Riona Mulcahy

Macular Pigment, Visual Function, and Macular Disease among Subjects with Alzheimer's Disease: An Exploratory Study

BACKGROUND The macula (central retina) contains a yellow pigment, comprising the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin, known as macular pigment (MP). The concentrations of MPs constituent carotenoids in retina and brain tissue correlate, and there is a biologically-plausible rationale, supported by emerging evidence, that MPs constituent carotenoids are also important for cognitive function. OBJECTIVE To investigate if patients with Alzheimers disease (AD) are comparable to controls in terms of MP and visual function. METHODS 36 patients with moderate AD and 33 controls with the same age range participated. MP was measured using dual-wavelength autofluorescence (Heidelberg Spectralis®); cognitive function was assessed using a battery of cognition tests (including Cambridge Neuropsychological Test Automated Battery). Visual function was recorded by measuring best corrected visual acuity (BCVA) and contrast sensitivity (CS). Serum L and Z concentrations (by HPLC) and age-related macular degeneration (AMD, by retinal examination) status were also assessed. RESULTS In the AD group, central MP (i.e., at 0.23°) and MP volume were significantly lower than the control group (p < 0.001 for both), as were measures of BCVA, CS, and serum L and Z concentrations (p < 0.05, for all). CONCLUSION AD patients were observed to exhibit significantly less MP, lower serum concentrations of L and Z, poorer vision, and a higher occurrence of AMD when compared to control subjects. A clinical trial in AD patients designed to investigate the impact of macular carotenoid supplementation with respect to MP, visual function, and cognitive function is merited.

The Impact of Supplemental Macular Carotenoids in Alzheimer's Disease: A Randomized Clinical Trial

BACKGROUND Patients with Alzheimers disease (AD) exhibit significantly less macular pigment (MP) and poorer vision when compared to control subjects. OBJECTIVE To investigate supplementation with the macular carotenoids on MP, vision, and cognitive function in patients with AD versus controls. METHODS A randomized, double-blind clinical trial with placebo and active arms. 31 AD patients and 31 age-similar control subjects were supplemented for six months with either Macushield (10 mg meso-zeaxanthin [MZ]; 10 mg lutein [L]; 2 mg zeaxanthin [Z]) or placebo (sunflower oil). MP was measured using dual-wavelength autofluorescence (Heidelberg Spectralis®). Serum L, Z, and MZ were quantified by high performance liquid chromatography. Visual function was assessed by best corrected visual acuity and contrast sensitivity (CS). Cognitive function was assessed using a battery of cognition tests, including the Cambridge Neuropsychological Test Automated Battery (CANTAB)). RESULTS Subjects on the active supplement (for both AD and non-AD controls) exhibited statistically significant improvement in serum concentrations of L, Z, MZ, and MP (p < 0.001, for all) and also CS at (p = 0.039). Also, for subjects on the active supplement, paired samples t-tests exhibited four significant results (from five spatial frequencies tested) in the AD group, and two for the non-AD group, and all indicating improvements in CS. We found no significant changes in any of the cognitive function outcome variables measured (p > 0.05, for all). CONCLUSION Supplementation with the macular carotenoids (MZ, Z, and L) benefits patients with AD, in terms of clinically meaningful improvements in visual function and in terms of MP augmentation.

Cognitive Function and Its Relationship with Macular Pigment Optical Density and Serum Concentrations of its Constituent Carotenoids

Abstract Background: Macular pigment (MP) levels correlate with brain concentrations of lutein (L) and zeaxanthin (Z), and have also been shown to correlate with cognitive performance in the young and elderly. Objective: To investigate the relationship between MP, serum concentrations of L and Z, and cognitive function in subjects free of retinal disease with low MP (Group 1, n = 105) and in subjects with AMD (Group 2, n = 121). Methods: MP was measured using customized heterochromatic flicker photometry and dual-wavelength autofluorescence; cognitive function was assessed using a battery of validated cognition tests; serum L and Z concentrations were determined by HPLC. Results: Significant correlations were evident between MP and various measures of cognitive function in both groups (r = –0.273 to 0.261, p≤0.05, for all). Both serum L and Z concentrations correlated significantly (r = 0.187, p≤0.05 and r = 0.197, p≤0.05, respectively) with semantic (animal) fluency cognitive scores in Group 2 (the AMD study group), while serum L concentrations also correlated significantly with Verbal Recognition Memory learning slope scores in the AMD study group (r = 0.200, p = 0.031). Most of the correlations with MP, but not serum L or Z, remained significant after controlling for age, gender, diet, and education level. Conclusion: MP offers potential as a non-invasive clinical biomarker of cognitive health, and appears more successful in this role than serum concentrations of L or Z.

