Longitudinal Study Of Ageing Cohort Research Articles

A transformer model for cause-specific hazard prediction

BackgroudModelling discrete-time cause-specific hazards in the presence of competing events and non-proportional hazards is a challenging task in many domains. Survival analysis in longitudinal cohorts often requires such models; notably when the data is gathered at discrete points in time and the predicted events display complex dynamics. Current models often rely on strong assumptions of proportional hazards, that is rarely verified in practice; or do not handle sequential data in a meaningful way. This study proposes a Transformer architecture for the prediction of cause-specific hazards in discrete-time competing risks. Contrary to Multilayer perceptrons that were already used for this task (DeepHit), the Transformer architecture is especially suited for handling complex relationships in sequential data, having displayed state-of-the-art performance in numerous tasks with few underlying assumptions on the task at hand.ResultsUsing synthetic datasets of 2000–50,000 patients, we showed that our Transformer model surpassed the CoxPH, PyDTS, and DeepHit models for the prediction of cause-specific hazard, especially when the proportional assumption did not hold. The error along simulated time outlined the ability of our model to anticipate the evolution of cause-specific hazards at later time steps where few events are observed. It was also superior to current models for prediction of dementia and other psychiatric conditions in the English longitudinal study of ageing cohort using the integrated brier score and the time-dependent concordance index. We also displayed the explainability of our model’s prediction using the integrated gradients method.ConclusionsOur model provided state-of-the-art prediction of cause-specific hazards, without adopting prior parametric assumptions on the hazard rates. It outperformed other models in non-proportional hazards settings for both the synthetic dataset and the longitudinal cohort study. We also observed that basic models such as CoxPH were more suited to extremely simple settings than deep learning models. Our model is therefore especially suited for survival analysis on longitudinal cohorts with complex dynamics of the covariate-to-outcome relationship, which are common in clinical practice. The integrated gradients provided the importance scores of input variables, which indicated variables guiding the model in its prediction. This model is ready to be utilized for time-to-event prediction in longitudinal cohorts.

Music and the aging brain - Exploring the role of long-term Carnatic music training on cognition and gray matter volumes.

Aging is a natural process and is often associated with an increased incidence of cognitive impairment. Physical exercise, diet, and leisure activities (music, dance, and art) are some of the lifestyle factors that contribute to healthy aging. The present study aims to explore the differences in cognitive functioning between aging individuals involved in musical activity throughout their lifetime and the ones who were not. Fifty-one healthy elderly individuals (50-80 years of age) residing in an urban locality were selected for the study from the Tata Longitudinal Study of Aging cohort. Participants were divided into two groups: Active musicians trained in Carnatic music for more than five years (n = 18) and age-matched non-musicians (n = 33). Addenbrooke cognitive examination-III, Hindi mental status examination, and trail-making test-B (TMT-B) were used to assess cognitive functioning. A Generalized Linear Regression Model was performed including covariates such as gender, age, and years of education. We also looked at the available brain magnetic resonance imaging data of a subset of our study population to inspect the volumetric differences between musicians and non-musicians. Our results showed that musicians had significantly better visuospatial abilities as compared to non-musicians (P = 0.043). Musicians (130.89 ± 45.16 s) also took less time to complete the TMT-B task than non-musicians (148.73 ± 39.65 s), although it was not a statistically significant difference (P =0.150). In addition, brain imaging data suggested that musicians had increased gray matter volumes in the right precuneus, right post-central gyrus, right medial and superior frontal gyrus, right orbital gyrus, left middle temporal gyrus, left cuneus, left fusiform gyrus, and bilateral cingulate gyrus. Our findings are indicative of music being an important attribute in improving cognitive reserve and predicting cognitive resilience. These findings pave the way to explore the utility of non-pharmacological interventions, such as Music Therapy (especially Carnatic music in the Indian context), as a potential factor for improving cognitive reserve in elderly individuals.

Beyond Inflammaging: The Impact of Immune System Aging on Age-Related Muscle Decline, Results From the InCHIANTI Study.

