Effect of fish-oil supplementation on mental well-being in older subjects: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: It is suggested that a low intake of fish and/or n-3 PUFA is associated with depressed mood. However, results from epidemiologic studies are mixed, and randomized trials have mainly been performed in depressed patients, yielding conflicting results. OBJECTIVE: We investigated the effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mental well-being in a double-blind, placebo-controlled trial. DESIGN: Independently living individuals (n = 302) aged > or =65 y were randomly assigned to consume 1800 mg/d EPA+DHA, 400 mg/d EPA+DHA, or placebo capsules for 26 wk. Changes in mental well-being were assessed as the primary outcome with the Center for Epidemiologic Studies Depression Scale (CES-D), Montgomery-Asberg Rating Scale (MADRS), Geriatric Depression Scale (GDS-15), and Hospital Anxiety and Depression Scale (HADS-A). RESULTS: Plasma concentrations of EPA+DHA increased by 238% in the high-dose and 51% in the low-dose fish-oil group compared with the placebo group, reflecting excellent compliance. Baseline CES-D scores ranged from 5.9 to 6.8 in the 3 groups and were not significantly different between groups. Mean changes in CES-D scores after 26 wk were -0.2, 0.2, and -0.4 (P = 0.87) in the high-dose fish oil, low-dose fish oil, and placebo groups, respectively. Treatment with neither 1800 mg nor 400 mg EPA+DHA differentially affected any of the measures of mental well-being after 13 or 26 wk of intervention compared with placebo. CONCLUSIONS: In this randomized, double-blind, placebo-controlled trial we observed no effect of EPA+DHA supplementation for 26 wk on mental well-being in the general older population studied. This trial was registered at clinicaltrials.gov as NCT00124852.

Community occupational therapy for older patients with dementia and their care givers: cost effectiveness study.

OBJECTIVE: To assess the cost effectiveness of community based occupational therapy compared with usual care in older patients with dementia and their care givers from a societal viewpoint. DESIGN: Cost effectiveness study alongside a single blind randomised controlled trial. SETTING: Memory clinic, day clinic of a geriatrics department, and participants' homes. Patients 135 patients aged > or =65 with mild to moderate dementia living in the community and their primary care givers. INTERVENTION: 10 sessions of occupational therapy over five weeks, including cognitive and behavioural interventions, to train patients in the use of aids to compensate for cognitive decline and care givers in coping behaviours and supervision. MAIN OUTCOME MEASURES: Incremental cost effectiveness ratio expressed as the difference in mean total care costs per successful treatment (that is, a combined patient and care giver outcome measure of clinically relevant improvement on process, performance, and competence scales) at three months after randomisation. Bootstrap methods used to determine confidence intervals for these measures. RESULTS: The intervention cost 1183 euros (848 pounds sterling, $1738) (95% confidence interval 1128 euros (808 pounds sterling, $1657) to 1239 euros (888 pounds sterling, $1820)) per patient and primary care giver unit at three months. Visits to general practitioners and hospital doctors cost the same in both groups but total mean costs were 1748 euros (1279 pounds sterling, $2621) lower in the intervention group, with the main cost savings in informal care. There was a significant difference in proportions of successful treatments of 36% at three months. The number needed to treat for successful treatment at three months was 2.8 (2.7 to 2.9). CONCLUSIONS: Community occupational therapy intervention for patients with dementia and their care givers is successful and cost effective, especially in terms of informal care giving.

Effects of community occupational therapy on quality of life, mood, and health status in dementia patients and their caregivers: a randomized controlled trial.

