Mind versus body: Perceived stress and biological stress are independently related to cognitive decline.

Chronic stress may increase risk of age-related cognitive decline. 'Stress', however, is a multidimensional construct and few studies have investigated the inter-relationship of subjective stress and biological stress with cognitive decline. In this study, we examine the relationship between perceived stress and two measures of biological stress - allostatic load, indexing stress at the physiological level and leukocyte telomere length, indexing stress at the cellular level - with cognitive decline over a 12-year period in adults aged 50 and older. 3,458 participants (aged ≥ 50) from The Irish Longitudinal study on Ageing with measurements of allostatic load, telomere length and perceived stress at baseline and repeated measures of cognitive function were included. Hierarchical linear regression models with adjustment for multiple potential confounders were applied, and repeated stratified by sex in sensitivity analyses. Higher perceived stress at baseline was associated with lower cognitive function (ß = -0.10, 95 % CI -0.12, -0.07, p <.001), with similar strength of associations across waves. There were significant interactions between measures of biological stress and wave; higher allostatic load was associated (X2(18) = 64.4; p <.001), and telomere length was borderline (X2(18) = 9.4; p =.09) associated with cognitive decline from 4-year follow-up onward. Sex stratified analyses revealed that the association between telomere length and cognitive decline was present in women only. Mutual adjustment did not attenuate associations in either case. The interactions between allostatic load and telomere length with perceived stress were not significant. Our findings suggest that subjective measures of stress and biological metrics may be independently related to cognitive function over time in older adults, hinting at the potential for different underlying mechanisms.

Assessing cognitive function in longitudinal studies of ageing worldwide: some practical considerations.

Over 55 million people live with dementia worldwide. With 40% of modifiable risk factors estimated to contribute to dementia, the potential for prevention is high, and preventive measures, at an early stage of cognitive decline, are likely to positively influence future dementia trends. Countries need reliable health data and adequate measurement tools to quantify, monitor and track early changes in cognitive capacity in the general population. Many cognitive tests exist; however, there is no consensus to date about which instruments should be employed, and important variations in measurement have been observed. In this narrative review, we present a number of cognitive tests that have been used in nationally representative population-based longitudinal studies of ageing. Longitudinal panel studies of ageing represent critical platforms towards capturing the process of cognitive ageing and understanding associated risk and protective factors. We highlight optimal measures for use at a population level and for cross-country comparisons, taking into consideration instrument reliability, validity, duration, ease of administration, costs, literacy and numeracy requirements, adaptability to sensory and fine motor impairments and portability to different cultural and linguistic milieux. Drawing upon the strengths and limitations of each of these tests, and the experience gained and lessons learnt from conducting a nationally representative study of ageing, we indicate a comprehensive battery of tests for the assessment of cognitive capacity, designed to facilitate its standardised operationalisation worldwide.

Exposure to the troubles in Northern Ireland, memory functioning, and social activity engagement: results from NICOLA.

We investigated the potential impact of a cohort traumatic exposure, the Troubles in Northern Ireland, on memory functioning in later life, and the potential moderating effect of social activity engagement. Using data from 6571 participants aged 60 + in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) cohort, we used a structural equation modelling framework to explore associations between traumatic exposure during the Troubles and memory functioning. As expected, social activity engagement was positively associated with memory functioning, ß = .102. Traumatic exposure was also positively associated with memory functioning, ß = .053. This association was stronger at low levels of social activity engagement; among those with higher levels, there was little association, interaction ß = - 0.054. The positive association between traumatic exposure during the Troubles and memory functioning was not moderated by the age at which the exposures occurred (based on analysis of a subsample with available data), interaction ß = - 0.015. We conclude that superior memory functioning was associated with higher levels of traumatic exposure during the Troubles, particularly among those with lower levels of social activity engagement, and regardless of the age at which the exposures occurred. Future longitudinal analyses are required to build on these results, which potentially have implications for life-course epidemiology, in relation to critical periods for traumatising experiences. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-022-00683-5.

Do Mini-Mental State Examination and Montreal Cognitive Assessment predict high-cost health care users? A competing risks analysis in The Irish Longitudinal Study on Ageing.