Aging is characterized by chronic low-level inflammation and is associated with geriatric syndromes such as sarcopenia and frailty. Our aim was to evaluate the longitudinal variation of muscle area, muscle quality, and muscle strength, relative to the variation of leukocyte-derived markers, and to assess the presence of a pathway of associations among derived leukocyte ratios, and the components of muscle health. The InCHIANTI is a longitudinal cohort study of aging that began in 1998 with follow-up visits every 3 years. Out of the 1 453 participants enrolled at baseline, this study includes 1 179 participants with complete data. Muscle strength was assessed by hand grip strength test, whereas muscle density and fat area were considered as indirect markers of muscle quality, derived from peripheral quantitative computed tomography of the calf. Muscle area was associated with neutrophil-to-lymphocyte ratio (NL-ratio), age, gender, comorbidities, and body mass index (BMI). Muscle density variation over time was inversely associated with age, comorbidities, and BMI, while being positively associated with monocyte-to-lymphocyte ratio (ML-ratio) and male gender. Fat area was inversely associated with age, interleukine-6 (IL-6), male gender, and NL-ratio, while being positively associated with ML-ratio, comorbidities, and BMI. Handgrip strength decreased with age, IL-6 levels, comorbidities, and NL-ratio, but increased with ML-ratio, being male, and having a higher BMI. In a path-analysis model, ML-ratio positively correlates with muscle mass, density, and strength, while NL-ratio only correlates inversely with muscle mass and density. NL-ratio and ML-ratio are associated with aging and may be implicated in age-related mechanisms that affect body composition and muscle strength. These ratios may represent a link between aging of the immune system and decline of muscle health with aging. However, further studies are needed to identify their usefulness for early detection of sarcopenia, myosteatosis, and frailty in the older adult.

Development and validation of a novel instrument to capture companion dog mortality data: the Dog Aging Project End of Life Survey.

The researchers and clinicians within the Dog Aging Project (DAP), a longitudinal cohort study of aging in companion dogs, created and validated a novel survey instrument titled the End of Life Survey (EOLS) to gather owner-reported mortality data about companion dogs. Bereaved dog owners who participated in the refinement, face validity assessment, or reliability assessment of the EOLS (n = 42) and/or completed the entire survey between January 20 and March 24, 2021 (646). The EOLS was created and modified by veterinary health professionals and human gerontology experts using published literature, clinical veterinary experience, previously created DAP surveys, and feedback from a pilot study conducted with bereaved dog owners. The EOLS was subjected to qualitative validation methods and post hoc free-text analysis to evaluate its ability to thoroughly capture scientifically relevant aspects of companion dogs' deaths. The EOLS was well received with excellent face validity as assessed by dog owners and experts. The EOLS had fair to substantial reliability for the 3 validation themes-cause of death (κ = 0.73; 95% CI, 0.5 to 0.95), perimortem quality of life (κ = 0.49; 95% CI, 0.26 to 0.73), and reason for euthanasia (κ = 0.3; 95% CI, 0.08 to 0.52)-and had no need for any substantial content alterations based on free-text analysis. The EOLS has proven to be a well-accepted, comprehensive, and valid instrument for capturing owner-reported companion dog mortality data and has the potential to enhance veterinarians' ability to care for the aging dog population by illuminating their understanding of companion dogs' end-of-life experiences.

Association of leukocyte telomere length with perceived physical fatigability

BackgroundLeukocyte telomere length (LTL) is a potential genomic marker of biological aging, but its relation to fatigability, a prognostic indicator of phenotypic aging (e.g., functional decline) is unknown. We hypothesized shorter LTL would predict greater perceived physical fatigability, but that this association would be attenuated by adjusting for chronological age. MethodsTwo generations of participants (N = 1997; 309 probands, 1688 offspring) were from the Long Life Family Study (age = 73.7 ± 10.4, range 60–108, 54.4 % women), a longitudinal cohort study of aging. LTL was assayed at baseline. Perceived physical fatigability was measured 8.0 ± 1.1 years later using the validated, self-administered 10-item Pittsburgh Fatigability Scale (PFS, 0–50, higher scores = greater fatigability). Generalized estimating equations were generated to model the association between LTL and PFS Physical scores. ResultsPrevalence of greater physical fatigability (PFS scores≥15) was 41.9 %. Using generalized estimating equations, a one kilobase pair shorter LTL was associated with higher PFS Physical scores (β = 1.8, p < .0001), accounting for family structure, and adjusting for field center, follow-up time, sex, and follow-up body mass index, physical activity, and chronic health conditions. When age was included as a covariate, the association was fully attenuated (β = 0.1, p = .78). ConclusionLTL may provide an alternative method for estimating an individual's lifetime exposure to chronic stressors, but does not appear to provide additional information not captured by chronological age. Further research is needed to characterize the interaction between age, LTL, and perceived fatigability, and develop a method of identifying individuals at risk for deleterious aging.

