Purpose: One possible contributing factor for cerebral blood flow (CBF) decline in normal aging is the increase in partial volume effects due to brain atrophy, as cortical thinning can exacerbate the contamination of gray-matter (GM) voxels by other tissue types. This work investigates CBF changes in normal aging of a large elderly cohort aged 54 to 84 and how correction for partial volume effects that would accommodate potential changes in GM might affect this. Methods: The study cohort consisted of 474 participants aged 54 to 84years using pseudo-continuous arterial spin labeling MRI. A volumetric pipeline and a surface-based pipeline were applied to measure global and regional perfusion. Volumetric regions of interest (ROIs) included GM, cerebral white matter, vascular territories, and the brain atlas from the UK Biobank. The cortical parcellation was using Desikan-Killiany atlas. Non-partial volume effect correction (PVEc) and PVEc GM-CBF changes with aging were modeled using linear regressions. Results: Global GM CBF decreased by 0.17mL/100g/min per year with aging before PVEc (p<0.05) and was 0.18mL/100g/min after PVEc (p<0.05). All cortical parcels exhibited CBF decreases with age before PVEc. After PVEc, seven parcels retained decreasing trends. However, GM CBF demonstrated increase with age after PVEc in three parcels. Conclusion: Although decreases in global perfusion are observed with aging before PVEc, perfusion variations appear to be more regionally selective after PVEc. This supports the understanding that variation in cerebral perfusion with age observed with imaging is influenced by regional changes in anatomy that can be accommodated with PVEc, but perfusion variation is still observable even after PVE is accounted for.

This study investigates the relationship between white matter hyperintensities (WMHs) and longitudinal cognitive decline in older adults. Using data from The Irish Longitudinal Study on Ageing (TILDA), we examined WMH characteristics, including volume, location, and microstructural integrity, in a community-dwelling population of 497 individuals over a six-year period. WMHs were categorised into phenotypes based on their size, fractional anisotropy (FA), and mean diffusivity (MD), with subtypes for periventricular and deep white matter lesions. We hypothesised that larger, microstructurally compromised lesions would be associated with accelerated cognitive decline. We isolated 11,933 WMHs, with an average of 24 WMHs per individual. Of these lesions, 6,056 (51%) were classified as Low Volume - High FA, 3193 (27%) were classified as Low Volume - Low FA and 2684 (22%) were classified as High Volume, Low FA. Our findings demonstrate that high-volume, low FA deep (p = 0.05) and periventricular (p = 0.004) lesions were significantly linked to cognitive decline (X = 12.9, p = 0.004), whereas small periventricular lesions with near normal microstructural properties do not predict cognitive decline. These results suggest that distinct WMH phenotypes may serve as markers for differential risks of cognitive impairment, providing potential targets for early intervention in at-risk populations.

Introduction:There is a critical link between vascular disease and the progression to dementia. The hippocampus has been implicated in memory and cognitive decline. In this study, we investigate the independent and moderating effects of increased arterial stiffness (AS) and reduced cerebral blood flow (CBF) on hippocampal volume (HV) in a large MRI sample of community-dwelling older adults from the Irish Longitudinal Study on Ageing (TILDA). Methods:Longitudinal data from study participants for Wave 1 (2009-2011) and Wave 3 (2014-2015) were included. This included health and social information as well as a nurse-administered health assessment. Patients who had complete AS, CBF and MR-hippocampal measurements were included. Pseudo-continuous arterial spine labelling was performed to quantify whole CBF. Volumetric analysis was performed using FreeSurfer 6.0 recon-all processing pipeline. Results:395 patients met inclusion criteria. This four-year follow up longitudinal study demonstrated that (i) prolonged elevated AS (at wave 1 and wave 3), (ii) the interaction between higher AS at wave 1 and lower CBF at wave 3 and (iii) the interaction between prolonged elevated AS (at wave 1 and wave 3) and reduced CBF at wave 3 were associated with smaller HV. Conclusion:Increased arterial stiffness and reduced CBF were not independently associated with smaller HV. However, in combination, persistently elevated AS and reduced CBF is associated with smaller HV. These effects were equally exerted across all hippocampal subfields tested. Our findings suggest a lag effect in the arterial stiffness and hippocampal volume relationship. We propose that the subsequent reduction in cerebral blood flow observed with elevated arterial stiffness may be the missing link in the pathway associating arterial stiffness with hippocampal atrophy.