OBJECTIVES: Policymakers want to better identify in advance the 10% of people who account for approximately 75% of health care costs. We evaluated how well Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) predicted high costs in Ireland. METHODS/DESIGN: We used five waves from The Irish Longitudinal Study on Ageing, a biennial population-representative survey of people aged 50+ (2010-2018). We used competing risks analysis where our outcome of interest was "high costs" (top 10% at any wave) and the competing outcome was dying or loss to follow-up without first having the high-cost outcome. Our binary predictors of interest were a 'low score' (bottom 10% in the sample) in MMSE (≤25 pts) and MoCA (≤19 pts) at baseline, and we calculated sub-hazard ratios after controlling for sociodemographic, clinical and functional factors. RESULTS: Of 5856 participants, 1427 (24%) had the 'high cost' outcome; 1463 (25%) had a competing outcome; and 2966 (51%) completed eight years of follow-up without either outcome. In multivariable regressions a low MoCA score was associated with high costs (SHR: 1.38 (95% CI: 1.2-1.6) but a low MMSE score was not. Low MoCA score at baseline had a higher true positive rate (40%) than did low MMSE score (35%). The scores had similar association with exit from the study. CONCLUSIONS: MoCA had superior predictive accuracy for high costs than MMSE but the two scores identify somewhat different types of high-cost user. Combining the approaches may improve efforts to identify in advance high-cost users.

Sleep duration, sleep problems, and perceived stress are associated with hippocampal subfield volumes in later life: findings from The Irish Longitudinal Study on Ageing.

STUDY OBJECTIVES: This study examines the cross-sectional and 2-year follow-up relationships between sleep and stress and total hippocampal volume and hippocampal subfield volumes among older adults. METHODS: Four hundred seventeen adults (aged 68.8 ± 7.3; 54% women) from the Irish Longitudinal Study on Ageing completed an interview, a questionnaire, and multiparametric brain magnetic resonance imaging. The relationships between self-reported sleep duration, sleep problems, perceived stress, and total hippocampal volume were examined by using ordinary least squares regressions. Linear mixed-effects models were used to investigate the relationships between sleep duration, sleep problems, perceived stress, changes in these measures over 2-years, and hippocampal subfield volumes. RESULTS: No cross-sectional and follow-up associations between sleep and total hippocampal volume and between stress and total hippocampal volume were found. By contrast, Long sleep (≥9-10 h/night) was associated with smaller volumes of molecular layer, hippocampal tail, presubiculum, and subiculum. The co-occurrence of Short sleep (≤6 h) and perceived stress was associated with smaller cornu ammonis 1, molecular layer, subiculum, and tail. Sleep problems independently and in conjunction with higher stress, and increase in sleep problems over 2 years were associated with smaller volumes of these same subfields. CONCLUSION: Our study highlights the importance of concurrently assessing suboptimal sleep and stress for phenotyping individuals at risk of hippocampal subfield atrophy.

StrokeCog Markov Model: Projected Prevalent and Incident Cases of Stroke and Poststroke Cognitive Impairment to 2035 in Ireland.

BACKGROUND AND PURPOSE: Cognitive impairment no dementia (CIND) and dementia are common stroke outcomes, with significant health and societal implications for aging populations. These outcomes are not included in current epidemiological models. We aimed to develop an epidemiological model to project incidence and prevalence of stroke, poststroke CIND and dementia, and life expectancy, in Ireland to 2035, informing policy and service planning. METHODS: We developed a probabilistic Markov model (the StrokeCog model) applied to the Irish population aged 40 to 89 years to 2035. Data sources included official population and hospital-episode statistics, longitudinal cohort studies, and published estimates. Key assumptions were varied in sensitivity analysis. Results were externally validated against independent sources. The model tracks poststroke progression into health states characterized by no cognitive impairment, CIND, dementia, disability, stroke recurrence, and death. RESULTS: We projected 69 051 people with prevalent stroke in Ireland in 2035 (22.0 per 1000 population [95% CI, 20.8-23.1]), with 25 274 (8.0 per 1000 population [95% CI, 7.1-9.0]) of those projected to have poststroke CIND, and 12 442 having poststroke dementia (4.0 per 1000 population [95% CI, 3.2-4.8]). We projected 8725 annual incident strokes in 2035 (2.8 per 1000 population [95% CI, 2.7-2.9]), with 3832 of these having CIND (1.2 per 1000 population [95% CI, 1.1-1.3]), and 1715 with dementia (0.5 per 1000 population [95% CI, 0.5-0.6]). Life expectancy for stroke survivors at age 50 was 23.4 years (95% CI, 22.3-24.5) for women and 20.7 (95% CI, 19.5-21.9) for men. CONCLUSIONS: This novel epidemiological model of stroke, poststroke CIND, and dementia draws on the best available evidence. Sensitivity analysis indicated that findings were robust to assumptions, and where there was uncertainty a conservative approach was taken. The StrokeCog model is a useful tool for service planning and cost-effectiveness analysis and is available for adaptation to other national contexts.

