Abstract
Recently, a consensus working group provided new terminology for a common disease entity, limbic predominant age-related TDP-43 encephalopathy (LATE), and its neuropathological substrate ...(LATE-NC). LATE-NC not only often co-occurs with Alzheimer disease neuropathological change (ADNC), but also may present in isolation. The present study aimed to investigate potential risk factors and neuropathological characteristics associated with LATE-NC. A sample of 616 autopsied participants (>75 years at death), with TDP-43 immunohistochemical studies performed, was obtained from the National Alzheimer’s Coordinating Center. Logistic regression analyses examined associations between demographic, clinical and neuropathological characteristics and LATE-NC (TDP-43 in amygdala, hippocampus, or entorhinal/inferior temporal cortex) (alpha = 0.05). Adjusted models indicated that ADNC, hippocampal sclerosis (HS), arteriolosclerosis, and limbic or amygdala-predominant Lewy body disease (LBD), but not other LBD subtypes, were associated with higher odds of LATE-NC, whereas congestive heart failure (CHF) and motor problems as first predominant symptom were associated with lower odds of LATE-NC. Our findings corroborate previous studies indicating associations between LATE-NC and ADNC, HS, and arteriolosclerosis. Novel findings suggest the association with LATE-NC is restricted to amygdala/limbic-predominant subtype of LBD, and a possible protective (or competing risk) association with CHF. This study may inform future hypothesis-driven research on LATE-NC, a common brain disease of aging.
Context Some evidence suggests that treating vascular risk factors and performing mentally stimulating activities may delay cognitive impairment onset in older adults. Exposure to a complex ...neighborhood environment may be one mechanism to help delay cognitive decline. Evidence acquisition PubMed, Web of Science, and ProQuest Dissertation and Theses Global database were systematically reviewed, identifying 25 studies published from February 1, 1989 to March 5, 2016 (data synthesized, May 3, 2015 to October 7, 2016). The review was restricted to quantitative studies focused on: (1) neighborhood social and built environment and cognition; and (2) community-dwelling adults aged ≥45 years. Evidence synthesis The majority of studies were cross-sectional, U.S.-based, and found at least one significant association. The diversity of measures and neighborhood definitions limited the synthesis of findings in many instances. Evidence was moderately strong for an association between neighborhood SES and cognition, and modest for associations between neighborhood demographics, design, and destination accessibility and cognition. Most studies examining effect modification found significant associations, with some evidence for effect modification of the neighborhood SES−cognition association by individual-level SES. No studies had low risk of bias and many tested multiple associations that increased the chance of a statistically significant finding. Considering the studies to date, the evidence for an association between neighborhood characteristics and cognition is modest. Conclusions Future studies should include longitudinal measures of neighborhood characteristics and cognition; examine potential effect modifiers, such as sex and disability; and study mediators that may help elucidate the biological mechanisms linking neighborhood environment and cognition.
Greenspace exposure has been associated with physical activity, but few studies have investigated its association with physical activity in the residential neighborhood. This study investigates ...whether greater amounts of neighborhood open space and forest are associated with neighborhood-based walking in older adults.
In 2020, cross-sectional analyses were conducted on those aged ≥65 years from the 2017 National Household Travel Survey. Minutes of neighborhood walking per day were derived from travel diaries. Green land cover measures from the 2011 National Land Cover Dataset were linked to respondent data by the U.S. census tract. Adjusted linear regression models, using weights accounting for survey sampling, tested the associations between the percentage of green land cover in the neighborhood (open space, forest) and minutes of neighborhood walking per day. Adjusted models were stratified to examine whether the associations varied by an individual- and neighborhood-level SES, sex, and race/ethnicity.
Respondents (N=72,753) were aged 74 (SD=7) years on average. Greater percentage of open space was associated with more neighborhood walking in African Americans (estimate=0.069, 95% CI=0.005, 0.133). Greater percentage of forest was associated with more neighborhood walking in the overall sample (estimate=0.028, 95% CI=0.006, 0.050), women (estimate=0.025, 95% CI=0.005, 0.045), and Whites (estimate=0.034, 95% CI=0.004, 0.064).
