Association of improved air quality with lower dementia risk in older women.

Late-life ambient air pollution is a risk factor for brain aging, but it remains unknown if improved air quality (AQ) lowers dementia risk. We studied a geographically diverse cohort of older women dementia free at baseline in 2008 to 2012 (n = 2,239, aged 74 to 92). Incident dementia was centrally adjudicated annually. Yearly mean concentrations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were estimated using regionalized national universal kriging models and averaged over the 3-y period before baseline (recent exposure) and 10 y earlier (remote exposure). Reduction from remote to recent exposures was used as the indicator of improved AQ. Cox proportional hazard ratios (HRs) for dementia risk associated with AQ measures were estimated, adjusting for sociodemographic, lifestyle, and clinical characteristics. We identified 398 dementia cases during follow up (median = 6.1 y). PM2.5 and NO2 reduced significantly over the 10 y before baseline. Larger AQ improvement was associated with reduced dementia risks (HRPM2.5 0.80 per 1.78 µg/m3, 95% CI 0.71-0.91; HRNO2 0.80 per 3.91 parts per billion, 95% CI 0.71-0.90), equivalent to the lower risk observed in women 2.4 y younger at baseline. Higher PM2.5 at baseline was associated with higher dementia risk (HRPM2.5 1.16 per 2.90 µg/m3, 95% CI 0.98-1.38), but the lower dementia risk associated with improved AQ remained after further adjusting for recent exposure. The observed associations did not substantially differ by age, education, geographic region, Apolipoprotein E e4 genotypes, or cardiovascular risk factors. Long-term AQ improvement in late life was associated with lower dementia risk in older women.

20-year depressive symptoms, dementia, and structural neuropathology in older women.

INTRODUCTION: The course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes. METHODS: Utilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study. In a subsample of 569 women who underwent structural magnetic resonance imaging, we examined whether estimates of cerebrovascular disease and Alzheimer's disease (AD)-related neurodegeneration were associated with identified trajectories. RESULTS: Five trajectories of depressive symptoms and dementia risk were identified. Compared to women with minimal symptoms, women who reported mild and stable and emerging depressive symptoms were at the highest risk of developing dementia and had more cerebrovascular disease and AD-related neurodegeneration. DISCUSSION: There are heterogeneous profiles of depressive symptoms and dementia risk. Common neuropathological factors may contribute to both depression and dementia. Highlights The progression of depressive symptoms and concurrent dementia risk is heterogeneous. Emerging depressive symptoms may be a prodromal symptom of dementia. Cerebrovascular disease and AD are potentially shared neuropathological factors.

Longitudinal analyses indicate bidirectional associations between loneliness and health.

OBJECTIVES: To evaluate temporal dynamics between loneliness and both objective and subjective health (i.e. functional impairment and self-rated health) in mid- to late-adulthood. METHOD: We applied bivariate dual-change-score models to longitudinal data from 3 Swedish twin studies (N = 1,939) to explore dynamic associations between loneliness and health across 3 age ranges (50-69, 70-81, and 82+ years) to investigate whether associations between loneliness and health change with age due to increasing incidence of chronic health conditions and bereavement. RESULTS: Results showed bidirectional associations between loneliness and both objective and subjective health, with adverse impacts of loneliness observed on subsequent subjective and objective health beginning at age 70. Associations between health and subsequent loneliness were observed after age 82 and varied for subjective and objective health, with subjective health associated with less loneliness and objective health associated with greater loneliness. CONCLUSIONS: Our results indicate dynamic associations between loneliness and health with age in mid- to late-adulthood, with earlier impacts of loneliness on health and later impacts of health on loneliness that vary for objective and subjective measures of health. These findings suggest impacts of health on loneliness may arise later in life when worsening health or mobility interfere with social interaction.

Air quality improvement and cognitive decline in community-dwelling older women in the United States: A longitudinal cohort study.