Recent research has indicated that the relationship between age-related cognitive decline and falling may be mediated by the individual's capacity to quickly cancel or inhibit a motor response. This longitudinal investigation demonstrates that higher white matter fibre density in the motor inhibition network paired with low physical activity was associated with falling in elderly participants. We measured the density of white matter fibre tracts connecting key nodes in the inhibitory control network in a large sample (n = 414) of older adults. We modelled their self-reported frequency of falling over a 4-year period with white matter fibre density in pathways corresponding to the direct and hyperdirect cortical-subcortical loops implicated in the inhibitory control network. Only connectivity between right inferior frontal gyrus and right subthalamic nucleus was associated with falling as measured cross-sectionally. The connectivity was not, however, predictive of future falling when measured 2 and 4 years later. Higher white matter fibre density was associated with falling, but only in combination with low levels of physical activity. No such relationship existed for selected control brain regions that are not implicated in the inhibitory control network. Albeit statistically robust, the direction of this effect was counterintuitive (more dense connectivity associated with falling) and warrants further longitudinal investigation into whether white matter fibre density changes over time in a manner correlated with falling, and mediated by physical activity.

ObjectivesThis study investigates the mediating roles of autonomic function and mental health in the association between sleep and cognitive decline in adults aged 50 and above.MethodA total of 2,697 participants with observations on sleep and mediators at baseline and repeated measures of cognitive function (MMSE) were included. Clusters of individuals with similar cognitive trajectories (high-stable, mid-stable and low-declining) were identified. Multinomial logistic regressions were used to estimate the likelihood of membership to each trajectory group based on sleep duration and disturbance. Finally, mediation analysis tested potential mediating effects of autonomic function and mental health underpinning the sleep-cognition relationship.ResultsShort (p = .028), long (p =.019), and disturbed sleep (p =.008) increased the likelihood of a low-declining cognitive trajectory. Mental health measures fully attenuated relationships between cognitive decline and short or disturbed sleep but not long sleep. No autonomic function mediation was observed.ConclusionOlder adults with short or disturbed sleep are at risk of cognitive decline due to poor mental health. Individuals with long sleep are also at risk, however, the acting pathways remain to be identified. These outcomes have clinical implications, potentially identifying intervention strategies targeting mental health and sleep as prophylactic measures against dementia.

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 (beta = -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 (X-(18)(2) = 64.4; p <.001), and telomere length was borderline (X-(18)(2) = 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.

