Genome-wide association study of preserved ratio impaired spirometry (PRISm).

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV1) <80% predicted and FEV1/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities. METHODS: We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed. RESULTS: 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (rg) between PRISm and spirometric COPD (rg=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (rg=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits. CONCLUSION: This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 (HLX), rs62018863 (TMEM114) and rs185937162 (HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity.

Identification of circulating proteins associated with general cognitive function among middle-aged and older adults.

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.

Synaptic resilience is associated with maintained cognition during ageing.

INTRODUCTION: It remains unclear why age increases risk of Alzheimer's disease and why some people experience age-related cognitive decline in the absence of dementia. Here we test the hypothesis that resilience to molecular changes in synapses contribute to healthy cognitive ageing. METHODS: We examined post-mortem brain tissue from people in mid-life (n = 15), healthy ageing with either maintained cognition (n = 9) or lifetime cognitive decline (n = 8), and Alzheimer's disease (n = 13). Synapses were examined with high resolution imaging, proteomics, and RNA sequencing. Stem cell-derived neurons were challenged with Alzheimer's brain homogenate. RESULTS: Synaptic pathology increased, and expression of genes involved in synaptic signaling decreased between mid-life, healthy ageing and Alzheimer's. In contrast, brain tissue and neurons from people with maintained cognition during ageing exhibited decreases in synaptic signaling genes compared to people with cognitive decline. DISCUSSION: Efficient synaptic networks without pathological protein accumulation may contribute to maintained cognition during ageing.

Are neuropsychiatric symptoms a marker of small vessel disease progression in older adults? Evidence from the Lothian Birth Cohort 1936.

BACKGROUND: Neuropsychiatric symptoms could form part of an early cerebral small vessel disease prodrome that is detectable before stroke or dementia onset. We aimed to identify whether apathy, depression, anxiety, and subjective memory complaints associate with longitudinal white matter hyperintensity (WMH) progression. METHODS: Community-dwelling older adults from the observational Lothian Birth Cohort 1936 attended three visits at mean ages 73, 76, and 79 years, repeating MRI, Mini-Mental State Examination, neuropsychiatric (Dimensional Apathy Scale, Hospital Anxiety and Depression Scale), and subjective memory symptoms. We ran regression and mixed-effects models for symptoms and normalised WMH volumes (cube root of WMH:ICV × 10). RESULTS: At age 73, 76, and 79, m = 672, n = 476, and n = 382 participants attended MRI respectively. Worse apathy at age 79 was associated with WMH volume increase (ß = 0.27, p = 0.04) in the preceding 6 years. A 1SD increase in apathy score at age 79 associated with a 0.17 increase in WMH (ß = 0.17 normalised WMH percent ICV, p = 0.009). In apathy subscales, executive (ß = 0.13, p = 0.05) and emotional (ß = 0.13, p = 0.04) scores associated with increasing WMH more than initiation scores (ß = 0.11, p = 0.08). Increasing WMH also associated with age (ß = 0.40, p = 0.002) but not higher depression (ß = -0.01, p = 0.78), anxiety (ß = 0.05, p = 0.13) scores, or subjective memory complaints (ß = 1.12, p = 0.75). CONCLUSIONS: Apathy independently associates with preceding longitudinal WMH progression, while depression, anxiety, and subjective memory complaints do not. Patients with apathy should be considered for enrolment to small vessel disease trials.

Predictors of longitudinal cognitive ageing from age 70 to 82 including APOE e4 status, early-life and lifestyle factors: the Lothian Birth Cohort 1936.