BACKGROUND: Late-life exposure to ambient air pollution is a modifiable risk factor for dementia, but epidemiological studies have shown inconsistent evidence for cognitive decline. Air quality (AQ) improvement has been associated with improved cardiopulmonary health and decreased mortality, but to the best of our knowledge, no studies have examined the association with cognitive function. We examined whether AQ improvement was associated with slower rate of cognitive decline in older women aged 74 to 92 years. METHODS AND FINDINGS: We studied a cohort of 2,232 women residing in the 48 contiguous US states that were recruited from more than 40 study sites located in 24 states and Washington, DC from the Women's Health Initiative (WHI) Memory Study (WHIMS)-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO) study. They were predominantly non-Hispanic White women and were dementia free at baseline in 2008 to 2012. Measures of annual (2008 to 2018) cognitive function included the modified Telephone Interview for Cognitive Status (TICSm) and the telephone-based California Verbal Learning Test (CVLT). We used regionalized universal kriging models to estimate annual concentrations (1996 to 2012) of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) at residential locations. Estimates were aggregated to the 3-year average immediately preceding (recent exposure) and 10 years prior to (remote exposure) WHIMS-ECHO enrollment. Individual-level improved AQ was calculated as the reduction from remote to recent exposures. Linear mixed effect models were used to examine the associations between improved AQ and the rates of cognitive declines in TICSm and CVLT trajectories, adjusting for sociodemographic (age; geographic region; race/ethnicity; education; income; and employment), lifestyle (physical activity; smoking; and alcohol), and clinical characteristics (prior hormone use; hormone therapy assignment; depression; cardiovascular disease (CVD); hypercholesterolemia; hypertension; diabetes; and body mass index [BMI]). For both PM2.5 and NO2, AQ improved significantly over the 10 years before WHIMS-ECHO enrollment. During a median of 6.2 (interquartile range [IQR] = 5.0) years of follow-up, declines in both general cognitive status (ß = -0.42/year, 95% CI: -0.44, -0.40) and episodic memory (ß = -0.59/year, 95% CI: -0.64, -0.54) were observed. Greater AQ improvement was associated with slower decline in TICSm (ßPM2.5improvement = 0.026 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.001, 0.05; ßNO2improvement = 0.034 per year for improved NO2 by each IQR = 3.92 parts per billion [ppb] reduction, 95% CI: 0.01, 0.06) and CVLT (ßPM2.5 improvement = 0.070 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.02, 0.12; ßNO2improvement = 0.060 per year for improved NO2 by each IQR = 3.97 ppb reduction, 95% CI: 0.005, 0.12) after adjusting for covariates. The respective associations with TICSm and CVLT were equivalent to the slower decline rate found with 0.9 to 1.2 and1.4 to 1.6 years of younger age and did not significantly differ by age, region, education, Apolipoprotein E (ApoE) e4 genotypes, or cardiovascular risk factors. The main limitations of this study include measurement error in exposure estimates, potential unmeasured confounding, and limited generalizability. CONCLUSIONS: In this study, we found that greater improvement in long-term AQ in late life was associated with slower cognitive declines in older women. This novel observation strengthens the epidemiologic evidence of an association between air pollution and cognitive aging.

Cognitive Reserve, Alzheimer's Neuropathology, and Risk of Dementia: A Systematic Review and Meta-Analysis.

Cognitive reserve (CR) may reduce the risk of dementia. We summarized the effect of CR on progression to mild cognitive impairment (MCI) or dementia in studies accounting for Alzheimer's disease (AD)-related structural pathology and biomarkers. Literature search was conducted in Web of Science, PubMed, Embase, and PsycINFO. Relevant articles were longitudinal, in English, and investigating MCI or dementia incidence. Meta-analysis was conducted on nine articles, four measuring CR as cognitive residual of neuropathology and five as composite psychosocial proxies (e.g., education). High CR was related to a 47% reduced relative risk of MCI or dementia (pooled-hazard ratio: 0.53 [0.35, 0.81]), with residual-based CR reducing risk by 62% and proxy-based CR by 48%. CR protects against MCI and dementia progression above and beyond the effect of AD-related structural pathology and biomarkers. The finding that proxy-based measures of CR rivaled residual-based measures in terms of effect on dementia incidence underscores the importance of early- and mid-life factors in preventing dementia later.

Particulate matter and episodic memory decline mediated by early neuroanatomic biomarkers of Alzheimer's disease.

