Association of plasma biomarkers of Alzheimer's disease and related disorders with cognition and cognitive decline: The MYHAT population-based study.

INTRODUCTION: Plasma biomarkers of Alzheimer's disease and related dementias predict global cognitive performance and decline over time; it remains unclear how they associate with changes in different dementia syndromes affecting distinct cognitive domains. METHODS: In a prospective study with repeated assessments of a randomly selected population-based cohort (n = 787, median age 73), we evaluated performance and decline in different cognitive domains over up to 8 years in relation to plasma concentrations of amyloid beta 42/40 (Aß42/40) ratio, phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP). RESULTS: Cross-sectionally, memory showed the strongest associations with p-tau181, and attention, executive, and visuospatial functions with NfL. Longitudinally, memory decline was distinguishable with all biomarker profiles dichotomized according to data-driven cutoffs, most efficiently with Aß42/40. GFAP and Aß42/40 were the best discriminators of decline patterns in language and visuospatial functions, respectively. DISCUSSION: These relatively non-invasive tests may be beneficial for clinical screening after replication in other populations and validation through neuroimaging or cerebrospinal fluid analysis. HIGHLIGHTS: We performed a prospective study with up to 8 years of repeated domain-specific cognitive assessments and baseline plasma Alzheimer's disease and related dementias biomarker measurements in a randomly selected population-based cohort. We considered distinct growth curves of trajectories of different cognitive domains and survival bias induced by missing data by adding quadratic time and applying joint modeling technique. Cross-sectionally, memory showed the strongest associations with plasma phosphorylated tau181, while attention, executive, and visuospatial functions were most strongly associated with neurofilament light chain. Longitudinally, memory and visuospatial declines were most efficiently distinguished by dichotomized amyloid beta 42/40 profile among all plasma biomarkers, while language was by dichotomized glial fibrillary acidic protein. These relatively non-invasive tests may be beneficial for clinical screening; however, they will need replication in other populations and validation through neuroimaging and/or cerebrospinal fluid assessments.

Ethnoracial Identity and Cognitive Impairment: A Community Study.

BACKGROUND: Identifying potentially modifiable risk factors associated with MCI in different ethnoracial groups could reduce MCI burden and health inequity in the population. METHODS: Among 2845 adults aged 65+ years, we investigated potential risk exposures including education, physical and mental health, lifestyle, and sensory function, and their cross-sectional associations with MCI. We compared proportions of exposures between Black and White participants and explored relationships among race, MCI, and exposures. Logistic regression modeled MCI as a function of each exposure in the overall sample adjusting for age, sex, educational level, and race, and investigating race*exposure interactions. RESULTS: Compared with White participants, Black participants had greater odds of MCI (OR 1.53; 95% CI, 1.13 to 2.06) and were more likely to report depressive symptoms, diabetes, and stroke, to have high blood pressure and BMI, and to be APOE - 4 carriers. Exposures associated with higher odds of MCI were diabetes, stroke, lifetime smoking, sleep disturbances, social isolation, loneliness, depression and anxiety symptoms, and vision and hearing loss. There were no significant interactions between race and any exposure. CONCLUSIONS: Black participants had 53% higher odds of MCI adjusting for age, sex, and education. The same exposures were associated with MCI in Black and White participants.

Recruitment of a Diverse Community-based Older Adult Cohort for a Longitudinal Aging Study: The 15104 Seniors Project.

INTRODUCTION: Enrolling individuals from underrepresented ethnoracial groups in aging research is often a challenge. METHODS: We sought a diverse sample of older adults from a small-town area for a longitudinal aging study. We employed an intensive community engagement approach encompassing a range of recruitment strategies. RESULTS: Over 4 years a steady trickle of individuals, 66% self-identifying as Black, signed up for study information; the proportion of those who eventually enroll in the study has been rising each year, from 68% to 94%. Community events, word-of-mouth referrals, and mailed postcards brought in the most contacts. The highest percentage of contacts who ultimately enrolled were from postcards, flyers, and word-of-mouth. Significantly more word-of-mouth referrals were endorsed by Black individuals than White and by Black men than other race/sex groups. CONCLUSIONS: We have had some success in building relationships and trust with the local community, enrolling Black study participants in a proportion equal to their representation in the target community using a variety of recruitment methods. Patience, immersion in the community, and partnerships with key community members alongside traditional advertisements, and the utilization of study participants as recruiters are critical to designing optimal, targeted, recruitment strategies.