Discovering why some people's cognitive abilities decline more than others is a key challenge for cognitive ageing research. The most effective strategy may be to address multiple risk factors from across the life-course simultaneously in relation to robust longitudinal cognitive data. We conducted a 12-year follow-up of 1091 (at age 70) men and women from the longitudinal Lothian Birth Cohort 1936 study. Comprehensive repeated cognitive measures of visuospatial ability, processing speed, memory, verbal ability, and a general cognitive factor were collected over five assessments (age 70, 73, 76, 79, and 82 years) and analysed using multivariate latent growth curve modelling. Fifteen life-course variables were used to predict variation in cognitive ability levels at age 70 and cognitive slopes from age 70 to 82. Only APOE e4 carrier status was found to be reliably informative of general- and domain-specific cognitive decline, despite there being many life-course correlates of cognitive level at age 70. APOE e4 carriers had significantly steeper slopes across all three fluid cognitive domains compared with non-carriers, especially for memory (ß = -0.234, p < 0.001) and general cognitive function (ß = -0.246, p < 0.001), denoting a widening gap in cognitive functioning with increasing age. Our findings suggest that when many other candidate predictors of cognitive ageing slope are entered en masse, their unique contributions account for relatively small proportions of variance, beyond variation in APOE e4 status. We conclude that APOE e4 status is important for identifying those at greater risk for accelerated cognitive ageing, even among ostensibly healthy individuals.

Cognitive Change Before Old Age (11 to 70) Predicts Cognitive Change During Old Age (70 to 82).

Identifying predictors of cognitive decline in old age helps us understand its mechanisms and identify those at greater risk. Here, we examined how cognitive change from ages 11 to 70 is associated with cognitive change at older ages (70 to 82 years) in the Lothian Birth Cohort 1936 longitudinal study (N = 1,091 at recruitment). Using latent-growth-curve models, we estimated rates of change from ages 70 to 82 in general cognitive ability (g) and in three cognitive domains: visuospatial, memory, and processing speed. We found that g accounted for 71.3% of interindividual change variance. Greater cognitive gain from ages 11 to 70 predicted slower decline in g over 12 subsequent years (ß = 0.163, p = .001), independently of cognitive level in childhood and at age 70, and domain-specific change beyond g. These results contribute to the goal of identifying people at higher risk of age-related cognitive decline.

Association of Life-Course Neighborhood Deprivation With Frailty and Frailty Progression From Ages 70 to 82 Years in the Lothian Birth Cohort 1936.

Neighborhood features have been postulated to be key predictors of frailty. However, evidence is mainly limited to cross-sectional studies without indication of long-term impact. We explored how neighborhood social deprivation (NSD) across the life course is associated with frailty and frailty progression among older Scottish adults. Participants (n = 323) were persons selected from the Lothian Birth Cohort 1936 with historical measures of NSD in childhood (1936-1955), young adulthood (1956-1975), and mid- to late adulthood (1976-2014). Frailty was measured 5 times between the ages of 70 and 82 years using the Frailty Index. Confounder-adjusted life-course models were assessed using a structured modeling approach; associations were estimated for frailty at baseline using linear regression and for frailty progression using linear mixed-effects models. Accumulation was the most appropriate life-course model for males; greater accumulated NSD was associated with higher frailty at baseline (b = 0.017, 95% confidence interval: 0.005, 0.029). Among females, the mid- to late adulthood sensitive period was the best-fitting life-course model, and higher NSD in this period was associated with widening frailty trajectories (b = 0.005, 95% confidence interval: 0.0004, 0.009). To our knowledge, this is the first investigation of the life-course impact of NSD on frailty in a cohort of older adults. Policies designed to address deprivation and inequalities across the full life course may support healthy aging.

Pulmonary Function and Blood DNA Methylation: A Multiancestry Epigenome-Wide Association Meta-analysis.