Evidence suggests exposure to particulate matter with aerodynamic diameter <2.5 µm (PM2.5) may increase the risk for Alzheimer's disease and related dementias. Whether PM2.5 alters brain structure and accelerates the preclinical neuropsychological processes remains unknown. Early decline of episodic memory is detectable in preclinical Alzheimer's disease. Therefore, we conducted a longitudinal study to examine whether PM2.5 affects the episodic memory decline, and also explored the potential mediating role of increased neuroanatomic risk of Alzheimer's disease associated with exposure. Participants included older females (n = 998; aged 73-87) enrolled in both the Women's Health Initiative Study of Cognitive Aging and the Women's Health Initiative Memory Study of Magnetic Resonance Imaging, with annual (1999-2010) episodic memory assessment by the California Verbal Learning Test, including measures of immediate free recall/new learning (List A Trials 1-3; List B) and delayed free recall (short- and long-delay), and up to two brain scans (MRI-1: 2005-06; MRI-2: 2009-10). Subjects were assigned Alzheimer's disease pattern similarity scores (a brain-MRI measured neuroanatomical risk for Alzheimer's disease), developed by supervised machine learning and validated with data from the Alzheimer's Disease Neuroimaging Initiative. Based on residential histories and environmental data on air monitoring and simulated atmospheric chemistry, we used a spatiotemporal model to estimate 3-year average PM2.5 exposure preceding MRI-1. In multilevel structural equation models, PM2.5 was associated with greater declines in immediate recall and new learning, but no association was found with decline in delayed-recall or composite scores. For each interquartile increment (2.81 µg/m3) of PM2.5, the annual decline rate was significantly accelerated by 19.3% [95% confidence interval (CI) = 1.9% to 36.2%] for Trials 1-3 and 14.8% (4.4% to 24.9%) for List B performance, adjusting for multiple potential confounders. Long-term PM2.5 exposure was associated with increased Alzheimer's disease pattern similarity scores, which accounted for 22.6% (95% CI: 1% to 68.9%) and 10.7% (95% CI: 1.0% to 30.3%) of the total adverse PM2.5 effects on Trials 1-3 and List B, respectively. The observed associations remained after excluding incident cases of dementia and stroke during the follow-up, or further adjusting for small-vessel ischaemic disease volumes. Our findings illustrate the continuum of PM2.5 neurotoxicity that contributes to early decline of immediate free recall/new learning at the preclinical stage, which is mediated by progressive atrophy of grey matter indicative of increased Alzheimer's disease risk, independent of cerebrovascular damage.

Neuroticism predicts fear of falling after hip fracture.

OBJECTIVES: Fear of falling (FoF) is common and associated with poorer functional outcomes after hip fracture. We sought to differentiate patterns of FoF at 4 and 12 weeks after surgical repair for hip fracture and examine predictors of FoF. METHODS/DESIGN: Secondary analysis of existing data from a 52-week prospective study examining recovery after hip fracture. Participants (N = 263) were aged 60 and older with recent hip fracture recruited from eight hospitals. FoF was measured 4 and 12 weeks postfracture with the Short Falls Efficacy Scale-International. Latent class mixed models were constructed to identify distinct patterns of FoF from 4 to 12 weeks postfracture and predictors of FoF. Predictors examined included age, gender, neuroticism, depression, negative affect, perceived social support, medical comorbidity, functional ability, cognition, and pain. RESULTS: Three latent classes of FoF were identified: a group with minimal FoF at weeks 4 and 12 (72%), a group with high FoF that decreased (17%), and a group with high FoF that increased from week 4 to 12 (11%). In a multivariate model, higher neuroticism was associated with greater risk for high FoF (increasing or decreasing), whereas higher premorbid medical comorbidity was associated with increasing FoF, poorer premorbid functional ability was associated with decreasing FoF, and social support was not significantly associated. CONCLUSIONS: Older adults with higher neuroticism are more likely to have FoF in the first 12 weeks after a hip fracture. Screening for neuroticism in health care settings might identify individuals who would benefit from interventions to improve outcomes during recovery.

Mild cognitive impairment, psychiatric symptoms, and executive functioning in patients with Parkinson's disease.

