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Objectives Loneliness in the aging population is associated with decreased cognitive function and increased neuropathology; less is understood about the association of loneliness and cognitive resilience (CR), defined as the discordance between a person’s actual and expected cognition given their neuropathology. Here we assess the effect of loneliness and change in loneliness on CR at end of life and across older adulthood. Methods Data were combined from 2 longitudinal studies of older adults. CR proximate to death (CRlast_level) and across time (CRslope) was obtained by independently regressing global cognition and change in cognition onto multiple neuropathology indicators and extracting the resulting residuals. We used a series of simple linear regression models to assess the effect of loneliness level and change on CRlast_level and CRslope. Results Higher baseline loneliness was associated with lower CRlast_level (β = −0.11, 95% confidence interval [95% CI; −0.18, −0.04], p < .01); higher baseline loneliness and increasing loneliness over time was associated with lower CRslope (β = −0.13, 95% CI [−0.22, −0.05], p < .01 and β = −0.12, 95% CI [−0.20, −0.04], p < .01, respectively). Results were robust to covariate inclusion and independent of objective social isolation. Discussion Higher and increasing loneliness was associated with lower CR in the face of neuropathology. These results suggest that some individuals are less resilient to the accumulation of neuropathology than others, and experiencing high/increasing loneliness is a key factor putting some at risk. Interventions aimed at optimizing cognitive function across older adults should include loneliness reduction as a potential area of focus.

Dementia algorithms are often developed in cross-sectional samples but implemented in longitudinal studies to ascertain incident dementia. However, algorithm performance may be higher in cross-sectional settings, and this may impact estimates of risk factor associations.We used data from the Religious Orders Study and the Memory and Aging Project (N = 3460) to assess the performance of example algorithms in classifying prevalent dementia in cross-sectional samples versus incident dementia in longitudinal samples. We used an applied example and simulation study to characterize the impact of varying sensitivity, specificity, and unequal sensitivity or specificity between exposure groups (differential performance) on estimated hazard ratios from Cox models.Using all items, algorithm sensitivity was higher for prevalent (0.796) versus incident dementia (0.719); hazard ratios had slight bias. Sensitivity differences were larger using a subset of items (0.732 vs. 0.600) and hazard ratios were 13%-19% higher across adjustment sets compared to estimates using gold-standard dementia status. Simulations indicated specificity and differential algorithmic performance between exposure groups may have large effects on hazard ratios.Algorithms developed using cross-sectional data may be adequate for longitudinal settings when performance is high and non-differential. Poor specificity or differential performance between exposure groups may lead to biases.

Social engagement is known to improve health; less is known about whether social activities at the core of African American life decrease mortality risk in this minoritized population. This study investigated whether and which aspects of social engagement predict mortality risk in older African Americans.Data from 768 African Americans (aged ∼73 years; nondemented at baseline) participating in the Minority Aging Research Study, a longitudinal community-based, cohort study of aging, was collected between 2004 and 2020 and analyzed in 2020. Participants self-reported late-life social activity, social network size, life space, and purpose in life at baseline and completed approximately 6.5 years of annual follow-up (range=15.70). Cox models included time from baseline to death or censoring and an indicator for death versus censored with age, sex, education, cardiovascular disease risk factor burden, depressive symptomatology, and motor gait performance as covariates.As of March 2020, 25% of participants died (n=192; age at death ∼83 years). In fully adjusted Cox models, mortality risk decreased by 34% (hazard ratio=0.66; 95% CI=0.48, 0.91; p=0.012) for those with higher compared with that for those with lower social activity generally, with community/volunteer-, group-, and socially-related activities specifically driving these results.Engaging in late-life social activity, especially group- and socially-based activities, was most consistently and robustly associated with reduced mortality risk in African Americans regardless of health. These results lay the foundation for considering community-based approaches to increase and/or maintain social participation in older African Americans as a potential means by which to increase longevity in this population.