Rationale: Methylation integrates factors present at birth and modifiable across the lifespan that can influence pulmonary function. Studies are limited in scope and replication. Objectives: To conduct large-scale epigenome-wide meta-analyses of blood DNA methylation and pulmonary function. Methods: Twelve cohorts analyzed associations of methylation at cytosine-phosphate-guanine probes (CpGs), using Illumina 450K or EPIC/850K arrays, with FEV1, FVC, and FEV1/FVC. We performed multiancestry epigenome-wide meta-analyses (total of 17,503 individuals; 14,761 European, 2,549 African, and 193 Hispanic/Latino ancestries) and interpreted results using integrative epigenomics. Measurements and Main Results: We identified 1,267 CpGs (1,042 genes) differentially methylated (false discovery rate, <0.025) in relation to FEV1, FVC, or FEV1/FVC, including 1,240 novel and 73 also related to chronic obstructive pulmonary disease (1,787 cases). We found 294 CpGs unique to European or African ancestry and 395 CpGs unique to never or ever smokers. The majority of significant CpGs correlated with nearby gene expression in blood. Findings were enriched in key regulatory elements for gene function, including accessible chromatin elements, in both blood and lung. Sixty-nine implicated genes are targets of investigational or approved drugs. One example novel gene highlighted by integrative epigenomic and druggable target analysis is TNFRSF4. Mendelian randomization and colocalization analyses suggest that epigenome-wide association study signals capture causal regulatory genomic loci. Conclusions: We identified numerous novel loci differentially methylated in relation to pulmonary function; few were detected in large genome-wide association studies. Integrative analyses highlight functional relevance and potential therapeutic targets. This comprehensive discovery of potentially modifiable, novel lung function loci expands knowledge gained from genetic studies, providing insights into lung pathogenesis.

Contribution of white matter hyperintensities to ventricular enlargement in older adults.

Lateral ventricles might increase due to generalized tissue loss related to brain atrophy. Alternatively, they may expand into areas of tissue loss related to white matter hyperintensities (WMH). We assessed longitudinal associations between lateral ventricle and WMH volumes, accounting for total brain volume, blood pressure, history of stroke, cardiovascular disease, diabetes and smoking at ages 73, 76 and 79, in participants from the Lothian Birth Cohort 1936, including MRI data from all available time points. Lateral ventricle volume increased steadily with age, WMH volume change was more variable. WMH volume decreased in 20% and increased in remaining subjects. Over 6 years, lateral ventricle volume increased by 3% per year of age, 0.1% per mm Hg increase in blood pressure, 3.2% per 1% decrease of total brain volume, and 4.5% per 1% increase of WMH volume. Over time, lateral ventricle volumes were 19% smaller in women than men. Ventricular and WMH volume changes are modestly associated and independent of general brain atrophy, suggesting that their underlying processes do not fully overlap.

A comparison of blood and brain-derived ageing and inflammation-related DNA methylation signatures and their association with microglial burdens.

Inflammation and ageing-related DNA methylation patterns in the blood have been linked to a variety of morbidities, including cognitive decline and neurodegenerative disease. However, it is unclear how these blood-based patterns relate to patterns within the brain and how each associates with central cellular profiles. In this study, we profiled DNA methylation in both the blood and in five post mortem brain regions (BA17, BA20/21, BA24, BA46 and hippocampus) in 14 individuals from the Lothian Birth Cohort 1936. Microglial burdens were additionally quantified in the same brain regions. DNA methylation signatures of five epigenetic ageing biomarkers ('epigenetic clocks'), and two inflammatory biomarkers (methylation proxies for C-reactive protein and interleukin-6) were compared across tissues and regions. Divergent associations between the inflammation and ageing signatures in the blood and brain were identified, depending on region assessed. Four out of the five assessed epigenetic age acceleration measures were found to be highest in the hippocampus (ß range = 0.83-1.14, p ≤ 0.02). The inflammation-related DNA methylation signatures showed no clear variation across brain regions. Reactive microglial burdens were found to be highest in the hippocampus (ß = 1.32, p = 5 × 10-4 ); however, the only association identified between the blood- and brain-based methylation signatures and microglia was a significant positive association with acceleration of one epigenetic clock (termed DNAm PhenoAge) averaged over all five brain regions (ß = 0.40, p = 0.002). This work highlights a potential vulnerability of the hippocampus to epigenetic ageing and provides preliminary evidence of a relationship between DNA methylation signatures in the brain and differences in microglial burdens.

Impact of COVID-19 lockdown on psychosocial factors, health, and lifestyle in Scottish octogenarians: The Lothian Birth Cohort 1936 study.