Lifestyle and incident dementia: A COSMIC individual participant data meta­analysis.

INTRODUCTION: The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS: We combined data from 21 prospective cohorts across six continents (N = 31,680) and conducted cohort-specific Cox proportional hazard regression analyses in a two-step individual participant data meta-analysis. RESULTS: A one-standard-deviation increase in LIBRA score was associated with a 21% higher risk for dementia. The association was stronger for Asian cohorts compared to European cohorts, and for individuals aged ≤75 years (vs older), though only within the first 5 years of follow-up. No interactions with sex, education, or socioeconomic position were observed. DISCUSSION: Modifiable risk and protective factors appear relevant for dementia risk reduction across diverse geographical and sociodemographic groups. HIGHLIGHTS: A two-step individual participant data meta-analysis was conducted. This was done at a global scale using data from 21 ethno-regionally diverse cohorts. The association between a modifiable dementia risk score and dementia was examined. The association was modified by geographical region and age at baseline. Yet, modifiable dementia risk and protective factors appear relevant in all investigated groups and regions.

Marijuana use among community-dwelling older adults: A population-based study.

OBJECTIVES: There is a paucity of population-level data on marijuana use and mental health and functioning in older adults. METHODS: We analyzed cross-sectional data (n = 910) from a well-characterized cohort, the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. MYHAT is an age-stratified random sample of the population age 65 years and older from a small-town in the USA. Half the sample was female and half were over 75 (Mean age = 77). Most participants were non-Hispanic White. Marijuana use was assessed by self-report and symptoms of mood disorders were screened using the modified Centers for Epidemiological Studies-Depression Scale and the Generalized Anxiety Disorder screener. Cognition was assessed by the Mini-Mental State Examination and a neuropsychological test battery; functioning using the OARS Activities of Daily Living and Instrumental Activities of Daily Living; and overall assessment using the Clinical Dementia Rating (CDR®). RESULTS: One in five MYHAT participants had a history of marijuana use and 5% reported recent use, primarily for pain (41%) and recreation/relaxation (37%). Recent use was associated with cigarette and alcohol use, symptoms of depression or anxiety, and impairments in attention. CONCLUSIONS: Twenty-percent of community-dwelling older adults living in a US state where recreational marijuana use is illegal had a history of marijuana use. Recent marijuana use was less common but, consistent with prior research, associated with other substance use and poorer mental health.

Benzodiazepine use and risk of incident MCI and dementia in a community sample.

OBJECTIVES: Older adults commonly take benzodiazepines (BZDs) that may have long-term adverse cognitive effects. We investigated whether BZD use was related to developing mild cognitive impairment (MCI) or dementia in cognitively normal older adults in the community. SETTING/PARTICIPANTS: A population-based cohort (n = 1959) of adults aged 65 and over, recruited from communities of low socioeconomic status. MEASUREMENTS: BZD use, Clinical Dementia Rating (CDR), anxiety symptoms, depression symptoms, sleep difficulties, and APOE genotype. DESIGN: We examined time from study entry to MCI (CDR = 0.5) and time from study entry to dementia (CDR ≥ 1) in participants who were cognitively normal at baseline (CDR = 0). We used survival analysis (Cox model), adjusted for age, sex, education, sleep, anxiety, and depression. For all the models, we included an interaction term between BZD use and APOE*4. RESULTS: Taking BZDs was significantly associated with higher risk of developing MCI, but not of developing dementia. The effect was not affected by APOE genotype. CONCLUSIONS: In a population-based sample of cognitively normal older adults, BZD use is associated with developing MCI, but not dementia. BZD use may be a potentially modifiable risk factor for MCI.

Social Isolation and Loneliness in a Population Study of Cognitive Impairment: The MYHAT Study.

