Outdoor green space exposure and brain health measures related to Alzheimer's disease: a rapid review.

OBJECTIVES: Summarise studies of outdoor green space exposure and brain health measures related to Alzheimer's disease and related disorders (ADRD), and determine scientific gaps for future research.
DESIGN: Rapid review of primary research studies. METHODS AND OUTCOMES: PubMed, Embase and Web of Science Core Collection were searched for articles meeting the criteria published on/before 13 February 2020. The review excluded papers not in English, focused on transient states (eg, mental fatigue) or not using individual-level measures of brain health (eg, average school test scores). Brain health measures of interest included cognitive function, clinical diagnosis of cognitive impairment/dementia/ADRD and brain biomarkers such as those from MRI, measures typically associated with ADRD risk and disease progression.
RESULTS: Twenty-two papers were published from 2012 to 2020, 36% on <18 years old, 32% on 18-64 years old and 59% on ≥65 years old. Sixty-four per cent defined green space based on the Normalised Difference Vegetation Index ('greenness'/healthy vegetation) and 68% focused on cognitive measures of brain health (eg, memory). Seventeen studies (77%) found green space-brain health associations (14 positive, 4 inverse). Greater greenness/green space was positively associated various cognitive domains in 10 studies and with MRI outcomes (regional brain volumes, cortical thickness, amygdala integrity) in three studies. Greater neighbourhood greenness was associated with lower odds/risk of cognitive impairment/ADRD in some studies but increased odds/risk in others (n=4 studies).
CONCLUSIONS: Published studies suggest positive green space-brain health associations across the life course, but the methods and cohorts were limited and heterogeneous. Future research using racially/ethnically and geographically diverse cohorts, life course methods and more specific green space and brain health measures (eg, time spent in green spaces, ADRD biomarkers) will strengthen evidence for causal associations. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Three major databases covering biomedical, psychological, environmental and social science topics and a range of keywords were searched to find pertinent studies regarding associations between green space exposure and Alzheimer’s disease and related disorders brain health measures.

Published literature reviews on green space and health and reference lists from the final sample of papers were reviewed to help ensure pertinent papers were included.

This study was limited to a single reviewer and thus, the methods used to search, screen, select and chart the final sample of papers could not be duplicated/adjudicated by additional reviewers.

As a rapid review, this study was not aimed at providing a quantitative evaluation of the evidence or risk of bias, and may have missed papers that would have been ascertained if additional reviewers were available.

Introduction

Nature contact involves time spent in green spaces (eg, gardens, parks, forests) and blue spaces (eg, lakes, rivers) where people live, work and play. Preliminary studies suggest associations between nature contact and health including reductions in depression, anxiety and cardiovascular risk factors; improved attention and mood; and increased physical activity.1 Studies also suggest associations with brain health across the life course.2–8 For instance, greater neighbourhood greenness (ie, healthy vegetation) has been associated with lower odds of Alzheimer’s disease (AD) in older adults.9

AD and related disorders (ADRD) affect approximately 50 million people worldwide, and 15% of older adults have mild cognitive impairment, a frequent antecedent to dementia.10 11 Older age, lower educational attainment and genetics (eg, apolipoprotein E (APOE) ε4 allele carriers) are some of the strongest predictors of AD risk and late-life cognitive decline.12 Clinicians diagnose AD using biomarkers and/or cognitive assessments. Diagnostic biomarkers include cerebrospinal fluid (CSF) or positron emission (PET) scan biomarkers measuring brain amyloid beta and phosphorylated tau, the proteins responsible for AD neuropathology (ie, plaques and tangles).13 14 Cognitive tests for AD typically evaluate memory of personal events (ie, episodic memory), the hallmark cognitive domain affected early in the disease course.15 Episodic memory problems are correlated with atrophy of the hippocampus, and thus, MRI brain biomarkers such as hippocampal atrophy help support AD diagnosis and predict AD incidence and disease progression.16 Other dementia disorders typically affect different cognitive domains/brain regions in the early stages of disease, and later stages of ADRD can affect additional cognitive domains and brain regions.15

The psychological and financial burden of ADRD on patients and families is substantial.17 18 Healthcare systems are ill prepared to deal with the increase in ADRD prevalence accompanying the rapidly rising population of older adults,19 and no effective treatments are currently available. Therefore, an accumulating body of research has focused on individual-level and community-level interventions that may be help prevent or delay ADRD. Provided there is supporting evidence, neighbourhood green space is one such community-level feature that may be promoted to improve lifelong brain health. Healthy brain development during childhood and maintenance of brain health throughout adulthood, assisted by living near health-enhancing green spaces, may help reduce ADRD risk.