OBJECTIVE: Mild cognitive impairment (MCI) and psychiatric symptoms (anxiety, depression, and apathy) are common in Parkinson's disease (PD). While studies have supported the association between psychiatric symptoms and cognitive performance in PD, it is unclear if the magnitude of link between psychiatric symptoms and cognitive health is stronger by MCI status. The purpose of this study was to examine the association between cognitive performance and psychiatric symptoms in PD and whether MCI status moderates this association. METHODS/DESIGN: Participants (N = 187) completed a comprehensive neuropsychological assessment that included measures of attention, language, executive function (EF), visuospatial ability, episodic memory, and psychiatric symptoms. Participants were classified as PD-MCI (N = 73) or PD-normal cognition (NC; N = 114). Linear regression analyses were conducted to examine the association between psychiatric symptoms and cognitive performance and the moderating effect of PD-MCI status. RESULTS: There were no differences in mean psychiatric symptoms between PD-MCI and PD-NC. Psychiatric symptoms were predominantly associated with worse EF. The magnitude of the association between anxiety and worse EF was larger in participants with PD-MCI compared with PD-NC. A multivariable regression analysis examining the independent contributions of each symptom demonstrated the most robust association between EF and anxiety. CONCLUSIONS: Symptoms of anxiety, depression, and apathy are associated with worse executive functioning in individuals with PD. PD-MCI may be important in moderating the association between cognitive performance, specifically anxiety, and EF. Factors that promote cognitive resilience may serve as key therapeutic modalities in managing neuropsychiatric symptoms in PD.

Particulate Air Pollutants and Trajectories of Depressive Symptoms in Older Women.

OBJECTIVES: Although several environmental factors contribute to the etiology of late-life depressive symptoms, the role of ambient air pollution has been understudied. Experimental data support the neurotoxicity of airborne particulate matter with aerodynamic diameter of ≤2.5 µm (PM2.5), but it remains unclear whether long-term exposure is associated with late-life depressive symptoms. Our secondary aim was to explore whether the observed associations between exposure and depressive symptoms are explained by dementia risk. DESIGN, SETTING, AND PARTICIPANTS: Prospective community-dwelling cohort study from the Women's Health Initiative Study of Cognitive Aging (1999-2010). Our analyses included 1,989 older women (baseline age 73.3 ± 3.75) with no prior depression or cognitive impairment. MEASUREMENTS: Participants completed annual assessments of depressive symptoms (15-item Geriatric Depression Scale). Average ambient PM2.5 exposure at the residential location was estimated by spatiotemporal modeling for the 3-years preceding each neuropsychological assessment. Participants underwent separate annual examinations for incident dementia defined by DSM-IV. Latent-class mixture models examined the association between PM2.5 and identified trajectories of symptoms. RESULTS: Six trajectories of depressive symptoms were identified. Across all women, PM2.5 exposure was positively associated with depressive symptoms. The effect was especially strong in two clusters with sustained depressive symptoms (n = 625 sustained-mild [31%]; n = 125 sustained-moderate; [6%]). Among those with sustained-moderate symptoms, the estimated adverse effect of PM2.5 exposure was greater than that of hypertension. Among women without dementia, associations were modestly attenuated. CONCLUSION: Long-term exposure to ambient fine particles was associated with increased depressive symptoms among older women without prior depression or cognitive impairment.

Integrated Exposure Therapy and Exercise Reduces Fear of Falling and Avoidance in Older Adults: A Randomized Pilot Study.

OBJECTIVES: To evaluate the safety and acceptability of a novel 8-week intervention integrating exercise, exposure therapy, cognitive restructuring, and a home safety evaluation, conducted by a physical therapist, in reducing fear of falling and activity avoidance. To collect preliminary evidence of efficacy. DESIGN: Randomized pilot study comparing the intervention to time- and attention-equivalent fall prevention education. SETTING: Participants' homes. PARTICIPANTS: 42 older adults with disproportionate fear of falling (high fear, low to moderate objective fall risk). MEASUREMENTS: Falls Efficacy Scale-International, modified Activity Card Sort, satisfaction, falls. RESULTS: Relative to education, the intervention reduced fear of falling (d = 1.23) and activity avoidance (d = 1.02) at 8 weeks, but effects eroded over a 6-month follow-up period. The intervention did not increase falls, and participants rated the exercise, exposure therapy, and non-specific elements as most helpful. CONCLUSIONS: An integration of exercise and exposure therapy may help older adults with disproportionate fear of falling, but modifications to the intervention or its duration may be needed to maintain participants' gains.

