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Apr 13, 2023 472 likes •795 views

Air pollution, a novel risk factor for late life dementia? Dr Ruth Peters Dementia Late 18th century: from Latin, from demens , dement- 'out of one's mind a serious mental disorder caused by brain disease or injury, that affects

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Air pollution, a novel risk factor for late life dementia?

Dr Ruth Peters

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Dementia

  • Late 18th century: from Latin, from demens,

dement- 'out of one's mind‘

  • a serious mental disorder caused by brain disease
  • r injury, that affects the ability to think, remember

and behave normally (OED)

  • The word dementia describes a set of symptoms

that may include memory loss and difficulties with thinking, problem-solving or language. These changes are often small to start with, but for someone with dementia they have become severe enough to affect daily life. (Alzheimer’s Society UK) An umbrella term for a syndrome (includes Alzheimers disease, vascular dementia, multi-infarct dementia etc:)

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Cognitive decline

  • A deterioration in cognitive function greater than that

expected with age

  • Dementia is diagnosed when cognitive decline is

severe enough to interfere with activities of daily living

  • Cognitive function includes a wide range of

processes associated with day to day activities

  • Assessment of function via neuropsychological tests
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Cognitive domains Perceptual-motor function Visual perception Visuoconstructional reasoning Perceptual-motor coordination Language Object naming Word finding Fluency Grammar and syntax Learning and memory Free recall Cued recall Recognition memory Semantic and autobiographical long-term memory Implicit learning Social cognition Recognition of emotions Theory of mind Insight Executive function Planning Decision making Working memory Responding to feedback Inhibition Flexibility

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Why do we care?

Dementia is a distressing, disabling, degenerative and eventually fatal condition There is no imminent cure

Lobo et al 2000

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What can we do?

  • Emphasis now turning to prevention/delay of cognitive decline
  • Huge amount of work looking at risk factors
  • Lifestyle risk factors
  • Clinical risk factors
  • Public Health messages starting to include dementia as a key

non-communicable disease (See Blackfriars Consensus UK https://www.gov.uk/government/news/call-for-new-policy-focus-on- brain-health-to-reduce-the-risk-of-dementia )

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Lifestyle risk factors

Poor diet Obesity Smoking

Lack of physical activity Low education Alcohol?

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Clinical Risk factors

Hypertension High cholesterol Diabetes

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Clinical risk factors Outcome

High cholesterol Hypertension Diabetes

smoking

  • besity

Low physical activity

Cognitive decline/dementia

Lifestyle risk factors Inflammatory processes Increasing cardiovascular risk

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Conversation with a cardiologist…..

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Air pollution

Particulate matter

  • Ultra fine particulate matter <0.1µm (UFPM)
  • Fine particulate matter <2.5µm (PM2.5)
  • Coarse particulate Matter <10 µm (PM10)

Gaseous pollutants

  • Ozone
  • Nitrogen dioxide
  • Carbon monoxide
  • Sulphur dioxide

http://www.engineeringtoolbox.com/ particle-sizes-d_934.html

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Air pollution and cardiovascular risk

Evidence for long term exposure and increased risk of cardiovascular and cerebrovascular events

Level of Exposure to Fine Particulate Matter and the Risk of Death from Cardiovascular Causes in Women.

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Furthermore….

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Short term exposure also associated with increased risk…

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Inflammation and air pollution

Block & Calderon-Garciduenas 2009 Trends in Neuroscience doi:10.1016/j.tins.2009.05.009

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Air pollution and risk of cognitive decline/dementia

Systematic review

  • Searched MEDLINE, Embase and PsychINFO from

inception to 1st Nov 2013 using terms related to air pollution and dementia or cognitive function.

  • 1551 records after duplicates removed
  • 10 full text articles
  • 8 retained of those….
  • 6 reported on historical exposure to air pollution and

later cognitive function ‘prevalence’ studies

  • 2 reported on change in cognitive function, incident

cognitive decline

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Air pollution and risk of cognitive decline/dementia

Prevalence studies

  • 1. Department of Veterans Affairs Normative Aging Study (NAS), 680 men,

USA

  • 2. MOBILIZE Boston Study, 765 men and women, USA
  • 3. Chinese longitudinal Health Longevity Survey (CLHLS) 3rd wave, 7358

men and women, China

  • 4. Chinese longitudinal Health Longevity Survey (CLHLS) 3rd and 4th waves,

15973 men and women, China

  • 5. Study on the influence of lung function inflammation and Aging (SALIA),

4874 women, Germany

  • 6. 3rd National Health and Nutrition Examination Survey (NHANESIII), 1479

men and women, USA.

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Air pollution assessment of outcome

Mini Mental State Exam

Short screening test

  • NAS, Mobilize Boston, CLHLS 3rd wave, CLHLS 3rd and 4th waves

Tests used vary by study, little overlap

Neuropsychological test battery

  • NAS, Mobilize Boston

Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery

Comprehensive neuropsychological test battery

  • SALIA
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Prevalence studies – assessment of exposure

Exposure

Residential distance to a busy street <=50m, 50- 100, >100m

(SALIA)

Black carbon

(NAS & MOBILIZE Boston)

Residential distance to a major roadway

(MOBILIZE Boston)

Chinese Air Pollution Index

(CLHLS 3rd and 3rd & 4th waves)

PM10

(SALIA)

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Air Pollution, prevalence studies, results,

NAS

  • doubling of BC exposure over the previous year - MMSE <26 OR1.3 (1.1:1.6).