BACKGROUND: Cure of dementia is not possible, but quality of life of patients and caregivers can be improved. Our aim is to investigate effects of community occupational therapy on dementia patients' and caregivers' quality of life, mood, and health status and caregivers' sense of control over life. METHODS: Community-dwelling patients aged 65 years or older, with mild-to-moderate dementia, and their informal caregivers (n = 135 couples of patients with their caregivers) were randomly assigned to 10 sessions of occupational therapy over 5 weeks or no intervention. Cognitive and behavioral interventions were used to train patients in the use of aids to compensate for cognitive decline and caregivers in coping behaviors and supervision. Outcomes, measured at baseline, 6 weeks, and 12 weeks, were patients' and caregivers' quality of life (Dementia Quality of Life Instrument, Dqol), patients' mood (Cornell Scale for Depression, CSD), caregivers' mood (Center for Epidemiologic Studies Depression Scale, CES-D), patients' and caregivers' health status (General Health Questionnaire, GHQ-12), and caregivers' sense of control over life (Mastery Scale). RESULTS: Improvement on patients' Dqol overall (0.8; 95% confidence interval [CI], 0.6-.1, effect size 1.3) and caregivers' Dqol overall (0.7; 95% CI, 0.5-.9, effect size 1.2) was significantly better in the intervention group as compared to controls. Scores on other outcome measures also improved significantly. This improvement was still significant at 12 weeks. CONCLUSION: Community occupational therapy should be advocated both for dementia patients and their caregivers, because it improves their mood, quality of life, and health status and caregivers' sense of control over life. Effects were still present at follow-up.

The association of betaine, homocysteine and related metabolites with cognitive function in Dutch elderly people.

The importance of the one-carbon metabolites, choline and homocysteine, to brain function is well known. However, the associations between the one-carbon metabolites choline, betaine, methionine and dimethylglycine with cognition in elderly are unclear. We therefore examined the associations of these metabolites with cognition in a double-blind, placebo-controlled trial. Individuals (n 195) were randomized to receive daily oral capsules with either 1000 microg cobalamin (vitamin B12), or 1000 microg cobalamin plus 400 microg folic acid, or placebo for 24 weeks. Concentrations of homocysteine, methionine, choline, betaine and dimethylglycine were assessed before and after 12 and 24 weeks of treatment. Cognitive function, including domains of attention, construction, sensomotor speed, memory and executive function, was assessed before and after 24 weeks of treatment. At baseline, elevated plasma homocysteine was associated with lower performance of attention, construction, sensomotor speed and executive function. In addition, betaine was positively associated with better performance of construction, sensomotor speed and executive function, whereas elevated concentrations of methionine were positively associated with sensomotor speed. Daily combined supplementation with cobalamin plus folic acid decreased total homocysteine concentrations by 36%, and increased betaine concentrations by 38%. Participants with the largest increases in betaine concentrations showed a borderline significant (P = 0.07) higher memory performance compared to those without it. Although this trial observed associations of homocysteine and betaine with cognitive domains prior to supplementation, decreased concentrations of homocysteine were not related to improved cognitive performance. There was a tendency of participants with the largest increases in betaine concentrations to show the greatest improvement in memory function.

Community based occupational therapy for patients with dementia and their care givers: randomised controlled trial.

OBJECTIVE: To determine the effectiveness of community based occupational therapy on daily functioning of patients with dementia and the sense of competence of their care givers. DESIGN: Single blind randomised controlled trial. Assessors were blinded for treatment allocation. SETTING: Memory clinic and day clinic of a geriatrics department and participants' homes. PARTICIPANTS: 135 patients aged > or =65 with mild to moderate dementia living in the community and their primary care givers. INTERVENTIONS: 10 sessions of occupational therapy over five weeks, including cognitive and behavioural interventions, to train patients in the use of aids to compensate for cognitive decline and care givers in coping behaviours and supervision. MAIN OUTCOME MEASURES: Patients' daily functioning assessed with the assessment of motor and process skills (AMPS) and the performance scale of the interview of deterioration in daily activities in dementia (IDDD). Care giver burden assessed with the sense of competence questionnaire (SCQ). Participants were evaluated at baseline, six weeks, and three months. RESULTS: Scores improved significantly relative to baseline in patients and care givers in the intervention group compared with the controls (differences were 1.5 (95% confidence interval 1.3 to 1.7) for the process scale; -11.7 (-13.6 to -9.7) for the performance scale; and (11.0; 9.2 to 12.8) for the competence scale). This improvement was still significant at three months. The number needed to treat to reach a clinically relevant improvement in motor and process skills score was 1.3 (1.2 to 1.4) at six weeks. Effect sizes were 2.5, 2.3, and 1.2, respectively, at six weeks and 2.7, 2.4, and 0.8, respectively, at 12 weeks. CONCLUSIONS: Occupational therapy improved patients' daily functioning and reduced the burden on the care giver, despite the patients' limited learning ability. Effects were still present at 12 weeks, which justifies implementation of this intervention. TRIAL REGISTRATION: Clinical Trials NCT00295152 [ClinicalTrials.gov].

Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial.

BACKGROUND: Vitamin B-12 deficiency is associated with cognitive impairment in older people. However, evidence from randomized trials of the effects of vitamin B-12 supplementation on cognitive function is limited and inconclusive. OBJECTIVE: The objective was to investigate whether daily supplementation with high doses of oral vitamin B-12 alone or in combination with folic acid has any beneficial effects on cognitive function in persons aged >/=70 y with mild vitamin B-12 deficiency. DESIGN: In a double-blind, placebo-controlled trial, 195 subjects were randomly assigned to receive 1000 microg vitamin B-12, 1000 microg vitamin B-12 + 400 microg folic acid, or placebo for 24 wk. Vitamin B-12 status was assessed on the basis of methylmalonic acid, total homocysteine (tHcy), and holotranscobalamin (holoTC) concentrations before and after 12 and 24 wk of treatment. Cognitive function was assessed before and after 24 wk of treatment with the use of an extensive neuropsychologic test battery that included the domains of attention, construction, sensomotor speed, memory, and executive function. RESULTS: Vitamin B-12 status did not change significantly after treatment in the placebo group; however, oral vitamin B-12 supplementation corrected mild vitamin B-12 deficiency. Vitamin B-12 + folic acid supplementation increased red blood cell folate concentrations and decreased tHcy concentrations by 36%. Improvement in memory function was greater in the placebo group than in the group who received vitamin B-12 alone (P = 0.0036). Neither supplementation with vitamin B-12 alone nor that in combination with folic acid was accompanied by any improvement in other cognitive domains. CONCLUSION: Oral supplementation with vitamin B-12 alone or in combination with folic acid for 24 wk does not improve cognitive function.

Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial.

BACKGROUND: Supplementation with high doses of oral cobalamin is as effective as cobalamin administered by intramuscular injection to correct plasma markers of vitamin B(12) deficiency, but the effects of lower oral doses of cobalamin on such markers are uncertain. METHODS: We conducted a randomized, parallel-group, double-blind, dose-finding trial to determine the lowest oral dose of cyanocobalamin required to normalize biochemical markers of vitamin B(12) deficiency in older people with mild vitamin B(12) deficiency, defined as a serum vitamin B(12) level of 100 to 300 pmol/L (135-406 pg/mL) and a methylmalonic acid level of 0.26 mumol/L or greater. We assessed the effects of daily oral doses of 2.5, 100, 250, 500, and 1000 mug of cyanocobalamin administered for 16 weeks on biochemical markers of vitamin B(12) deficiency in 120 people. The main outcome measure was the dose of oral cyanocobalamin that produced 80% to 90% of the estimated maximal reduction in the plasma methylmalonic acid concentration. RESULTS: Supplementation with cyanocobalamin in daily oral doses of 2.5, 100, 250, 500, and 1000 mug was associated with mean reductions in plasma methylmalonic acid concentrations of 16%, 16%, 23%, 33%, and 33%, respectively. Daily doses of 647 to 1032 mug of cyanocobalamin were associated with 80% to 90% of the estimated maximum reduction in the plasma methylmalonic acid concentration. CONCLUSION: The lowest dose of oral cyanocobalamin required to normalize mild vitamin B(12) deficiency is more than 200 times greater than the recommended dietary allowance, which is approximately 3 mug daily.

Effectiveness of nutritional supplements on cognitive functioning in elderly persons: a systematic review.

