Abstract
Exposure to particulate matter is associated with adverse health outcomes such as cardiovascular and neurological diseases. However, there are few intervention studies that have examined short-term changes in air particulate exposure and cognitive outcomes. Data from 119 participants were analyzed in the Home Air Filtration for Traffic-Related Air Pollution (HAFTRAP) study, a pragmatic randomized crossover trial. Participants were randomized to receive a high efficiency particulate arrestance (HEPA) air purifier for one month, a washout period of one month, then a sham unit for one month or vice versa. Time to complete Trail Making Test – Parts A and B were recorded at the beginning and end of each intervention period. Although there was no significant overall difference in completion times of the Trail Making Tests between HEPA and sham filtration, age was a significant moderator (test for interaction p = 0.02). Participants 40 years or older with HEPA filtration completed Part B 12% significantly faster than participants who had sham filtration in the preceding month (54.0 versus 61.4 s, ratio of means = 0.88, p = 0.02). No significant reduction in completion time was observed for participants < 40 years old. Among older healthy adults, there was an improvement in cognition following one month of in-home HEPA filtration. Further research is needed on the short-term effects of air pollution among individuals with some level of cognitive impairment.
Keywords: Air pollution, Particulate matter, Cognitive outcome, Air filtration
Subject terms: Diseases, Environmental sciences, Health care, Medical research, Neuroscience, Risk factors
Introduction
Living or working near highways and dense traffic has been linked to increased mortality and morbidity in adults via multiple pathways, including respiratory illness and cardiovascular disease1. It has also been associated with neurological outcomes, such as Alzheimer’s and Parkinson’s diseases2. Air pollution near highways is a mixture of particles, such as ultrafine particles (UFP, ≤ 0.1 micrometers in aerodynamic diameter) and black carbon; and gasses, such as nitrogen dioxide3. Exposure to particulate matter (PM) and other air pollution in urban areas is largely due to roadway emissions and indoor activities such as cooking4, exposures that can be difficult to avoid. High efficiency particulate arrestance (HEPA) air filtration systems are one approach to reducing exposure to PM5,6.
Previous studies have reported that highway-related PM is associated with adverse cognitive outcomes. A randomized crossover trial that assessed PM concentrations in cars showed worse ability to multitask and react to other cars on the road when the air filter was not reducing concentrations of UFP and other PM7. Short-term observational exposure studies have also reported that cognitive outcomes were associated with higher concentrations of PM2.5 in both young adult and elderly populations8,9.
To date, few studies have examined the potential benefit of in-home air filtration units that reduce highway-related PM on cognitive outcomes. As air purifiers are increasingly being used and recommended for homeowners10 to reduce a wide range of PM11, it is of interest to examine whether these units are capable of improving cognitive function for residents living near highways. The aim of this secondary outcome analysis of a pragmatic randomized crossover trial was to assess whether there was a benefit to cognitive function from HEPA air filtration for urban-dwelling, near-highway residents. Assessment of cognitive function was a secondary outcome in the trial whose primary aim was reduction in blood pressure12. The study methods have been previously published13 and the trial was registered on ClinicalTrials.gov (NCT04279249) on February 19, 2020. The trial received approval from the UConn Health Institutional Review Board Human Subjects Protection Program and was conducted according to the Declaration of Helsinki. All participants provided written informed consent.
Methods
Study participants
The Home Air Filtration for Traffic-Related Air Pollution (HAFTRAP) trial12 recruited participants through word of mouth and door-to-door canvassing, including outreach by community-based organizations in the neighborhoods. The trial enrolled individuals who were 30 years of age or older, lived full time in residences within 200 m of highways in Somerville, Massachusetts, had the cognitive capacity to fill out questionnaires, and spoke English or Spanish. The trial excluded individuals who were taking anti-hypertensive medications or had a history of major cardiovascular events. Individuals were also excluded if they currently smoked/vaped or allowed indoor smoking/vaping, because air purifiers have limited efficacy against these indoor sources. Additionally, participants were not enrolled if they had occupational or regular exposures to traffic pollution outside of the home, or significant combustion sources inside the home, other than cooking. Participants were enrolled between September and April, 2020–2024. The trial sought to enroll participants in cooler months when near highway concentrations of UFP tend to be higher14.