This study aimed to investigate the relationship between John Henryism, a psychological trait typified by high-effort active coping that has been associated with adverse health outcomes among Blacks, and cognitive decline.In a cohort of community-dwelling older Black adults ( N = 611), we investigated the relationship between John Henryism and cognitive decline. John Henryism was measured using the John Henryism Active Coping Scale (JHACS), a nine-item validated measure of self-reported high-effort coping (mean [standard deviation] = 16.9 [4.8]; range, 4-27). We implemented a three-step modeling process using mixed-effects models to assess the relationship between the JHACS and global cognitive function as well as five cognitive domains. We adjusted for demographics and for factors known to be associated with cognitive function and decline including vascular risk factors, discrimination, and income.The trait of high-effort active coping was associated with lower-average cognitive function ( β = -0.07, 95% confidence interval = -0.10 to -0.03), but not with decline. The results remained after further adjustment for experiences of discrimination, income, and vascular risk factors. In domain-specific analyses, we found that the JHACS was associated with baseline levels of working memory, semantic memory, and visuospatial ability, but not decline.These results highlight the importance of using culturally specific measures in considering the heterogeneity of cognitive health outcomes in minoritized populations. Understanding how stress responses relate to late-life cognition among older Black adults could help promote aspects of behavioral resilience along with healthful coping responses.

Background: An anthocyanidin, pelargonidin, primarily found in berries, has antioxidant and anti-inflammatory properties, and is associated with better cognition and reduced Alzheimer’s dementia risk. Objective: This study investigated if pelargonidin or berry intake is associated with Alzheimer’s disease (AD) neuropathology in human brains. Methods: The study was conducted among 575 deceased participants (age at death = 91.3±6.1 years; 70% females) of the Rush Memory and Aging Project, with dietary data (assessed using a food frequency questionnaire) and neuropathological evaluations. Calorie-adjusted pelargonidin intake was modeled in quartiles and berry intake as continuous (servings/week). Mean amyloid-beta load and phosphorylated tau neuronal neurofibrillary tangle density across multiple cortical regions were assessed using immunohistochemistry. Global AD pathology burden, a quantitative summary score of neurofibrillary tangles, and diffuse and neuritic plaques using Bielschowsky silver stains in multiple brain regions, was also assessed. Results: In a linear regression model adjusted for age at death, sex, education, APOE ɛ4 status, vitamin E, and vitamin C, participants in the highest quartile of pelargonidin intake when compared to those in the lowest quartile, had less amyloid-β load (β (SE) = –0.293 (0.14), p = 0.038), and fewer phosphorylated tau tangles (β (SE) = –0.310, p = 0.051). Among APOE ɛ4 non-carriers, higher strawberry (β (SE) = –0.227 (0.11), p = 0.037) and pelargonidin (Q4 versus Q1: β (SE) = –0.401 (0.16), p = 0.011; p trend = 0.010) intake was associated with less phosphorylated tau tangles, no association was observed in APOE ɛ4 carriers. Berry intake was not associated with AD pathology. However, excluding participants with dementia or mild cognitive impairment at baseline, strawberry (p = 0.004) and pelargonidin (ptrend = 0.007) intake were associated with fewer phosphorylated tau tangles. Conclusion: Higher intake of pelargonidin, a bioactive present in strawberries, is associated with less AD neuropathology, primarily phosphorylated tau tangles.

