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The value of a public health lens in dementia research

Seb Walsh (MBChB, MPhil, MFPH)

NIHR Doctoral Fellow in Public Health Medicine, University of Cambridge

06/02/2025

MELODEM

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Outline

  1. The Public Health Lens
  2. Example 1: Risk Reduction
  3. Example 2: Amyloid Immunotherapies

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  • From Boston, studied medicine at MIT

  • Bacteriologist

  • Founded School of Public Health at Yale and was President of American PH Association

Charles-Edward Winslow

(1877-1957)

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Public Health in 1920

Public health is the science and the art of preventing disease, prolonging life, and promoting physical health and efficiency through organized community efforts for the sanitation of the environment, the control of community infections, the education of the individual in principles of personal hygiene, the organization of medical and nursing service for the early diagnosis and preventive treatment of disease, and the development of the social machinery which will ensure to every individual in the community a standard of living adequate for the maintenance of health.”

“Ignoring all minor specialties there must be at least the following seven types of highly qualified persons in this field:

  1. The physician
  2. The epidemiologist
  3. The nurse
  4. The engineer
  5. The bacteriologist
  6. The statistician
  7. The social worker”

Winslow, 1920. Science

The Untilled Fields of Public Health

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Public Health – updates since 1920

#1

The burden of disease has changed

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#2

The age structure has changed

Public Health – updates since 1920

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Public Health – updates since 1920

Rose, 1985. International Journal of Epidemiology

Sick Individuals and Sick Populations

Geoffrey Rose

1926 - 1993

Determinants of individual cases

Vs. Determinants of incidence rate

#3

Risk exists on a continuum

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Public Health – updates since 1920

Low risk

High risk

Proportion of the population

Individual-level approach

Population-level approach

Rose, 1992. Oxford Medical Publications

The Strategy of Preventive Medicine

A large number of people at a small risk may give rise to more cases of disease than the small number who are at a high risk”

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Arapakis et al., 2020. BMJ Open

Dementia and disadvantage in the USA and England: population-based comparative study

Public Health – updates since 1920

#4

Inequality exists on a continuum

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Adapted from: Adams et al., 2016. PLOS Medicine

Population interventions for diet and obesity

Public Health – updates since 1920

#5

Reach ≠ Equity

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Fruit

Individuals’ Health State & Medical Needs (Dementia morbidity)

Distal Branches

Health Behaviours & Social Networks (Risk factor status)

Trunk

Social Determinants of Health (Population-level factors)

Proximal Branches

Neighbourhood & Community (Community assets)

Roots and Soil

Deep Societal Factors

(Sexism, Racism, Homophobia, Climate Change, Inequality)

Images generated by Google Gemini

BRAIN HEALTH

EQUALI-TREE!!

#6

Prevention at different levels

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Research

Research Output

Enduring Impact

Research

Research Output

Research

Research Output

Research

Research Output

Research

Research Output

How do we reduce dementia morbidity by as much as possible?

Walsh et al., 2022. Lancet Neurology

The relevance of social and commercial determinants for neurological health

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Outline

  1. The Public Health Lens
  2. Example 1: Risk Reduction
  3. Example 2: Amyloid Immunotherapies

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DEMENTIA RISK

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Livingston et al., 2024. The Lancet

Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission

Distal Branches

Health Behaviours & Social Networks

(Risk factor status)

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Most cases (70-80%) of future dementia will occur in people who are not in the high-risk group

Check your priors

Walsh et al., 2024. Alzheimer’s & Dementia

How many future dementia cases would be missed by a high-risk screening programme?

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Measures applied to populations, groups, areas, jurisdictions, or institutions with the aim of changing the social conditions (including cultural, physical, commercial, economic, environmental, occupational, or legislative conditions to make them less conducive to the development or maintenance of the modifiable lifecourse risk factors for dementia and/or more conducive to the development or maintenance of the modifiable lifecourse protective factors for dementia.’

Population-level approach to dementia risk reduction

Walsh et al., 2023. Public Health

What is a population-level approach to prevention, and how could we apply it to dementia risk reduction?