CLHLS

  • a point increase in API - MMSE <18 OR1.09 (1.01:1.18) and worsening MMSE by

0.52 points (0.27:0.75). MOBILIZE Boston

  • living nearer to a busy road (per 851.2m) - MMSE <26 only in those with
  • a College education OR1.54 (1.10:2.17)
  • or aged ≤77 years OR1.34 (1.01:1.76).
  • For BC (for a 0.11µg/m3 greater exposure during the preceding yr) MMSE <26

OR1.15(0.99:1.34) SALIA

  • traffic and PM10 exposure over five years - worse cognitive performance on the

CERAD battery and Stroop test. NHANES III

  • greater exposure to PM10 (per 10µg/m3) or ozone (per 10ppb) over the preceding

year - poorer cognitive performance on all tests except simple reaction time

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Air pollution – incidence studies

Study N Follow up Cognitive assessment Outcome Measure of exposure to air pollution Nurses’ Health Study 19409 females Assessed at 1.9 and 4.3 years TICs (validated telephone interview) Composite measures

  • f cognition

via z scores Meteorological and Geographic Information System (GIS) data for each geocoded residential location for PM10, PM2.5. PM2.5-10 calculated from difference. Averaged exposure over 1988, 1 month, 1 year, 2 years and 5 years before first test RE- GARDS Study 20,150 males and females Baseline then annual telephone contact 6 item telephone assessment Score <=4 classified as incident cognitive impairment Environmental Protection Agency air quality ground level monitoring stations and aerosol optical depth data from satellites combined to provide 1 year mean exposure PM2.5 per participant using an algorithm up to and including the date of the baseline visit

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Air pollution – incidence studies, results

Study Outcome Nurses’ Health Study Z score change per 10 µg/m3 increase in PM2.5, preceding month

  • 0.002 (-0.016:0.012)

preceding year

  • 0.016 (-0.034:0.003)

preceding 2 years

  • 0.015 (-0.034:0.003)

preceding 5 years

  • 0.020 (-0.038:0.002)

since 1988

  • 0.018 (-0.035:-0.002)

REGARDS Study By 10 µg/m3 increase in PM2.5. Logistic regression for incident cognitive impairment; OR0.98 (0.72-1.34)

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More recent work…

Incident cognitive decline

  • Tonne et al 2014 Longitudinal Whitehall II cohort,

London UK.

  • N=2767 Males and females
  • 5 year follow up

Incident dementia

  • Oudin et al 2015 Longitudinal Betula study, Umea,

Sweden

  • N=1806 Males and females
  • 15 year follow up
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Whitehall cohort

  • Air pollution assessed between 2003-2009
  • Cognitive function assessed 2002-2004 and 2007-2009
  • Neuropsychological battery
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The authors conclude ‘This study provides support for an association between particulate air pollution and some measures of cognitive function as well as decline over time in cognition’

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Betula study

  • Air pollution assessed 2009-2010,
  • Sensitivity analysis with air pollution back extrapolated

to levels more likely at study start 1993-1995

  • Measured nitrogen oxide
  • Dementia assessed at baseline 1993-1995 and every 5

years.

  • Incident cases identified using the DSM-IV

supplemented by medical data and imaging where available

The authors conclude, ‘If the associations we observed are causal, then air pollution from traffic might be an important risk factor for vascular dementia and Alzheimer’s disease’

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Limitations

  • Different populations
  • Different assessments of exposure to pollutants
  • Different assessment of outcome
  • Many possible confounders not addressed/adjusted for eg

exposure to in home wood-smoke etc:

  • Most studies cross sectional
  • Timing of exposure and assessments not clear in many

reports

  • Very little longitudinal data where exposure occurred

before outcome!

  • Impossible to aggregate data
  • Impossible to infer clinically or environmentally relevant
  • utcomes
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Conclusions

  • Air pollution may contribute to dementia risk

but nothing can be concluded from the existing evidence base.

  • More robust studies are needed.
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Thank you, Questions?

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Pollutant Primary/ Secondary Averagin g Time Level Form Carbon Monoxide primary 8-hour 9 ppm Not to be exceeded more than once per year 1-hour 35 ppm Lead primary and secondary Rolling 3 month average 0.15 μg/m3 (1) Not to be exceeded Nitrogen Dioxide primary 1-hour 100 ppb 98th percentile of 1-hour daily maximum concentrations, averaged over 3 years primary and secondary Annual 53 ppb (2) Annual Mean Ozone primary and secondary 8-hour 0.075 ppm (3) Annual fourth-highest daily maximum 8-hr concentration, averaged over 3 years Particle Pollution PM2.5 primary Annual 12 μg/m3 annual mean, averaged over 3 years secondary Annual 15 μg/m3 annual mean, averaged over 3 years primary and secondary 24-hour 35 μg/m3 98th percentile, averaged over 3 years PM10 primary and secondary 24-hour 150 μg/m3 Not to be exceeded more than once per year

  • n average over 3 years

Sulfur Dioxide primary 1-hour 75 ppb (4) 99th percentile of 1-hour daily maximum concentrations, averaged over 3 years secondary 3-hour 0.5 ppm Not to be exceeded more than once per year

http://ec.europa.eu/environm ent/air/quality/standards. htm http://www3.epa.gov/ttn/naa qs/criteria.html