Supplemental Retinal Carotenoids Enhance Memory in Healthy Individuals with Low Levels of Macular Pigment in A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

BACKGROUND There is a biologically plausible rationale whereby the dietary carotenoids lutein (L), zeaxanthin (Z), and meso-zeaxanthin (MZ), which are collectively referred to as macular pigment (MP) in the central retina (macula), support the maintenance of cognition via their antioxidant and anti-inflammatory properties. OBJECTIVE To investigate the impact of supplemental L, Z, and MZ on memory, executive function, and verbal fluency among healthy individuals with low MP levels. METHODS In this double-blind, placebo-controlled, randomized clinical trial, subjects (n = 91; mean±SD age = 45.42±12.40; % male = 51.6) consumed a daily formulation of 10 mg L, 10 mg MZ, and 2 mg Z (n = 45) or placebo (n = 46) for 12 months. Cognitive domains assessed included verbal and visual learning, immediate and delayed memory, executive function, and verbal fluency. MP and serum carotenoid concentrations of L, Z, and MZ were also measured. RESULTS Following 12-month supplementation, individuals in the active group exhibited statistically significant improvements in memory when compared to the placebo group (paired associated learning [PAL] memory score [rANOVA, p = 0.009]; PAL errors [rANOVA, p = 0.017]). Furthermore, the observed reduction in the number of errors made in the PAL task among those in the intervention group was positively and significantly related to observed increases in MP volume (p = 0.005) and observed increases in serum concentrations of L (p = 0.009). CONCLUSION This randomized, double-blind, placebo-controlled clinical trial demonstrates a memory-enhancing effect of daily supplementation with L, Z, and MZ in healthy subjects with low MP at baseline. The implications of these findings for intellectual performance throughout life, and for risk of cognitive decline in later life, warrant further study.

Phospholipid oxidation and carotenoid supplementation in Alzheimer’s disease patients

Abstract Alzheimers disease (AD) is a progressive, neurodegenerative disease, characterised by decline of memory, cognitive function and changes in behaviour. Generic markers of lipid peroxidation are increased in AD and reactive oxygen species have been suggested to be involved in the aetiology of cognitive decline. Carotenoids are depleted in AD serum, therefore we have compared serum lipid oxidation between AD and age‐matched control subjects before and after carotenoid supplementation. The novel oxidised phospholipid biomarker 1‐palmitoyl‐2‐(5′‐oxo‐valeroyl)‐sn‐glycero‐3‐phosphocholine (POVPC) was analysed using electrospray ionisation tandem mass spectrometry (MS) with multiple reaction monitoring (MRM), 8‐isoprostane (IsoP) was measured by ELISA and ferric reducing antioxidant potential (FRAP) was measured by a colorimetric assay. AD patients (n=21) and healthy age‐matched control subjects (n=16) were supplemented with either Macushield™ (10 mg meso‐zeaxanthin, 10 mg lutein, 2 mg zeaxanthin) or placebo (sunflower oil) for six months. The MRM‐MS method determined serum POVPC sensitively (from 10 &mgr;l serum) and reproducibly (CV=7.9%). At baseline, AD subjects had higher serum POVPC compared to age‐matched controls, (p=0.017) and cognitive function was correlated inversely with POVPC (r=−0.37; p=0.04). After six months of carotenoid intervention, serum POVPC was not different in AD patients compared to healthy controls. However, POVPC was significantly higher in control subjects after six months of carotenoid intervention compared to their baseline (p=0.03). Serum IsoP concentration was unrelated to disease or supplementation. Serum FRAP was significantly lower in AD than healthy controls but was unchanged by carotenoid intervention (p=0.003). In conclusion, serum POVPC is higher in AD patients compared to control subjects, is not reduced by carotenoid supplementation and correlates with cognitive function. Graphical abstract Figure. No Caption available. HighlightsPOVPC can be determined in serum using a robust and sensitive MS‐MRM method.POVPC is higher in AD patient serum compared to age‐matched controls.POVPC correlates inversely with mini‐mental state examination.POVPC is increased in control sera after carotenoid supplementation.

