Table 2.

Summary of quality assessment for eligible studies on air pollution and late-life cognitive health identified through 31 December 2020.

Study focus	Citation/cohort	Study strengthsa					New to the review	Noted study limitationsb
		Exposure assessment and variability	Outcome assessment	No substantial issues with confounding/inappropriate adjustment	No substantial issues with cohort formation/loss to follow-up	Generalizability
Cognitive level	(Ailshire and Crimmins 2014)/HRS	—	Yes	Yes	Yes	Yes	—	No individual-level exposure assessment, restricted to regions near regulatory monitors.
Cognitive level	(Ailshire And Clarke 2015)/ACL Survey	—	—	—	Yes	Yes	—	No individual-level exposure assessment, restricted to regions near regulatory monitors; insensitive test of cognition will likely only pick up highly impaired; crude age and education adjustment.
Cognitive level	(Chen et al. 2020)/TIGER	—	—	—	—	Yes	Yes	Limited exposure variability; reporting on outcome definition is unclear; inappropriate adjustment for a potential intermediate; no information on correlates of attrition.
Cognitive level	(Chen and Schwartz 2009)/NHANES III	—	Yes	—	Yes	Yes	—	No individual-level exposure assessment, restricted to regions near regulatory monitors; adjusted for age in 10-year bands, different adjustment for socioeconomic status across exposures, specifically some models of ${\mathrm{PM}}_{10}$ not adjusted for both race/ethnicity and socioeconomic status.
Cognitive level	(Gatto et al. 2014)/WISH, BVAIT, and ELITE	—	Yes	Yes	—	—	—	Only modest capture of local exposure gradients; cohort was extremely healthy for age due to inclusion/exclusion criteria of original randomized controlled trials.
Cognitive level	(Kim et al. 2019)/Voluntary community-based sample	Yes	—	—	—	Yes	Yes	Outcome was below threshold on dementia screening test after excluding persons with dementia or mild cognitive impairment; crude age adjustment, inappropriate adjustment for intermediates, reported only stratified analysis without justification.
Cognitive level	(Lo et al. 2019)/TLSA	—	—	—	—	Yes	Yes	No individual-level exposure assessment or information on exposure distribution; insensitive test of cognition will likely only pick up highly impaired; inappropriate adjustment for IADLs; lack of information on loss to follow-up despite use of repeated measures for cross-sectional analysis.
Cognitive level	(Power et al. 2011)/NAS	Yes	Yes	—	Yes	Yes	—	Inappropriate adjustment for intermediates.
Cognitive level	(Ranft et al. 2009)/SALIA	—	Yes	—	Yes	Yes	—	Relatively little exposure variability in recent exposure for rural participants, modest capture of local exposure gradients; crude adjustment for age and socioeconomic status, inappropriate adjustment for co-morbidities.
Cognitive level	(Rocha et al. 2020)/ELSA-Brasil	Yes	Yes	Yes	—	Yes	Yes	Excluded substantial proportion of sample for missing exposure data.
Cognitive level	(Salinas-Rodríguez et al. 2018)/ENSANUT-2012	—	Yes	Yes	Yes	Yes	Yes	No individual-level exposure assessment, limited capture of local air pollution exposure gradients.
Cognitive level	(Schikowski et al. 2015)/SALIA	—	Yes	Yes	Yes	Yes	—	Relatively little variation in PM across study participants.
Cognitive level	(Shin et al. 2019)/KFACS	—	Yes	—	Yes	Yes	Yes	Limited exposure variation, exposure estimation poorly documented, no individual-level exposure assessment; inappropriate adjustment for comorbidities.
Cognitive level	(Tallon et al. 2017)/NSHAP	—	Yes	Yes	Yes	Yes	Yes	Excluded one-third of participants from analyses with ${\mathrm{NO}}_2$ exposure, spatial resolution is limited, especially for ${\mathrm{NO}}_2$.
Cognitive level	(Tzivian et al. 2016)/Heinz Nixdorf RECALL	—	Yes	Yes	Yes	Yes	Yes	Limited exposure variability.
Cognitive level	(Wellenius et al. 2012a)/MOBILIZE Boston	Yes	Yes	Yes	—	Yes	—	Lack of information on loss to follow-up despite use of repeated measures for cross-sectional analysis.