BACKGROUND: Little is known about effects of COVID-19 lockdown on psychosocial factors, health and lifestyle in older adults, particularly those aged over 80 years, despite the risks posed by COVID-19 to this age group. METHODS: Lothian Birth Cohort 1936 members, residing mostly in Edinburgh and the surrounding Lothians regions in Scotland, mean age 84 years (SD = 0.3), responded to an online questionnaire in May 2020 (n = 190). We examined responses (experience and knowledge of COVID-19; adherence to guidance; impact on day-to-day living; social contact; self-reported physical and mental health; loneliness; and lifestyle) and relationships between previously-measured characteristics and questionnaire outcomes. RESULTS: Four respondents experienced COVID-19; most had good COVID-19 knowledge (94.7%) and found guidance easy to understand (86.3%). There were modest declines in self-reported physical and mental health, and 48.2% did less physical activity. In multivariable regression models, adherence to guidance by leaving the house less often associated with less professional occupational class (OR = 0.71, 95%CI 0.51-0.98) and poorer self-rated general health (OR = 0.62, 95%CI 0.42-0.92). Increased internet use associated with female sex (OR = 2.32, 95%CI 1.12-4.86) and higher general cognitive ability (OR = 1.53, 95%CI 1.03-2.33). Loneliness associated with living alone (OR = 0.15, 95%CI 0.07-0.31) and greater anxiety symptoms (OR = 1.76, 95%CI 0.45-1.24). COVID-19 related stress associated with lower emotional stability scores (OR = 0.40, 95%CI 0.24-0.62). Decreased physical activity associated with less professional occupational class (OR = 1.43, 95%CI 1.04-1.96), and lower general cognitive ability (OR = 0.679, 95%CI 0.491-0.931). CONCLUSIONS: Characteristics including cognitive function, occupational class, self-rated health, anxiety, and emotional stability, may be related to risk of poorer lockdown-related psychosocial and physical outcomes.

Epigenetic predictors of lifestyle traits applied to the blood and brain.

Modifiable lifestyle factors influence the risk of developing many neurological diseases. These factors have been extensively linked with blood-based genome-wide DNA methylation, but it is unclear if the signatures from blood translate to the target tissue of interest-the brain. To investigate this, we apply blood-derived epigenetic predictors of four lifestyle traits to genome-wide DNA methylation from five post-mortem brain regions and the last blood sample prior to death in 14 individuals in the Lothian Birth Cohort 1936. Using these matched samples, we found that correlations between blood and brain DNA methylation scores for smoking, high-density lipoprotein cholesterol, alcohol and body mass index were highly variable across brain regions. Smoking scores in the dorsolateral prefrontal cortex had the strongest correlations with smoking scores in blood (r = 0.5, n = 14, P = 0.07) and smoking behaviour (r = 0.56, n = 9, P = 0.12). This was also the brain region which exhibited the largest correlations for DNA methylation at site cg05575921 - the single strongest correlate of smoking in blood-in relation to blood (r = 0.61, n = 14, P = 0.02) and smoking behaviour (r = -0.65, n = 9, P = 0.06). This suggested a particular vulnerability to smoking-related differential methylation in this region. Our work contributes to understanding how lifestyle factors affect the brain and suggest that lifestyle-related DNA methylation is likely to be both brain region dependent and in many cases poorly proxied for by blood. Though these pilot data provide a rarely-available opportunity for the comparison of methylation patterns across multiple brain regions and the blood, due to the limited sample size available our results must be considered as preliminary and should therefore be used as a basis for further investigation.

Comparison of structural MRI brain measures between 1.5 and 3 T: Data from the Lothian Birth Cohort 1936.