Abstract Aims Cognitive impairment has been associated with kidney function and chronic kidney disease. Whether this association is due to accelerated cardiovascular disease (CVD) or an independent specific kidney function effect related to toxins is unclear. We investigated the impact of an array of clinical factors, inflammatory biomarkers, and cardiovascular biomarkers on the association between kidney function, cognitive function, and structural brain abnormalities. Methods and results We used data from the first and third waves of the TILDA Study, a population-representative prospective cohort of Irish adults aged 50 years and over, based on stratified random sampling (n = 3774). The MRI sub-study included participants who consented to MRI brain imaging in addition to the health assessment. Multivariable linear and mixed-effect longitudinal regression models were fitted separately for each kidney marker/estimated glomerular filtration rate (eGFR) equation after adjusting for baseline age and demographics, clinical vascular risk factors, and biomarkers. Unadjusted analyses showed an association between low eGFR, cognitive dysfunction, and cognitive decline (P < 0.001 for all kidney markers). Kidney function markers were also associated with white matter disease [OR = 3.32 (95% CI: 1.11, 9.98)], total grey matter volume (β = -0.17, 95% CI -0.27 to -0.07), and regional grey matter volumes within areas particularly susceptible to hypoxia (P < 0.001 for all). All the associations decreased after adjusting for age and were also diminished after adjusting for CVD biomarkers. Age and CVD-biomarker score were significant mediators of the adjusted associations between eGFR and cognitive status. These results remained consistent for cross-sectional and longitudinal outcomes and specific cognitive domains. Conclusion Decreased kidney function was associated with cerebrovascular disease. The association appeared to be mediated predominantly by age and the combination of CVD markers [namely N-terminal pro-B-type natriuretic peptide (NT-proBNP) and Growth Differentiation Factor 15 (GDF15)], supporting the idea that shared biological pathways underline both diseases. Further mechanistic studies of the specific molecular mechanisms that lead to both kidney and cognitive decline are warranted.

BACKGROUND:Older adults have both the highest risk of contracting SARS-CoV-2 and in many jurisdictions have had additional restrictions placed on the social interactions. As a result, the COVID-19 pandemic has led to increased depression and loneliness among older adults. Using data from an established cohort of older adults, the aims of this study was to describe changes in loneliness and depression and to examine the directionality of the association between depression and loneliness over a 5-year period that included the early months of the pandemic.METHODS:Data were from The Irish Longitudinal Study on Ageing (TILDA), a large cohort of community-dwelling adults aged 54+. We applied an auto-regressive cross-lagged panel modelling approach to estimate the effect of depression on loneliness and vice versa over three time points.RESULTS:Both depression and loneliness increased significantly in the early months of the pandemic. While the association between loneliness and depression was bi-directional, loneliness was a stronger predictor of depression.CONCLUSION:The strength and bi-directionality of the association between loneliness and depression suggests that interventions to alleviate loneliness may also help reduce depressive symptoms and vice versa.

Objectives: To investigate whether tooth loss was associated with regional grey matter volume (GMV) in a group of community dwelling older men and women from Ireland.Methods: A group of 380 dementia-free men and women underwent a dental examination and had a Magnetic Resonance Imaging (MRI) scan as part of The Irish Longitudinal Study of Aging (TILDA). Cortical parcellation was conducted using Freesurfer utilities to produce volumetric measures of gyral based regions of interest. Analysis included multiple linear regression to investigate the association between tooth loss and regional GMVs with adjustment for various confounders.Results: The mean age of participants was 68.1 years (SD 7.3) and 51.6% of the group were female. 50 (13.2%) of the participants were edentulous, 148 (38.9%) had 1-19 teeth, and 182 (47.9%) had >20 teeth. Multiple liner regression analysis with adjustment for a range of potential confounders showed associations between the number of teeth and GMVs in the paracentral lobule and the cuneus cortex. In the paracentral lobule, comparing participants with 1-19 teeth versus edentates there was an increase in GMV of beta=323.0mm3 (95% Confidence Interval [CI] 84.5, 561.6) and when comparing participants with >20 teeth to edentates there was an increase of beta=382.3mm3 (95% CI 126.9, 637.7). In the cuneus cortex, comparing participants with >20 teeth to edentates there was an increase in GMV of beta=380.5mm3 (95% CI 69.4, 691.5).Conclusions: In this group of older men and women from Ireland, the number of teeth was associated with GMVs in the paracentral lobule and the cuneus cortex independent of various known confounders.Clinical significance: Although not proof of causation, the finding that tooth loss was associated with regional reduced GMV in the brain may represent a potential explanatory link to the observed association between tooth loss and cognitive decline.

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.