In this study, we examined associations of social isolation and loneliness with cognitive impairment among older adults from a Rust Belt region in Southwest Pennsylvania. We used data from the population-based Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. We found that (a) 11 items combined into two reliable composites of social isolation and loneliness; (b) unique to this study, providing unpaid help to others was an indicator of reduced social isolation; (c) social isolation and loneliness were positively associated with cognitive impairment; and (d) these associations were appreciably attenuated by general health and physical functional status and depressive symptoms, respectively. We concluded that social isolation and loneliness are differentially associated with older adults' cognitive health, and that their effects might operate through separate pathways. Approaches to address social isolation and loneliness should consider the community context and its implications for older adults' cognitive health.

Plasma biomarkers identify older adults at risk of Alzheimer's disease and related dementias in a real-world population-based cohort.

INTRODUCTION: Plasma biomarkers-cost effective, non-invasive indicators of Alzheimer's disease (AD) and related disorders (ADRD)-have largely been studied in clinical research settings. Here, we examined plasma biomarker profiles and their associated factors in a population-based cohort to determine whether they could identify an at-risk group, independently of brain and cerebrospinal fluid biomarkers. METHODS: We measured plasma phosphorylated tau181 (p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and amyloid beta (Aß)42/40 ratio in 847 participants from a population-based cohort in southwestern Pennsylvania. RESULTS: K-medoids clustering identified two distinct plasma Aß42/40 modes, further categorizable into three biomarker profile groups: normal, uncertain, and abnormal. In different groups, plasma p-tau181, NfL, and GFAP were inversely correlated with Aß42/40, Clinical Dementia Rating, and memory composite score, with the strongest associations in the abnormal group. DISCUSSION: Abnormal plasma Aß42/40 ratio identified older adult groups with lower memory scores, higher dementia risks, and higher ADRD biomarker levels, with potential implications for population screening. HIGHLIGHTS: Population-based plasma biomarker studies are lacking, particularly in cohorts without cerebrospinal fluid or neuroimaging data. In the Monongahela-Youghiogheny Healthy Aging Team study (n = 847), plasma biomarkers associated with worse memory and Clinical Dementia Rating (CDR), apolipoprotein E ε4, and greater age. Plasma amyloid beta (Aß)42/40 ratio levels allowed clustering participants into abnormal, uncertain, and normal groups. Plasma Aß42/40 correlated differently with neurofilament light chain, glial fibrillary acidic protein, phosphorylated tau181, memory composite, and CDR in each group. Plasma biomarkers can enable relatively affordable and non-invasive community screening for evidence of Alzheimer's disease and related disorders pathophysiology.

It goes both ways: The relationship between anxiety and mild cognitive impairment.

OBJECTIVE: To investigate the relationship between anxiety and mild cognitive impairment (MCI), and whether it is mediated by perceived stress, at the population level. METHOD AND DESIGN: In a longitudinal study of 368 adults aged 65+ from a population-based cohort, we annually assessed anxiety symptoms (GAD-7), perceived stress (PSS-4), and ratings on the Clinical Dementia Rating (CDR®), where CDR = 0.5 was operationalized as MCI. Examining data from three consecutive assessment waves, we first determined the associations between anxiety at the first wave with MCI at the third wave, and vice versa. We then used mediation analyses to determine whether the pathways in both directions were mediated by perceived stress at the second wave, adjusting for demographics and other relevant covariates. RESULTS: We confirmed significant bidirectional longitudinal associations between anxiety and MCI. Perceived stress was detected as a significant mediator for both pathways between anxiety and MCI, explaining 37.1% of the total effect (TE) of anxiety on incident MCI while conversely explaining 27.1% of the TE of MCI on anxiety. CONCLUSIONS: A bidirectional relationship with a 2-year lag between anxiety and MCI was mediated through perceived stress. Clinicians should be sensitive both to potential consequent anxiety when patients present with cognitive impairment, and to potential incipient MCI when the presenting complaint is anxiety. Managing stress may help mitigate adverse outcomes.

Sex differences in dementia risk and risk factors: Individual-participant data analysis using 21 cohorts across six continents from the COSMIC consortium.