Multi-scanner MRI studies are reliant on understanding the apparent differences in imaging measures between different scanners. We provide a comprehensive analysis of T1 -weighted and diffusion MRI (dMRI) structural brain measures between a 1.5 T GE Signa Horizon HDx and a 3 T Siemens Magnetom Prisma using 91 community-dwelling older participants (aged 82 years). Although we found considerable differences in absolute measurements (global tissue volumes were measured as ~6-11% higher and fractional anisotropy [FA] was 33% higher at 3 T than at 1.5 T), between-scanner consistency was good to excellent for global volumetric and dMRI measures (intraclass correlation coefficient [ICC] range: .612-.993) and fair to good for 68 cortical regions (FreeSurfer) and cortical surface measures (mean ICC: .504-.763). Between-scanner consistency was fair for dMRI measures of 12 major white matter tracts (mean ICC: .475-.564), and the general factors of these tracts provided excellent consistency (ICC ≥ .769). Whole-brain structural networks provided good to excellent consistency for global metrics (ICC ≥ .612). Although consistency was poor for individual network connections (mean ICCs: .275-.280), this was driven by a large difference in network sparsity (.599 vs. .334), and consistency was improved when comparing only the connections present in every participant (mean ICCs: .533-.647). Regression-based k-fold cross-validation showed that, particularly for global volumes, between-scanner differences could be largely eliminated (R2 range .615-.991). We conclude that low granularity measures of brain structure can be reliably matched between the scanners tested, but caution is warranted when combining high granularity information from different scanners.

Life Course Air Pollution Exposure and Cognitive Decline: Modelled Historical Air Pollution Data and the Lothian Birth Cohort 1936.

BACKGROUND: Air pollution has been consistently linked with dementia and cognitive decline. However, it is unclear whether risk is accumulated through long-term exposure or whether there are sensitive/critical periods. A key barrier to clarifying this relationship is the dearth of historical air pollution data. OBJECTIVE: To demonstrate the feasibility of modelling historical air pollution data and using them in epidemiologicalmodels. METHODS: Using the EMEP4UK atmospheric chemistry transport model, we modelled historical fine particulate matter (PM2.5) concentrations for the years 1935, 1950, 1970, 1980, and 1990 and combined these with contemporary modelled data from 2001 to estimate life course exposure in 572 participants in the Lothian Birth Cohort 1936 with lifetime residential history recorded. Linear regression and latent growth models were constructed using cognitive ability (IQ) measured by the Moray House Test at the ages of 11, 70, 76, and 79 years to explore the effects of historical air pollution exposure. Covariates included sex, IQ at age 11 years, social class, and smoking. RESULTS: Higher air pollution modelled for 1935 (when participants would have been in utero) was associated with worse change in IQ from age 11-70 years (ß = -0.006, SE = 0.002, p = 0.03) but not cognitive trajectories from age 70-79 years (p > 0.05). There was no support for other critical/sensitive periods of exposure or an accumulation of risk (all p > 0.05). CONCLUSION: The life course paradigm is essential in understanding cognitive decline and this is the first study to examine life course air pollution exposure in relation to cognitive health.

Prevalence of Mild Cognitive Impairment in the Lothian Birth Cohort 1936.

BACKGROUND: The Lothian Birth Cohort 1936 (LBC1936) is a highly phenotyped longitudinal study of cognitive and brain ageing. Given its substantial clinical importance, we derived an indicator of mild cognitive impairment (MCI) and amnestic and nonamnestic subtypes at 3 time points. METHODS: MCI status was derived at 3 waves of the LBC1936 at ages 76 (n=567), 79 (n=441), and 82 years (n=341). A general MCI category was derived as well as amnestic MCI (aMCI) and nonamnestic MCI (naMCI). A comparison was made between MCI derivations using normative data from the LBC1936 cohort versus the general UK population. RESULTS: MCI rates showed a proportional increase at each wave between 76 and 82 years from 15% to 18%. Rates of MCI subtypes also showed a proportional increase over time: aMCI 4% to 6%; naMCI 12% to 16%. Higher rates of MCI were found when using the LBC1936 normative data to derive MCI classification rather than UK-wide norms. CONCLUSIONS: We found that MCI and aMCI rates in the LBC1936 were consistent with previous research. However, naMCI rates were higher than expected. Future LBC1936 research should assess the predictive factors associated with MCI prevalence to validate previous findings and identify novel risk factors.

Home garden use during COVID-19: Associations with physical and mental wellbeing in older adults.