Green space exposure may benefit brain health through a number of pathways.1 20 They provide enriching, physical activity promoting and stress reducing environments that consequently may be associated with better brain health by affecting cerebral blood flow, angiogenesis, vascular integrity, cell proliferation/survival, vascular dysregulation and/or inflammation.21–25 Green space exposure may reduce stress and mental fatigue and improve attention, consistent with the stress recovery theory and attention restoration theory.26–28 Studies are available to support both theories. For instance, living within one mile of green spaces and visiting green spaces have been associated with experiencing less stress,29 and gardening has been found to reduce levels of salivary cortisol, a stress hormone.30 In adults, mood, restoration and sustained attention were improved after participating in a nature walk intervention in urban and rural locales.28 These psychological benefits over the long term may additionally benefit mental health (eg, anxiety, depression), factors associated with brain health including ADRD risk.31 Microbial and antigenic exposures from nature contact,32 especially during childhood, may affect lifelong immune function and contribute to healthy microbiomes, which have been associated with mental health and AD.33–35 Green spaces provide areas for recreational exercise. Exposure and access to natural places have been associated with greater physical activity in children through older adults,36 37 and obtaining greater physical activity has been associated with reduced brain atrophy, cognitive decline and ADRD risk.38 39 Natural areas provide spaces for social gathering and engagement.40 Higher levels of social engagement have been associated with better cognitive function and reduced AD risk.41 42 Lastly, natural areas and parks have been associated with lower levels of harmful air pollutants, including particular matter ≤10µm in size (PM10) and nitrogen dioxide (NO2)43 44 that have been associated with worse cognition and greater ADRD risk.45 The mechanisms by which air pollution affects the brain have been hypothesised to be direct and/or indirect (eg, systemic inflammation, adsorbed compounds).46

The budding and cross-disciplinary field of research on green spaces and ADRD/brain health will benefit from a review of pertinent studies spanning multiple disciplines. Literature used to inform primary research tends to be siloed to a researcher’s area of expertise or based on limited or discipline-specific search terms. Given the nascent state of green space and ADRD-related brain health research and the lack of published literature reviews focused on the topic, this rapid review employed scoping aims. Rapid reviews are increasingly used in research to address the need for more readily available summaries of available evidence that cannot be achieved through the lengthy and resource-intensive process of systematic reviews.47 Scoping reviews are useful in summarising new topics of research, findings for a broader set of health outcomes, or topics that may not have enough evidence amassed to assess the weight of evidence or risk of bias.47–49

The number of studies on green space and health has risen dramatically in the last decade,50 but it remains unclear how many studied brain health outcomes. Therefore, consistent with the major goals of a scoping review,48 49 51 52 this rapid review aimed: (1) to summarise the extant literature on green space-brain health associations across the life course, potentially providing impetus for future systematic reviews and (2) to identify knowledge gaps to inform future research. The primary intent was to identify and describe current evidence for benefits to cognition and brain structure/function due to green space exposure. These benefits may develop and persist in early- and mid-life to reduce ADRD risk in late life.

Methods

Patient and public involvement

Patients and the public were not involved as this study focuses on a review of published papers with no analysis of participant data.

Identification and study selection

A single reviewer was available for this study. On 13 February 2020, PubMed, Web of Science Core Collection and Embase were queried for the following keywords: ‘greenspace or green space or greenness or parks or park or park space or parkspace’ and ‘cognition or cognitive or memory or brain ageing or Alzheimer or Alzheimer’s or dementia or cognitive impairment’. To help ensure the 13 February review did not miss pertinent papers, a second search of the three databases was performed on 18 July 2020, for the following keywords: ‘neighbourhood environment or wilderness or greenery or natural space or natural environment or public garden or recreational resource or Normalised Difference Vegetation Index (NDVI) or built environment or open space or woodland’ and ‘brain volume or brain atrophy or neurodegenerative disease or Alzheimer biomarker or cognition or cognitive or memory or brain ageing or Alzheimer or Alzheimer’s or dementia or cognitive impairment’. The keywords searched reflected the brain health measures of interest that are typically associated with ADRD risk/disease progression, including cognitive function, clinical diagnosis of cognitive impairment/dementia/ADRD and biomarkers such as those from brain imaging (eg, MRI).

The 18 July 2020 search was restricted to papers published on or before 13 February, 2020, to be consistent with the original search. A limitation of the 18 July 2020 search was the restriction to a search of titles in Web of Science. A full-text search led to 8574 papers that could not be feasibly reviewed based on available time and resources (ie, this is a rapid review). Of note, the final list of included papers from the February 13 search was ascertained either from the search of PubMed and Embase or the review of resulting titles from the search of full texts in Web of Science (ie, not from a full text review of papers in Web of Science). This suggests that the July search of titles in Web of Science was unlikely to have missed pertinent papers, but the possibility remains. A detailed description of the search strategy is provided in online supplemental figure 1.