Cognitive level	(Wurth et al. 2018)/BPRHS	—	Yes	—	—	Yes	Yes	Limited exposure variation, no individual-level exposure assessment; no adjustment for calendar time (necessary because a single monitor was used to assess exposure based on individual’s cognitive test date); lack of information on loss to follow-up despite use of repeated measures for cross-sectional analysis.
Cognitive level	(Yao et al. 2021)/CLHLS	—	Yes	Yes	—	Yes	Yes	Use self-report for assessment of distance to road; excluded 23% due to missing MMSE data.
Cognitive level	(Younan et al. 2020a)/WHIMS-MRI and WHISCA	Yes	Yes	—	Yes	—	Yes	Inappropriate adjustment for intermediates; MRI sample appears extremely healthy based on sample characteristics.
Cognitive level	(Zeng et al. 2010)/CLHLS	—	Yes	Yes	Yes	Yes	—	API is a crude measure combining multiple air pollutants with variable correlation, measured at the community level.
Neuroimaging level and cognitive level	(Crous-Bou et al. 2020)/ALFA	—	Yes	Yes	Yes	—	Yes	Did not report exposure contrast associated with reported effect estimate; enriched in participants who are APOE E4 positive, have a family history of dementia.
Neuroimaging level and cognitive level	(Nußbaum et al. 2020)/1000BRAINS	—	Yes	Yes	Yes	Yes	Yes	Limited exposure variability.
Neuroimaging level	(Casanova et al. 2016)/WHIMS-MRI	Yes	Yes	—	—	—	Yes	Adjustment for intermediates in presented models; no comparison of MRI subcohort to full cohort; MRI sample appears extremely healthy based on sample characteristics.
Neuroimaging level	(Chen et al. 2015)/WHIMS-MRI	—	Yes	Yes	—	—	—	$\sim 11\%$ of the cohort were missing $>40\%$ of ${\mathrm{PM}}_{2.5}$ data for the exposure assessment period and point estimates are attenuated, but remain statistically significant when excluding this group; no comparison of MRI subcohort to full cohort; MRI sample appears extremely healthy based on sample characteristics.
Neuroimaging level	(Erickson et al. 2020)/UK Biobank	Yes	Yes	—	—	—	Yes	Inappropriate adjustment for intermediates or consequences of exposure or outcome; no comparison of MRI subcohort to full cohort; sample is much healthier than general UK population.
Neuroimaging level	(Gale et al. 2020)/UK Biobank	Yes	—	—	—	—	Yes	Unclear if volumes standardized by intracranial volume, no information on MRI processing pipeline, left/right separated without confirmation of effect modification; inappropriate adjustment for intermediates or consequences of exposure or outcome, a proxy of exposure; no comparison of MRI subcohort to full cohort; sample is much healthier than general UK population.
Neuroimaging level	(Hedges et al. 2019)/UK Biobank	Yes	—	—	—	—	Yes	Unclear if volumes standardized by intracranial volume, no information on MRI processing pipeline, left/right separated without confirmation of effect modification; inappropriate adjustment for intermediates or consequences of exposure or outcome, a proxy of exposure; no comparison of MRI subcohort to full cohort; sample is much healthier than general UK population.
Neuroimaging level	(Hedges et al. 2020)/UK Biobank	Yes	—	—	—	—	Yes	Unclear if volumes standardized by intracranial volume, no information on MRI processing pipeline, left/right separated without confirmation of effect modification; inappropriate adjustment for intermediates or consequences of exposure or outcome, a proxy of exposure; no comparison of MRI subcohort to full cohort; sample is much healthier than general UK population.
Neuroimaging level	(Iaccarino et al. 2021)/IDEAS	—	Yes	—	—	—	Yes	No individual-level exposure assessment; inappropriate adjustment for intermediates; selection based on cognitive status could cause collider bias; highly selected clinical sample of people with uncertain cognitive impairment etiology who access tertiary care.
Neuroimaging level	(Kulick et al. 2017)/NOMAS	Yes	Yes	Yes	—	Yes	Yes	No comparison of MRI subcohort to full cohort.
Neuroimaging level	(Power et al. 2018a)/ARIC	—	Yes	Yes	—	Yes	Yes	Limited exposure variation for site-specific analyses, selection based on cognitive status could cause collider bias.
Neuroimaging level	(Wilker et al. 2015)/FOS	Yes	Yes	Yes	—	Yes	—	No comparison of MRI subcohort to full cohort.