Age Differences in Death and Suicidal Ideation in Anxious Primary Care Patients.

OBJECTIVES: The objective of this study was to examine age differences in the likelihood of endorsing of death and suicidal ideation in primary care patients with anxiety disorders. METHOD: Participants were drawn from the Coordinated Anxiety Learning and Management (CALM) Study, an effectiveness trial for primary care patients with panic disorder (PD), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), and/or social anxiety disorder (SAD). RESULTS: Approximately one third of older adults with anxiety disorders reported feeling like they were better off dead. Older adults with PD and SAD were more likely to endorse suicidal ideation lasting at least more than half the prior week compared with younger adults with these disorders. Older adults with SAD endorsed higher rates of suicidal ideation compared with older adults with other anxiety disorders. Multivariate analyses revealed the importance of physical health, social support, and comorbid MDD in this association. CONCLUSIONS: Suicidal ideation is common in anxious, older, primary care patients and is particularly prevalent in socially anxious older adults. Findings speak to the importance of physical health, social functioning, and MDD in this association. CLINICAL IMPLICATIONS: When working with anxious older adults it is important to conduct a thorough suicide risk assessment and teach skills to cope with death and suicidal ideation-related thoughts.

Stability of Genetic and Environmental Contributions to Anxiety Symptoms in Older Adulthood.

Anxiety symptoms are common in later life and are associated with diverse adverse health outcomes. Little is known about how genetic and environmental influences on anxiety symptoms might vary across older adulthood. The purpose of this study was to explore change and stability of contributions to anxiety symptoms across older adulthood. We examined data from the Swedish Adoption/Twin Study of Aging (SATSA). Between the years 1984 and 2010, 2021 participants (including 753 complete twin pairs) completed up to seven assessments containing two measures of anxiety symptoms. Longitudinal genetic simplex models were fit to examine the stability and change in genetic and environmental influences. Amplification of genetic factors at ages 75-80 suggests tentative new genetic contributions to anxiety symptoms. These findings suggest that the heritability of anxiety symptoms may increase later in life. Physiological factors associated with aging are discussed as potential factors explaining this increase.

Fear of Falling after Hip Fracture: Prevalence, Course, and Relationship with One-Year Functional Recovery.

OBJECTIVES: The effect of fear of falling (FoF) on recovery 1 year after hip fracture is not well known. Furthermore, the potential influence of premorbid function has not been explored. We aimed to describe rates of FoF after hip fracture, to assess the association of FoF with functional recovery 1 year post-fracture, and to evaluate the potential moderating effect of premorbid function on the relationship between FoF and functional recovery. DESIGN: Secondary analysis of data from a prospective, longitudinal observational study to assess genetic factors influencing functional and psychological outcomes after hip fracture over 52 weeks. SETTING: Eight area hospitals in St. Louis, MO. PARTICIPANTS: 241 cognitively intact individuals 60 years of age or older requiring surgical repair for hip fracture. MEASUREMENTS: Fear of falling was measured by the short Falls Efficacy Scale-International 4 and 12 weeks post-fracture. The primary outcome was probability of full recovery 52 weeks post-fracture assessed with the Functional Recovery Score. RESULTS: High rates of FoF were seen at 4 (60.5%) and 12 weeks (47.0%) post-fracture. Week 12 FoF was associated with lower odds of recovery for those with high function pre-fracture (odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.72, 0.93), but not for those with impaired activities of daily living performance (OR: 1.04, 95% CI: 0.91, 1.19). CONCLUSIONS: Fear of falling is common after hip fracture and is associated with poorer functional recovery 1 year after fracture, particularly in patients with high premorbid function. Fear of falling is a modifiable problem that represents a potential target for interventions to improve functional outcomes after hip fracture.

Activity, balance, learning, and exposure (ABLE): a new intervention for fear of falling.