INTRODUCTION: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. METHODS: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and women-to-men ratio of hazard ratios (RHRs) for associations between RFs and all-cause dementia were derived from mixed-effect Cox models. RESULTS: Incident dementia occurred in 2089 (66% women) participants over 4.6 years (median). Women had higher dementia risk (HR, 1.12 [1.02, 1.23]) than men, particularly in low- and lower-middle-income economies. Associations between longer education and former alcohol use with dementia risk (RHR, 1.01 [1.00, 1.03] per year, and 0.55 [0.38, 0.79], respectively) were stronger for men than women; otherwise, there were no discernible sex differences in other RFs. DISCUSSION: Dementia risk was higher in women than men, with possible variations by country-level income settings, but most RFs appear to work similarly in women and men.

Anticholinergic Drug Burden and Risk of Incident MCI and Dementia: A Population-based Study.

OBJECTIVE: We investigated whether anticholinergic drug use was related to developing mild cognitive impairment (MCI) or dementia in older adults at the population level. METHODS: We used an Anticholinergic Rating (ACR) scale, Clinical Dementia Rating, APOE genotype, and number of prescription medications. We examined time to incident MCI and incident dementia in a population-based cohort (n=1959). We assessed whether developing MCI or dementia was associated with (1) any anticholinergic drug use, (2) total ACR score, or (3) number of anticholinergic drugs taken. RESULTS: Taking any anticholinergic drug was significantly associated with higher risk of developing MCI; however, higher ACR score or higher number of anticholinergic drugs, compared with lower, were not associated with greater risk of developing MCI. We found no significant relationship between anticholinergic use and developing dementia. The relationship between anticholinergic use and cognitive outcome was not affected by APOE genotype. CONCLUSIONS: Among cognitively normal older adults in a population-based sample, anticholinergic drug use is independently associated with subsequently developing MCI, but not dementia. Thus, anticholinergic drug use may influence risk of MCI that is nonprogressive to dementia and potentially be a modifiable risk factor for MCI.

Predictors of Driving Cessation in Older Adults: A 12-year Population-based Study.

BACKGROUND: Changes in physical health and cognition during aging can result in some older adults to stop driving. In this population-based longitudinal study, we describe potential predictors of driving cessation in older adults. METHODS: Age-stratified random population cohort of 1982 adults aged 65 years and older drawn from voter registration lists. Participant characteristics were measured using demographics, physical and self-rated health, sleeping habits, driving status, cognitive screening, modified Center for Epidemiologic Studies-Depression scale, clinical dementia rating, and mini-mental state examination. RESULTS: Over 12 years of follow-up, 390 participants stopped driving. These individuals were older, more likely to be women and to have a clinical dementia rating score ≥1, had worse self-reported health, and more symptoms of depression, compared with those who were still driving. In addition, individuals with lower test performance in all cognitive domains, loss of visual acuity and fields, and bilateral hearing loss were more likely to stop driving. CONCLUSIONS: Age, sex, cognitive impairments, physical health, and depressive symptoms were associated with driving cessation in this cohort. By identifying potential driving cessation predictors, health care providers and families may better recognize these risk factors and begin the driving cessation discussion early.

Dose-response relationship between late-life physical activity and incident dementia: A pooled analysis of 10 cohort studies of memory in an international consortium.

INTRODUCTION: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear. METHODS: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incident dementia among older adults. RESULTS: Using no physical activity as a reference, dementia risk decreased with duration of physical activity up to 3.1 to 6.0 hours/week (hazard ratio [HR] 0.88, 95% confidence interval [CI] 0.67 to 1.15 for 0.1 to 3.0 hours/week; HR 0.68, 95% CI 0.52 to 0.89 for 3.1 to 6.0 hours/week), but plateaued with higher duration. For the amount of physical activity, a similar pattern of dose-response curve was observed, with an inflection point of 9.1 to 18.0 metabolic equivalent value (MET)-hours/week (HR 0.92, 95% CI 0.70 to 1.22 for 0.1 to 9.0 MET-hours/week; HR 0.70, 95% CI 0.53 to 0.93 for 9.1 to 18.0 MET-hours/week). DISCUSSION: This cross-national analysis suggests that performing 3.1 to 6.0 hours of physical activity and expending 9.1 to 18.0/MET-hours of energy per week may reduce dementia risk.