Is there a bidirectional association between sedentary behaviour and cognitive decline in older adults? Findings from the Irish Longitudinal Study on Ageing.

Research on whether sedentary behaviour (SB) is related to cognitive decline in older individuals is conflicting, potentially caused by methodological differences in previous studies. To inform public health policies, we analysed both the forward and reverse association across four-years between subjective TV time and objectively-measured SB and four cognitive outcome measures in older adults. The Irish Longitudinal Study on Ageing (TILDA) quantified time spent watching TV using a questionnaire and objective physical activity patterns with a GENEActiv accelerometer. Mixed model analysis examined whether these two measures of SB related to changes in cognitive function (immediate and delayed recall, MMSE, and animal naming task) during a four-year follow-up period. Furthermore, the reverse association between changes in cognition over the preceding four years and SB was investigated. We included 1,276 participants (67 ± 9 years). Longitudinally, every hour of objective SB per day was associated with a -0.01 (95%CI = -0.03;-0.00) lower MMSE score per year. Reversely, a worse decline in immediate and delayed recall over the preceding waves was related to slightly more objective SB (B = -0.24 (95%CI = -0.41;-0.07)) and TV time (B = -0.25 (95%CI = -0.48;-0.03)) at the end of those four years. To conclude, in healthy older individuals, higher levels of objective SB are related to cognitive decline across a four-year follow-up, although the magnitude and clinical relevance are questionable. As preceding cognitive decline is associated with more SB across follow-up, this suggests that a bidirectional association is plausible.

Hemodynamic and structural brain measures in high and low sedentary older adults.

Due to its cardiovascular effects sedentary behaviour might impact cerebrovascular function in the long term, affecting cerebrovascular regulatory mechanisms and perfusion levels. Consequently this could underly potential structural brain abnormalities associated with cognitive decline. We therefore assessed the association between sedentary behaviour and brain measures of cerebrovascular perfusion and structural abnormalities in community-dwelling older adults. Using accelerometery (GENEActiv) data from The Irish Longitudinal Study on Ageing (TILDA) we categorised individuals by low- and high-sedentary behaviour (≤8 vs >8 hours/day). We examined prefrontal haemoglobin oxygenation levels using Near-Infrared Spectroscopy during rest and after an orthostatic challenge in 718 individuals (66 ± 8 years, 52% female). Global grey matter cerebral blood flow, total grey and white matter volume, total and subfield hippocampal volumes, cortical thickness, and white matter hyperintensities were measured using arterial spin labelling, T1, and FLAIR MRI in 86 individuals (72 ± 6 years, 55% female). While no differences in prefrontal or global cerebral hemodynamics were found between groups, high-sedentary individuals showed lower hippocampal volumes and increased white matter hyperintensities compared to their low-sedentary counterparts. Since these structural cerebral abnormalities are associated with cognitive decline and Alzheimer's disease, future work exploring the causal pathways underlying these differences is needed.

Social factors may mediate the relationship between subjective age-related hearing loss and episodic memory.