Participant homes were randomized in a blinded manner to 30 days of either HEPA or sham filtration, with air purifiers placed in the living room and bedroom, followed by a 30-day washout period, and then a subsequent 30-day period of the alternative intervention. Air purifiers were running virtually all the time in nearly all participants’ living room and bedroom during the preceding 30 days, and confirmed by HOBO Plug Load Data Loggers in a subset of 45 homes15. In the subset of 19 homes that had air monitoring, HEPA filtration reduced indoor PM2.5 concentration by 52% (mean 2.5 vs. 5.2 µg/m3) and indoor UFP by 32% (mean 4706 vs. 6925 particles/cm3) in comparison to sham filtration12. Figure 1 summarizes the pattern of PM2.5 and PNC concentrations over a 24-hour period.
Fig. 1.
Pattern of PM2.5 and PNC concentrations over a 24-hour period during sham and HEPA filtration. (A) PM2.5 concentrations; (B) PNC concentrations. Hourly arithmetic means with 95% confidence intervals, where each hour represents the mean of all recorded measurements within that period of time.
Trail making test
Participants completed the Trail Making Test, which is used to assess cognitive function and has been shown to be effective in quantifying cognitive impairment in healthy adults16 over short time periods17. Participants completed the test in the early morning at their home at the beginning and end of each intervention period, resulting in the test being completed four times by each participant. Tests were administered in-person by the trial manager who was not blind to the type of filtration. Participants were timed for sequentially connecting numbers (Part A) and sequentially connecting alternating numbers and letters (Part B). Part A of the Trail Making Test assesses visual memory and motor speed skills, while Part B assesses executive function and mental flexibility18. For Part A, a completion time of 29 s is considered average and > 78 s is deficient. For Part B, a completion time of 75 s is considered average and > 273 s is deficient19.
Statistical analyses
Over-dispersed Poisson regression models were used to compare the Trail Making Test – Part A and Part B completion times between the HEPA and sham filtration groups at the end of the intervention periods, as time was considered a count variable and the distribution of times were right-skewed (Fig. 2). The model included sequence and period effects and was adjusted for the corresponding Trail Making Test completion time at the start of each intervention period. Results were also adjusted for number of hours per day spent indoors at home a week prior to the Trail Making Test, and Perceived Stress Scale (PSS-4) score and outdoor temperature at the time of completing the Trail Making Test. Adjusting the results for the number of hours per day spent indoors at home accounted for some participants spending more time inside the home and thus receiving potentially more benefit from air purification. Perceived Stress Scale (PSS-4) scores were included in the models as perceived stress has been linked to worse cognitive outcomes among healthy younger and older adults20,21. Similarly, outdoor temperature has been associated with a significant effect on scores for Part A of the Trail Making Test22.
Fig. 2.
Distribution of Trail Making Test – Part A and Part B completion times at the end of the intervention periods by age category. (A) Part A < 40 years (N = 138); (B) Part A ≥ 40 years (N = 100); (C) Part B < 40 years (N = 138); (D) Part B ≥ 40 years (N = 100). Each bar shows the number of tests completed within that time interval (seconds).
The Trail Making Test learning effect was assessed using the first three consecutive Trail Making Test completion times from the 67 participants who were randomly assigned to receive the sham then HEPA sequence. Because these participants received one month of sham filtration first, followed by a one-month washout period, their first three consecutive Trail Making Test results could not be affected by HEPA filtration. Thus, improvements in completion times should primarily due to retaking the test rather than filtration. These 67 participants’ Trail Making Test – Part A and Part B completion times were compared across the three timepoints using over-dispersed Poisson regression models.