The metabolic landscape of brain alterations in Alzheimer's disease.

Impairment of brain glucose metabolism has been frequently described in Alzheimer's disease (AD). Moreover, the strongest predictor of the lifetime incidence of AD is the ε4 allele of APOE, a protein involved in lipid metabolism. These connections between AD and metabolism provide motivation to perform an in-depth metabolic profiling of human brain tissue for different stages of AD pathophysiology. Brain tissue samples were obtained from the Religious Orders Study and Memory and Aging Project (ROS/MAP) at the Rush Alzheimer's Disease Center. Furthermore, ROS/MAP collects extensive phenotyping of the participants' cognitive trajectories as well as postmortem pathology. Metabolic profiling was performed on Metabolon's untargeted platform, yielding 1,055 quantified metabolites. Generalized linear models with appropriate linkage functions for continuous or categorical AD-related phenotypes were used to discover the association of metabolic profiles with AD-related phenotypes, such as amount of amyloid and tangles in brain, global burden of pathology, NIA-Reagan score, diagnosis (derived from Braak and CERAD scores), clinical diagnosis at the time of death, global cognition assessed during the visit before death, estimated decline of global cognition over lifetime. The models included confounder correction for age, gender, body mass index, years of education, post mortem interval, number of APOEε4 alleles, and medications. We found 263 metabolites to be significantly associated (adjusted p-value <0.05) with one of the AD phenotypes. 137 of these metabolites were significantly associated with three or more phenotypes. Of these, nine could be replicated using an independent autopsy cohort from Mayo Clinic, five could also be replicated using a published study based on Baltimore Longitudinal Study of Aging cohort. The associated metabolites are involved in various metabolic processes known to be involved in AD pathogenesis, such as amino acid metabolism, urea cycle, and polyamine metabolism. In addition, we have identified several novel associations that could uncover the interdependence of different AD-associated metabolic processes. We have generated a comprehensive landscape of AD-associated metabolites and associated processes. These will be instrumental to fill the gap in our understanding of the metabolic components of AD pathophysiology.

The Factor Structure of Items Assessing Subjective Memory: Between-Persons and Within-Persons across Time

Introduction: Current understanding of the psychometric properties of items intended to assess the multidimensional construct of subjective memory (SM) is limited, as longitudinal studies of aging commonly use single items or brief sets of items to assess SM. Investigating how SM items cluster within individuals over time would increase the understanding of how combining these items impacts their utility as an early indicator of cognitive change in the aging trajectory. To address this need, the current study examined the factor structure of a brief set of SM items in an existing longitudinal study focused on cognitive aging at both the within-person and between-person levels. Methods: Data were drawn from the Einstein Aging Study, a longitudinal cohort study of aging (N = 1,239, M_age = 77.51, SD = 5.03; 69.50% white; 24.27% black; 6.23% other). Community-dwelling older adults from an urban area of New York City were interviewed annually. At each wave, participants responded to 6 items intended to assess SM. Items assessed participants’ perceived memory decline as well as current memory ability. Multilevel exploratory factor analyses examined which factor solution best fit the data at between-person and within-person levels. Results: Factor structure of the SM items varied at the two levels. At the within-person level, two factors emerged, whereas at the between-person level, a single factor best represented the SM items. Items assessing perceived declines in memory functioning tended to have similar trajectories, while items assessing current memory ability were less related to change over time. Conclusion: Items appeared to assess two different dimensions of SM when examining within-person changes in SM across time; however, the item structure suggested no other items covaried systematically within persons over time. In contrast to the conceptualization of SM as a multidimensional construct, our findings suggest that when measuring SM between individuals, SM items tend to capture a single dimension underlying SM. This may be due to the long retrospection period of items assessing perceived memory ability. A single item assessing perceived memory decline in older adults without evidence of objective cognitive impairment may be sufficient to monitor memory change in clinical or research settings.