Objectives: To investigate whether the relationship between subjective age-related hearing loss (SARHL) and episodic memory functioning is mediated by measures of social functioning.Methods: Using data from 8,163 adults over 50 that participated in the Irish Longitudinal Study of Ageing (three waves, each two years apart), we used a multiple mediation model within a Structural Equation Modelling framework to explore potential social mediators of the relationship between SARHL and episodic memory functioning, controlling for demographic and health covariates.Results: Neither the direct effect of self-reported hearing difficulties on memory functioning (ß = -.03), nor the total effect (ß = .01), were significant. A small inconsistent indirect effect of self-reported hearing difficulties on episodic memory via weekly social activity engagement (ß = -.002) was found.Conclusions: Self-reported hearing difficulties may exert an indirect effect on episodic memory via weekly social activity engagement. The findings may have implications for identification of individuals at risk of memory decline in later life.

Indoor particulate air pollution from open fires and the cognitive function of older people.

Exposure to indoor air pollution is known to affect respiratory and cardiovascular health, but little is known about its effects on cognitive function. We measured the concentrations and magnetite content of airborne particulate matter (PM) in the indoor environment arising from burning peat, wood or coal in residential open fires. Highest indoor PM2.5 concentrations (60 µg/m3 i.e. 2.4 times the WHO-recommended 24-h mean) occurred when peat was burned, followed by burning of coal (30 µg/m3) and wood (17 µg/m3). Conversely, highest concentrations of coarser PM (PM10-2.5) were associated with coal burning (20 µg/m3), with lower concentrations emitted during burning of wood (10 µg/m3) and peat (8 µg/m3). The magnetic content of the emitted PM, greatest (for both PM size fractions) when coal was burned, is similar to that of roadside airborne PM. Exposure to PM, and to strongly magnetic airborne PM, can be greater for individuals spending ~5 h/day indoors with a coal-burning open fire for 6 months/year compared to those commuting via heavily-trafficked roads for 1 h/day for 12 months/year. Given these high indoor PM and magnetite concentrations, and the reported associations between (outdoor) PM and impaired neurological health, we used individual-level data from The Irish Longitudinal Study on Ageing (TILDA) to examine the association between the usage of open fires and the cognitive function of older people. Using a sample of nearly seven thousand older people, we estimated multi-variate models of the association between cognitive function and open fire usage, in order to account for relevant confounders such as socio-economic status. We found a negative association between open fire usage and cognitive function as measured by widely-used cognitive tests such as word recall and verbal fluency tests. The negative association was largest and statistically strongest among women, a finding explained by the greater exposure of women to open fires in the home because they spent more time at home than men. Our findings were also robust to stratifying the sample between old and young, rich and poor, and urban and rural.

Hair glucocorticoids and resting-state frontal lobe oxygenation: Findings from The Irish Longitudinal Study on Ageing.

Cerebral blood flow and oxygenation are crucial for maintaining healthy brain structure and function, with hypoperfusion and hypometabolism associated with neurodegenerative and neuropsychiatric conditions. Chronic stress and elevated cortisol have also been associated with cognitive decline, poor mental health and peripheral vascular and cerebrovascular changes. It is plausible that glucocorticoids could alter brain structure and function through increased vulnerability to hypoperfusion and reduced oxygenation. The aim of the current study was to investigate the association between hair glucocorticoids (GCs) and frontal lobe oxygenation using near-infra red spectroscopy (NIRS) in a population sample of 1078 older adults. Data from Wave 3 of The Irish Longitudinal Study of Ageing was analysed. Hair samples were taken for the analysis of glucocorticoids and NIRS was used to measure frontal lobe oxygenation. After both minimal and full adjustment for covariates, hair cortisol and the cortisol-to-cortisone ratio were associated with lower Tissue Saturation Index (TSI; cortisol: B = -0.37, CI -0.60 to -0.14, p = .002; ratio: B = -0.43, CI -0.70 to -0.16, p = .002). Cortisone was not significantly associated with TSI (B = -0.17, CI -0.55 to.21, p = .388). The finding of an inverse relationship between frontal lobe oxygenation and GCs as assessed over a period of months may indicate that reduced oxygenation is one pathway through which chronically elevated GCs affect brain health and function. However, no causality can be inferred from the current data and prospective studies are required to interrogate this.