As it was previously shown that performance on the Trail Making Test decreases with increasing age19, as well as reported in a systematic review that a general decline in cognition due to PM exposure begins at age 4023, the moderating effect of age was assessed by dichotomizing participant’s age as < 40 years versus 40 years or older and a cross-product term was included in the models to assess its significance. The cross-product term consisted of the intervention (HEPA vs. sham) and the dichotomized age (< 40 years versus ≥ 40 years).
All statistical analyses were carried out using SAS 9.4 (SAS Institute Inc., Cary, NC), and results with p-values < 0.05 were deemed statistically significant.
Results
Of the 156 participants enrolled in the trial, 37 did not complete the Trail Making Test at all four home visits; 2 moved outside the study area, 1 had a phone survey, 23 had paper forms misplaced, and 11 opted not to complete the Trail Making Test at one or more of the home visits. The remaining 119 participants had complete data for the Trail Making Test at all four home visits and are included in the analyses. There were no appreciable differences in participant characteristics between the 26 who are excluded for administrative reasons and the 119 who are included in the analyses (Table 1). However, the 11 participants who opted not to complete the Trail Making Test were generally older, less educated, and more likely to be unemployed, which may explain their longer Trail Making Test completion times.
Table 1.
Characteristics of participants at trial entry.
| Administrative (N = 26) |
Incomplete (N = 11) |
Analyzed (N = 119) |
|
|---|---|---|---|
| Age in years, mean (sd) | 41.5 (10.9) | 48.0 (15.0) | 40.8 (9.4) |
|
Age category, n (%) < 40 years 40 years or older |
14 (53.8) 12 (46.2) |
2 (18.2) 9 (81.8) |
69 (58.0) 50 (42.0) |
|
Sex, n (%) Male Female |
10 (38.5) 16 (61.5) |
3 (27.3) 8 (72.7) |
50 (42.0) 69 (58.0) |
|
Ethnicity and race, n (%) Hispanic White, non-Hispanic Black, non-Hispanic Asian, non-Hispanic |
5 (19.2) 18 (69.2) 1 (3.9) 2 (7.7) |
3 (27.3) 8 (72.7) 0 (5.0) 0 (5.0) |
21 (17.6) 81 (68.1) 7 (5.9) 10 (8.4) |
|
Highest level of education, n (%) Grade or high school Some college College or university degree Graduate degree |
5 (19.2) 1 (3.9) 7 (26.9) 13 (50.0) |
2 (18.2) 2 (18.2) 5 (45.4) 2 (18.2) |
11 (9.2) 15 (12.6) 31 (26.1) 62 (52.1) |
|
Work status, n (%) Unemployed Part-time working Full-time working |
2 (7.7) 6 (23.1) 18 (69.2) |
6 (54.5) 1 (9.1) 4 (36.4) |
19 (16.0) 12 (10.1) 88 (73.9) |
|
Total annual household income, n (%) < $48,000 $48,000 to $84,999 $85,000 or greater Declined to answer |
0 (0.0) 1 (3.8) 19 (73.1) 6 (23.1 |
1 (9.1) 1 (9.1) 5 (45.4) 4 (36.4) |
10 (8.4) 17 (14.3) 74 (62.2) 18 (15.1) |
|
Weight status, n (%) Healthy Overweight Obesity |
9 (34.6) 8 (30.8) 9 (34.6) |
5 (45.4) 4 (36.4) 2 (18.2) |
52 (43.7) 36 (30.2) 31 (26.1) |
| Time spent inside home (hours per day), mean (sd) | 18.0 (3.3) | 17.3 (3.5) | 19.1 (3.6) |
| Perceived Stress Scale (PSS-4), mean (sd) | 4.6 (3.6) | 4.1 (2.9) | 3.2 (2.6) |
| Outdoor temperature in Fahrenheit, mean (sd) | 45.1 (8.3) | 47.4 (12.8) | 39.8 (12.8) |
| Trail Making Test – Part A (seconds), mean (sd) | ----- | 49.3 (49.8) | 24.3 (12.6) |
| Trail Making Test – Part B (seconds), mean (sd) | ----- | 118.6 (94.8) | 70.7 (42.9) |
As all participants received both HEPA and sham filtration in a crossover manner, the 119 participants are included twice in the analyses, once in the HEPA group and once in the sham group. Characteristics of younger (< 40 years) and older (≥ 40 years) participants are shown in Table 2. The difference in mean age was almost 15 years (34.5 versus 49.4 years). Older participants were generally less educated, were less likely to work full-time, more likely to be female, and to have obesity. Although the mean Trail Making Test completion time for older participants was 4 s longer for Part A and 14 s longer for Part B, the mean times at the start of the intervention period were within the range of adults with normal cognitive function16,24.