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Existing dementia prevention literature

Walsh et al., 2023. JPAD

Are Population-Level Approaches to Dementia Risk Reduction Under-Researched?

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Complex Evidence Review

Walsh et al., 2024. Lancet eClinicalMedicine

Population-level interventions for the primary prevention of dementia: a complex evidence review

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Evidence grading

High confidence

Comprehensive, consistent, and robust evidence, across a range of contexts

Moderate confidence

Consistent and robust evidence, but only in a limited number of contexts

Low confidence

Clear signal that the intervention can work, but lack of consistency or comprehensiveness

Walsh et al., 2024. Lancet eClinicalMedicine

Population-level interventions for the primary prevention of dementia: a complex evidence review

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How

Walsh et al., 2024. Lancet eClinicalMedicine

Population-level interventions for the primary prevention of dementia: a complex evidence review

Risk Factor

Fiscal Interventions

Marketing/Advertising Interventions

Availability Interventions

Legislative Interventions

Tobacco

(T1) Excise taxes on tobacco

(T2) Plain packaging, large health warnings�(T3) Comprehensive bans on advertising

(T4) Eliminate exposure to second-hand tobacco smoke in all public places

 

Excess Alcohol

(A1) Excise taxes on alcohol�(A2) Minimum unit pricing

(A3) Comprehensive restrictions on advertising - including targeting young people

(A4) Restrictions on the physical availability of retailed alcohol (e.g. reduced hours of sale)

 

Obesity

(O1) Taxation on unhealthy products e.g. sugar-sweetened beverages

(O2) Restrict marketing of unhealthy foods to children�(O3) Menu labelling in food service

(O4) Limit portion and package size to reduce energy intake

(O5) Public food procurement policies to promote healthy diets

(O6) Reformulation policies for healthier food and beverage products

Physical Inactivity

 

 

(P1) Urban and transport planning and design to provide compact neighbourhoods providing mixed-land use and connected networks for walking and cycling and equitable access to public open spaces

Hypertension

 

 

(H1) Public food procurement and service policies to reduce sodium intake

(H2) Reformulation policies for sodium reduction

TBI

 

 

 

(Tr1) Mandate motorcycle helmets (all ages)�(Tr2) Mandate bicycle helmets (children)

Low Education

(E1) Remove financial barriers to school attendance

 

(E2) Free lunches in primary schools, where there would otherwise be a lack of adequate food

(E3) Raise mandatory school leavers age

Air Pollution

 

 

(Ai1) Replacement and maintenance programmes providing cleaner cooking stoves for those currently using biomass fuels on traditional stoves or open fires

(Ai2) Reduce density of traffic, including (e.g. low emission zones)�(Ai3) Postpone non-essential polluting activities on high-pollution days

Hearing Impairment

 

 

 (He1) Reduce worksite noise through improving equipment where feasible; and provide adequate hearing protection, with regular monitoring

(Data from high-income countries only, low-/ middle-income countries, or both)

(T1) (A1) (A2) (O1)

Increase taxation on

tobacco, alcohol, and SSBs

(Ai2)

Measures to reduce traffic density e.g. LEZs

(He1)

Monitor and reduce worksite noise; and provide adequate hearing protection

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How

Walsh et al., 2024. Lancet eClinicalMedicine

Population-level interventions for the primary prevention of dementia: a complex evidence review

Intervention

Estimated effect size(s)

Key source(s) of evidence of effectiveness and effect estimate(s)

Key considerations

Further planning/ implementation guidance

(He1) Worksites exceeding recognised noise thresholds should reduce noise through improving equipment where feasible, and should provide and mandate the use of adequate hearing protection, with regular monitoring

60% reduction in occupationally-acquired hearing impairment��Avoidance of hearing loss OR 0.4 (95% CI 0.23, 0.69), at 5 years

Tikka et al., 2017. Interventions to prevent occupational noise‐induced hearing loss. Cochrane review

Worksites exceeding recognised thresholds (80 dB(A)) should provide and mandate the use of adequate hearing protection, with regular audiometric monitoring of those working in areas which continue to exceed thresholds despite installation of quieter equipment

WHO, 2018.