The impact of glucocorticoid medication use on hair cortisol and cortisone in older adults: Data from the Irish Longitudinal Study on Ageing.

Research focusing on the hair concentration of cortisol and cortisone has significantly developed over the last two decades and has huge potential to provide relevant insights into stress-related diseases. However it is not clearly understood exactly how glucocorticoid (GC) medications, which are commonly prescribed drugs particularly among older adults, may affect hair cortisol and cortisone levels. The aim of this study was to examine associations of the use of GC medications with hair cortisol and cortisone concentrations in a sample of older adults. Hair samples and data were collected from participants at Wave 3 of The Irish Longitudinal Study of Ageing (TILDA). Results showed that before and after controlling for socio-demographic, health and hair characteristics, the use of systemic GCs was associated with decreased hair cortisone (B= -0.34 95 % CI -0.53, -0.16, p < 0.001). However, the use of local GCs was associated with increased hair cortisol (B = 0.39 95 % CI 0.18, 0.61). Further analysis suggests that the latter finding may be the result of use of topical steroid creams/ointments. These data add to the scant literature on the impact of steroid medication use on hair cortisol and cortisone in non-clinical populations, providing further evidence that future hair GC studies need to consider steroid medication use.

The Association Between Hair Cortisol, Hair Cortisone, and Cognitive Function in a Population-Based Cohort of Older Adults: Results From The Irish Longitudinal Study on Ageing.

Experimental evidence to date largely supports an association between the stress hormone cortisol and cognitive performance. Older adults, in particular, may be vulnerable to the neurotoxic effects of prolonged increases in cortisol; however, the assessment of chronic hormone levels has previously been challenging. Hair cortisol analysis has advantages over other cortisol metrics for this purpose as it facilitates the assessment of total hormone secretion over several months. Cortisol and cortisone were measured in the scalp hair of 1,876 older adults from The Irish Longitudinal Study on Ageing. Participants underwent a battery of cognitive tests assessing global function, memory, executive function, and processing speed. After adjustment for hair characteristics, demographics, metabolic risk factors, cardiovascular conditions, and depression, regression analysis revealed an inverse relationship of hair glucocorticoids to immediate (cortisol: ß = -.12, p = .032; cortisone: ß = -.021, p = .036) and delayed (cortisol: ß = -.13, p = .003; cortisone: ß = -.23, p = .006) word recall performance. They were also associated with more errors on the Mini-Mental State Examination (cortisol: incidence rate ratio (IRR) = 1.06, p = .008; cortisone: IRR = 1.14, p = .002) and Montreal Cognitive Assessment (cortisone: IRR = 1.06, p = .015). Higher hair glucocorticoids are inversely associated with memory and global cognition in a population-based sample of older adults. Future work should explore the prognostic significance of these findings.

Lonely SARTs: loneliness and sustained attention in the Irish longitudinal study of aging.

Based on biologically plausible mechanisms and previous research, it is possible to hypothesize a reciprocal association between sustained attention and loneliness. We investigated this association using a cross-lagged modeling approach. Using data from 6,239 participants aged over 50 in TILDA, a nationally representative study of aging, we used structural equation models to investigate potential cross-lagged associations between sustained attention and loneliness, measured at baseline and again after four years. Sustained attention at baseline had a small association with loneliness four years later, but loneliness at baseline was not associated with sustained attention at follow-up. Auto-regressive associations were strong for both loneliness over time and sustained attention over time. Sustained attention may account for a small proportion of the variance in loneliness over time among older adults, and may constitute a risk factor in the development of loneliness. Implications for the identification of at-risk individuals and the prevention of loneliness are discussed.

Circulating Micronutrient Biomarkers Are Associated With 3 Measures of Frailty: Evidence From the Irish Longitudinal Study on Ageing.