Titles were screened for topics definitely or possibly related to green space and ADRD-related brain health. Titles potentially related were included in the abstract review (eg, green space and child development, neighbourhood environment and AD, built environments and ageing, outdoors and mental health). After review, abstracts that moved on to full-text review had exposures/outcomes directly pertinent to this study, focused on associations between green space and other measures but mentioned brain health measures as covariates, or seemed possibly relevant by including closely related exposures or outcomes (eg, mental health, frailty, built environment, nature contact). Full texts included in the final sample reported associations between green space exposure and brain health outcomes in the main text or online supplemental file.

Articles were excluded if they: (1) were not in English; (2) were not primary research studies; (3) were focused on indoor green space/views; (4) used virtual reality to simulate green spaces; (5) were ecological studies (eg, average school test scores); (6) were focused on attention restoration or mental fatigue (transient states) or (7) centred on green space activities such as gardening without an adequate control/comparison group to sufficiently capture green space as the main exposure. Reference lists from the final sample and published green space-health reviews were reviewed to identify other studies meeting the eligibility criteria.1–8

Charting and summarising the data

Papers were described by study design, location, age groups, green space and brain health measures and definitions, statistical methods and main findings (these data were charted into online supplemental tables 1–4). Key study elements were tabulated separately for three major age groups: children (0–17 years), adults (18–64 years) and older adults (≥65 years). Findings were stratified by age because while studies of children focus on the critical period of childhood development, studies of 18–64 years old focus on working adults and studies of ≥65 years old focus on retirement-age individuals. Green space exposures and brain health can differ substantially during these life stages. Results (positive, inverse, null associations) were summarised according to age groups, green space measures, brain health measures and examined green space-brain health associations to characterise the scope of the evidence to date.

Results

Overall study characteristics

The final sample included 22 papers (figure 1).9 53–73 Post hoc additions to the final sample, published on or before 13 February 2020, included one paper previously known by the author53 and one paper identified from the final sample reference lists.73 Tables 1–4 and online supplemental tables 1–4 summarise study characteristics and findings. Eight-two per cent (n=18)9 54–58 60–64 66–69 71–73 of studies were published on/after 2017 (range: 2012–2020). Seven studies (32%) were in the UK, four (18%) in China, three in Spain (14%), two each (9%) in the USA and Canada and one each (4%) in Bulgaria, Germany, New Zealand and multiple regions (Spain, UK, the Netherlands) (figure 2). Eight studies (36%) focused on <18 years old (childhood),54 56 63 65–68 70 seven (32%) focused on 18–64 years old (adulthood),53 55 57 60 62 63 72 and 13 (59%) focused on ≥65 years old (older adulthood)9 53 55 58–64 69 71 73 (figure 3). Fourteen studies (64%)9 53–64 68 were based on population-based cohorts or random sampling strategies. Two studies (9%) examined life course associations, both investigating childhood and mid-life park space exposures and cognitive change in late life.63 64

Figure 1

Sample size flow diagram (see online supplemental figure 1 for full details).

Figure 2

Number of studies by country.

Figure 3

Number of studies by age group.

Seventeen studies (77%) found associations (14 positive,9 54–56 60–67 72 73 4 inverse57–60) and 5 (23%) found no associations53 68–71 between greenness/green space and brain health (tables 1–4, figure 4). Twelve studies (55%) reported a combination of positive, inverse and/or null associations.54 55 57 58 60 62–66 72 73 All but one study69 employed multivariable linear or logistic regression accounting for key confounders (ie, age, sex, socioeconomic status (SES)) and 12 (55%)9 53–56 58 59 61 62 64 65 70 used regression methods accounting for data clustering/multilevel data.

Figure 4

Number of studies by green space-brain health association. Cog, cognition; Dx, diagnosis of cognitive impairment/dementia; Greenness, measure of greenness such as Normalised Difference Vegetation Index, % green space, per cent or amount of neighbourhood composed of green space/park space; other green space, time spent in green space, distance to nearest green/park space and/or self-reported measures.

Findings by age group

Children: Five54 56 65–67 of the eight studies54 56 63 65–68 70 found green space-brain health associations in children (five positive, zero inverse) (table 1). Greater neighbourhood greenness/green space was associated with working memory,54 56 attention54 65 and intellectual development67 and with specific brain regions.66 Null associations were found between greater greenness/green space and intelligence,63 alerting,65 orienting,65 executive processing/function,65 68 fluid ability,68 crystallised ability,68 working memory68 and attention.54 65 68 Time spent in green space measured via global positioning system (GPS) tracking was not associated with multiple cognitive domains (eg, visual and verbal memory, processing speed).70