We examined the relationship between hippocampal subfield volumes and cognitive decline over a 4-year period in a healthy older adult population with the goal of identifying subjects at risk of progressive cognitive impairment which could potentially guide therapeutic interventions and monitoring. 482 subjects (68.1 years +/− 7.4; 52.9% female) from the Irish Longitudinal Study on Ageing underwent magnetic resonance brain imaging and a series of cognitive tests. Using K-means longitudinal clustering, subjects were first grouped into three separate global and domain-specific cognitive function trajectories; High-Stable, Mid-Stable and Low-Declining. Linear mixed effects models were then used to establish associations between hippocampal subfield volumes and cognitive groups. Decline in multiple hippocampal subfields was associated with global cognitive decline, specifically the presubiculum (estimate −0.20; 95% confidence interval (CI) -0.78 – −0.02; p = 0.03), subiculum (−0.44; −0.82 – −0.06; p = 0.02), CA1 (−0.34; −0.78 – −0.02; p = 0.04), CA4 (−0.55; −0.93 – −0.17; p = 0.005), molecular layer (−0.49; −0.87 – −0.11; p = 0.01), dentate gyrus (−0.57; −0.94 – −0.19; p = 0.003), hippocampal tail (−0.53; −0.91 – −0.15; p = 0.006) and HATA (−0.41; −0.79 – −0.03; p = 0.04), with smaller volumes for the Low-Declining cognition group compared to the High-Stable cognition group. In contrast to global cognitive decline, when specifically assessing the memory domain, cornu ammonis 1 subfield was not found to be associated with low declining cognition (−0.14; −0.37 – 0.10; p = 0.26). Previously published data shows that atrophy of specific hippocampal subfields is associated with cognitive decline but our study confirms the same effect in subjects asymptomatic at time of enrolment. This strengthens the predictive value of hippocampal subfield atrophy in risk of cognitive decline and may provide a biomarker for monitoring treatment efficacy.

NT-proB-type Natriuretic Peptide (NTproBNP) is a hormone released in response to changes in pressure inside the heart often related to heart failure and other cardiac problems. Early evidence shows significant correlations between brain structure and markers of heart failure including ejection fraction and NTproBNP. We sought to investigate if levels of this biomarker are related to cognitive decline over 10 years in older adults participating in the Irish Longitudinal Study on Ageing (TILDA), a nationally representative cohort of adults aged 50 years and older residing across Ireland. Levels of NTproBNP were measured in 4,105 participants, mean age 61.5 years and 53.8% women, from blood drawn at baseline (Wave 1: 2009-2011). Verbal memory (10-word immediate and delayed recall) and verbal fluency/ executive function (animal naming) were measured every two-years over a 10-year follow-up (Wave 1 – 6) and were used to create a composite score at each wave which served as a measure of global cognitive function. Linear mixed effect models with adjustment for covariates were performed. Model 1 included age, age^2, sex, education; Model 2 included Model 1 + cardiovascular diseases (heart failure, heart attack, stroke, tia, hypertension, diabetes), lifestyle factors (smoking, alcohol, physical activity, waist-hip ratio) and depression. NTproBNP was significantly and negatively associated with cognitive function at Wave 3 (B = -0.13, 95%CI = -0.20, -0.05), Wave 4 (B = -0.24, 95%CI = -0.31, -0.16), Wave 5 (B = -0.25, 95%CI = -0.32, -0.17) and Wave 6 (B = -0.26, 95%CI = -0.34, -0.17) (p<.001) ( Figure 1 ). After further adjustment, the associations remained significant. These results suggest that NTproBNP may be useful as an early indicator of cognitive decline in older adults for those with and without current cardiovascular diseases.