OBJECTIVES: To examine the associations between 3 frailty instruments and circulating micronutrients in a large representative sample of older adults. DESIGN: Cross-sectional data from a nationally representative cohort study conducted between October 2009 and July 2011. PARTICIPANTS AND SETTING: Adults age ≥50 years (n = 4068) living in the community in Ireland. MEASUREMENTS: Circulating micronutrients (lutein, zeaxanthin, folate, vitamin B-12, and vitamin D) were measured, transformed, and standardized. Frailty was assessed using the Frailty Phenotype, the Frailty Index, and the FRAIL Scale (fatigue, resistance, ambulation, illnesses, and loss of weight), instruments. Multinomial logistic regression determined associations between micronutrients and prefrailty or frailty. Models were adjusted for sociodemographic, lifestyle, health, and seasonal factors. RESULTS: Adjusting for age, sex, and educational attainment, all 3 measures of frailty were associated with lower levels of lutein [relative risk ratios (RRRs): 0.43‒0.63], zeaxanthin (RRRs: 0.49‒0.63), and vitamin D (RRRs: 0.51‒0.75), and with the accumulation of micronutrient insufficiencies (RRRs: 1.42‒1.90). Attenuated but significant associations were also observed with all measures of prefrailty for lutein, vitamin D, and number of micronutrient insufficiencies. The associations with frailty persisted following additional adjustment for social, lifestyle, and health and seasonal factors, and following multiple test correction. CONCLUSIONS AND IMPLICATIONS: We have presented the most consistent evidence in the largest study to date that micronutrient concentrations are associated with prefrailty and frailty in older adults. Our data suggest that low micronutrient status has potential as an easily modifiable marker and intervention target for frailty and supports further investigation into micronutrient supplementation and fortification to prevent frailty and disability among older adults.

Fear of falling: A manifestation of executive dysfunction?

OBJECTIVE: Fear of falling (FoF) may be an early marker of decline in global cognitive functioning, but associations with specific domains of cognitive functioning are unclear. The aim was to examine associations between FoF and 4-year decline in memory, processing speed, and executive functioning in adults aged 50 years and older. METHODS: Data were from 5174 participants (mean age = 62.6 ± 8.9 years, range = 50-91, 54.5% female) in The Irish Longitudinal Study on Ageing, a population-based study. MEASUREMENTS: FoF was self-reported in 2009 to 2011. Immediate and delayed recall, Colour Trails 1 and 2, choice reaction time, sustained attention to response task, and verbal fluency were measured in 2009 to 2011 and 2014 to 2015. Prospective associations between FoF and domains of cognitive functioning were examined using linear mixed modelling. Adjustment was made for demographic and health factors. Interactions with age were examined. RESULTS: In 2009 to 2011, 20.6% of participants reported FoF. No statistically significant interaction of FoF with age was found for any of the associations (P ≥ .06). Participants with FoF had greater decline on delayed recall (B = -0.19; 95% CI, -0.32 to -0.06), verbal fluency (B = -0.52; 95% CI, -0.88 to -0.18); and the ln-transformed scores for the Colour Trails 1 test (B = -0.04; 95% CI, -0.07 to -0.01) and the Colour Trails 2 test (B = -0.04; 95% CI, -0.06 to -0.02) than participants without FoF. No statistically significant associations were found for any of the other outcomes. CONCLUSIONS: FoF may be an indicator of decline in domains of cognitive functioning, particularly those related to executive function and processing speed. However, studies with longer follow-up and/or higher average age are required to confirm this.

Baseline Mobility is Not Associated with Decline in Cognitive Function in Healthy Community-Dwelling Older Adults: Findings From The Irish Longitudinal Study on Ageing (TILDA).