Table 1

Summary of green space-brain health associations by age group

Citation*	Sample size	Population based/ random sample	Location	Children(<18 years)	Adults(18–64 years)	Older adults(≥65 years)
Brown9	249 405	Yes	USA			+
Cherrie63	281	Yes	UK	N	N	+
Cherrie64	281	Yes	UK			+N
Clarke53	949	Yes	USA		N	N
Dadvand65	2593	No	Spain	+N
Dadvand54	987	Yes	Spain	+N
Dadvand66	253	No	Spain	+N
Dzhambov72	112	No	Bulgaria		+N
de Keijzer55	6506	Yes	UK		+N	+N
Flouri56	4758	Yes	UK	+
Hystad57	6658	Yes	Canada		- N
Kuhn73	341	No	Germany			+N
Liao67	1312	No	China	+
Reuben68	1658	Yes	UK	N
Wang69	3544	No	China			N
Ward70	72	No	New Zealand	N
Wu59	2424	Yes	UK			–
Wu58	7505	Yes	UK			- N
Yu71	3240	No	China			N
Yuchi60	678 000	Yes	Canada		+ -	+ -
Zhu61	6994	Yes	China			+
Zijlema62	1628	Yes	Spain, UK, Netherlands		+N	+N
Studies with positive associations				5	4	8
Studies with inverse associations				0	2	3
Studies with null associations				6	6	8
Total studies				8	7	13

*Full list of papers found in online supplemental text 1.

+, positive association; -, inverse association; N, null association.

Adults (18–64 years): Five of the seven studies53 55 57 60 63 72 found green space-brain health associations in adults (four positive,55 60 62 72 two inverse57 60 (table 1). Increased residential distance to natural outdoor environments was associated with longer cognitive test completion times,62 and greater neighbourhood greenness was positively and inversely associated with dementia diagnoses (detailed in ‘older adults’ section below).60 Greater neighbourhood greenness was cross-sectionally associated with better global cognition72 and was associated with slower longitudinal decline on global cognition, reasoning and verbal fluency.55 Additionally, greater neighbourhood green space was associated with greater cortical thickness in the prefrontal cortex, bilateral fusiform gyrus, left precuneus and insula, and right cuneus as measured via MRI.72 Null associations were found between greater neighbourhood greenness/green space or 5-year change in greenness and measures of global cognition,53 72 intelligence,63 reaction time,57 reasoning,57 memory,55 57 72 naming72 and visual attention/executive processing.62 No associations were found between self-reported visits or time spent in natural environments and visual attention/executive processing,62 and no associations were observed between greater greenness and cortical thickness of other brain MRI regions (eg, right cuneus and insula).72 Lastly, inverse associations were found between 5-year change in neighbourhood greenness and reasoning.57

Older adults (≥65 years). Ten of 13 studies9 53 55 58–64 69 71 73 found green space-brain health associations in older adults (eight positive,9 55 60–64 73 three inverse58–60 (table 1). Greater neighbourhood greenness was associated with lower risk of AD,9 non-AD60 and Parkinson’s disease diagnoses60 in some studies, but increased risk of cognitive impairment58 59 and AD diagnoses60 in others. Greater neighbourhood greenness/green space was positively associated with intelligence,63 64 global cognition,55 reasoning,55 verbal fluency55 and visual attention/executive processing.55 62–64 In addition, greater green space (ie, forests) was associated with better amydala integrity measured via MRI.73 Null associations were found between neighbourhood greenness/green space and intelligence,63 64 global cognition,53 69 71 short-term memory55 and visual attention/executive processing.62 Time spent in natural environments was not associated with visual attention/executive processing.62 Lastly, urban green space was not associated with brain integrity measured via MRI.73

Findings by green space measure

Green space definitions included: (1) greenness measured using the NDVI or Enhanced Vegetation Index (EVI)9 54 55 57 60–62 65–69 71 72; (2) tree canopy/cover measured using vegetation continuous fields (VCF)54; (3) neighbourhood percentage green/park space or park area53 56 58 59 63 64 73; (4) time spent in green space (objective or self-reported)62 70; (5) self-reported amount of natural environment near residence62 and (6) distance from residence to natural outdoor environment62 (table 2). Three studies examined more than one green space measure: (1) NDVI and VCF54; (2) NDVI and EVI55; and (3) NDVI, distance to natural outdoor environment, and self-reported green space measures.62 Most studies measured green space in the residential neighbourhood, although a few additionally measured green space surrounding schools and school routes.64 65 No studies examined work area green spaces. NDVI was the most commonly used measure. The boundaries used to define green space exposures varied greatly (eg, 100–1500 m radial buffers around residences, 1000 m buffers around postcode centroids, US Census tracts, 50 m buffers around school route).