BACKGROUND: The effectiveness of nutritional supplementation in improving cognitive functioning is evaluated in elderly people. METHODS: The authors systematically reviewed randomized controlled trials that compared nutritional supplementation with a placebo treatment. Trials were identified from a MEDLINE search and from reference lists of identified studies and review articles. From each trial, information was gathered on the number and age of persons studied; the type, dosage, and duration of the intervention; and the assessed outcome measures. RESULTS: From 1086 titles, 571 articles were excluded based on their titles. Of the remaining 467 articles, the abstracts were read and 422 articles were excluded based on information found there. The remaining articles were screened for quality aspects of the study design, leaving 21 proper randomized, controlled trials. These trials are discussed in three groups according to the type of supplementation: multinutrient intervention or single components with or without a putative mechanism. Twelve studies, which were evenly distributed among the three supplement groups, found significantly positive effects of nutritional intervention on cognitive functioning, whereas nine studies did not. None of the studies found a significantly negative effect of nutritional intervention. CONCLUSIONS: Shortcomings in methodology varying from the duration of intervention to outcome measures partly explain discrepancies in findings. Despite the heterogeneity in trial design, the results of this review suggest that nutritional supplements may improve the cognitive functioning of elderly persons and do no harm. Further well-designed studies are needed to support these findings.

Cerebral oxygenation responses to standing in elderly patients with predominantly diastolic dysfunction.

Patients with left ventricular dysfunction may have different orthostatic responses of blood pressure (BP) and cerebral oxygenation than healthy elderly subjects. We investigated orthostatic changes in systemic haemodynamic variables and cerebral oxygenation in 21 elderly patients with heart failure New York Heart Association class I-III in stable condition (age 70-83 years) after withdrawal of furosemide and captopril for 2 weeks, and in 18 healthy elderly subjects (age 70-84 years). Frontal cortical concentration changes of oxyhaemoglobin ([O2Hb]) and deoxyhaemoglobin ([HHb]) were continuously measured by near-infrared spectrophotometry and BP changes by Finapres before and during 10 min of standing. Upon standing [O2Hb] reflecting blood flow, changed by -1.2 +/- 0.9 micromol L-1 (mean +/- SEM) in the patients, whereas it decreased by -4.5 +/- 0.6 micromol L-1 (P<0.01) in the healthy subjects after standing (P<0.05 between groups). [HHb] reflecting the sum of cerebral blood flow, arterial oxygen saturation and cerebral oxygen uptake, increased by 1.5 +/- 0.5 micromol L-1 (P<0.05) and 1.7 +/- 0.6 micromol L-1 (P<0.05), respectively. Compared with healthy elderly subjects, elderly patients with left ventricular dysfunction showed smaller orthostatic [O2Hb] decreases (P<0.01), in relation to higher orthostatic BP rises (P<0.05). These findings indicate that BP changes and an altered cardiovascular balance may influence orthostatic cortical haemodynamic responses in elderly subjects.

Neurohormonal effects of furosemide withdrawal in elderly heart failure patients with normal systolic function.

BACKGROUND: In heart failure patients, diuretics cause renin-angiotensin-aldosterone system (RAS) activation, which may lead to increased morbidity and mortality despite short-term symptomatic improvement. AIM: To determine changes in RAS activation and clinical correlates following furosemide withdrawal in elderly heart failure patients without left ventricular systolic dysfunction. METHODS AND RESULTS: We performed clinical assessments and laboratory determinations of aldosterone, plasma renin activity (PRA), atrial natriuretic peptide (ANP), norepinephrine, and endothelin in 29 heart failure patients [aged 75.1+/-0.7 (mean+/-S.E.M.) years], before, 1 and 3 months after placebo-controlled furosemide withdrawal. Recurrent congestion occurred in 2 of 19 patients withdrawn, and in 1 of 10 patients continuing on furosemide. Three months after withdrawal, PRA had decreased -1.61+/-0.71 nmol/l/h (P<0.05). Decreases in aldosterone levels did not reach significance (-0.17+/-0.38 nmol/l). The decreases in PRA after withdrawal correlated with decreases in systolic (r(s)=0.61, P=0.020) and diastolic blood pressure (r(s)=0.80, P=0.01). Successful withdrawal was associated with increases in norepinephrine (+0.58+/-0.22 nmol/l) and ANP (+3.5+/-1.3 pmol/l) (P<0.05) after 1 month, but these changes did not persist after 3 months. Endothelin levels did not change in both groups. CONCLUSION: Successful furosemide withdrawal in elderly heart failure patients causes persistent decreases in RAS activation.