Type of neighborhood green land cover (open space versus forest) may be differentially associated with neighborhood walking depending on race/ethnicity. This study suggests a possible association between greater neighborhood open space and greater walking among African Americans that must be confirmed in future studies.
Primary age-related tauopathy is increasingly recognized as a separate neuropathological entity different from Alzheimer's disease. Both share the neuropathological features of tau aggregates and ...neuronal loss in the temporal lobe, but primary age-related tauopathy lacks the requisite amyloid plaques central to Alzheimer's disease. While both have similar clinical presentations, individuals with symptomatic primary age-related tauopathy are commonly of more advanced ages with milder cognitive dysfunction. Direct comparison of the neuropsychological trajectories of primary age-related tauopathy and Alzheimer's disease has not been thoroughly evaluated and thus, our objective was to determine how cognitive decline differs longitudinally between these two conditions after the onset of clinical symptoms. Data were obtained from the National Alzheimer's Coordinating Center on participants with mild cognitive impairment at baseline and either no neuritic plaques (i.e. primary age-related tauopathy) or moderate to frequent neuritic plaques (i.e. Alzheimer neuropathological change) at subsequent autopsy. For patients with Alzheimer's disease and primary age-related tauopathy, we compared rates of decline in the sum of boxes score from the CDR® Dementia Staging Instrument and in five cognitive domains (episodic memory, attention/working memory, executive function, language/semantic memory, and global composite) using z-scores for neuropsychological tests that were calculated based on scores for participants with normal cognition. The differences in rates of change were tested using linear mixed-effects models accounting for clinical centre clustering and repeated measures by individual. Models were adjusted for sex, age, education, baseline test score, Braak stage, apolipoprotein ε4 (APOE ε4) carrier status, family history of cognitive impairment, and history of stroke, hypertension, or diabetes. We identified 578 participants with a global CDR of 0.5 (i.e. mild cognitive impairment) at baseline, 126 with primary age-related tauopathy and 452 with Alzheimer's disease. Examining the difference in rates of change in CDR sum of boxes and in all domain scores, participants with Alzheimer's disease had a significantly steeper decline after becoming clinically symptomatic than those with primary age-related tauopathy. This remained true after adjusting for covariates. The results of this analysis corroborate previous studies showing that primary age-related tauopathy has slower cognitive decline than Alzheimer's disease across multiple neuropsychological domains, thus adding to the understanding of the neuropsychological burden in primary age-related tauopathy. The study provides further evidence to support the hypothesis that primary age-related tauopathy has distinct neuropathological and clinical features compared to Alzheimer's disease.
In the 1930s, Black, working-class, and immigrant neighborhoods were color coded on maps (i.e., redlining) indicating investment risk, which negatively impacted mortgage attainment/homeownership for ...these groups and led to long-standing segregation by race/ethnicity and socioeconomic status. Limited studies have investigated the health impacts of redlining, particularly among older adults who tend to stay closer to their residences. This study examines whether older adults in historically redlined neighborhoods report less neighborhood walking and whether associations vary by race/ethnicity and income.
The sample included 4,651 individuals aged ≥65 years from the 2017 U.S. National Household Travel Survey. U.S. Census tract‒based redlining scores were 1=best, 2=still desirable, 3=definitely declining, and 4=hazardous. Multivariable negative binomial regression tested the associations between redlining and neighborhood walking/day in the overall sample and with stratification by poverty status (analyzed in 2022).
Participants were on average aged 73 years, and 11% were African/American Black, 75% were White, 8% were Hispanic/Latinx, and 6% were of other race/ethnicity. Participants reported a mean of 7.1 neighborhood walking minutes/day (SD=20.6), and 60% lived in definitely declining or hazardous neighborhoods. Individuals in hazardous neighborhoods (versus those in best neighborhoods) reported less neighborhood walking (prevalence ratio=0.64; 95% CI=0.43, 0.97). Among those living in poverty, living in definitely declining and hazardous neighborhoods was associated with less neighborhood walking (prevalence ratio=0.39 95% CI=0.20, 0.79 and 0.39 95% CI=0.18, 0.82, respectively).