Predicting hearing aid use in adults: the Beaver Dam Offspring Study

Objective The purpose of this study was to (i) develop a model that predicts hearing aid (HA) use and (ii) determine if model fit is improved by adding factors not typically collected in audiological evaluations. Design Two models were created and evaluated. The “clinical” model used factors typically collected during audiologic clinical evaluations. The “expanded” model considered additional clinical, health and lifestyle factors to determine if the model fit could be improved (compared to clinical model). Models were created with least absolute shrinkage and selection operator (LASSO) logistic regression with 10-fold cross validation. Predictive ability was evaluated via receiver operating characteristic curves and concordance statistics (c-statistics). Study sample This study included 275 participants from the Beaver Dam Offspring Study, a prospective longitudinal cohort study of aging, with a treatable level of hearing loss and no HA use at baseline. Results The clinical and expanded models report predictors important for HA use. The c-statistics of the clinical (0.80) and expanded (0.79) models were not significantly different (p = 0.41). Conclusions Similar predictive abilities of models suggest audiological evaluations perform well in predicting HA use.

Association Between Abdominal Aortic Calcification, Bone Mineral Density, and Fracture in Older Women.

Although a relationship between vascular disease and osteoporosis has been recognized, its clinical importance for fracture risk evaluation remains uncertain. Abdominal aortic calcification (AAC), a recognized measure of vascular disease detected on single-energy images performed for vertebral fracture assessment, may also identify increased osteoporosis risk. In a prospective 10-year study of 1024 older predominantly white women (mean age 75.0 ± 2.6 years) from the Perth Longitudinal Study of Aging cohort, we evaluated the association between AAC, skeletal structure, and fractures. AAC and spine fracture were assessed at the time of hip densitometry and heel quantitative ultrasound. AAC was scored 0 to 24 (AAC24) and categorized into low AAC (score 0 and 1, n = 459), moderate AAC (score 2 to 5, n = 373), and severe AAC (score >6, n = 192). Prevalent vertebral fractures were calculated using the Genant semiquantitative method. AAC24 scores were inversely related to hip BMD ( r s = -0.077, p = 0.013), heel broadband ultrasound attenuation ( r s = -0.074, p = 0.020), and the Stiffness Index ( r s = -0.073, p = 0.022). In cross-sectional analyses, women with moderate to severe AAC were more likely to have prevalent fracture and lumbar spine imaging-detected lumbar spine fractures, but not thoracic spine fractures (Mantel-Haenszel test of trend p < 0.05). For 10-year incident clinical fractures and fracture-related hospitalizations, women with moderate to severe AAC (AAC24 score >1) had increased fracture risk (HR 1.48; 95% CI, 1.15 to 1.91; p = 0.002; HR 1.46; 95% CI, 1.07 to 1.99; p = 0.019, respectively) compared with women with low AAC. This relationship remained significant after adjusting for age and hip BMD for clinical fractures (HR 1.40; 95% CI, 1.08 to 1.81; p = 0.010), but was attenuated for fracture-related hospitalizations (HR 1.33; 95% CI, 0.98 to 1.83; p = 0.073). In conclusion, older women with more marked AAC are at higher risk of fracture, not completely captured by bone structural predictors. These findings further support the concept that vascular calcification and bone pathology may share similar mechanisms of causation that remain to be fully elucidated © 2019 American Society for Bone and Mineral Research.

Hand and knee osteoarthritis are associated with reduced diameters in retinal vessels: the AGES-Reykjavik study.