The COVID-19 pandemic has affected many aspects of people's lives. Lockdown measures to reduce the spread of COVID-19 have been more stringent for those aged over 70, at highest risk for the disease. Here, we examine whether home garden usage is associated with self-reported mental and physical wellbeing in older adults, during COVID-19 lockdown in Scotland. This study analysed data from 171 individuals (mean age 84 ± 0.5 years) from the Lothian Birth Cohort 1936 study who completed an online survey approximately two months after lockdown commenced (May/June, 2020), and reported having access to a home garden. The survey also included items on garden activities (gardening, relaxing), frequency of garden usage during lockdown, and measures of self-rated physical health, emotional and mental health, anxiety about COVID-19, and sleep quality. Ordinal regression models were adjusted for sex, living alone, education, occupational social class, anxiety and depressive symptoms, body mass index, and history of diabetes and cardiovascular disease. Neither gardening nor relaxing in the garden were associated with health outcomes. However, higher frequency of garden usage during lockdown was associated with better self-rated physical health (P = 0.005), emotional and mental health (P = 0.04), sleep quality (P = 0.03), and a composite health score (P = 0.001), after adjusting for covariates. None of the garden measures were associated with perceived change in physical health, mental and emotional health, or sleep quality, from pre-lockdown levels. The results of the current study provide support for positive health benefits of spending time in a garden-though associations may be bidirectional-and suggest that domestic gardens could be a potential health resource during the COVID-19 pandemic.

An epigenetic predictor of death captures multi-modal measures of brain health.

Individuals of the same chronological age exhibit disparate rates of biological ageing. Consequently, a number of methodologies have been proposed to determine biological age and primarily exploit variation at the level of DNA methylation (DNAm). A novel epigenetic clock, termed 'DNAm GrimAge' has outperformed its predecessors in predicting the risk of mortality as well as many age-related morbidities. However, the association between DNAm GrimAge and cognitive or neuroimaging phenotypes remains unknown. We explore these associations in the Lothian Birth Cohort 1936 (n = 709, mean age 73 years). Higher DNAm GrimAge was strongly associated with all-cause mortality over the eighth decade (Hazard Ratio per standard deviation increase in GrimAge: 1.81, P < 2.0 × 10-16). Higher DNAm GrimAge was associated with lower age 11 IQ (ß = -0.11), lower age 73 general cognitive ability (ß = -0.18), decreased brain volume (ß = -0.25) and increased brain white matter hyperintensities (ß = 0.17). There was tentative evidence for a longitudinal association between DNAm GrimAge and cognitive decline from age 70 to 79. Sixty-nine of 137 health- and brain-related phenotypes tested were significantly associated with GrimAge. Adjusting all models for childhood intelligence attenuated to non-significance a small number of associations (12/69 associations; 6 of which were cognitive traits), but not the association with general cognitive ability (33.9% attenuation). Higher DNAm GrimAge associates with lower cognitive ability and brain vascular lesions in older age, independently of early-life cognitive ability. This epigenetic predictor of mortality associates with different measures of brain health and may aid in the prediction of age-related cognitive decline.

Dietary patterns, cognitive function, and structural neuroimaging measures of brain aging.

OBJECTIVE: To examine the cross-sectional associations between dietary patterns and cognitive and neuroimaging indices of brain health concurrently in the same sample of healthy older adults. METHODS: Dietary patterns were derived from a 130-item food frequency questionnaire for 511 individuals in the Lothian Birth Cohort 1936 (mean age 79.3 ± 0.6 years). Composite scores for global cognitive function, visuospatial ability, processing speed, memory, and verbal ability were assessed. Brain volumes and white matter microstructure were assessed in participants (n = 358) who also underwent structural magnetic resonance imaging. RESULTS: A Mediterranean-style dietary pattern and a processed dietary pattern were identified using principal component analysis of food frequency questionnaire items. In fully-adjusted linear regression models, adherence to the Mediterranean-style pattern was associated with better verbal ability (ß = 0.121, P = 0.002). Associations with global cognitive function (ß = 0.094, P = 0.043), visuospatial ability (ß = 0.113, P = 0.019), and memory (ß = 0.105, P = 0.029) did not survive correction for multiple comparisons. Associations between the processed pattern and lower cognitive scores were attenuated by around 50% following adjustment for prior (childhood) cognitive ability; only an association with verbal ability remained (ß = -0.130, P = 0.001). Neither dietary pattern was associated with brain volumes or white matter microstructure. Specific Mediterranean diet features-green leafy vegetables and a low intake of red meat-were associated with better cognitive functioning. CONCLUSIONS: These observational findings suggest that adherence to a Mediterranean-style diet is associated with better cognitive functioning, but not better brain structural integrity, in older adults.