Table 2

Summary of green space-brain health associations by green space measure

Citation*	Sample size	Population based/ random sample	Location	Longitudinal green space	Greenness(NDVI, EVI)	Percent/ area park space	Percent green space	Time spent in green space	Distance to natural outdoor environment	Other green space
Brown9	249 405	Yes	USA	No	+
Cherrie63	281	Yes	UK	Yes		+N
Cherrie64	281	Yes	UK	Yes		+N
Clarke53	949	Yes	USA	No		N
Dadvand65	2593	No	Spain	No	+N
Dadvand54	987	Yes	Spain	Yes	+N
Dadvand66	253	No	Spain	Yes	+N
Dzhambov72	112	No	Bulgaria	No	+N
De Keijzer55	6506	Yes	UK	Yes	+N
Flouri56	4758	Yes	UK	No			+
Hystad57	6658	Yes	Canada	Yes	- N
Kuhn73	341	No	Germany	No			+N
Liao67	1312	No	China	No	+
Reuben68	1658	Yes	UK	Yes	N
Wang69	3544	No	China	No	N
Ward70	72	No	New Zealand	No				N
Wu59	2424	Yes	UK	No			–
Wu58	7505	Yes	UK	No			- N
Yu71	3240	No	China	No	N
Yuchi60	678 000	Yes	Canada	Yes	+ -
Zhu61	6994	Yes	China	Yes	+
Zijlema62	1628	Yes	Spain, UK, Netherlands	No	N			N	+	N
Studies with positive associations					9	2	2	0	1	0
Studies with inverse associations					2	0	2	0	0	0
Studies with null associations					10	3	2	2	0	1
Total studies					14	3	4	2	1	1

*Full list of papers found in online supplemental text 1.

-, inverse association; +, positive association; EVI, enhanced vegetation index; N, null association; NDVI, Normalised Difference Vegetation Index.

NDVI: Ten of 14 studies9 54 55 57 60–62 65–69 71 72 using NDVI found associations (nine positive,9 54 55 60 61 65–67 72 two inverse57 60 (table 2). Of the studies with positive findings, one examined MRI brain measures66 and three examined risk/odds of cognitive impairment/dementia.9 60 61 The remaining studies with positive findings focused on various cognitive domains. In studies with inverse associations, 5-year NDVI increase was associated with worse reasoning in 40–69 years old57 and greater greenness was associated with lower risk of non-AD dementia and Parkinson’s disease among 45–84 years old.60

Park space: Two63 64 of three studies on percent/amount of residential park space found positive associations with cognitive change in late life (table 2). These positive associations were restricted to childhood and mid-life park space exposures and cognitive changes from ages 70 to 76. No associations were observed between early-life and mid-life exposures and cognitive changes from ages 11 to 76 or between late-life park space exposure and cognitive changes at any age (11–76 years). The third study found no associations between neighbourhood park area and cognition.53

Other measures: Measures of time spent in green space based on objective GPS tracking70 or self-report62 were not associated with cognition. Positive associations were observed between percentage residential green space derived from land use data and spatial working memory,56 and between distance to the nearest natural outdoor environment and visual attention/executive processing.62 Greater amounts of forest surrounding the residence were associated with greater amygdala integrity, whereas amount of neighbourhood urban green space was not associated with MRI measures of brain integrity.73 Percentage green space and private gardens based on land use data was inversely associated with odds of cognitive impairment/dementia.58 59 Tree canopy/cover (VCF) was not associated with attention in children.54 Lastly, self-reported amount of residential natural environment was not associated with visual attention/executive processing.62

Findings by brain health measure

Fifteen studies (68%) examined cognitive function.53–57 62–65 67–72 A range of cognitive domains were assessed, including but not limited to global cognition, working memory, attention, reasoning, verbal fluency and executive function. Five studies (23%)58 59 61 69 71 used the Mini Mental State Exam, a global cognition screening test, while the remaining used a variety of other instruments. Five studies (23%)9 58–61 examined diagnosis of cognitive impairment or dementia (including AD and Parkinson disease) and three focused on brain MRI.66 72 73 Eight studies (36%)54 55 60 61 63–65 68 used longitudinal data on brain health, but only five (23%)55 60 63–65 actually examined longitudinal changes in brain health (ie, cognitive decline or dementia risk).

Ten studies (45%) found associations between green space and cognition (nine positive,54–56 62–65 67 72 one inverse57) (table 3). Greater greenness/green space was associated with global cognition, working memory, spatial working memory attention, visual attention, reasoning, fluency and measures of intelligence and childhood intellectual development, as delineated in the sections further above. The three studies using brain MRI found positive associations between greenness/green space and certain brain regions,66 cortical thickness72 and amygdala integrity.73 Two studies found positive associations between greenness/green space and AD,9 non-Alzheimer’s dementia60 and Parkinson’s disease60 diagnoses, whereas three found inverse associations with AD60 or cognitive impairment/dementia diagnoses.58 59