To investigate the association between osteoarthritis (OA) and microvascular pathology, we examined the relationship between retinal microvascular caliber and osteoarthritis of the hand and knee in an elderly population. The AGES-Reykjavik is a population-based, multidisciplinary longitudinal cohort study of aging. Retinal vessel caliber, hand osteoarthritis and total knee joint replacements due to OA were examined in 4757 individuals (mean age 76 ± 5years; 57% female). Incident knee joint replacements during 5-year follow-up (n = 2961, mean age 75 ± 5years; 58% female) were also assessed. Logistic regression analysis, adjusting for age, sex, and body mass index, showed an association between narrow arteriolar caliber and hand OA, as well as knee replacement. After adjustment for other covariates, including statin therapy, this association was significant for both hand OA in men and women [OR 1.10(1.03-1.17), p < 0.01] (per unit standard deviation decrease in CRAE) and TKR prevalence [OR 1.15 (1.01-1.32), p = 0.04], especially for men [OR 1.22 (1.00-1.51) p = 0.04] and also for incident TKRs in men [OR 1.50 (1.07-2.10), p = 0.04]. Narrow venular caliber was associated with hand OA in women [OR 1.10 (1.01-1.21), p = 0.03]. Retinal arterial narrowing in hand and knee OA is present in males as well as females. Venular narrowing in hand OA in women was an unexpected finding and is in contrast with the venular widening usually observed in cardiovascular diseases.

Association of Cadmium and Lead Exposure With the Incidence of Contrast Sensitivity Impairment Among Middle-aged Adults

Contrast sensitivity (CS) is an important indicator of visual function that affects daily life, including mobility, visually intensive tasks, safety, and autonomy. Understanding the risk factors for CS impairment could prevent decreases in visual function. To determine the incidence of and factors associated with CS impairment in a large cohort. The Beaver Dam Offspring Study is an ongoing longitudinal cohort study of aging involving adults in Beaver Dam, Wisconsin. Participants who were free of CS impairment in both eyes at baseline were included (N = 1983). Baseline data collection occurred from June 8, 2005, through August 4, 2008, when the participants ranged from 21 to 84 years of age. Two follow-up examinations occurred at 5-year intervals: one was conducted between July 12, 2010, and March 21, 2013, and the other between July 1, 2015, and November 13, 2017. Data analysis was performed from November 27, 2017, to February 27, 2018. Contrast sensitivity testing was conducted with Pelli-Robson letter sensitivity charts, and incident impairment was defined as a log CS score less than 1.55 in either eye at any follow-up examination. Cadmium and lead levels were measured in whole blood with inductively coupled plasma mass spectrometry. Associations between baseline characteristics and CS impairment incidence were examined using Cox proportional hazard models and quantified as hazard ratios (HRs) with 95% CI. Of the 1983 participants included, 1028 (51.8%) were female and 955 (48.2%) were male, with a mean (SD) age of 48 (9.3) years. The 10-year cumulative incidence of CS impairment was 24.8% (95% CI, 22.9-26.8), similar in women (24.9%) and men (24.6%), and highest in the oldest age group (65-84 years) at 66.3%. In multivariable models, cadmium level in the highest quintile (HR, 1.35; 95% CI, 1.02-1.78), older age (HR, 1.36; 95% CI, 1.25-1.47), larger waist circumference (HR, 1.06; 95% CI, 1.01-1.11), and more plaque sites (1-3 sites: HR, 1.43; 95% CI, 1.07-1.92; 4-6 sites: HR, 2.75; 95% CI, 1.26-6.05) were among the factors associated with increased risk, while male sex (HR, 0.77; 95% CI, 0.60-0.98) and any alcohol consumption (HR, 0.61; 95% CI, 0.43-0.88) were associated with decreased risk. Results were similar when smoking status replaced cadmium exposure in the models. Lead level was not associated with increased risk. This study's findings suggest that incident CS impairment was common in the 10-year follow-up, with cadmium, but not lead, exposure associated with increased risk. The associations of diminished CS with other modifiable risk factors found appear to imply that changes in behavior may reduce future incidence of CS impairment.

Ethnic and Gender Differences in Preferred Activities among Māori and non-Māori of Advanced age in New Zealand.

This study explored active aging for older Māori and non-Māori by examining their self-nominated important everyday activities. The project formed part of the first wave of a longitudinal cohort study of aging well in New Zealand. Māori aged 80 to 90 and non-Māori aged 85 were recruited. Of the 937 participants enrolled, 649 answered an open question about their three most important activities. Responses were coded under the World Health Organization's International Classification of Functioning, Disability and Health (ICF), Activities and Participation domains. Data were analyzed by ethnicity and gender for first in importance, and all important activities. Activity preferences for Māori featured gardening, reading, walking, cleaning the home, organized religious activities, sports, extended family relationships, and watching television. Gendered differences were evident with walking and fitness being of primary importance for Māori men, and gardening for Māori women. Somewhat similar, activity preferences for non-Māori featured gardening, reading, and sports. Again, gendered differences showed for non-Māori, with sports being of first importance to men, and reading to women. Factor analysis was used to examine the latent structural fit with the ICF and whether it differed for Māori and non-Māori. For Māori, leisure and household activities, spiritual activities and interpersonal interactions, and communicating with others and doing domestic activities were revealed as underlying structure; compared to self-care, sleep and singing, leisure and work, and domestic activities and learning for non-Māori. These findings reveal fundamental ethnic divergences in preferences for active aging with implications for enabling participation, support provision and community design.