Frailty in older adults is associated with greater risk of cognitive decline. Brain connectivity insights could help understand the association, but studies are lacking. We applied connectome-based predictive modeling to a 32-item self-reported Frailty Index (FI) using resting state functional MRI data from The Irish Longitudinal Study on Ageing. A total of 347 participants were included (48.9% male, mean age 68.2 years). From connectome-based predictive modeling, we obtained 204 edges that positively correlated with the FI and composed the "frailty network" characterised by connectivity of the visual network (right); and 188 edges that negatively correlated with the FI and formed the "robustness network" characterized by connectivity in the basal ganglia. Both networks' highest degree node was the caudate but with different patterns: from caudate to visual network in the frailty network; and to default mode network in the robustness network. The FI was correlated with walking speed but not with metrics of global cognition, reinforcing the matching between the FI and the brain connectivity pattern found (main predicted connectivity in basal ganglia).

This study explores the relationship of life-course intergenerational social mobility with cognitive function and brain structure in older adults using Diagonal Reference Models. Data from the Irish Longitudinal Study on Ageing, a population-based cohort of adults aged 50 years and older (N = 4 620 participants; mean age: 66.1; standard deviation: 9.1; 55% female) was used for analysis. Brain magnetic resonance imaging data were available for 464 participants. Social mobility was characterized as the difference between childhood socioeconomic position (SEP; ie, father's occupation) and adulthood SEP (ie, own occupation). The Montreal Cognitive Assessment (MoCA), the Mini-Mental State Examination (MMSE), cortical thickness, and total gray matter volume (GMV) served as global cognitive and brain measures. Exploratory analyses included the volumes of the ventromedial prefrontal cortex (vmPFC), anterior cingulate (AC), hippocampus, and amygdala. A social gradient in cognitive function was observed among the intergenerationally stable; brain structure was not as clearly socially patterned. Adulthood SEP was significantly associated with MoCA (weight = 0.76; p < .001), MMSE (weight = 0.91; p < .001), GMV (weight = 0.77; p = .002), and AC volume (weight = 0.76; p < .001), whereas childhood SEP was associated with vmPFC volume (weight = 1.00; p = .003). There was no independent association of social mobility with any of the outcomes. Together our results suggest that both childhood and adulthood SEP are important in shaping later-life brain health, but that adulthood SEP predominates in terms of its influence. This is potentially an important insight as it suggests that brain health may be modifiable if socioeconomic circumstances change.

Background:Frailty in older adults has been associated with reduced brain health. However, structural brain signatures of frailty remain understudied. Our aims were: (1) Explore associations between a frailty index (FI) and brain structure on magnetic resonance imaging (MRI). (2) Identify the most important FI features driving the associations. Methods:We designed a cross-sectional observational study from a population-based study (The Irish Longitudinal Study on Aging: TILDA). Participants aged ≥50 years who underwent the wave 3 MRI sub-study were included. We measured cortex, basal ganglia, and each of the Desikan-Killiany regional volumes. Age-and sex-adjusted correlations were performed with a 32-item self-reported FI that included conditions commonly tested for frailty in research and clinical settings. A graph theory analysis of the network composed by each FI item and cortex volume was performed. White matter fiber integrity was quantified using diffusion tensor imaging (DTI). Results:In 523 participants (mean age 69, 49% men), lower cortex and thalamic volumes were independently associated with higher FI. Sensory and functional difficulties, diabetes, polypharmacy, knee pain, and self-reported health were the main FI associations with cortex volume. In the network analysis, cortex volume had a modest influence within the frailty network. Regionally, higher FI was significantly associated with lower volumes in both orbitofrontal and temporal cortices. DTI analyses revealed inverse associations between the FI and the integrity of some association bundles. Conclusion:The FI used had a recognizable but subtle structural brain signature in this sample. Only some FI deficits were directly associated with cortex volume, suggesting scope for developing FIs that include metrics more specifically related with brain health in future aging neuroscience studies.