The relationship between alcohol use and dementia in adults aged more than 60 years: a combined analysis of prospective, individual-participant data from 15 international studies.

AIM: To synthesize international findings on the alcohol-dementia relationship, including representation from low- and middle-income countries. METHODS: Individual participant data meta-analysis of 15 prospective epidemiological cohort studies from countries situated in six continents. Cox regression investigated the dementia risk associated with alcohol use in older adults aged over 60 years. Additional analyses assessed the alcohol-dementia relationship in the sample stratified by sex and by continent. Participants included 24 478 community dwelling individuals without a history of dementia at baseline and at least one follow-up dementia assessment. The main outcome measure was all-cause dementia as determined by clinical interview. RESULTS: At baseline, the mean age across studies was 71.8 (standard deviation = 7.5, range = 60-102 years), 14 260 (58.3%) were female and 13 269 (54.2%) were current drinkers. During 151 636 person-years of follow-up, there were 2124 incident cases of dementia (14.0 per 1000 person-years). When compared with abstainers, the risk for dementia was lower in occasional [hazard ratio (HR) = 0.78; 95% confidence interval (CI) = 0.68-0.89], light-moderate (HR = 0.78; 95% CI = 0.70-0.87) and moderate-heavy drinkers (HR = 0.62; 95% CI = 0.51-0.77). There was no evidence of differences between life-time abstainers and former drinkers in terms of dementia risk (HR = 0.98; 95% CI = 0.81-1.18). In dose-response analyses, moderate drinking up to 40 g/day was associated with a lower risk of dementia when compared with lif-time abstaining. Among current drinkers, there was no consistent evidence for differences in terms of dementia risk. Results were similar when the sample was stratified by sex. When analysed at the continent level, there was considerable heterogeneity in the alcohol-dementia relationship. CONCLUSIONS: Abstinence from alcohol appears to be associated with an increased risk for all-cause dementia. Among current drinkers, there appears to be no consistent evidence to suggest that the amount of alcohol consumed in later life is associated with dementia risk.

Psychosocial implications of early COVID-19 restrictions on older adults in a small-town region in Southwestern, Pennsylvania (USA).

OBJECTIVES: The restrictions put in place in 2020 to mitigate the spread of the coronavirus disease 2019 limited or eliminated social connections that are vital for psychosocial well-being. The objectives of this research were to examine the impact of early pandemic-related restrictions on feelings of loneliness, depression, and anxiety as well as social activity disruption and their concomitant associations in a sample of community-dwelling older adults residing in a small-town region in the USA. DESIGN AND SETTING: Cross-sectional data collected from an ongoing population-based cohort study in Southwestern, Pennsylvania. PARTICIPANTS: Analyses included 360 adults aged 65 years and older whose annual study assessment occurred during the first 120 days of pandemic-related restrictions. MEASUREMENTS: Self-reported feelings of loneliness, depression, and anxiety due to the pandemic-related restrictions were each measured using a single question. Depressive symptoms and anxiety were also assessed with the modified Center for Epidemiologic Studies-Depression and Generalized Anxiety Disorder-7 item tools. Disruption in a variety of common social activities was also assessed. RESULTS: Feeling lonely affected 36% of participants who were more likely to be female, not currently married, and living alone. Giving up in-person visits with family was associated with significantly higher odds of feeling lonely, and feeling lonely was associated with significantly higher odds of feelings of anxiety and depression. CONCLUSIONS: Loneliness is a serious outcome of pandemic-related restrictions among older adults, potentially linked to loss of connection with family, and may be associated with increased feelings of depression and anxiety.

Associations between social connections and cognition: a global collaborative individual participant data meta-analysis.