Although sex differences have been noted in cellular function and behavior, therapy efficacy, and disease incidence and outcomes, the adoption of sex as a biological variable in tissue engineering and regenerative medicine remains limited. Furthering the development of personalized, precision medicine requires considering biological sex at the bench and in the clinic. This review provides the basis for considering biological sex when designing tissue-engineered constructs and regenerative therapies by contextualizing sex as a biological variable within the tissue engineering triad of cells, matrices, and signals. To achieve equity in biological sex within medicine requires a cultural shift in science and engineering research, with active engagement by researchers, clinicians, companies, policymakers, and funding agencies. Expected final online publication date for the Annual Review of Biomedical Engineering, Volume 25 is June 2023. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Background Medicare fee-for-service (FFS) claims data are increasingly leveraged for dementia research. Few studies address the validity of recent claim data to identify dementia, or carefully evaluate characteristics of those assigned the wrong diagnosis in claims. Methods We used claims data from 2014 to 2018, linked to participants administered rigorous, annual dementia evaluations in 5 cohorts at the Rush Alzheimer’s Disease Center. We compared prevalent dementia diagnosed through the 2016 cohort evaluation versus claims identification of dementia, applying the Bynum-standard algorithm. Results Of 1 054 participants with Medicare Parts A and B FFS in a 3-year window surrounding their 2016 index date, 136 had prevalent dementia diagnosed during cohort evaluations; the claims algorithm yielded 217. Sensitivity of claims diagnosis was 79%, specificity 88%, positive predictive value 50%, negative predictive value 97%, and overall accuracy 87%. White participants were disproportionately represented among detected dementia cases (true positive) versus cases missed (false negative) by claims (90% vs 75%, respectively, p = .04). Dementia appeared more severe in detected than missed cases in claims (mean Mini-Mental State Exam = 15.4 vs 22.0, respectively, p < .001; 28% with no limitations in activities of daily living versus 45%, p = .046). By contrast, those with “over-diagnosis” of dementia in claims (false positive) had several worse health indicators than true negatives (eg, self-reported memory concerns = 51% vs 29%, respectively, p < .001; mild cognitive impairment in cohort evaluation = 72% vs 44%, p < .001; mean comorbidities = 7 vs 4, p < .001). Conclusions Recent Medicare claims perform reasonably well in identifying dementia; however, there are consistent differences in cases of dementia identified through claims than in rigorous cohort evaluations.

In May 2021, the M/V X-Press Pearl cargo ship caught fire 18 km off the west coast of Sri Lanka and spilled ∼1680 tons of spherical pieces of plastic or “nurdles” (∼5 mm; white in color). Nurdles a...

The coronavirus disease 2019 (COVID-19) pandemic thrust the field of public health into the spotlight. For many epidemiologists, biostatisticians, and other public health professionals, this caused the professional aspects of our lives to collide with the personal, as friends and family reached out with concerns and questions. Learning how to navigate this space was new for many of us and required refining our communication style depending on context, setting, and audience. Some of us took to social media, utilizing our existing personal accounts to share information after sorting through and summarizing the rapidly emerging literature to keep loved ones safe. However, those in our lives sometimes asked unanswerable questions, or began distancing themselves when we suggested more stringent guidance than they had hoped for, causing additional stress during an already traumatic time. We often had to remind ourselves that we were also individuals experiencing this pandemic and that our time-intensive efforts were meaningful, relevant, and impactful. As this pandemic and other public health crises continue, we encourage members of our discipline to consider how we can best use shared lessons from this period and to recognize that our professional knowledge, when used in our personal lives, can promote, protect, and bolster confidence in public health.

Vitamin D purportedly protects against cognitive decline and dementia based on observational data using circulating 25-hydroxyvitamin D (25(OH)D). Little is known about vitamin D in the human brain and the association with dementia or neuropathology.Decedents of the Rush Memory and Aging Project (n = 290) had vitamin D concentrations measured in four brain regions. Associations with cognitive and neuropathological outcomes were estimated using linear and logistic regression.The main form of vitamin D in all brain regions measured was 25(OH)DHigher brain 25(OH)D

Not all older adults with dementia-related neuropathology in their brains experience cognitive decline or impairment. Instead, some people maintain relatively normal cognitive functioning despite neuropathologic burden, a phenomenon called cognitive resilience. Using a longitudinal, epidemiological, clinical-pathologic cohort study of older adults in the United States ( N = 348), the present research investigated associations between well-being and cognitive resilience. Consistent with preregistered hypotheses, results showed that higher eudaimonic well-being (measured via the Ryff Psychological Well-Being Scale) and higher hedonic well-being (measured via the Satisfaction with Life Scale) were associated with better-than-expected cognitive functioning relative to one’s neuropathological burden (i.e., beta-amyloid, neurofibrillary tangles, Lewy bodies, vascular pathologies, hippocampal sclerosis, and TDP-43). The association of eudaimonic well-being in particular was present above and beyond known cognitive resilience factors (i.e., socioeconomic status, education, cognitive activity, low neuroticism, low depression) and dementia risk factors (i.e., apolipoprotein E [ ApoE] genotype, medical comorbidities). This research highlights the importance of considering eudaimonic well-being in efforts to prevent dementia.