Vascular risk assessment in older adults without a history of cardiovascular disease

Modern cardiovascular risk prediction tools, which have their genesis in the Framingham Heart Study, have allowed more accurate risk stratification and targeting of treatments worldwide over the last seven decades. Better cardiovascular risk factor control during this time has led to a reduction in cardiovascular mortality and, at least in part, to improved life expectancy. As a result, western societies as a whole have seen a steady increase in the proportion of older persons in their populations. Unfortunately, several studies have shown that the same tools which have contributed to this increase cannot be reliably extrapolated for use in older generations. Recent work has allowed recalibration of existing models for use in older populations but these modified tools still require external validation before they can be confidently applied in clinical practice. Another complication is emerging evidence that aggressive risk factor modification in older adults, particularly more frail individuals, may actually be harmful. This review looks at currently available cardiovascular risk prediction models and the specific challenges faced with their use in older adults, followed by analysis of recent attempts at recalibration for this cohort. We discuss the issue of frailty, looking at our evolving understanding of its constituent features and various tools for its assessment. We also review work to date on the impact of frailty on cardiovascular risk modification and outline its potentially central role in determining the most sensible approach in older patients. We summarise the most promising novel markers of cardiovascular risk which may be of use in improving risk prediction in older adults in the future. These include markers of vascular compliance (such as aortic pulse wave velocity and pulse wave analysis), of endothelial function (such as flow mediated dilation, carotid intima-media thickness and coronary artery calcium scores), and also biochemical and circulating cellular markers.

SUPPLEMENTAL RETINAL CAROTENOIDS ENHANCE MEMORY IN HEALTHY INDIVIDUALS WITH LOW LEVELS OF MACULAR PIGMENT IN A RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL

P4-560 SUPPLEMENTAL RETINAL CAROTENOIDS ENHANCE MEMORY IN HEALTHY INDIVIDUALS WITH LOW LEVELS OF MACULAR PIGMENT IN A RANDOMIZED, DOUBLE BLIND, PLACEBO-CONTROLLED CLINICAL TRIAL Rebecca Power, Robert Coen, Stephen Beatty, Riona Mulcahy, Rachel Moran, Jim Stack, Alan Howard, John Nolan, Nutrition Research Centre Ireland, Waterford, Ireland; Mercer’s Institute for Successful Ageing, St. James’s Hospital, Dublin, Ireland; Age-Related Care Unit, University Hospital Waterford, Waterford, Ireland; Howard Foundation, Cambridge, United Kingdom. Contact e-mail: rpower@wit.ie

288Are we Appropriately Catheterising our Older Inpatients

Background: Older patients are perceived to be catheterised inappropriately during hospitalisation, leading to an increased number of urinary tract infections – an issue of concern, in the context of the emergent increase in resistant microorganisms (1). Methods: We predefined the following indications as valid reasons for catheterisation: acute urinary retention, need for accurate fluid balance, maintain skin integrity, long term catheter that needs to be changed, palliative care. The clinical notes of 114 patients admitted under medical teams on five wards were reviewed, over a four day period, using the retrospective analysis method. We looked for documentation about the indication and insertion of urethral catheters. Where we could not find an explicit indication, we read all the notes prior to catheterisation to ascertain whether catheterisation was indeed necessary. The data acquired from the medical notes was then compared with local and international guidelines (2). Results: Out of 114 patients in total, 20 older patients had an indwelling urinary catheter inserted during their admission. 15 catheters were inserted in ED and 5 on the wards. Catheterisation met the predefined criteria for appropriateness in 16(12 in ED & 4 on the wards) out of 20 cases, the indication being explicit in 6 cases and implicit, from notes review, in 10. 16 out of 20 cases had incomplete documentation about the procedure, whilst this information was absent in 4 cases. Conclusions: We have determined that, in 4 out of 20 cases, urethral catheters were inserted inappropriately. The indication for insertion was not specified in 14 cases. The documentation about the procedure and the post-insertion care was absent in 4 cases and incomplete in 16 cases. We feel that time has come to introduce a clear protocol for urinary catheter insertion. References: 1. Catheter-Associated Infections Pathogenesis Affects Prevention, Barbara W. Trautner, Rabih O. Darouiche, 2. www.nice.org.uk/guidance/qs61/chapter/quality-statement-4-urinary-catheters