BACKGROUND: Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between social connection markers and the rate of annual change in cognition (ie, global and domain-specific), as well as sex differences, using an individual participant data meta-analysis. METHODS: We harmonised data from 13 longitudinal cohort studies of ageing in North America, South America, Europe, Africa, Asia, and Australia. Studies were eligible for inclusion if they had baseline data for social connection markers and at least two waves of cognitive scores. Follow-up periods ranged from 0 years to 15 years across cohorts. We included participants with cognitive data for at least two waves and social connection data for at least one wave. We then identified and excluded people with dementia at baseline. Primary outcomes were annual rates of change in global cognition and cognitive domain scores over time until final follow-up within each cohort study analysed by use of an individual participant data meta-analysis. Linear mixed models within cohorts used baseline social connection markers as predictors of the primary outcomes. Effects were pooled in two stages using random-effects meta-analyses. We assessed the primary outcomes in the main (partially adjusted) and fully adjusted models. Partially adjusted models controlled for age, sex, and education; fully adjusted models additionally controlled for diabetes, hypertension, smoking, cardiovascular risk, and depression. FINDINGS: Of the 40 006 participants in the 13 cohort studies, we excluded 1392 people with dementia at baseline. 38 614 individual participants were included in our analyses. For the main models, being in a relationship or married predicted slower global cognitive decline (b=0·010, 95% CI 0·000-0·019) than did being single or never married; living with others predicted slower global cognitive (b=0·007, 0·002-0·012), memory (b=0·017, 0·006-0·028), and language (b=0·008, 0·000-0·015) decline than did living alone; and weekly interactions with family and friends (b=0·016, 0·006-0·026) and weekly community group engagement (b=0·030, 0·007-0·052) predicted slower memory decline than did no interactions and no engagement. Never feeling lonely predicted slower global cognitive (b=0·047, 95% CI 0·018-0·075) and executive function (b=0·047, 0·017-0·077) decline than did often feeling lonely. Degree of social support, having a confidante, and relationship satisfaction did not predict cognitive decline across global cognition or cognitive domains. Heterogeneity was low (I2=0·00-15·11%) for all but two of the significant findings (association between slower memory decline and living with others [I2=58·33%] and community group engagement, I2=37·54-72·19%), suggesting robust results across studies. INTERPRETATION: Good social connections (ie, living with others, weekly community group engagement, interacting weekly with family and friends, and never feeling lonely) are associated with slower cognitive decline. FUNDING: EU Joint Programme-Neurodegenerative Disease Research grant, funded by the National Health and Medical Research Council Australia, and the US National Institute on Aging of the US National Institutes of Health.

Education, Occupational Complexity, and Incident Dementia: A COSMIC Collaborative Cohort Study.

BACKGROUND: Education and occupational complexity are main sources of mental engagement during early life and adulthood respectively, but research findings are not conclusive regarding protective effects of these factors against late-life dementia. OBJECTIVE: This project aimed to examine the unique contributions of education and occupational complexity to incident dementia, and to assess the mediating effects of occupational complexity on the association between education and dementia across diverse cohorts. METHOD: We used data from 10,195 participants (median baseline age = 74.1, range = 58∼103), representing 9 international datasets from 6 countries over 4 continents. Using a coordinated analysis approach, the accelerated failure time model was applied to each dataset, followed by meta-analysis. In addition, causal mediation analyses were performed. RESULT: The meta-analytic results indicated that both education and occupational complexity were independently associated with increased dementia-free survival time, with 28%of the effect of education mediated by occupational complexity. There was evidence of threshold effects for education, with increased dementia-free survival time associated with 'high school completion' or 'above high school' compared to 'middle school completion or below'. CONCLUSION: Using datasets from a wide range of geographical regions, we found that both early life education and adulthood occupational complexity were independently predictive of dementia. Education and occupational experiences occur during early life and adulthood respectively, and dementia prevention efforts could thus be made at different stages of the life course.

Ambient fine particulate matter exposure and incident mild cognitive impairment and dementia.