Table 3

Summary of green space-brain health associations by brain health measure

Citation*	Sample size	Population based / random sample	Location	Longitudinal brain health measure	Cognition	MRI brain regions	Diagnosis of cognitive impairment/ dementia
Brown9	249 405	Yes	USA	No			+
Cherrie63	281	Yes	UK	Yes	+N
Cherrie64	281	Yes	UK	Yes	+N
Clarke53	949	Yes	USA	No	N
Dadvand65	2593	No	Spain	Yes	+N
Dadvand54	987	Yes	Spain	Yes	+N
Dadvand66	253	No	Spain	No		+N
Dzhambov72	112	No	Bulgaria	No	+	+N
De Keijzer55	6506	Yes	UK	Yes	+N
Flouri56	4758	Yes	UK	No	+
Hystad57	6658	Yes	Canada	No	- N
Kuhn73	341	No	Germany	No		+N
Liao67	1312	No	China	No	+
Reuben68	1658	Yes	UK	Yes	N
Wang69	3544	No	China	No	N
Ward70	72	No	New Zealand	No	N
Wu59	2424	Yes	UK	No			–
Wu58	7505	Yes	UK	No			- N
Yu71	3240	No	China	No	N
Yuchi60	678 000	Yes	Canada	Yes			+ -
Zhu61	6994	Yes	China	Yes			+
Zijlema62	1628	Yes	Spain, UK, Netherlands	No	+N
Studies with positive associations					9	3	3
Studies with inverse associations					1	0	3
Studies with null associations					12	3	1
Total studies					15	3	5

*Full list of papers found in online supplemental text 1.

+, positive association; -, inverse association; N, null association.

Effect modification

Effect modification is variation in the association between an exposure and outcome depending on the value of another factor. Seven55 57 58 61 63 64 67 of 11 studies9 54–58 61 63–65 67 found effect modification (online supplemental table 4). Green space-brain health associations were stronger in/limited to women55 57 63; APOE ε4 non-carriers61 63 and those with lower occupational class,63 higher education levels,55 lower body mass index67 and younger age61 (in study of older adults). Associations also were stronger among residents of conurbations58 (urbanised area comprised of multiple cities/towns), areas with lower traffic accident densities64 and areas of higher deprivation.55 Other studies found no effect modification by neighbourhood SES,9 56 65 sex,64 maternal education,65 residential stability/years in residence,56 race,57 marital status,57 city57 or household income.57

Mediation

Three65 71 72 of seven studies53 55 62 65 67 71 72 suggested mediation, which is the presence of an intermediary variable associated with both the exposure and outcome that potentially explains the causal mechanism linking the two variables (online supplemental table 4). Traffic-related air pollution (elemental carbon in residence) mediated associations between school greenness and working memory and attentiveness in children65 and self-reported physical activity mediated associations between greater residential greenness and global cognition in older adults.71 Associations between greater neighbourhood greenness and better global cognition among middle-aged adults were mediated by lower waist circumference but not by systolic blood pressure, total cholesterol, glucose, air pollution (NO2) or traffic-related noise.72 The other four studies found no mediation of green space-brain health associations by physical activity,53 55 62 social measures (eg, interaction, loneliness),53 perceived mental health,62 traffic noise annoyance,62 worry about air pollution62 or air pollution levels (ie, PM2.5).55

Discussion

Evidence was found for associations between green space exposure measured at various life stages and brain health. Seventy-one per cent of NDVI studies (greenness) found positive associations. Greater neighbourhood greenness/green space was positively associated with multiple cognitive domains, brain regions and lower odds/risk of AD and non-AD dementia. However, some studies found inverse or null associations, few studies were conducted within each major age group, and the studies employed limited and heterogeneous methods and definitions. The remainder of this section focuses on the second aim of the scoping review, which is to identify scientific gaps for future research.

Brain health measures

The diversity of employed brain health measures limits study comparisons. Measures of attention were associated with green space in more than one study,54 62 65 but additional research is needed to confirm these associations. Studies more frequently assessed executive function, attention, and working memory, and fewer examined short-term or long-term memory, language/fluency, processing speed or visuospatial function. The focus on the former cognitive domains may be due to data availability, but also potential hypothesised underlying mechanisms relating green space and brain health, in which green space exposure restores attention and reduces mental fatigue/stress.26–28 Nonetheless, green space exposures may be associated with other cognitive measures reflecting brain regions susceptible to green space-related behaviours/exposures. New studies are needed to assess green space associations with cognitive domains commonly affected in typical and atypical AD presentations, including episodic memory,15 visuospatial processing74 and language.75 These cognitive domains have been associated with physical activity, social engagement and air pollution exposure76–78 and are important to investigate in future studies given the plausible mechanisms relating green spaces and these health behaviours/exposures (as detailed in introduction).

Greater greenness/green space displayed mixed associations (positive/inverse) with diagnoses of cognitive impairment or dementia. The mixed findings may be explained by the employed study methods, as three of the four studies were cross-sectional and none examined or controlled for early-life and mid-life factors beyond educational attainment. With the onset of health problems or cognitive symptoms, individuals may be more likely to move to greener rural and suburban areas where there are assisted living and nursing care residences. Thus, the associations between greater late-life neighbourhood greenness/green space and increased odds/risk of cognitive impairment may be explained by reverse causality/self-selection into greener neighbourhoods in later life. Reverse causality will need to be ruled out in future studies by using more sophisticated study designs and methods (eg, life course, instrumental variables).