OBJECTIVE: Fear of falling is an important problem among older adults, even those with relatively low rates of objective fall risk, who are often overlooked as targets for intervention. METHOD: We developed and pilot tested a new intervention, Activity, Balance, Learning, and Exposure (ABLE), in a sample of 10 older adults with excessive fear of falling. The ABLE intervention integrates exposure therapy and cognitive restructuring with a home safety evaluation and an exercise program and is conducted in the home. In this pilot project, ABLE was jointly conducted by a physical therapist and a psychologist with expertise in geriatric anxiety disorders. RESULTS: The intervention was feasible and acceptable and resulted in decreases in fear and activity avoidance for most participants. One participant experienced an injurious fall. DISCUSSION: We learned a number of important lessons resulting in modifications to the inclusion criteria, assessments, and intervention over the course of this pilot study. Results suggest that ABLE has promise for treating excessive fear of falling in the elderly and support testing the intervention in a larger randomized trial. Copyright © 2016 John Wiley & Sons, Ltd.

Age moderates response to acceptance and commitment therapy vs. cognitive behavioral therapy for chronic pain.

OBJECTIVE: The purpose of this study was to examine age differences in response to different forms of psychotherapy for chronic pain. METHODS: We performed a secondary analysis of 114 adults (ages 18-89 years) with a variety of chronic, nonmalignant pain conditions randomly assigned to 8 weeks of group-administered acceptance and commitment therapy (ACT) or cognitive behavioral therapy (CBT). Treatment response was defined as a drop of at least three points on the Brief Pain Inventory-interference subscale. RESULTS: Older adults were more likely to respond to ACT, and younger adults to CBT, both immediately following treatment and at 6-month follow-up. There were no significant differences in credibility, expectations of positive outcome, attrition, or satisfaction, although there was a trend for the youngest adults (ages 18-45 years) to complete fewer sessions. CONCLUSIONS: These data suggest that ACT may be an effective and acceptable treatment for chronic pain in older adults.

Anxiety is associated with increased risk of dementia in older Swedish twins.

INTRODUCTION: We asked whether anxiety is associated with prospective risk of dementia, and the extent to which genetic influences mediate this association. METHODS: Nondemented twins (n = 1082) from the Swedish Adoption Twin Study of Aging completed an assessment of anxiety symptoms in 1984 and were followed for 28 years. RESULTS: Baseline anxiety score, independent of depressive symptoms, was significantly associated with incident dementia over follow-up (hazard ratio [HR] = 1.04; 95% confidence interval [CI] = 1.01-1.06). There was 48% increased risk of becoming demented for those who had experienced high anxiety at any time compared with those who had not. In co-twin analyses, the association between anxiety symptoms and dementia was greater for dizygotic (HR = 1.11; 95% CI = 1.02-1.20) compared with monozygotic twins (HR = 1.06; 95% CI = 0.95-1.20), indicating genetic mediation. DISCUSSION: Anxiety symptoms were associated with increased risk of dementia. Genetic factors common to dementia and anxiety partially mediated this association.

A new measure of fear of falling: psychometric properties of the fear of falling questionnaire revised (FFQ-R).

BACKGROUND: Although fear of falling is prevalent among older adults recovering from hip fracture, current instruments are inadequate due to focus on specific situations and measurement of self-efficacy rather than fear. METHODS: The authors revised and tested a form of the Fear of Falling Questionnaire with three groups of older adults: 405 recovering from hip fracture, 89 healthy community dwelling, and 42 with severe fear of falling. Test-retest reliability was evaluated in a subsample of 16 hip fracture patients. Internal consistency was compared across all groups. Construct validity was established through factor analysis, convergent validity with a measure of fall-related self-efficacy, and discriminant validity with measures of depression and affect. RESULTS: A revised two-factor, six-item scale appears to have adequate psychometric properties. Scores were lower in the healthy comparison group relative to the hip fracture and fear of falling groups. Cronbach's α ranged from 0.72-0.83, with test-retest reliability of 0.82. Correlations with a measure of fall-related self-efficacy were moderate for the hip fracture group (0.42) and high with the healthy comparison (0.68) and fear of falling (0.70) groups. Correlations with depression and negative and positive affect were low to moderate. CONCLUSIONS: The Fear of Falling Questionnaire - Revised shows promise as a self-report measure of fear of falling, and is one of the first to be tested in older adults recovering from hip fracture. Advantages are that it is global rather than situation-specific and measures fear rather than self-efficacy. Future research on this scale is recommended in other older adult samples for whom fear of falling is relevant.