A history of traumatic brain injury (TBI) has been considered a risk factor for Alzheimer dementia. However, the specific association of TBI, even without loss of consciousness (LOC), with pathologic findings that underlie Alzheimer dementia, including Alzheimer disease (AD), non-AD neurodegenerative, and vascular pathologic findings, remains unclear.To examine the association between TBI with and without LOC and neuropathologic findings in community-based cohorts.This cross-sectional analysis used neuropathologic data from 1689 participants from the Religious Orders Study, the Rush Memory and Aging Project, and the Minority Aging Research Study. These studies began enrollment in 1994, 1997, and 2004, respectively. The current study's data set was frozen on April 3, 2021, when the mean (SD) length of follow-up for the participants was 8.7 (5.5) years.Traumatic brain injury exposure was assessed using a standardized, self-reported questionnaire at baseline and annual follow-up visits. Participants were categorized into those (1) without TBI exposure (n = 1024), (2) with TBI with LOC (n = 161), or (3) with TBI without LOC (n = 504).Neuropathologic measures of amyloid-β, paired helical filament tangles, neocortical Lewy bodies, transactive response DNA-binding protein 43, hippocampal sclerosis, gross infarcts, and microinfarcts were assessed. Multiple linear regression and logistic regression models were used to determine whether TBI with or without LOC (compared with no TBI exposure as the reference group) was associated with neuropathologic outcomes after adjusting for age at death, sex, and educational level. Whether the apolipoprotein E (APOE) ε4 allele and sex differences modified associations was also examined.A total of 1689 participants (1138 [67%] women and 551 [33%] men; mean [SD] age at death, 89.2 [6.7] years; 80 [5%] Black, 46 [3%] Latino, 1639 [97%] non-Latino, and 1601 [95%] White) participated in the study. Compared with participants without TBI, participants with TBI with LOC had a greater amyloid-β load (estimate, 0.25; 95% CI, 0.06-0.43; P = .008) and higher odds of having 1 or more gross infarcts (odds ratio [OR], 1.45; 95% CI, 1.04-2.02; P = .02) and 1 or more microinfarcts (OR, 1.70; 95% CI, 1.21-2.38; P = .002), particularly subcortical microinfarcts (OR, 1.85; 95% CI, 1.23-2.79; P = .002). Those with TBI without LOC had higher odds of neocortical Lewy bodies (OR, 1.37; 95% CI, 1.01-1.87; P = .04) and 1 or more cortical microinfarcts (OR, 1.43; 95% CI, 1.09-1.87; P = .008). The association of TBI with and without LOC with vascular pathologic outcomes persisted after controlling for vascular risk factors and vascular disease burden. Traumatic brain injury with or without LOC was not associated with paired helical filament tangles, transactive response DNA-binding protein 43, or hippocampal sclerosis. No interactions occurred with APOE ε4 or sex.This cross-sectional analysis suggests that a history of TBI, even without LOC, is associated with age-related neuropathologic outcomes, both neurodegenerative and vascular. The variation in the neuropathologic outcomes in individuals with and without LOC may provide clues to potential mechanisms, diagnoses, and management in persons with TBI.

Objectives The goal of this paper was to examine associations between personality traits and resilience to neuropathologic burden. Method Using data from the Religious Orders Study and the Rush Memory and Aging Project, we identified a total of 1,375 participants with personality, cognitive, and post-mortem neuropathology data. We regressed cognition onto pathology and extracted the residuals as an indicator of cognitive resilience. We then modeled the effect of Big Five personality traits on cognitive resilience, adjusting for demographics, APOE status, medical comorbidities, and cognitive activity. The analytic plan was preregistered prior to data access or analysis, and all scripts and outputs are available online. Results Higher neuroticism was associated with greater vulnerability to pathology. Results from exploratory analyses suggest that higher conscientiousness was associated with less cognitive decline relative to the amount of pathology, or greater resilience. Education and cognitive activity did not moderate these associations. Discussion Personality may have a pathoplastic effect on neuropathology, as low neuroticism and high conscientiousness are associated with better function despite neuropathologic burden.