Clinical diagnoses may be biased by cultural or education factors that may increase or decrease the chance of receiving a diagnosis irrespective of disease presence. For instance, minorities may be more likely to receive dementia diagnoses if educational and cultural differences are unaccounted for in cognitive testing or if a higher prevalence of comorbidities increases ADRD risk.79 Nevertheless, diagnoses are clinically significant measures of brain health, particularly when made by specialists with expertise in discerning the presence and aetiology of dementia, and thus are useful measures for future green space-brain health research in older adults.

To date, three studies investigated associations between green space and MRI biomarkers, specifically regional brain volumes,66 measures of structural integrity73 and measures of cortical thickness72 obtained from structural MRI. The study of associated brain regions66 used an intensive method of analysis (examining associations for each three-dimensional pixel (voxel) of brain image) that significantly limited the number of confounders included in the multivariable analyses. An alternative to the voxel-wise analysis, which would allow controlling for multiple important confounders, would be to measure brain health/atrophy using regional brain volumes (mm3) and cortical thickness determined through standardised segmentation techniques.80 The findings for associations between greater greenness/green space and greater amygdala integrity and cortical thickness will need to be replicated. Lastly, measures of global brain atrophy from MRI, such as total grey matter volume or ventricular volume, may be a useful addition for future studies under the presumption that green space exposures affect overall brain development and ageing.

Green space measures

This review suggests that NDVI is a valuable measure for future studies of green space and brain health. However, NDVI does not assess tree canopy/cover or other qualities of green spaces (eg, park amenities).20 Future work will need to consistently incorporate quality measures including tree canopy/cover, availability of park amenities (eg, walking trails), and safe walking routes/sidewalks, which will help identify types of green space environments20 most effective at promoting brain health.

Studies measuring percentage of the neighbourhood composed of green space (ie, parks) found positive,56 63 64 73 inverse58 59 and null associations,53 58 63 64 73 warranting additional studies. Compared with NDVI (greenness), percentage green space may better capture access to green spaces. For instance, associations with NDVI measures can be affected by the chosen cut points to define healthy vegetation (eg, NDVI >0.40 or NDVI >0.60), the satellite image used to derive NDVI (affected by season and cloud cover), or green space fragmentation (pockets) that can skew mean NDVI values.20 Green space access may be a stronger predictor of healthy behaviours such as physical activity, particularly among socioeconomically disadvantaged individuals with limited resources and opportunities for exercise.81 Other measures of green space access to should be investigated (eg, number of neighbourhood parks) to determine the strongest predictors of both healthy behaviours and better brain health.

The single study incorporating self-reported measures of green space exposure found no associations.62 Objective green space measures are necessary to suggest target amounts and qualities of green space for interventions, plans and policies. However, self-reported and perceived measures may be useful in tandem with objective measures. Valid and reliable green space questionnaires would minimise burden and data security concerns in attempting to derive objective measures from residential addresses across the life span.

The majority of studies did not measure actual exposure to green spaces (ie, time spent in green spaces).62 70 Travel diaries could be used to assess time spent in green spaces, although compliance in diary completion and misreporting may be an issue.82 Although studies have successfully incorporated GPS to investigate neighbourhood environmental exposures and outcomes including physical activity,83–85 costs, difficulty in recruiting, participant time required and non-compliance can be a hurdle.86 Despite these limitations, GPS and travel diary measures of time spent in green space provide increased specificity of exposure needed to make informed decisions about green space-brain health associations. If individuals live in neighbourhoods with greater access to green space but they do not regularly spend time in those spaces, then associations with brain health observed in prior research have been spurious or biased by residual confounding.

Places for estimating green space exposures may depend on the age group under study, but only two studies measured non-residential exposures.64 65 Green space exposure may occur most frequently in residential and school environments among children; residential, working and recreational environments among working adults; and residential and recreational environments among older adults.64 84 Future studies will benefit from a more comprehensive assessement of places for green space exposures, and longitudinal studies following individuals progressing through these life stages should keep age-based differences in activity spaces in mind.