OBJECTIVES: Few studies examine the relationship between Timed Up-and-Go (TUG), a commonly used clinical test, and cognitive decline. This study examines whether TUG, usual gait speed (UGS), and dual-task gait speed (DTGS) predict decline in global cognition, executive function, processing speed, memory, and attention with follow-up of up to 5.9 years. DESIGN: Longitudinal study. SETTING: The Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort study. PARTICIPANTS: Community-dwelling adults aged ≥65 years, with Mini-Mental State Examination (MMSE) score ≥18 and no known history of memory impairment, dementia, Alzheimer's disease or Parkinson's disease were included (N = 2,250). MEASUREMENTS: Participants completed mobility tasks during the baseline health assessment and cognitive tasks during interviews conducted at 2 year intervals (waves 1, 2, and 3) and health assessments (waves 1 and 3). Linear and Poisson mixed effects regression models were used to examine longitudinal associations between mobility and each cognitive test, adjusting for sociodemographics and physical and mental health. RESULTS: There was little evidence of an association between TUG, UGS, or DTGS with decline in cognitive function after adjusting for confounders. CONCLUSIONS: These mobility tasks are not sensitive predictors of cognitive decline in this high-functioning, community-dwelling sample; nonetheless, limited decline in cognitive function was observed during follow-up. Further work with longer follow-up and/or analysis of more specific and comprehensive measures associated with gait is required.

The Relationship Between Plasma Concentrations of Lutein and Zeaxanthin with Self-Reported and Actual Prevalence of AMD in an Irish Population-Based Sample.

PURPOSE: To investigate plasma lutein (L) and zeaxanthin (Z) concentrations with grading-confirmed and self-reported prevalence of age-related macular degeneration (AMD). MATERIAL AND METHODS: Data collected from a nationally representative prospective cohort study of community-dwelling adults aged 50 years and over in the Republic of Ireland. Participants underwent a computer-assisted personal interview and a center-based health assessment. Plasma concentrations of L and total Z (Z and meso-zeaxanthin [MZ]) were measured by high performance liquid chromatography, and retinal photographs were graded using a version of the AMD International Classification and Grading System. Consumption of supplements containing L and/or Z and/or MZ was recorded as supplement use. Four groups were identified: Group 1 (n = 24): AMD-afflicted and correctly aware; Group 2 (n = 264): AMD-afflicted but unaware; Group 3 (n = 41): AMD-free and incorrectly believed that they were afflicted with the condition; Group 4 (n = 4094): AMD-free and correctly self-reported absence of AMD. RESULTS: Of 4,423 participants with plasma concentrations of L and Z and gradable retinal photographs, 288 (6.5%) were afflicted with AMD, and 65 (1.5%) self-reported AMD. Controlling for family history and age, the relationship between grading-confirmed AMD and plasma L was positive and significant (p < 0.001). Mean plasma concentrations of L in Group 2 (mean = 0.2162 ± 0.132 µmol) and Group 4 (mean = 0.2040 ± 0.121 µmol/L) were significantly lower than Group 1 (mean = 0.4691 ± 0.0.372 µmol/L) and Group 3 (mean = 0.3176 ± 0.0.235 µmol/L). Supplement use was reported by 41.7% and 17.1% of participants in Groups 1 and 3, respectively, but only 2.7% and 1.9% of participants in Groups 2 and 4, respectively. CONCLUSION: A belief that one suffers from AMD, whether justified or not, is associated with supplement use and with higher plasma concentrations of L.

Plasma Lutein and Zeaxanthin Are Associated With Better Cognitive Function Across Multiple Domains in a Large Population-Based Sample of Older Adults: Findings from The Irish Longitudinal Study on Aging.

BACKGROUND: Low blood serum or plasma concentrations of the xanthophyll carotenoids lutein and zeaxanthin have been implicated in poorer cognitive health in older adults. However, equivocal results from smaller studies and clinical trials highlight the need for large population-based studies with comprehensive measures of cognitive function and adjustment for multiple confounders to examine such associations in more depth. METHODS: In the current study, we investigated the association between plasma lutein and zeaxanthin and domain-specific cognitive performance in 4,076 community-dwelling adults aged 50 years or older from The Irish Longitudinal Study on Ageing. Mixed-effects models were fitted with adjustment for demographic and socioeconomic factors, health conditions, and health behaviors. RESULTS: Higher plasma lutein and zeaxanthin were independently associated with better composite scores across the domains of global cognition, memory, and executive function. We also found evidence that higher plasma zeaxanthin, but not lutein, was associated with better processing speed. These associations were consistent across domains. CONCLUSIONS: Further investigation of the prognostic value of carotenoid concentrations, and their changes, on cognition in similar population-based samples longitudinally is warranted.