Increasingly being recognized is the role of the complex microenvironment to regulate cell phenotype; however, the cell culture systems used to study these effects in vitro are lagging. The complex microenvironment is host to a combination of biological interactions, chemical factors, and mechanical stimuli. Many devices have been designed to probe the effects of one mechanical stimulus, but few are capable of systematically interrogating all combinations of mechanical stimuli with independent control. To address this gap, we have developed the MechanoBioTester platform, a decoupled, multi-stimulus cell culture model for studying the cellular response to complex microenvironments in vitro. The system uses an engineered elastomeric chamber with a specially defined region for incorporating different target materials to act as the cell culture substrate. We have tested the system with several target materials including: polydimethylsiloxane elastomer, polyacrylamide gel, poly(1,8-octanediol citrate) elastomer, and type I collagen gel for both 2D and 3D co-culture. Additionally, when the chamber is connected to a flow circuit and our stretching device, stimuli in the form of fluid flow, cyclic stretch, and hydrostatic pressure are able to be imparted with independent control. We validated the device using experimental and computational methods to define a range of capabilities relevant to physiological microenvironments. The MechanoBioTester platform promises to function as a model system for mechanobiology, biomaterial design, and drug discovery applications that focus on probing the impact of a complex microenvironment in an in vitro setting. The protocol described within provides the details characterizing the MechanoBioTester system, the steps for fabricating the MechanoBioTester chamber, and the procedure for operating the MechanoBioTester system to stimulate cells.

Introduction: Although some members of families with autosomal dominant Alzheimer's disease mutations learn their mutation status, most do not. How knowledge of mutation status affects clinical disease progression is unknown. This study quantifies the influence of mutation awareness on clinical symptoms, cognition, and biomarkers. / Methods: Mutation carriers and non‐carriers from the Dominantly Inherited Alzheimer Network (DIAN) were stratified based on knowledge of mutation status. Rates of change on standard clinical, cognitive, and neuroimaging outcomes were examined. / Results: Mutation knowledge had no associations with cognitive decline, clinical progression, amyloid deposition, hippocampal volume, or depression in either carriers or non‐carriers. Carriers who learned their status mid‐study had slightly higher levels of depression and lower cognitive scores. / Discussion: Knowledge of mutation status does not affect rates of change on any measured outcome. Learning of status mid‐study may confer short‐term changes in cognitive functioning, or changes in cognition may influence the determination of mutation status.

Because dementia is progressive, incident cases are on average milder than prevalent cases, affecting the performance of cognitive tests and questions on functional limitations (i.e., cognition/functional limitation items) used for dementia assessment. Longitudinal studies assess incident cases, while cross-sectional studies assess prevalent cases, but differences are not typically considered when researchers select items to include in studies. We used longitudinal data from the Religious Orders Study and Memory and Aging Project (ROSMAP) (n = 3,446) collected between 1994 and 2021 to characterize differences in associations between items (cognition: 35 items; functional limitations: 14 items) and incident or prevalent dementia using multinomial regression models with generalized estimating equations, controlling for ROSMAP cohort (Religious Orders Study or Memory and Aging Project), age, sex, race, and education. The association between a given item and incident dementia was significantly weaker than the association between the same item and prevalent dementia for 46 of 49 items. However, there was variability, with larger differences for some items, including naming a pencil (prevalence odds ratio = 0.02 (95% confidence interval: 0.02, 0.03); incidence odds ratio = 0.10 (95% confidence interval: 0.06, 0.17); P for difference

Blood vessels in the body are multiphasic organs with microenvironmental niches specific to the cells that inhabit each section. Electrospinning is a fabrication technique used to produce nano- to microfibrous architectures capable of mimicking native extracellular matrix structure. Likewise, polycitrate elastomers are favorable luminal materials for vascular applications because of their hemocompatibility and mechanical properties. Here we describe the procedure for fabricating a biphasic polycitrate elastomer, collagen, and elastin electrospun composite to spatially tailor both composition and architecture for recapitulating the intimal and medial layers of the blood vessel in a vascular graft.