Neuroimaging level	(Wilker et al. 2016a)/MADRC	Yes	Yes	Yes	—	—	Yes	Highly selected clinical sample.
Neuroimaging level	(Younan et al. 2020b)/WHIMS-MRI	Yes	Yes	Yes	Yes	—	Yes	MRI sample appears extremely healthy based on sample characteristics.
Cognitive level and cognitive change	(Cullen et al. 2018)/UK Biobank	Yes	—	Yes	—	—	Yes	Time period elapsed and limited number of assessments may limit ability to detect change given age of sample; not representative of sampling frame and low participation rate; sample is much healthier than general UK population.
Cognitive level and cognitive change	(Kulick et al. 2020)/WHICAP and NOMAS	—	Yes	Yes	—	Yes	Yes	Low exposure variability within NOMAS participants; no comparison of MRI subcohort to full cohort.
Cognitive level and cognitive change	(Tonne et al. 2014)/Whitehall II	—	Yes	—	Yes	Yes	—	Relatively little variation in total ${\mathrm{PM}}_{10}$ and total ${\mathrm{PM}}_{2.5}$ across study participants, no individual-level exposure assessment; did not report whether they adjusted for time-by-covariate interactions in analyses of cognitive change.
Cognitive change	(Cleary et al. 2018)/National AD Centers Database	—	Yes	—	—	—	Yes	No individual-level exposure, low spatial resolution of model, use of tertiles for exposure; did not specify if including cross-product terms to adjust for confounding of decline; highly selected clinical sample and required development of cognitive impairment during follow-up; enriched in participants who are APOE E4 positive, have a family history of dementia, or have rare dementias.
Cognitive change	(Colicino et al. 2014)/NAS	Yes	Yes	—	—	Yes	Yes	Inappropriate adjustment for potential intermediates; no discussion of extent or correlates of attrition during follow-up.
Cognitive change	(Oudin et al. 2017)/Betula	—	Yes	Yes	Yes	Yes	Yes	Exposures were predicted for 2009–2010, but outcome follow-up spanned 1993–2010.
Cognitive change	(Petkus et al. 2020)/WHISCA	Yes	Yes	—	—	Yes	Yes	Inappropriate adjustment for intermediates; no discussion of extent or correlates of attrition during follow-up.
Cognitive change	(Petkus et al. 2021)/WHIMS-ECHO	Yes	Yes	—	—	Yes	Yes	Inappropriate adjustment for intermediates; recruitment required survival to age 80, no discussion of extent or correlates of attrition during follow-up.
Cognitive change	(Weuve et al. 2012)/NHS	Yes	Yes	Yes	—	Yes	—	No discussion of correlates of attrition during follow-up.
Prevalent dementia	(Dimakakou et al. 2020)/UK Biobank	—	—	—	—	—	Yes	No information on exposure distribution, no information on how exposure was linked to participants; reliance on medical records; inappropriate adjustment for potential consequences of disease, no adjustment for individual-level SES; sample is much healthier than general UK population, inclusion of young participants not at risk of dementia; not representative of sampling frame and low participation rate.
Incident dementia or other incident cognitive impairment	(Ailshire and Walsemann 2021)/HRS	—	Yes	Yes	—	Yes	Yes	No individual-level exposure assessment; no information on proportion of persons lost to follow-up or correlates of attrition
Incident dementia or other incident cognitive impairment	(Carey et al. 2018)/CPRD	—	—	—	—	Yes	Yes	Limited exposure variation, no individual-level exposure assessment; reliance on medical records/claims data; no adjustment for individual-level education; no discussion of extent or correlates of attrition during follow-up.
Incident dementia or other incident cognitive impairment	(Cerza et al. 2019)/Rome Longitudinal Cohort	—	—	Yes	Yes	Yes	Yes	Exposures were predicted for 2009–2010, but outcome follow-up started in 2001; reliance on hospital admissions for identifying dementia.
Incident dementia or other incident cognitive impairment	(Chang et al. 2014)/NHIRD Taiwan	—	—	—	—	—	—	No individual-level exposure estimates, exposure averaging period depended on date of censoring; use of ICD-9-CM codes for identification of dementia, youngest participants not at risk of dementia given $<65\text{years}$ of age for duration of follow-up; no adjustment for education, inappropriate adjustment for multiple potential mediating health conditions in all presented models; no information on attrition or its correlates; inclusion criteria required respiratory tract infection, which may have resulted in selection of sicker or more susceptible persons.
