALA acid deficiency alters the course of brain development, perturbs the composition of brain cell membranes, neurones, oligodendrocytes and astrocytes, as well as sub cellular particles such as myelin, nerve endings (synaptosomes) and mitochondria. These alterations induce physicochemical modifications in membranes, lead to biochemical and physiological perturbations, and results in neurosensory and behavioural upset. Consequently, the nature of polyunsaturated fatty acids (in particular omega-3, ALA and DHA) present in formula milks for infants (premature and term) conditions the visual, neurological and cerebral abilities, including intellectual. Dietary omega-3 fatty acids are involved in the prevention of some aspects of ischemic cardiovascular disease (including at the level of cerebral vascularization), and in some neuropsychiatric disorders, particularly depression, as well as in dementia, including Alzheimer's disease and vascular dementia. The implication of omega-3 fatty acids in major depression and bipolar disorder (manic-depressive illness) is under evaluation. Their dietary deficiency (and altered hepatic metabolism) can prevent the renewal of membranes and consequently accelerate cerebral ageing; nonetheless, the respective roles of the vascular component on one hand and the cerebral parenchyma itself on the other have not yet been clearly elucidated. Low fat diet may have adverse effects on mood. The nature of the amino acid composition of dietary proteins contributes to cerebral function; taking into account that tryptophan plays a special role. In fact, some indispensable amino acids present in dietary proteins participate to elaborate neurotransmitters (and neuromodulators). The regulation of glycaemia (thanks to the ingestion of food with a low glycaemic index ensuring a low insulin level) improves the quality and duration of intellectual performance, if only because at rest the brain consumes more than 50% of dietary carbohydrates, approximately 80% of which are used only for energy purpose. In infants, adults and aged, as well as in diabetes, poorer glycaemic control is associated with lower performances, for instance on tests of memory. At all ages, and more specifically in aged people, some cognitive functions appear sensitive to short term variations in glucose availability. The presence of dietary fibbers is associated with higher alertness ratings and ensures less perceived stress. Although an increasing number of genetic factors that may affect the risk of neurodegenerative disorders are being identified, number of findings show that dietary factors play major roles in determining whether the brain age successfully of experiences neurodegenerative disorders. Effects of micronutrients have been examined in the accompanying paper.

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Effects of nutrients (in food) on the structure and function of the nervous system: update on dietary requirements for brain. Part 1: micronutrients.

Role of cobalamin intake and atrophic gastritis in mild cobalamin deficiency in older Dutch subjects.

Background. Mild cobalamin (Cbl) deficiency is frequently found in older persons and is associated with cognitive and cerebral abnormalities. The effects of Cbl supplementation on these abnormalities are largely unknown. 
Methods. In a single-blind, placebo-controlled intervention study, 16 healthy community-dwelling elderly subjects with low plasma Cbl concentration and no cognitive impairments were studied. Subjects underwent 1 month of treatment with placebo, followed by 5 months of treatment with intramuscular injections of hydroxycobalamin. Before and after measurements of plasma cobalamin, total homocysteine (tHcy), methylmalonic acid (MMA), quantitative electroencephalograph (qEEG), and psychometric tests were taken. 
Results. After Cbl supplementation, plasma Cbl concentrations increased, and plasma MMA and tHcy concentrations decreased. The performance on the Verbal Word Learning Test, Verbal Fluency and Similarities improved. qEEG showed more fast activity and less slow activity. Lower plasma tHcy concentrations were related to increased fast activity on qEEG on the one hand and improved performance on the Verbal Word Learning Test and Similarities on the other. Increased fast or decreased slow activity on qEEG was associated with improved performance on the Verbal Word Learning Test, Similarities and Verbal Fluency. 
Conclusions. Electrographic signs of improved cerebral function and improved cognitive function were found after Cbl supplementation in older subjects with low plasma Cbl concentrations who were free of significant cognitive impairment. These improvements were related to a reduction of plasma tHcy concentration.

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Cobalamin Supplementation Improves Cognitive and Cerebral Function in Older, Cobalamin-Deficient Persons

Objetives
To determine the prevalence of malnutrition and its relation to various factors in community-dwelling elderly with newly diagnosed Alzheimer’s disease (AD)

Nutritional status of community-dwelling elderly with newly diagnosed Alzheimer's disease: prevalence of malnutrition and the relation of various factors to nutritional status.

Background: It is still a commonly held belief that many of the frequently found low cobalamin (Cbl, vitamin B12) levels in older people do not represent deficiency and are therefore without clinical significance and should not be treated. In this study this notion will be challenged. Methods: In this prospective observational cohort design we studied 28 patients aged 65 years and older with low plasma Cbl (≤150 pmol/l). A number of haematological (Hb, MCV, five- and six-lobed granulocytes), metabolic (plasma levels of methylmalonic acid and homocysteine), and gastrointestinal (plasma pepsinogen A and C and protein-bound and free Cbl absorption) parameters, and the response to Cbl treatment, were measured. Cbl deficiency was considered to be present when at least one of the following three criteria was fulfilled: (1) haematological or metabolic abnormalities compatible with Cbl deficiency; (2) Cbl malabsorption or atrophic gastritis; (3) a response to Cbl supplementation. Results: Haematological or metabolic abnormalities were identified in 27 patients. Atrophic gastritis and Cbl malabsorption were identified in, respectively, 15 and 23 patients. Each treated patient showed a haematological or metabolic response to Cbl supplementation. All patients were considered Cbl deficient: 18 patients (64%) fulfilled three criteria of Cbl deficiency, eight (29%) fulfilled two criteria and two (7%) fulfilled one criterion. Conclusions: According to the generally accepted and a wide variety of criteria, we found that older patients with low Cbl levels were cobalamin deficient. Therefore, these patients should receive Cbl supplementation.

https://home.kpn.nl/hindrikdejong/TheNedJouMed-2000-57.pdf

Clinical significance of low cobalamin levels in older hospital patients.

Aims To investigate the nasal absorption of hydroxocobalamin in 10 healthy elderly adults. Methods In a cross-over study, blood samples were collected before administration of the drug and after 10, 20, 30, 40, 60, 120, 180 and 240 min. The plasma cobalamin concentration was determined by competitive radioisotope binding technique. Results The maximal plasma cobalamin concentration (Cmax) after nasal administration of 750 microg hydroxocobalamin was 1900 +/- 900 pmol l(-1) (mean +/- s.d.). The maximal plasma cobalamin concentration was reached in 35 +/- 13 min (t[max]). The Cmax after nasal administration of 1500 microg hydroxocobalamin was 3500 +/- 2500 pmol l(-1) with a t(max) of 28 +/- 16 min. Both the AUC(0,240 min) and AUC(0,00) increased significantly with an increase of the dose from 750 microg to 1500 microg (P = 0.037 and P = 0.028, respectively). The nasal spray was well tolerated. No signs of irritation or local sensitivity were noted. Conclusions The nasal absorption of hydroxocobalamin in healthy elderly adults is rapid, high and well tolerated.

/pdf/nasal-absorption-of-hydroxocobalamin-in-healthy-elderly-3zv61bc6b1.pdf

D.Z.B. van Asselt

Papers

Role of cobalamin intake and atrophic gastritis in mild cobalamin deficiency in older Dutch subjects.

Cobalamin Supplementation Improves Cognitive and Cerebral Function in Older, Cobalamin-Deficient Persons

Nutritional status of community-dwelling elderly with newly diagnosed Alzheimer's disease: prevalence of malnutrition and the relation of various factors to nutritional status.

Clinical significance of low cobalamin levels in older hospital patients.

Nasal absorption of hydroxocobalamin in healthy elderly adults