Table 2.
Characteristics of analyzed participants at the start of the intervention period by age category.
| < 40 years (N = 138) |
40 years or older (N = 100) |
|
|---|---|---|
|
Randomized to sequence, n (%) HEPA then sham filtrationSham then HEPA filtration |
62 (44.9) 76 (55.1) |
42 (42.0) 58 (58.0) |
| Age in years, mean (sd) | 34.5 (2.8) | 49.4 (8.4) |
|
Sex, n (%) Male Female |
66 (47.8) 72 (52.2) |
34 (34.0) 66 (66.0) |
|
Ethnicity and race, n (%) Hispanic White, non-Hispanic Black, non-Hispanic Asian, non-Hispanic |
28 (20.3) 84 (60.9) 10 (7.2) 16 (11.6) |
14 (14.0) 78 (78.0) 4 (4.0) 4 (4.0) |
|
Highest level of education, n (%) Grade or high school Some college College or university degree Graduate degree |
10 (7.2) 6 (4.4) 46 (33.3) 76 (55.1) |
12 (12.0) 24 (25.0) 16 (16.0) 48 (48.0) |
|
Work status, n (%) Unemployed Part-time working Full-time working |
14 (10.1) 8 (5.8) 116 (84.1) |
24 (24.0) 16 (15.0) 60 (60.0) |
|
Total annual household income, n (%) < $48,000 $48,000 to $84,999 $85,000 or greater Declined to answer |
8 (5.8) 12 (8.7) 98 (71.0) 20 (14.5) |
12 (12.0) 22 (22.0) 50 (50.0) 16 (16.0) |
|
Weight status, n (%) Healthy Overweight Obesity |
74 (53.6) 38 (27.6) 26 (18.8) |
30 (30.0) 34 (34.0) 36 (36.0) |
| Time spent inside home (hours per day), mean (sd) | 18.9 (3.8) | 18.7 (3.5) |
| Perceived Stress Scale (PSS-4), mean (sd) | 3.2 (2.9) | 2.9 (2.7) |
| Outdoor temperature in Fahrenheit, mean (sd) | 43.6 (13.2) | 44.3 (13.9) |
| Trail Making Test – Part A (seconds), mean (sd) | 21.2 (9.1) | 25.2 (16.2) |
| Trail Making Test – Part B (seconds), mean (sd) | 58.3 (28.9) | 72.7 (50.0) |
Mean completion times at the end of the intervention period for Parts A and B of the Trail Making Test between HEPA and sham filtration are shown in Table 3. No significant differences between HEPA and sham filtration were observed for Trail Making Test – Part A, and the mean completion times of approximately 20 s were similar between the two filtration groups and between younger and older participants (Fig. 3).
Table 3.
Trail Making Test – Part A and Part B completion times at the end of the intervention period.