Incident dementia or other incident cognitive impairment	(Chen et al. 2017a)/Ontario Population Health and Environment Cohort	—	—	—	—	Yes	Yes	No individual-level exposure assessment, poor resolution for ozone; reliance on medical records/claims data; crude adjustment for SES; no discussion of extent or correlates of attrition during follow-up.
Incident dementia or other incident cognitive impairment	(Chen et al. 2017b)/Ontario Population Health and Environment Cohort	—	—	—	—	Yes	Yes	Proximity to major roadways based on postcode centroid; reliance on medical records/claims data; crude adjustment for SES, adjustment for mediators in primary analyses; no discussion of extent or correlates of attrition during follow-up.
Incident dementia or other incident cognitive impairment	(Grande et al. 2020)/SNAC-K	—	—	—	Yes	Yes	Yes	Limited exposure variability; partial reliance on medical records for identification of dementia without information on frequency of identification through this method; inappropriate adjustment for intermediates.
Incident dementia or other incident cognitive impairment	(He et al. 2020)/ZJMPHS	—	Yes	Yes	Yes	Yes	Yes	No individual-level exposure assessment, spatial resolution is limited.
Incident dementia or other incident cognitive impairment	(Ilango et al. 2020)/NPHS and CCHS participants	—	—	Yes	—	Yes	Yes	Lacking information on how air pollution linked to participant location; reliance on medical records/claims data; no discussion of extent or correlates of attrition during follow-up.
Incident dementia or other incident cognitive impairment	(Jung et al. 2015)/NHIRD Taiwan	—	—	—	—	Yes	—	No individual-level exposure estimates; use of ICD-9-CM codes for identification of dementia; no adjustment for education or socioeconomic status; no information on attrition or its correlates.
Incident dementia or other incident cognitive impairment	(Li et al. 2019)/NHIRD Taiwan	—	—	—	—	Yes	Yes	No individual-level exposure assessment; use of ICD-9-CM codes for identification of dementia; crude adjustment for SES; case-control design assumes no informative attrition.
Incident dementia or other incident cognitive impairment	(Loop et al. 2013)/REGARDS	—	Yes	Yes	—	Yes	—	No individual-level exposure estimates; no information on correlates of attrition and requirement of completion of two cognitive assessments for inclusion in analysis.
Incident dementia or other incident cognitive impairment	(Oudin et al. 2016)/Betula	—	—	Yes	Yes	Yes	—	Exposures were predicted for 2009–2010, but outcome follow-up spanned 1993–2010, results using back-extrapolated exposure predictions were reported to be similar, but data not shown; partial reliance on medical records for identification of dementia.
Incident dementia or other incident cognitive impairment	(Oudin et al. 2018)/Betula	Yes	—	Yes	—	Yes	Yes	Partial reliance on medical records for identification of dementia; did not address loss to follow-up as a potential source of bias.
Incident dementia or other incident cognitive impairment	(Paul et al. 2020)/SALSA	Yes	Yes	Yes	Yes	Yes	Yes	Nothing of note.
Incident dementia or other incident cognitive impairment	(Ran et al. 2021)/Chinese EHS	—	—	Yes	—	—	Yes	Limited exposure variability; reliance on medical records; no information on correlates of attrition; fee charged for participant enrollment.
Incident dementia or other incident cognitive impairment	(Shi et al. 2020)/Medicare fee-for-service beneficiaries	—	—	—	Yes	Yes	Yes	No individual-level exposure assessment; reliance on claims data; crude adjustment for SES
Incident dementia or other incident cognitive impairment	(Smargiassi et al. 2020)/QICDSS	—	—	—	—	Yes	Yes	No individual-level exposure assessment, distance to road based on postcode centroid; reliance on medical records/claims data; no adjustment for individual-level SES; no information on correlates of attrition.
Incident dementia or other incident cognitive impairment	(Wang et al. 2020)/CLHLS	Yes	—	—	—	Yes	Yes	No information on timing of follow-up assessment; inappropriate adjustment for intermediates; no discussion of selective survival to enrollment or correlates of attrition despite large loss to follow-up.
Incident dementia or other incident cognitive impairment	(Wu et al. 2015)/Case–control	—	Yes	—	—	Yes	Yes	Inadequate documentation of exposure model validation, used tertiles of exposure; large differences in age across cases and controls may result in positivity violations; unclear whether case-control selection related to exposure.
