Background: Cognitive reserve is most commonly measured using socio-behavioural proxy variables. These variables are easy to collect, have a straightforward interpretation, and are widely associated with reduced risk of dementia and cognitive decline in epidemiological studies. However, the specific proxies vary across studies and have rarely been assessed in complete models of cognitive reserve (i.e. alongside both a measure of cognitive outcome and a measure of brain structure). Complete models can test independent associations between proxies and cognitive function in addition to the moderation effect of proxies on the brain-cognition relationship. Consequently, there is insufficient empirical evidence guiding the choice of proxy measures of cognitive reserve and poor comparability across studies. Method: In a cross-sectional study, we assessed the validity of 5 common proxies (education, occupational complexity, verbal intelligence, leisure activities, and exercise) and all possible combinations of these proxies in 2 separate community-dwelling older adult cohorts: The Irish Longitudinal Study on Ageing (TILDA; N = 313, mean age = 68.9 years, range = 54–88) and the Cognitive Reserve/Reference Ability Neural Network Study (CR/RANN; N = 234, mean age = 64.49 years, range = 50–80). Fifteen models were created with 3 brain structure variables (grey matter volume, hippocampal volume, and mean cortical thickness) and 5 cognitive variables (verbal fluency, processing speed, executive function, episodic memory, and global cognition). Results: No moderation effects were observed. There were robust positive associations with cognitive function, independent of brain structure, for 2 individual proxies (verbal intelligence and education) and 16 composites (i.e. combinations of proxies). Verbal intelligence was statistically significant in all models. Education was significant only in models with executive function as the cognitive outcome variable. Three robust composites were observed in more than two-thirds of brain-cognition models: the composites of (1) occupational complexity and verbal intelligence, (2) education and verbal intelligence, and (3) education, occupational complexity, and verbal intelligence. However, no composite had larger average effects nor was more robust than verbal intelligence alone. Conclusion: These results support the use of verbal intelligence as a proxy measure of CR in cross-sectional studies of cognitively healthy older adults.

This study examined the associations of body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and physical activity (PA) with gray matter cerebral blood flow (CBF_GM) in older adults. Cross-sectional data was used from the Irish Longitudinal Study on Ageing (n = 495, age 69.0 ±7.4 years, 52.1% female). Whole-brain CBF_GM was quantified using arterial spin labeling MRI. Results from multivariable regression analysis revealed that an increase in BMI of 0.43 kg/m², WHR of 0.01, or WC of 1.3 cm were associated with the same reduction in CBF_GM as 1 year of advancing age. Participants overweight by BMI or with high WHR/WC reporting low/moderate PA had up to 3 ml/100g/min lower CBF_GM (p ≤ .011); there was no significant reduction for those reporting high PA. Since PA could potentially moderate obesity/CBF associations, this may be a cost-effective and relatively easy way to help mitigate the negative impact of obesity in an older population, such as cerebral hypoperfusion, which is an early mechanism in vascular dementia and Alzheimer's disease.

Fried's frailty phenotype (FP) is defined by exhaustion (EX), unexplained weight loss (WL), weakness (WK), slowness (SL) and low physical activity (LA). Three or more components define the frail state, and one or two the prefrail. We described longitudinal transitions of FP states and components in The Irish Longitudinal Study on Ageing (TILDA). We included participants aged ≥50 years with FP information at TILDA wave 1 (2010), who were followed-up over four longitudinal waves (2012, 2014, 2016, 2018). Next-wave transition probabilities were estimated with multi-state Markov models. 5683 wave 1 participants were included (2612 men and 3071 women; mean age 63.1 years). Probabilities from non-frail to prefrail, and non-frail to frail were 27% and 2%, respectively. Prefrail had a 32% probability of reversal to non-frail, and a 10% risk of progression to frail. Frail had an 18% probability of reversal to prefrail and 31% risk of death. Probabilities of transitioning from not having to having a component were: 17% for LA, 11% for SL, 9% for EX, 7% for WL and 6% for WK. Probabilities of having a FP component and dying were: 17% for WL, 15% for WK, 14% for SL, 13% for EX, and 10% for LA. Probabilities of having a component and recovering at the next wave were: 59% for WL, 58% for EX, 40% for WK, 35% for LA and 23% for SL. FP states and components are characterized by dynamic longitudinal transitions. Opportunities exist for reducing the probability of adverse transitions.

To establish normative reference values for total grey matter cerebral blood flow (CBFGM) measured using pseudo-continuous arterial spin labelling (pCASL) MRI in a large cohort of community-dwelling adults aged 54 years and older. Quantitative assessment of CBFGM may provide an imaging biomarker for the early detection of those at risk of neurodegenerative diseases, such as Alzheimer's and dementia. However, the use of this method to differentiate normal age-related decline in CBFGM from pathological reduction has been hampered by the lack of reference values for cerebral perfusion. The study cohort comprised a subset of wave 3 (2014-2015) participants from The Irish Longitudinal Study on Ageing (TILDA), a large-scale prospective cohort study of individuals aged 50 and over. Of 4309 participants attending for health centre assessment, 578 individuals returned for 3T multi-parametric MRI brain examinations. In total, CBFGM data acquired from 468 subjects using pCASL-MRI were included in this analysis. Normative values were estimated using Generalised Additive Models for Location Shape and Scale (GAMLSS) and are presented as percentiles, means and standard deviations. The mean age of the cohort was 68.2 ± 6.9 years and 51.7% were female. Mean CBFGM for the cohort was 36.5 ± 8.2 ml/100 g/min. CBFGM decreased by 0.2 ml/100 g/min for each year increase in age (95% CI = -0.3, -0.1; p ≤ 0.001) and was 3.1 ml/100 g/min higher in females (95% CI = 1.6, 4.5; p ≤ 0.001). This study is by far the largest single-site study focused on an elderly community-dwelling cohort to present normative reference values for CBFGM measured at 3T using pCASL-MRI. Significant age- and sex-related differences exist in CBFGM.

Assessment of the cerebrovascular and cardiovascular response to standing has prognostic value for a range of outcomes in the older adult population. Studies generally attempt to control for standing speed differences by asking participants to stand in a specified time but little is known about the range of transition times observed. This study aimed to characterize how standing speed associates with cardiovascular and cerebrovascular measures following transition from supine to standing. Continuous cerebral oxygenation, heart rate, systolic and diastolic blood pressure were monitored for 3 minutes after transitioning from supine to standing. An algorithm was used to calculate the time taken to transition from existing Finometer data (from the height correction unit). Linear mixed-effects models were used to assess the influence of transition time on each of the signals while adjusting for covariates. Transition time ranged from 2 to 27 s with 17% of participants taking >10 s to stand. Faster transition was associated with a more extreme decrease 10 s after standing but improved recovery at 20 s for cerebral oxygenation and blood pressure. Standing faster was associated with an elevated heart rate on initiation of stand and a quicker recovery 10 to 20 s after standing. The speed of transitioning from supine to standing position is associated with cardiovascular and cerebrovascular response in the early period after standing (<40 s). Care should be taken in the interpretation of findings which may be confounded by standing speed and statistical adjustment for standing time should be applied where appropriate.