Neurofibrillary Tangle Stage and the Rate of Progression of Alzheimer Symptoms

The heterogeneity of rate of clinical progression among patients with Alzheimer disease leads to difficulty in providing clinical counseling and diminishes the power of clinical trials using disease-modifying agents. To gain a better understanding of the factors that affect the natural history of progression in Alzheimer disease for the purpose of improving both clinical care and clinical trial design. A longitudinal cohort study of aging from 2005 to 2014 in the National Alzheimer Coordinating Center. Clinical evaluation of the participants was conducted in 31 National Institute on Aging's Alzheimer Disease Centers. Nine hundred eighty-four participants in the National Alzheimer Coordinating Center cohort study who died and underwent autopsy and met inclusion and exclusion criteria. We sought to model the possibility that knowledge of neurofibrillary tangle burden in the presence of moderate or frequent plaques would add to the ability to predict clinical rate of progression during the ensuing 2 to 3 years. We examined the National Alzheimer Coordinating Center autopsy data to evaluate the effect of different neurofibrillary tangle stages on the rates of progression on several standard clinical instruments: the Clinical Dementia Rating Scale sum of boxes, a verbal memory test (logical memory), and a controlled oral word association task (vegetable naming), implementing a reverse-time longitudinal modeling approach in conjunction with latent class estimation to adjust for unmeasured sources of heterogeneity. Several correlations between clinical variables and neurocognitive performance suggest a basis for heterogeneity: Higher education level was associated with lower Clinical Dementia Rating Scale sum of boxes (β = -0.19; P < .001), and frequent vs moderate neuritic plaques were associated with higher Clinical Dementia Rating Scale sum of boxes (β = 1.64; P < .001) and lower logical memory score (β = -1.07; P = .005). The rate of change of the clinical and cognitive scores varied depending on Braak stage, when adjusting for plaques, age of death, sex, education, and APOE genotype. For example, comparing high vs low Braak stage with other variables fixed, the logical memory score decreased a substantial 0.38 additional units per year (95% CI, -0.70 to -0.06; P = .02). Using these data, we estimate that a 300-participant clinical trial with end point of a 20% improvement in slope in rate of change of Clinical Dementia Rating Scale sum of boxes has 89% power when all participants in the trial are from the high Braak stage, compared with 29% power if Braak stage had not used for eligibility. We found that knowledge of neurofibrillary tangle stage, modeled as the sort of information that could be available from tau positron-emission tomography scans and its use to determine eligibility to a trial, could dramatically improve the power of clinical trials and equivalently reduce the required sample sizes of clinical trials.

Altered levels of blood proteins in Alzheimer's disease longitudinal study: Results from Australian Imaging Biomarkers Lifestyle Study of Ageing cohort

IntroductionA blood-based biomarker panel to identify individuals with preclinical Alzheimer's disease (AD) would be an inexpensive and accessible first step for routine testing. MethodsWe analyzed 14 biomarkers that have previously been linked to AD in the Australian Imaging Biomarkers lifestyle longitudinal study of aging cohort. ResultsLevels of apolipoprotein J (apoJ) were higher in AD individuals compared with healthy controls at baseline and 18 months (P = .0003) and chemokine-309 (I-309) were increased in AD patients compared to mild cognitive impaired individuals over 36 months (P = .0008). DiscussionThese data suggest that apoJ may have potential in the context of use (COU) of AD diagnostics, I-309 may be specifically useful in the COU of identifying individuals at greatest risk for progressing toward AD. This work takes an initial step toward identifying blood biomarkers with potential use in the diagnosis and prognosis of AD and should be validated across other prospective cohorts.