Less neighborhood walking was reported among individuals living in neighborhoods with a historic redlining score of definitely declining or hazardous. Future studies using larger, more diverse cohorts may elucidate whether associations differ by race/ethnicity and geographic location/city.
To conduct a clinicopathologic study to characterize clinical and neuropathologic features associated with cognitive impairment in participants with no neuritic amyloid plaques (primary age-related ...tauopathy PART definite) and sparse neuritic plaques (amyloid sparse).
Using the National Alzheimer's Coordinating Center database, we identified 377 individuals who were PART definite (n = 170) or amyloid sparse (n = 207), clinically examined within 1 year of death, and autopsied at 1 of 26 National Institute on Aging-funded Alzheimer's Disease Centers. Factors associated with the odds of being symptomatic (global Clinical Dementia Rating CDR score >0) were identified with multivariable logistic regression.
PART-definite participants less often had a high Braak neurofibrillary tangle stage V or VI (4%) compared to amyloid sparse participants (28%,
< 0.001). Of the PART-definite participants, 98 were symptomatic and 72 asymptomatic according to their global CDR scores. PART-definite participants were less often symptomatic (58%) compared with amyloid sparse participants (80%,
< 0.001). Within the PART-definite group, independent predictors of symptomatic status included depression (adjusted odds ratio aOR 4.20, 95% confidence interval CI 2.15-8.19), Braak stage (aOR 1.42, 95% CI 1.04-1.95), and history of stroke (aOR 8.09, 95% CI 2.63-24.82). Within the amyloid sparse group, independent predictors of symptomatic status included education (aOR 0.80, 95% CI 0.65-0.99), Braak stage (aOR 1.91, 95% CI 1.07-3.43), and amyloid angiopathy (aOR 2.75, 95% CI 1.14-6.64).
These findings support the hypothesis that participants with PART have an amyloid-independent dementing Alzheimer disease-like temporal lobe tauopathy.
Preliminary studies suggest that neighborhood social and built environment (BE) characteristics may affect cognition in older adults. Older adults are particularly vulnerable to the neighborhood ...environment due to a decreasing range of routine travel with increasing age. We examined if multiple neighborhood BE characteristics are cross-sectionally associated with cognition in a diverse sample of older adults, and if the BE-cognition associations vary by individual-level demographics. The sample included 4539 participants from the Multi-Ethnic Study of Atherosclerosis. Multivariable linear regression was used to examine the associations between five BE measures and four cognitive measures, and effect modification by individual-level education and race/ethnicity. In the overall sample, increasing social destination density, walking destination density, and intersection density were associated with worse overall cognition, whereas increasing proportion of land dedicated to retail was associated with better processing speed. Effect modification results suggest that the association between urban density and worse cognition may be limited to or strongest in those of non-white race/ethnicity. Although an increase in neighborhood retail destinations was associated with better cognition in the overall sample, these results suggest that certain BE characteristics in dense urban environments may have a disproportionately negative association with cognition in vulnerable populations. However, our findings must be replicated in longitudinal studies and other regional samples.
•The neighborhood built environment may affect cognition and brain aging.•Few have studied built environment and cognition associations in older age.•Three measures consistent with urban density were associated with worse cognition.•Increased neighborhood retail destinations was associated with better cognition.•Negative associations were mostly limited to those of non-white race/ethnicity.
The Health Brain Initiative (HBI), established by University of Miami's Comprehensive Center for Brain Health (CCBH), follows racially/ethnically diverse older adults without dementia living in South ...Florida. With dementia prevention and brain health promotion as an overarching goal, HBI will advance scientific knowledge by developing novel assessments and non-invasive biomarkers of Alzheimer's disease and related dementias (ADRD), examining additive effects of sociodemographic, lifestyle, neurological and biobehavioral measures, and employing innovative, methodologically advanced modeling methods to characterize ADRD risk and resilience factors and transition of brain aging.