Increased perivascular space volume in white matter and basal ganglia is associated with cognition in Parkinson's Disease.

Perivascular spaces (PVS), fluid-filled compartments surrounding brain vasculature, are an essential component of the glymphatic system responsible for transport of waste and nutrients. Glymphatic system impairment may underlie cognitive deficits in Parkinson's disease (PD). Studies have focused on the role of basal ganglia PVS with cognition in PD, but the role of white matter PVS is unknown. This study examined the relationship of white matter and basal ganglia PVS with domain-specific and global cognition in individuals with PD. Fifty individuals with PD underwent 3T T1w magnetic resonance imaging (MRI) to determine PVS volume fraction, defined as PVS volume normalized to total regional volume, within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of global cognitive function (Montreal Cognitive Assessment, and global cognitive composite score), and cognitive-specific domains (executive function, memory, visuospatial function, attention, and language). Higher white matter rostral middle frontal PVS was associated with lower scores in both global cognitive and visuospatial function. In the basal ganglia higher PVS was associated with lower scores for memory with a trend towards lower global cognitive composite score. While previous reports have shown that greater amount of PVS in the basal ganglia is associated with decline in global cognition in PD, our findings suggest that increased white matter PVS volume may also underlie changes in cognition.

The Association between Exposure to Fine Particulate Matter and MRI-Assessed Locus Coeruleus Integrity in the Vietnam Era Twin Study of Aging (VETSA).

BACKGROUND: Increased exposure to ambient air pollution, especially fine particulate matter ≤2.5µm (PM2.5) is associated with poorer brain health and increased risk for Alzheimer's disease (AD) and related dementias. The locus coeruleus (LC), located in the brainstem, is one of the earliest regions affected by tau pathology seen in AD. Its diffuse projections throughout the brain include afferents to olfactory areas that are hypothesized conduits of cerebral particle deposition. Additionally, extensive contact of the LC with the cerebrovascular system may present an additional route of exposure to environmental toxicants. OBJECTIVE: Our aim was to investigate if exposure to PM2.5 was associated with LC integrity in a nationwide sample of men in early old age, potentially representing one pathway through which air pollution can contribute to increased risk for AD dementia. METHODS: We examined the relationship between PM2.5 and in vivo magnetic resonance imaging (MRI) estimates of LC structural integrity indexed by contrast to noise ratio (LCCNR) in 381 men [mean age=67.3; standard deviation (SD)=2.6] from the Vietnam Era Twin Study of Aging (VETSA). Exposure to PM2.5 was taken as a 3-year average over the most recent period for which data were available (average of 5.6 years prior to the MRI scan). We focused on LCCNR in the rostral-middle portion of LC due to its stronger associations with aging and AD than the caudal LC. Associations between PM2.5 exposures and LC integrity were tested using linear mixed effects models adjusted for age, scanner, education, household income, and interval between exposure and MRI. A co-twin control analysis was also performed to investigate whether associations remained after controlling for genetic confounding and rearing environment. RESULTS: Multiple linear regressions revealed a significant association between PM2.5 and rostral-middle LCCNR (ß=-0.16; p=0.02), whereby higher exposure to PM2.5 was associated with lower LCCNR. A co-twin control analysis found that, within monozygotic pairs, individuals with higher PM2.5 exposure showed lower LCCNR (ß=-0.11; p=0.02), indicating associations were not driven by genetic or shared environmental confounds. There were no associations between PM2.5 and caudal LCCNR or hippocampal volume, suggesting a degree of specificity to the rostral-middle portion of the LC. DISCUSSION: Given previous findings that loss of LC integrity is associated with increased accumulation of AD-related amyloid and tau pathology, impacts on LC integrity may represent a potential pathway through which exposure to air pollution increases AD risk. https://doi.org/10.1289/EHP14344.