Diabetes, Hemoglobin A1C, and Regional Alzheimer Disease and Infarct Pathology.

We examined the relationship of diabetes and hemoglobin A1C (A1C) to 2 common causes of dementia. The study included 1228 subjects who underwent annual clinical evaluations and a brain autopsy at death, as part of a Rush longitudinal cohort study of aging. A total of 433 subjects had A1C data available. Neuropathologic evaluations documented the size and location of infarcts. Modified silver stain-based Alzheimer disease (AD) measures included global and regional scores. We used regression analyses to examine associations of diabetes and A1C with overall and regional neuropathology. Diabetes [odds ratio (OR)=0.94; 95% confidence interval (CI), 0.73-1.20) and A1C (OR=0.83; 95% CI, 0.62-1.10) were not associated with global AD pathology across the brain, nor with overall or individual measures of neuropathology in mesial temporal or neocortical regions separately (all P>0.05). Diabetes was associated with a higher odds of any infarct (OR=1.43; 95% CI, 1.07-1.90), and particularly with gross (OR=1.53; 95% CI, 1.14-2.06) but not microinfarcts (P=0.06), and subcortical (OR=1.79; 95% CI, 1.34-2.39) but not cortical infarcts (P=0.83). In summary, we found no relationship of diabetes or A1C with global or regional AD pathology, including in the mesial temporal lobe. Diabetes is associated with gross subcortical infarcts. Our results suggest that the diabetes-dementia link is based on subcortical vascular pathology and not on regional AD pathology.

Cognitive decline is associated with risk aversion and temporal discounting in older adults without dementia.

Risk aversion and temporal discounting are preferences that are strongly linked to sub-optimal financial and health decision making ability. Prior studies have shown they differ by age and cognitive ability, but it remains unclear whether differences are due to age-related cognitive decline or lower cognitive abilities over the life span. We tested the hypothesis that cognitive decline is associated with higher risk aversion and temporal discounting in 455 older persons without dementia from the Memory and Aging Project, a longitudinal cohort study of aging in Chicago. All underwent repeated annual cognitive evaluations using a detailed battery including 19 tests. Risk aversion was measured using standard behavioral economics questions: participants were asked to choose between a certain monetary payment versus a gamble in which they could gain more or nothing; potential gamble gains varied across questions. Temporal discounting: participants were asked to choose between an immediate, smaller payment and a delayed, larger one; two sets of questions addressed small and large stakes based on payment amount. Regression analyses were used to examine whether prior rate of cognitive decline predicted level of risk aversion and temporal discounting, controlling for age, sex, and education. Over an average of 5.5 (SD=2.9) years, cognition declined at an average of 0.016 units per year (SD=0.03). More rapid cognitive decline predicted higher levels of risk aversion (p=0.002) and temporal discounting (small stakes: p=0.01, high stakes: p=0.006). Further, associations between cognitive decline and risk aversion (p=0.015) and large stakes temporal discounting (p=0.026) persisted in analyses restricted to persons without any cognitive impairment (i.e., no dementia or mild cognitive impairment); the association of cognitive decline and small stakes temporal discounting was no longer statistically significant (p=0.078). These findings are consistent with the hypothesis that subtle age-related changes in cognition can detrimentally affect individual preferences that are critical for maintaining health and well being.

English Longitudinal Study of Aging: can Internet/E-mail use reduce cognitive decline?

Cognitive decline is a major risk factor for disability, dementia, and death. The use of Internet/E-mail, also known as digital literacy, might decrease dementia incidence among the older population. The aim was to investigate whether digital literacy might be associated with decreased cognitive decline in older adulthood. Data from the English Longitudinal Study of Aging cohort with 6,442 participants aged 50-89 years, followed for 8 years, with baseline cognitive testing and four additional time points. The main outcome variable was the relative percentage change in delayed recall from a 10-word-list learning task across five separate measurement points. In addition to digital literacy, socioeconomic variables, including wealth and education, comorbidities, and baseline cognitive function were included in predictive models. The analysis used Generalized Estimating Equations. Higher education, no functional impairment, fewer depressive symptoms, no diabetes, and Internet/E-mail use predicted better performance in delayed recall. Digital literacy may help reduce cognitive decline among persons aged between 50 and 89 years.