Blood vessels in the body are multiphasic organs with microenvironmental niches specific to the cells that inhabit each section. Electrospinning is a fabrication technique used to produce nano- to microfibrous architectures capable of mimicking native extracellular matrix structure. Likewise, polycitrate elastomers are favorable luminal materials for vascular applications because of their hemocompatibility and mechanical properties. Here we describe the procedure for fabricating a biphasic polycitrate elastomer, collagen, and elastin electrospun composite to spatially tailor both composition and architecture for recapitulating the intimal and medial layers of the blood vessel in a vascular graft.

Higher vitamin K intakes have been associated with better cognitive function, suggestive of a vitamin K mechanistic effect or simply reflective of a healthy diet. To test the hypothesis that brain vitamin K is linked to cognitive decline and dementia, vitamin K concentrations were measured in four brain regions, and their associations with cognitive and neuropathological outcomes were estimated in 325 decedents of the Rush Memory and Aging Project. Menaquinone-4 (MK4) was the main vitamin K form in the brain regions evaluated. Higher brain MK4 concentrations were associated with a 17% to 20% lower odds of dementia or mild cognitive impairment (MCI) (

Collagen and single-stranded DNA (ssDNA) complex to self-assemble into fibers depending on the length of the ssDNA and the relative amounts of collagen and ssDNA in solution. We report for the first time that when monodisperse, random sequences of ssDNA in the range of 15-90 nucleotides and type I collagen were mixed together at room temperature, fibers several tens of micrometers in length and as large as 10 μm in diameter were formed. Fiber formation was rapid and spontaneous, requiring no further treatment after mixing. Most notably, more ssDNA oligomers were incorporated into the fibers formed using shorter ssDNA oligomers. Endothelial cells formed angiogenic-like structures using the fibers with elevated expression of von Willebrand factor for cells in direct contact with the fibers. These fibers open the door to future applications in the administration and functionality of ssDNA and collagen.

The remarkable underwater adhesion capacity of the invasive freshwater mussel species Dreissena polymorpha (zebra mussel) causes extensive damage each year. The adhesive interface between the subst...

Renewable energy sources are being increasingly adopted, however their efficiency is limited by their intermittent nature leading to a mismatch with peak energy grid loading hours and dumping of excess produced energy. To date, much of the focus in renewable vehicles has been on automobiles. This largely overlooks the contribution from recreational boating to greenhouse gas emissions. We demonstrate that a power-to-gas model utilizing excess renewable energy can support boating activities in Ontario, Canada. As a proof-of-concept, we designed the refueling infrastructure, the fHuel+™ refueling station, and the onboard hydrogen utilization system for a high-speed luxury boat, the Hydronautic+™. The concept is built around a localized hydrogen economy. The present report focuses on the design and implementation of a technology specific to the demonstration site, but the overarching goal is to use this project as a proof of concept applicable to other sites across Canada and the United States.

OBJECTIVE To test the hypothesis that Alzheimer's disease and related neuropathologies contribute to the association between hospitalization and cognitive decline in old age. METHODS As part of a longitudinal clinical-pathologic cohort study, 526 older persons (mean age at death = 90.9 years, 71% female) without dementia at baseline completed annual cognitive testing and were autopsied at death. Hospitalization information was obtained from linked Medicare claims records. Neuropathologic examination assessed β-amyloid burden, tau tangle density, neocortical Lewy bodies, hippocampal sclerosis, chronic gross and microscopic cerebral infarcts, and transactive response DNA binding protein 43 kDa. RESULTS Over a mean of 5.1 years, a total of 1,383 hospitalizations occurred, and the mean annual rate of hospitalization was 0.5 (standard deviation = 0.6, median = 0.4). Higher rate of hospitalization was not directly related to higher burden for any of the neuropathologic markers. Higher rate of hospitalization was associated with more rapid cognitive decline (estimate = -0.042, standard error [SE] = 0.012, p