Incident dementia or other incident cognitive impairment	(Yuchi et al. 2020)/MSP Registry	—	—	—	—	Yes	Yes	No individual-level exposure assessment; reliance on medical records/claims data; crude adjustment for SES, inappropriate adjustment for potential mediators; no information on attrition or its correlates.
Incident dementia or other incident cognitive impairment and neuroimaging level	(Chen et al. 2017c)/WHIMS	—	Yes	Yes	—	—	Yes	No individual-level exposure assessment for diesel; no comparison of MRI subcohort to full cohort, no discussion of extent of or correlates of attrition; MRI appears extremely healthy based on sample characteristics.

Note: ACL, Americans’ Changing Lives; AD, Alzheimer’s disease; ALFA, Alzheimer’s and Family; ARIC, Atherosclerosis Risk in Communities; BPRHS, Boston Puerto Rican Health Study; BVAIT, B-Vitamin Atherosclerosis Intervention Trial; CCHS, Canadian Community Health Survey; CLHLS, Chinese Longitudinal Healthy Longevity Survey; CPRD, Clinical Practice Research Datalink; EHS, Elderly Health Service; ELITE, Early versus Late Intervention Trial; ELSA-Brasil, Brazilian Longitudinal Study on Adult Health; ENSANUT-2012, National Survey of Health and Nutrition in Mexico in 2012; FOS, Framingham Offspring Study; Heinz Nixdorf RECALL, Heinz Nixdorf Risk factors, Evaluation of Coronary Calcium and Lifestyle study; HRS, Health and Retirement Study; IADL, instrumental activities of daily living; ICD-9, International Classification of Diseases, Ninth Revision; ICD-9-CM, International Classification of Diseases, Ninth Revision, Clinical Modification; IDEAS, Imaging Dementia – Evidence for Amyloid Scanning; KFACS, Korean Frailty and Aging Cohort Study; MADRC, Massachusetts Alzheimer’s Disease Research Center Longitudinal Cohort; MMSE, Mini-Mental State Examination; MOBILIZE, Maintenance of Balance, Independent Living, Intellect, and Zest in the Elderly; MRI, magnetic resonance imaging; MSP, Medical Service Plan; NAD, non-Alzheimer’s dementia; NAS, Normative Aging Study; NHANES III, Third National Health and Nutrition Examination Survey; NHIRD, National Health Insurance Research Database; NHS, Nurses’ Health Study; ${\mathrm{NO}}_2$ nitrogen dioxides; ${\mathrm{NO}}_{\mathrm{x}}$, nitrogen oxides; NOMAS, Northern Manhattan Study; NPHS, National Population Health Survey; NSHAP, National Social Health and Aging Study; PM, particulate matter; ${\mathrm{PM}}_{2.5}$, particulate matter with an aerodynamic $\text{diameter}\le 2.5\text{micrometers}$; ${\mathrm{PM}}_{10}$, particulate matter with an aerodynamic $\text{diameter}\le 10\text{micrometers}$; ${\mathrm{PM}}_{2.5–10}$, particulate matter with an aerodynamic diameter between 2.5 and 10 micrometers; QICDSS, Québec Integrated Chronic Disease Surveillance System; REGARDS, REasons for Geographic and Racial Differences in Stroke; SALIA, Study on the Influence of Air Pollution on Lung Function, Inflammation, and Aging; SALSA, Sacramento Area Latino Study on Aging; SES, socioeconomic status; SNAC-K, Swedish National Study of Aging and Care in Kungsholmen; TIGER, Taiwan Institute for Geriatric Epidemiological Research; TLSA, Taiwanese Longitudinal Study on Aging; WHICAP, Washington Heights-Inwood Community Aging Project; WHIMS-ECHO, Women’s Health Initiative Memory Study of the Epidemiology of Cognitive Health Outcomes; WHIMS-MRI, Women’s Health Initiative Memory Study Magnetic Resonance Imaging Study; WHISCA, Women’s Health Initiative Study of Cognitive Aging; WISH, Women’s Isoflavone Soy Health; ZJMPHS, Zhejiang Major Public Health Surveillance.

^aStudies that received a check mark for the study strength category were not found to have any substantial limitations in those categories. Substantial limitations in categories without a check mark are explained in the column farthest to the right.

^bStudy bias assessment pertains only to exposure-outcome associations that were unique to the sample population.