Temporal Discounting Is Associated with an Increased Risk of Mortality among Community-Based Older Persons without Dementia

BackgroundTemporal discounting is an important determinant of many health and financial outcomes, but we are not aware of studies that have examined the association of temporal discounting with mortality.MethodsParticipants were 406 older persons without dementia from the Rush Memory and Aging Project, a longitudinal cohort study of aging. Temporal discounting was measured using standard preference elicitation questions. Individual discount rates were estimated using a well-established hyperbolic function and used to predict the risk of mortality during up to 5 years of follow-up.ResultsThe mean estimate of discounting was 0.45 (SD = 0.33, range: 0.08–0.90), with higher scores indicating a greater propensity to prefer smaller immediate rewards over larger but delayed ones. During up to 5 years of follow-up (mean = 3.6 years), 62 (15% of 406) persons died. In a proportional hazards model adjusted for age, sex, and education, temporal discounting was associated with an increased risk of mortality (HR = 1.103, 95% CI 1.024, 1.190, p = 0.010). Thus, a person with the highest discount rate (score = 0.90) was about twice more likely to die over the study period compared to a person with the lowest discount rate (score = 0.08). Further, the association of discounting with mortality persisted after adjustment for the level of global cognitive function, the burden of vascular risk factors and diseases, and an indicator of psychological well being (i.e., purpose in life).ConclusionTemporal discounting is associated with an increased risk of mortality in old age after accounting for global cognitive function and indicators of physical and mental health.

Poor Decision Making Is Associated with an Increased Risk of Mortality among Community-Dwelling Older Persons without Dementia

Background: Decision making is thought to be an important determinant of health and well-being across the lifespan, but little is known about the association of decision making with mortality. Methods: Participants were 675 older persons without dementia from the Rush Memory and Aging Project, a longitudinal cohort study of aging. Baseline assessments of decision making were used to predict the risk of mortality during up to 4 years of follow-up. Results: The mean score on the decision making measure at baseline was 7.1 (SD = 2.9, range: 0–12), with lower scores indicating poorer decision making. During up to 4 years of follow-up (mean = 1.7 years), 40 (6% of 675) persons died. In a proportional hazards model adjusted for age, sex and education, the risk of mortality increased by about 20% for each additional decision making error (HR = 1.19, 95% CI = 1.07–1.32, p = 0.002). Thus, a person who performed poorly on the measure of decision making (score = 3, 10th percentile) was about 4 times more likely to die compared to a person who performed well (score = 11, 90th percentile). Further, the association of decision making with mortality persisted after adjustment for the level of cognitive function. Conclusion: Poor decision making is associated with an increased risk of mortality in old age even after accounting for cognitive function.

Relation of Late-Life Social Activity With Incident Disability Among Community-Dwelling Older Adults

We tested the hypothesis that a higher level of social activity was associated with decreased risk of incident disability in older adults. Data came from older adults in the Rush Memory and Aging Project, an ongoing longitudinal cohort study of aging. Analyses were restricted to persons without clinical dementia and reporting no need for help performing any task in the particular functional domain assessed. Participants were followed for an average of 5.1 years (SD = 2.5). Social activity, based on 6 items (visiting friends or relatives; going to restaurants, sporting events, or playing games; group meetings; church/religious services; day or overnight trips; unpaid community/volunteer work), was assessed at baseline. Disability in basic activities of daily living, mobility disability, and instrumental activities of daily living was assessed annually. Proportional hazard models adjusted for age, sex, and education were used to examine the association between social activity and incident disability. Fully adjusted models included terms for depression, vascular diseases and risk factors, body mass index, social networks, and self-reported physical activity. In fully adjusted models, among 954 persons without baseline disability, the risk of developing disability in activities of daily living decreased by 43% (hazard ratio = 0.57, 95% confidence interval = 0.46, 0.71) for each additional unit of social activity. Social activity was also associated with decreased risk of developing mobility disability (hazard ratio = 0.69, 95% confidence interval = 0.54, 0.88) and disability in instrumental activities of daily living (hazard ratio = 0.71, 95% confidence interval = 0.55, 0.93). Social activity is associated with a decreased risk of incident disability in activities of daily living, mobility, and instrumental activities of daily living, among community-dwelling older adults.