| Part A (seconds) | NHEPA, NSham | HEPA | Sham | Ratio of Means |
P-value |
|---|---|---|---|---|---|
| mean (se) | mean (se) | (95% CI) | |||
| Overall | 119, 119 | 20.3 (0.5) | 19.7 (0.5) |
1.03 (0.96, 1.10) |
0.38 |
| < 40 years of age | 69, 69 | 19.5 (0.6) | 18.7 (0.6) |
1.04 (0.95, 1.15) |
0.34 |
| 40 years or older | 50, 50 | 21.4 (0.8) | 21.2 (0.8) |
1.01 (0.92, 1.11) |
0.82 |
| Part B (seconds) | NHEPA, NSham | HEPA | Sham | Ratio of Means |
P-value |
|---|---|---|---|---|---|
| mean (se) | mean (se) | (95% CI) | |||
| Overall | 119, 119 | 53.6 (1.6) | 55.8 (1.6) |
0.96 (0.89, 1.04) |
0.33 |
| < 40 years of age | 69, 69 | 53.7 (2.0) | 51.4 (2.0) |
1.04 (0.94, 1.16) |
0.43 |
| 40 years or older | 50, 50 | 54.0 (2.4) | 61.4 (2.4) |
0.88 (0.79, 0.98) |
0.02 |
Results were adjusted for the corresponding Trail Making Test completion time at the start of each intervention period. Results were also adjusted for number of hours per day spent indoors at home a week prior to the Trail Making Test, and Perceived Stress Scale (PSS-4) score and outdoor temperature at the time of completing the Trail Making Test.
Fig. 3.
Comparison of Trail Making Test – Part A and Part B completion times at the end of the intervention periods between HEPA and sham filtration. (A) Trail Making Test – Part A; (B) Trail Making Test – Part B. Means with 95% confidence intervals of completion times between HEPA and sham filtration for younger (< 40 years) and older (≥ 40 years) participants. A significant benefit was only observed among older participants for Trail Making Test – Part B. No significant benefit for younger participants and none for Trail Making Test – Part A.
For Trail Making Test – Part B, the overall reduction in mean completion times between HEPA and sham filtration did not reach statistical significance but was significantly moderated by age (test for interaction p = 0.02, Fig. 3). Participants 40 years or older completed Part B 12% significantly faster after a month of HEPA filtration, on average, than participants who had experienced sham filtration (54.0 versus 61.4 s, ratio of means = 0.88, p = 0.02). Individual changes in Part B completion times during the HEPA and sham periods are displayed in Fig. 4. A greater percentage of faster completion times was observed among participants who had HEPA filtration (Fig. 4A). No significant reduction in completion time was observed for younger participants.
Fig. 4.
Individual changes in Trail Making Test – Part B completion time during the HEPA and sham filtration periods among older (≥ 40 years) participants. (A) HEPA filtration; (B) Sham filtration. Individual change (in seconds) = completion time at the end of intervention period minus completion time at the start of the intervention period. Bars below zero indicate a faster completion time and bars above zero indicate a slower completion time. Percentages below zero are the proportion of participants who had a faster completion time and percentages above zero are the proportion of participants who had a slower completion time. A greater percentage of faster completion times was observed among participants who had HEPA filtration (Fig. 4A).
As expected, the Trail Making Test had a learning effect among the 67 participants who were randomly assigned to receive the sham then HEPA sequence. For both Part A and for Part B, these participants’ completion times significantly improved with each subsequent visit; mean completion times for Part A were 24.4, 22.8, and 20.9 s, respectively and mean completion times for Part B were 70.0, 62.4, and 57.8 s, respectively.
Discussion
In this secondary outcome analysis of a pragmatic randomized crossover trial, with no restrictions on participants’ daily activities, a statistically significant improvement in cognitive performance on Part B of the Trail Making Test was observed for participants 40 years of age or older. This test assesses executive function and mental flexibility, and the effect was observed after a month of HEPA filtration compared to sham filtration. Participants 40 years or older completed Part B 12% faster after a month of HEPA compared to a month of sham filtration.
Other crossover trials of air filtration that examined the effect of air pollution on cognition have also reported that higher exposure to particulate matter was associated with worse executive function and attention switching7,25,26. These studies used different cognitive tests for these domains, namely the CANTAB test and Strategic Management Simulation. Studies have found no difference in visual memory or motor speed27,28 when using the psychomotor vigilance task and the simple reaction time test, the domains of cognition that was assessed in Trail Making Test – Part A.