Inflammation as a risk factor for the development of frailty in the Lothian Birth Cohort 1936.

BACKGROUND: Research suggests that frailty is associated with higher inflammation levels. We investigated the longitudinal association between chronic inflammation and frailty progression. METHODS: Participants of the Lothian Birth Cohort 1936, aged 70 at baseline were tested four times over 12 years (wave 1: n = 1091, wave 4: n = 550). Frailty was assessed by; the Frailty Index at waves 1-4 and Fried phenotype at waves 1, 3 and 4. Two blood-based inflammatory biomarkers were measured at wave 1: Fibrinogen and C-reactive protein (CRP). RESULTS: Fully-adjusted, linear mixed effects models showed higher Fibrinogen was significantly associated with higher wave 1 Frailty Index score (ß = 0.011, 95% CI[0.002,0.020], p < .05). Over 12 year follow-up, higher wave 1 CRP (ß = 0.001, 95% CI[0.000,0.002], p < .05) and Fibrinogen (ß = 0.004, 95% CI[0.001,0.007], p < .05) were significantly associated with increased Frailty Index change. For the Fried phenotype, wave 1 Pre-frail and Frail participants had higher CRP and Fibrinogen than Non-frail participants (p < .001). Logistic regression models calculated risk of worsening frailty over follow-up and we observed no significant association of CRP or Fibrinogen in minimally-adjusted nor fully-adjusted models. CONCLUSIONS: Findings showed a longitudinal association of higher wave 1 CRP and Fibrinogen on worsening frailty in the Frailty Index, but not Fried Phenotype. A possible explanation for this disparity may lie in the conceptual differences between frailty measures (a biopsychosocial vs physical approach). Future research, which further explores different domains of frailty, as well the associations between improving frailty and inflammation levels, may elucidate the pathway through which inflammation influences frailty progression. This may improve earlier identification of those at high frailty risk.

Change in Physical Activity, Sleep Quality, and Psychosocial Variables during COVID-19 Lockdown: Evidence from the Lothian Birth Cohort 1936.

(1) Objectives: The COVID-19 pandemic has disproportionately affected the lives of older people. In this study, we examine changes in physical activity, sleep quality, and psychosocial variables among older people during COVID-19 lockdown. We build on cross-sectional studies on this topic by assessing change longitudinally. We also examined whether participant characteristics including demographic, cognitive, personality, and health variables were related to more positive or negative changes during lockdown. (2) Methods: 137 older participants (mean age 84 years) from the Lothian Birth Cohort 1936 study were included in the analysis. They completed the same questionnaires assessing physical activity, sleep quality, mental wellbeing, social support, loneliness, neighbourhood cohesion, and memory problems before (mostly 2 years earlier) and again during national lockdown. (3) Results: On average, levels of physical activity were reduced (those doing minimal physical activity increased from 10% to 19%) and perceived social support increased during lockdown (effect size drm = 0.178). More positive change in the psychosocial and behavioural outcome variables during lockdown was associated with personality traits (greater intellect, emotional stability, and extraversion) and having a higher general cognitive ability. Participants with a history of cardiovascular disease, more symptoms of anxiety, or who lived alone were more likely to experience negative changes in the outcome variables during lockdown. (4) Discussion: These results provide further insight into the experiences of older people during the COVID-19 pandemic and could help to identify those at greatest risk of negative psychosocial or behavioural changes during this time.