Cobalamin-binding proteins in normal and cobalamin-deficient older subjects.

BACKGROUND: The causes of cobalamin (vitamin B(12)) deficiency in older people are only partly understood. We investigated the role of the cobalamin-binding proteins and tested the hypothesis that low saturated transcobalamin concentration is an early marker of cobalamin deficiency. METHODS: We measured saturated (holo) and unsaturated (apo) transcobalamin and haptocorrin concentrations in healthy middle-aged volunteers, healthy older volunteers, cobalamin-deficient older volunteers and cobalamin-deficient older patients. RESULTS: Holo and apo concentrations of transcobalamin and haptocorrin were similar in healthy middle-aged and older subjects. Holotranscobalamin concentrations were significantly decreased in cobalamin-deficient subjects but did not differ between healthy volunteers and patients. Furthermore, the relative amount of cobalamin on transcobalamin (i.e. holotranscobalamin/holotranscobalamin + holohaptocorrin) was similar in all four groups. CONCLUSIONS: Abnormalities of the cobalamin-binding proteins are not a cause of cobalamin deficiency in the aged. Plasma holotranscobalamin concentration did not differ between stages of cobalamin deficiency in older persons. Therefore, plasma holotranscobalamin is not an early marker of cobalamin deficiency in older people and has no additional value in the diagnostic work-up of reduced plasma cobalamin concentrations in older people.

Effects of furosemide versus captopril on postprandial and orthostatic blood pressure and on cerebral oxygenation in patients > or = 70 years of age with heart failure.

Elderly patients with heart failure are at risk of postprandial hypotension (PPH), orthostatic hypotension (OH), and concomitant cerebral oxygenation changes because of altered cardiovascular balance and the use of cardiovascular medications, such as furosemide and captopril. In 24 patients with heart failure (New York Heart Association class II to III, in stable condition, and receiving cardiovascular medication [aged 70 to 83 years]), blood pressure (BP) was measured by Finapres, and cortical concentrations of oxyhemoglobin and deoxyhemoglobin were measured using near-infrared spectroscopy during standing and after a 292-kcal carbohydrate meal. Tests were performed before and during therapy with furosemide 40 mg once daily (n = 11) or captopril 6.25 and 12.5 mg twice daily (n = 13) in a double-blind randomized trial. Before treatment, 13 of 24 patients had PPH, and 2 of 24 patients had OH. The first dose of furosemide significantly decreased postprandial systolic BP (p <0.05) and postprandial frontal cortical oxygenation (p <0.05), whereas the first dose of captopril did not. Furosemide and captopril did not significantly affect postprandial or orthostatic BP or cortical oxygenation after 2 weeks of treatment. Thus, PPH is a common phenomenon in elderly patients with heart failure, whereas OH is not. The first dose of furosemide 40 mg decreased postprandial systolic BP and frontal cortical oxygenation, in contrast with the first dose of captopril 6.25 mg and 2-week treatment with furosemide 40 mg once daily or captopril 12.5 mg twice daily. These findings indicate that initiating furosemide treatment worsens PPH, and furosemide is less safe in elderly patients with heart failure.

Evaluation of skills and knowledge on orthostatic blood pressure measurements in elderly patients.