BACKGROUND/OBJECTIVE: Poor air quality is implicated as a risk factor for cognitive impairment and dementia. Few studies have examined these associations longitudinally in well-characterized population-based cohorts with standardized annual assessment of both mild cognitive impairment (MCI) and dementia. We investigated the association between estimated ambient fine particulate matter (PM2.5 ) and risk of incident MCI and dementia in a post-industrial region known for historically poor air quality. SETTING/PARTICIPANTS: Adults aged 65+ years in a population-based cohort (n = 1572). MEASUREMENTS: Census tract level PM2.5 from Environmental Protection Agency (EPA) air quality monitors; Clinical Dementia Rating (CDR)®. DESIGN: We estimated ambient PM2.5 exposure (µg/m3 , single-year and 5-year averages) by geocoding participants' residential addresses to census tracts with daily EPA PM2.5 measurements from 2002 to 2014. Using Bayesian spatial regression modeling adjusted for age, sex, education, smoking history, and household income, we examined the association between estimated PM2.5 exposure and risk of incident MCI (CDR = 0.5) and incident dementia (CDR ≥ 1.0). RESULTS: Modeling estimated single-year exposure, each 1 µg/m3 higher ambient PM2.5 was associated with 67% higher adjusted risk of incident dementia (hazard ratio [HR] = 1.669, 95% credible interval [CI]: 1.298, 2.136) and 75% higher adjusted risk of incident MCI (HR = 1.746, 95% CI: 1.518, 2.032). Estimates were higher when modeling 5-year ambient PM2.5 exposure for incident dementia (HR = 2.082, 95% CI: 1.528, 3.015) and incident MCI (HR = 3.419, 95% CI: 2.806, 4.164). CONCLUSIONS: Higher estimated ambient PM2.5 was associated with higher risk of incident MCI and dementia, particularly when considering longer-term exposure, and independent of demographic characteristics and smoking history. Targeting poor air quality may be a reasonable population-wide intervention to reduce the risk of cognitive impairment in older adults, particularly in regions exceeding current recommendations for safe exposure to PM2.5 .

Driving Habits of Older Adults: A Population-based Study.

OBJECTIVES: To describe factors associated with driving history, habits, and self-reported driving difficulties of 1982 older adults in a population-based survey. SETTING: This was a community setting. PARTICIPANTS: Age-stratified random population sample drawn from publicly available voter registration list. DESIGN: Participants underwent assessments including cognitive testing and self-reported current and past driving status, instrumental activities of daily living, self-rated health, social supports, physical limitations, and depressive symptoms. We built multivariable logistic regression models to identify factors associated with never having driven, having ceased driving, and reporting difficulties while driving. RESULTS: In the multivariable model, "never drivers" were more likely than "ever drivers" to be older, female, less educated and to leave home less frequently. Former drivers were significantly older, more likely to be women, have lower test performance in the cognitive domain of attention, have more instrumental activity of daily living difficulties, leave home less frequently and have visual field deficits in the right eye than current drivers. Current drivers with reported driving difficulties were more likely than those without difficulties to have lower test performance in attention but higher in memory, were more likely to report depressive symptoms and to have both vision and hearing loss. CONCLUSION: Age, female sex, marital status, and education appear to be associated with driving cessation. Cognitive and functional impairments, mood symptoms and physical health also seem to influence driving cessation and reduction. Our findings may have implications for clinicians in assessing and educating their patients and families on driving safety.

Predictors of attrition in a longitudinal population-based study of aging.

BACKGROUND: Longitudinal studies predictably experience non-random attrition over time. Among older adults, risk factors for attrition may be similar to risk factors for outcomes such as cognitive decline and dementia, potentially biasing study results. OBJECTIVE: To characterize participants lost to follow-up which can be useful in the study design and interpretation of results. METHODS: In a longitudinal aging population study with 10 years of annual follow-up, we characterized the attrited participants (77%) compared to those who remained in the study. We used multivariable logistic regression models to identify attrition predictors. We then implemented four machine learning approaches to predict attrition status from one wave to the next and compared the results of all five approaches. RESULTS: Multivariable logistic regression identified those more likely to drop out as older, male, not living with another study participant, having lower cognitive test scores and higher clinical dementia ratings, lower functional ability, fewer subjective memory complaints, no physical activity, reported hobbies, or engagement in social activities, worse self-rated health, and leaving the house less often. The four machine learning approaches using areas under the receiver operating characteristic curves produced similar discrimination results to the multivariable logistic regression model. CONCLUSIONS: Attrition was most likely to occur in participants who were older, male, inactive, socially isolated, and cognitively impaired. Ignoring attrition would bias study results especially when the missing data might be related to the outcome (e.g. cognitive impairment or dementia). We discuss possible solutions including oversampling and other statistical modeling approaches.