Life course exposures

Many of the studies of middle-aged and older-aged adults were cross-sectional9 53 57–59 61 62 69 71–73 and lacked consideration of earlier life green space exposures.9 53 55 57–62 69 71–73 Childhood exposures may be most critical for determining late-life brain health by influencing healthy brain development. These neurodevelopmental benefits may impart cognitive reserve and resilience through older ages, which protects against ADRD neuropathology and resists symptoms despite neuropathology.87 Green space exposure patterns during childhood may also establish healthy habits including physical activity that continue through adulthood to boost and maintain brain health. The importance of including childhood measures in future studies also applies to confounders such as early-life personal and neighbourhood SES, which have been found to be associated with late-life cognitive health.88

Some evidence suggests that mid-life behaviours may be stronger predictors of late-life cognitive decline and dementia risk than late-life behaviours.89 90 In a similar fashion, green space exposures in mid-life versus late-life may be more strongly associated with late-life brain health. Mid-life exposures are of particular interest because the neuropathology associated with ADRD often starts decades prior to symptom development (ie, in mid-life).91 During mid-life, green space-related behaviours/exposures such as physical activity may help resist the development of ADRD neuropathology or decrease the neuropathological burden.92 Yet, even late-life green space exposures may help maintain brain health in older age by providing accessible places that encourage exercise, relaxation, and socialising. Life course studies are needed to determine the critical periods of green space exposure related to late-life brain health and ADRD risk.

Causal mechanisms

Traffic-related air pollution and self-reported physical activity were found to be mediators, providing preliminary evidence for these two causal mechanisms. Future evaluation of mediation by physical activity should use rigorous, objective measures such as those obtained from accelerometers. Social engagement and related measures were not found to be mediators, and mental health (eg, anxiety, depression) and immune function were not examined in any study. Altogether, few studies examined mediation, additional work is need to determine causal pathways for green space-brain health associations and future studies will need to employ rigorous methods to evaluate mediation.93

Future research directions

New studies will need to incorporate longitudinal measures of green space (accumulation of exposures and changes over time) and brain health. GPS-based measures of green activity spaces and time spent in green spaces will improve the quantification and quality assessment of green space exposures. Use of brain biomarkers such as structural and functional MRI, PET scans and CSF biomarkers to detect brain neurodegeneration/ADRD may provide biological evidence for associations. Green space exposures should temporally precede the brain health measures, and the validity and reliability of green space measures need to be established. Causal mechanisms need to be delineated through rigorous investigation of potential mediators. In addition, the evidence base will be strengthened by capitalising on natural experiments (eg, planned green space additions) to study green space associations with brain health.

Future studies will need to incorporate relevant factors insufficiently examined to date, including the potential impact of residential moves, seasonality of exposure/regional climate, bias due to self-selection into greener neighbourhoods (ie, reverse causality) and neighborhood-level confounders (eg, crime, population density). Research is needed on the pertinent places (eg, neighbourhood, work, recreational) and boundaries (eg, 1000 m buffer) for green space exposures. Studies need to determine if associations are present irrespective of or instead depend on race/ethnicity and culture, by demonstrating associations in multiple international contexts and in various regions of diverse countries such as the USA.

Limitations

Limitations of the reviewed studies include lack of consideration of early-life green space exposures and examination of actual time spent in green spaces. Thus, the studies were likely affected by misclassification/information bias. Selection bias was also likely for many of the studies that restricted to samples with non-missing data on exposures and outcomes.

This review may be limited by positive publication bias. In addition, papers may have been missed due to the nature of this rapid review, which was based on three databases, a restricted review of the Web of Science search results (detailed in the methods section and online supplemental figure 1), and a single reviewer. However, the review of reference lists and related reviews helped reduce the possibility. As this was a rapid review with scoping aims,47 49 51 52 it was never intended to systematically evaluate the evidence for risk of bias, which will be reserved for future systematic reviews.

Conclusion

This rapid review identified twenty-two studies of green space and brain health. The majority of studies were cross-sectional and the green space and brain health measures were heterogeneous. Despite the limitations, multiple studies investigating neighbourhood greenness found positive associations with brain health outcomes at various life stages. Thus, the evidence is suggestive that green space is associated with brain health and future systematic reviews are warranted. The observed positive associations need to be replicated in longitudinal and life course studies of diverse cohorts and in studies using more rigorous measurements and statistical methods. These improvements are needed to build a case for community-level green space interventions to impart brain resilience, maintain/improve cognition and reduce ADRD risk in late life.

Table 4

Findings by green space-brain health association investigated and author name

Green space measure*	Cognition			MRI			Diagnosis of cognitive impairment/dementia
	+	–	N	+	–	N	+	–	N
Greenness/NDVI	Dadvanda Dadvandb LiaoDe KeijzerZhuDzhambov	Hystad	Dadvanda Dadvandb ReubenDe KeijzerHystadZijlemaWangYu	Dadvandc Dzhambov		Dadvandc Dzhambov	YuchiBrown	Yuchi
Percent green/ park space	Cherried Cherriee Flouri		Cherried Cherriee Clarke	Kuhn		Kuhn		Wuf Wug	Wug
Time spent in green space			WardZijlema
Other	Zijlema		Zijlema

Year of publication: a2015; b2017; c2018; d2018; e2019; f2015; g2017.

*Full list of papers found in online supplemental text 1.

-, inverse association; +, positive association; N, null association; NDVI, Normalised Difference Vegetation Index.