ObjectiveTo determine whether emergent and urgent (nonelective) hospitalizations are associated with faster acceleration of cognitive decline compared to elective hospitalizations, accounting for prehospital decline.MethodsData came from the Rush Memory and Aging Project, a prospective cohort study of community-dwelling older persons without baseline dementia. Annual measures of cognition via a battery of 19 tests were linked to 1999 to 2010 Medicare claims records.ResultsOf 777 participants, 460 (59.2%) were hospitalized over a mean of 5.0 (SD = 2.6) years; 222 (28.6%) had at least one elective and 418 (53.8%) at least one nonelective hospitalization. Mixed-effects regression models estimated change in global cognition before and after each type of hospitalization compared to no hospitalization, adjusted for age, sex, education, medical conditions, length of stay, surgery, intensive care unit, and comorbidities. Persons who were not hospitalized had a mean loss of 0.051 unit global cognition per year. In comparison, there was no significant difference in rate of decline before (0.044 unit per year) or after (0.048 unit per year) elective hospitalizations. In contrast, decline before nonelective hospitalization was faster (0.076 unit per year; estimate = −0.024, SE = 0.011, p = 0.032), and accelerated by 0.036 unit (SE = 0.005, p < 0.001) to mean loss of 0.112 unit per year after nonelective hospitalizations, more than doubling the rate in those not hospitalized.ConclusionsNonelective hospitalizations are related to more dramatic acceleration in cognitive decline compared to elective hospitalizations, even after accounting for prehospital decline. These findings may inform which hospital admissions pose the greatest risk to the cognitive health of older adults.

BACKGROUND: MIND diet – a hybrid of the Mediterranean diet and the Dietary Approaches to Stop Hypertension diet – is associated with a slower cognitive decline and lower risk of Alzheimer’s dementia in older adults. OBJECTIVE: We aim to examine whether the association of the MIND diet with cognition is independent of common brain pathologies. METHODS: Utilizing data from the Rush Memory and Aging Project (MAP), a longitudinal clinical-pathologic study, we studied 569 decedents with valid dietary data, cognitive testing proximate to death, and complete autopsy data at the time of these analyses. A series of regression analyses were used to examine associations of the MIND diet, dementia-related brain pathologies, and global cognition proximate to death adjusting for age, sex, education, APOE ϵ4, late-life cognitive activities, and total energy intake. RESULTS: A higher MIND diet score was associated with better global cognitive functioning proximate to death ([Formula: see text] =0.119, SE=0.040, P-value=0.003), and neither the strength nor the significance of association changed substantially when Alzheimer’s disease (AD) pathology and other brain pathologies were included in the model. The [Formula: see text]-estimate after controlling for global AD pathology was 0.111 (SE=0.037, p=0.003). The MIND diet-cognition relationship remained significant when we restricted our analysis to individuals without mild cognitive impairment at the baseline ([Formula: see text] =0.121, SE=0.042, P-value=0.005) or in people diagnosed with postmortem diagnosis of AD based on NIA-Reagan consensus recommendations ([Formula: see text] =0.114, SE=0.050, P-value=0.023). CONCLUSION: MIND diet is associated with better cognitive functioning independently of common brain pathology, suggesting that the MIND diet may contribute to cognitive resilience in the elderly.

Objective To test whether postmortem MRI captures brain tissue characteristics that mediate the association between physical activity and cognition in older adults. Methods Participants (N = 318) were older adults from the Rush Memory and Aging Project who wore a device to quantify physical activity and also underwent detailed cognitive and motor testing. Following death, cerebral hemispheres underwent MRI to quantify the transverse relaxation rate R2, a metric related to tissue microstructure. For analyses, we reduced the dimensionality of the R2 maps from approximately 500,000 voxels to 30 components using spatial independent component analysis (ICA). Via path analysis, we examined whether these R2 components attenuated the association between physical activity and cognition, controlling for motor abilities and indices of common brain pathologies. Results Two of the 30 R2 components were associated with both total daily physical activity and global cognition assessed proximate to death. We visualized these components by highlighting the clusters of voxels whose R2 values contributed most strongly to each. One of these spatial signatures spanned periventricular white matter and hippocampus, while the other encompassed white matter of the occipital lobe. These two R2 components partially mediated the association between physical activity and cognition, accounting for 12.7% of the relationship (p = .01). This mediation remained evident after controlling for motor abilities and neurodegenerative and vascular brain pathologies. Conclusion The association between physically activity and cognition in older adults is partially accounted for by MRI-based signatures of brain tissue microstructure. Further studies are needed to elucidate the molecular mechanisms underlying this pathway.