There is neurobiological evidence that particulate matter exposure may reduce white matter in the brain29, specifically in the frontal and temporal lobes30. These lobes are responsible for the mental flexibility and executive function skills assessed by Part B of the Trail Making Test31. Thus, our finding of benefit of HEPA filtration on Part B is consistent with underlying neurobiological processes. Additionally, our result of benefit observed among participants 40 years or older is consistent with reports that the cognitive effects of air pollution are more pronounced beginning around age 4023.
Our results are also largely consistent with other intervention studies that observed the effects of reducing particulate matter exposure on cognitive outcomes among healthy adults. A randomized crossover trial among healthy office workers of a similar age range to ours reported that HEPA filtration improved executive functioning, with no differences between HEPA and sham filtration for visual or working memory32. Another randomized crossover trial comparing HEPA and sham filtration was performed among college-aged students. Students were provided air purifiers to use while they slept and were then given a cognitive test in the morning. Sham filtration was associated with slower memory, worse executive function, and lower global cognition25. Although the latter study was with younger people than ours, both crossover trials provide evidence of a possible benefit of HEPA filtration on cognition among healthy adults.
Our analysis has several strengths and limitations. Despite the assessment of age as a moderating effect being post hoc, a strength of our analysis is that the data arose from a crossover trial design in which participants were compared to themselves, eliminating time-invariant confounding. Our analysis also controlled time-varying confounders, such as time spent inside the home, ambient temperature and level of stress, which can affect results.
One limitation to the use of the Trail Making Test to assess cognitive function is that it has a learning effect, whereby participants’ completion times improve simply from retaking the test multiple times33, as in our crossover trial. Effects of this sort have been shown to be more common in younger adults34 and more common in short-term periods similar to the time-frame of our intervention periods17,35. Although the Trail Making Test has a learning effect, the improvement in completion times would be expected to be similar between the participants randomly assigned to the sham then HEPA sequence and those randomly assigned to the HEPA then sham sequence. There is also the possibility that the unblinded trial manager who administered the Trail Making Test may have affected the participant’s completion time by unconsciously motivating the participant. However, because the Trail Making Test is a standardized, objective measure of cognitive function that was completed by the participant who was blind to type of filtration, assessor bias was minimized.
Another limitation was the use of sham filtration which could have reduced UFP exposure6 through diffusional deposition, resulting in concentrations of UFP being reduced by air movement alone36. Reducing participants’ UFP exposure during the sham filtration period could have attenuated the effect between the HEPA and sham intervention periods. Our results are also limited in terms of generalizability as the sample of participants were predominantly of White race and generally had higher levels of education and household income. In addition, as none of the participants had preexisting cognitive impairments, our analysis is not relevant to the effectiveness of HEPA filtration among cognitively impaired individuals.
Conclusions
Our results suggest that, among older healthy adults living near highways in the Northeastern US, there was an improvement in cognition following one month of in-home HEPA filtration. Despite the strength of our trial design, there is a need for further research that employs methods with strong causal inference of short-term exposure to air particulates and cognitive outcomes, especially among individuals who have cognitive impairment.
Acknowledgements
We would like to thank our project manager, Teresa Vazquez-Dodero for administering the trail making tests and the trial participants for their time and being receptive to in-home visits.
Author contributions
NP, ME, and DB were responsible for drafting the manuscript. HG scored and prepared the Trail Making Tests for analysis. ME was responsible for the analysis of the data. RF contributed to the interpretation of the results.
Funding
NIEHS. Grant ID: R01 ES030289 and the School of Medicine at the University of Connecticut.
Data availability
The data used in this study is available upon request. Please contact the corresponding author Dr. Doug Brugge at [brugge@uchc.edu](mailto: brugge@uchc.edu) .
Declarations
Competing interests
The authors declare no competing interests.
Conflict of interest
None of the authors have relationships with industry. The air purifiers were custom adapted by the manufacturer, Austin Air, and sold at a discount based on bulk purchase. The manufacturer was not involved in any way in the design, conduct or analysis.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Nicholas Pellegrino and Misha Eliasziw contributed equally to this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data used in this study is available upon request. Please contact the corresponding author Dr. Doug Brugge at [brugge@uchc.edu](mailto: brugge@uchc.edu) .