HBI is a longitudinal, observational cohort study that will follow 500 deeply-phenotyped participants annually to collect, analyze, and store clinical, cognitive, behavioral, functional, genetic, and neuroimaging data and biospecimens. Participants are ≥50 years old; have no, subjective, or mild cognitive impairment; have a study partner; and are eligible to undergo magnetic resonance imaging (MRI). Recruitment is community-based including advertisements, word-of-mouth, community events, and physician referrals. At baseline, following informed consent, participants complete detailed web-based surveys (e.g., demographics, health history, risk and resilience factors), followed by two half-day visits which include neurological exams, cognitive and functional assessments, an overnight sleep study, and biospecimen collection. Structural and functional MRI is completed by all participants and a subset also consent to amyloid PET imaging. Annual follow-up visits repeat the same data and biospecimen collection as baseline, except that MRIs are conducted every other year after baseline.
HBI has been approved by the University of Miami Miller School of Medicine Institutional Review Board. Participants provide informed consent at baseline and are re-consented as needed with protocol changes. Data collected by HBI will lead to breakthroughs in developing new diagnostics and therapeutics, creating comprehensive diagnostic evaluations, and providing the evidence base for precision medicine approaches to dementia prevention with individualized treatment plans.
Health impact assessment (HIA) reports are used by government agencies, other organizations, and stakeholders to evaluate potential health effects of plans/policies/projects. HIAs have the potential ...to promote anti-racist practices. We developed and used the Tool for the Racial/Ethnic Equity Evaluation of Health Impact Assessments (TREE-HIA) to score 50 U.S. HIA reports on planning-related projects/plans involving parks and greenspaces (2005-2020). More recent and more comprehensive HIA reports addressed racial/ethnic equity to a greater degree (e.g., median TREE-HIA scores: −1.3 in 2009-2012, 4.0 in 2017-2020, where higher scores indicate greater racial/equity considerations). Overall, HIA reports addressed racial/ethnic equity to a lesser degree than expected given the principal tenet of equity guiding HIAs and urban planning alike (42% had negative TREE-HIA scores indicating inadequate racial/ethnic equity consideration). However, the limited number and types of HIAs included in this study may affect generalization to all HIAs.
HIAs incorporating racial/ethnic equity comprehensively throughout the HIA process will better enable urban planners, HIA practitioners, decision makers, and communities of color to work together to combat racist planning practices through the shared goals of addressing health disparities and equity. TREE-HIA provides professionals and researchers with a brief tool that can be used/adapted to guide and evaluate future HIAs for racial/ethnic equity considerations.
Nearly half of Americans do not meet the Surgeon General's recommendation of > or =30 minutes of physical activity daily. Some transit users may achieve 30 minutes of physical activity daily solely ...by walking to and from transit. This study estimates the total daily time spent walking to and from transit and the predictors of achieving 30 minutes of physical activity daily by doing so.
Transit-associated walking times for 3312 transit users were examined among the 105,942 adult respondents to the 2001 National Household Travel Survey, a telephone-based survey sponsored by the U.S. Department of Transportation to assess American travel behavior.
Americans who use transit spend a median of 19 minutes daily walking to and from transit; 29% achieve > or =30 minutes of physical activity a day solely by walking to and from transit. In multivariate analysis, rail users, minorities, people in households earning <$15,000 a year, and people in high-density urban areas were more likely to spend > or =30 minutes walking to and from transit daily.
Walking to and from public transportation can help physically inactive populations, especially low-income and minority groups, attain the recommended level of daily physical activity. Increased access to public transit may help promote and maintain active lifestyles. Results from this study may contribute to health impact assessment studies (HIA) that evaluate the impact of proposed public transit systems on physical activity levels, and thereby may influence choices made by transportation planners.
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