OBJECTIVES: orthostatic hypotension is a common and potentially dangerous condition in elderly patients, often accompanied by dizziness and falls. To diagnose orthostatic hypotension, many physicians rely on blood pressure measurements performed by nurses. DESIGN: observational and descriptive study. SETTING: departments of Internal Medicine, Geriatric Medicine, and Surgery in eight hospitals throughout the Netherlands. SUBJECTS: 170 nurses working with elderly people in a general hospital. We selected a sample of 10 nurses on 17 participating wards. METHODS: to evaluate nurses' skills and knowledge on blood pressure measurements to diagnose orthostatic hypotension, we performed standardized observations, based on published guidelines, of supine and standing blood pressure determination in patients over 65 years. RESULTS: the most important deviations in technique of orthostatic blood pressure measurement from the published guidelines were: time between measuring supine and standing blood pressure varied from 0-30 minutes; in 28% the arm position was not at heart level during standing blood pressure measurements; in 46% the cuff was placed incorrectly. CONCLUSIONS: the skills and knowledge of nurses to measure supine and standing blood pressure are inaccurate for diagnosing orthostatic hypotension in elderly patients. Large differences in measurement technique and timing of standing blood pressure could influence the individual detection and treatment of orthostatic hypotension and the reported prevalence of orthostatic hypotension. The blood pressure measurement procedure to diagnose orthostatic hypotension needs more standardization and implementation of guidelines in daily practice.

Simultaneous measurements of cerebral oxygenation changes during brain activation by near-infrared spectroscopy and functional magnetic resonance imaging in healthy young and elderly subjects.

Near infrared spectroscopy (NIRS) and functional magnetic resonance imaging (fMRI) both allow non-invasive monitoring of cerebral cortical oxygenation responses to various stimuli. To compare these methods in elderly subjects and to determine the effect of age on cortical oxygenation responses, we determined motor-task-related changes in deoxyhemoglobin concentration ([HHb]) over the left motor cortex in six healthy young subjects (age 35 +/- 9 years, mean +/- SD) and five healthy elderly subjects (age 73 +/- 3 years) by NIRS and blood-oxygen-level-dependent (BOLD) fMRI simultaneously. The motor-task consisted of seven cycles of 20-sec periods of contralateral finger-tapping at a rate as fast as possible alternated with 40-sec periods of rest. Time-locked averages over the seven cycles were used for further analysis. Task-related decreases in [HHb] over the motor cortex were measured by NIRS, with maximum changes of -0.83 +/- 0.38 mumol/L (P < 0.01) for the young and -0.32 +/- 0.17 mumol/L (P < 0.05) for the elderly subjects. The BOLD-fMRI signal increased over the cortex volume under investigation with NIRS, with maximum changes of 2.11 +/- 0.72% (P < 0.01) for the young and 1.75 +/- 0.71% (P < 0.01) for the elderly subjects. NIRS and BOLD-fMRI measurements showed good correlation in the young (r = -0.70, r(2) = 0.48, P < 0.001) and elderly subjects (r = -0.82, r(2) = 0.67, P < 0.001). Additionally, NIRS measurements demonstrated age-dependent decreases in task-related cerebral oxygenation responses (P < 0.05), whereas fMRI measurements demonstrated smaller areas of cortical activation in the elderly subjects (P < 0.05). These findings demonstrate that NIRS and fMRI similarly assess cortical oxygenation changes in young subjects and also in elderly subjects. In addition, cortical oxygenation responses to brain activation alter with aging.

Recruitment and coaching of healthy elderly subjects for invasive cardiovascular research with right-sided catheterisation.

BACKGROUND AND AIMS: Heart failure is primarily a disorder of the elderly. To investigate a non-invasive method to diagnose heart failure in the elderly, right-sided catheterisation was needed in healthy elderly subjects. We studied the feasibility of recruitment of healthy elderly subjects for this invasive investigation and aimed to identify the factors important for recruitment and for successful participation. METHODS: Healthy subjects, aged >/=65 years, were invited by advertisement in a local newspaper to participate in an invasive study, preceded by extensive medical examination. An experienced research nurse provided coaching and care on an individual basis. Motivation to participate, satisfaction and the expected and perceived burden were assessed with a questionnaire before and after catheterisation. RESULTS: From 180 subjects responding, 53 were invited for screening of whom 38 were included. Cardiovascular examination was the most important reason for participation. The questionnaire showed considerable satisfaction about the information and care given and about participating in the study in general. CONCLUSIONS: Recruitment of healthy elderly subjects for an invasive cardiovascular study is feasible. Individual coaching contributed to the satisfaction experienced. The appointment of an experienced research nurse appears important for successful recruitment and participation of healthy elderly subjects in an invasive cardiovascular study.