OBJECTIVE:To examine a novel measurement of autonomic innervation, the early heart rate response to orthostasis, in relation to sleep duration and disturbance (actigraphy-based and self-reported) in healthy older adults. DESIGN:Cross-sectional analyses of a nationally representative prospective cohort study, the Irish Longitudinal Study on Ageing (TILDA). PARTICIPANTS:Nine hundred sixty community-dwelling adults aged 50 and over (mean age 65.6 ± 8.1; 53% women). MEASUREMENT:Orthostatic heart rate response was measured during an active stand test. Beat-to-beat heart rate was monitored over 3 minutes using noninvasive digital photoplethysmography. Mean values at each 10-second time point after standing were generated and differences from baseline at each time point were used for analysis. Actigraphy-based sleep measures were extracted from wrist-worn GENEactiv devices; self-reported sleep measures using interview questions. RESULTS:Linear mixed-effects regression analyses, with inclusion of a large number of confounders, show that self-reported sleep duration and actigraphy-based sleep duration and disturbance were associated with altered orthostatic heart rate response, particularly within the first 20 seconds poststanding. Self-reported short sleep (β = -0.06; 95% confidence interval [CI]: -0.11, -0.01) and long sleep (β = -0.15; 95% CI: -0.24, -0.05) and actigraphy-based short sleep (β = -0.08; 95% CI: -0.14, -0.01) were characterized by a smaller increase at 10 seconds (p < .01). Actigraphy-based short sleep (β = 0.15; 95% CI: 0.08, 0.22) and sleep disturbance (β = 0.04; 95% CI: 0.02, 0.06) were associated with a slower return toward baseline at 20 seconds (p < .001). CONCLUSIONS:Our findings suggest sympathetic dysregulation, impaired vagal reactivation, and/or decreased baroreceptor sensitivity in the presence of shortened or disturbed sleep.

Background:Cognitive impairments are well-documented in multiple sclerosis (MS), while speech impairments are often overlooked despite their significant effect on quality of life. For effective clinical management of multisystem conditions such as MS, consideration should be given to the interaction between deficits in multiple domains, such as speech and cognition. To evaluate speech rate measures of spontaneous and read speech, in people with MS and to examine the link between speech and cognition. Methods:Forty-five people with MS and 25 controls underwent an extensive cognitive battery, including executive functioning, information processing and memory tasks, and completed two speech tasks: a reading task and a picture description task, from which speech rate measures were derived. Results:The progressive MS cohort had reduced articulation (p < 0.04) and speech rate (p < 0.02) compared to controls and those with relapsing MS. Regression models also revealed information processing speed accounted for 18% to 30% of the variance of spontaneous speech rate measures, and 27% of read speech. Executive functioning accounted for a further 10% of the variance of speech rate in those with MS. Conclusions:The present study suggests that speech production is contingent on cognitive ability, with information processing speed and executive functioning linked with speech timing patterns.

Objectives: To investigate whether tooth loss and related loss of occluding tooth pairs, were associated with cognitive decline in a group of community dwelling older men and women from Ireland. Methods: A group of 2508 men and women, aged 50-93 years, underwent a dental examination as part of The Irish Longitudinal Study of ageing (TILDA). Global cognitive function was assessed using the mini-mental state examination (MMSE). Analysis included multiple logistic regression with adjustment for various confounders. Results: The mean age of participants was 65.5 years (SD 8.1) and 55.3% of the group were female. Three hundred and twenty-nine (13.1%) of the cohort were classified as having a low MMSE with a score <= 27. After adjustment for confounding variables, compared to subjects with > 20 teeth, the odds ratio for a low MMSE amongst edentulous was 1.55 (95% CI 1.03-2.34) p = 0.03, and for those with 1-19 teeth was 1.38 (95% CI 1.03-1.84) p = 0.04. Having < 10 natural occluding pairs and < 4 posterior occluding pairs also associated with a low MMSE. Conclusions: In this cross-sectional cohort study, tooth loss and related loss of occluding tooth pairs were associated with a low MMSE in a group of older adults from Ireland, independent of various known confounders. Clinical Significance: Dentists should be aware of the potential systemic health implications of patients presenting with tooth loss. Tooth loss may be an important risk indicator for cognitive decline.

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.