Addressing the rising prevalence of hearing loss

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How

Mukadam et al., 2024. Lancet Healthy Longevity

Benefits of population-level interventions for dementia risk factors: an economic modelling study for England

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Expansion of

morbidity?

Dhana et al., 2022. The BMJ

Healthy lifestyle and life expectancy with and without Alzheimer’s dementia

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A different way to think about risk

Walsh et al., 2023. Public Health

What is a population-level approach to prevention, and how could we apply it to dementia risk reduction?

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Outline

  1. The Public Health Lens
  2. Example 1: Risk Reduction
  3. Example 2: Amyloid Immunotherapies

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Miracle Drugs

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Clinical Lens

  1. Does their efficacy outweigh their harms?

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Clinical Lens – Effect size

Liu et al., 2021. Lancet Psychiatry

The need to show minimum clinically important differences in Alzheimer's disease trials

Phase III Trial Data

Between Group Differences

Lecanemab 0.45

Donanemab 0.68

Minimum Clinically Important Difference

Within Person Change

MCI 0.98

Mild AD 1.63

(CDR-SB)

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Clinical Lens – Effect size

Walsh et al., 2024. Alzheimer’s & Dementia

Considering challenges for the new Alzheimer’s drugs: clinical, population, and health system perspectives

  • Integrated Alzheimer’s Disease Rating Scale (iADRS)
  • Perfect score 146, baseline score around 105
  • Placebo group declined by 13 points
  • Donanemab group declined by 10 points

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Clinical Lens - Concerns

Walsh et al., 2024. Alzheimer’s & Dementia

Considering challenges for the new Alzheimer’s drugs: clinical, population, and health system perspectives

Donanemab

Placebo

Any ARIA

36.8%

14.9%

Symptomatic ARIA-E

6.1%

0.1%

Large ARIA-H

0.4%

0.2%

Lecanemab

Placebo

Any ARIA

21.5%

9.5%

Symptomatic ARIA-E

2.8%

0%

Symptomatic ARIA-H

0.7%

0.2%

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Clinical Considerations

Walsh et al., 2024. Alzheimer’s & Dementia

Considering challenges for the new Alzheimer’s drugs: clinical, population, and health system perspectives

  1. Efficacy
    • Small offsetting of cognitive decline at 18 months
    • Between-group difference not noticeable to a clinician at 18 months
    • Uncertainty about long-term effects�
  2. Side effects
    • Mild/asymptomatic side effects frequent
    • Significant side effects relatively rare
    • Uncertainty about long-term effects

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Population Perspective

Walsh et al., 2024. Alzheimer’s & Dementia

Considering challenges for the new Alzheimer’s drugs: clinical, population, and health system perspectives

  1. Will efficacy translate to effectiveness?

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Walsh et al., 2024. Alzheimer’s & Dementia

Considering challenges for the new Alzheimer’s drugs: clinical, population, and health system perspectives

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Pittock et al., 2023. Neurology

Eligibility for Anti-Amyloid Treatment in a Population-Based Study of Cognitive Aging

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Population Perspective

Walsh et al., 2024. Alzheimer’s & Dementia

Considering challenges for the new Alzheimer’s drugs: clinical, population, and health system perspectives

  1. Will efficacy translate to effectiveness?
    • Trial cohorts highly unrepresentative of those living with Alzheimer’s disease in the community
    • If access restricted to those who meet eligibility criteria, few get the drugs (therefore minimal effect on overall morbidity).
    • If given to a broader group, likely reduced effect size and increased side effect rate (meaning reduced/negative effect on overall morbidity).

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Health System Perspective

Walsh et al., 2024. Alzheimer’s & Dementia

Considering challenges for the new Alzheimer’s drugs: clinical, population, and health system perspectives

  1. Who should be offered them and how?

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Health System Perspective

Walsh et al., 2024. Alzheimer’s & Dementia

Considering challenges for the new Alzheimer’s drugs: clinical, population, and health system perspectives

  • Cost and financial opportunity cost
  • Process and resource opportunity cost

GP

Memory Clinic

Amyloid status

MRI head

Genotype (+ counselling)

70-95% ”fail” screening

Neurology

Weeks

Months

Months

“The cost-effectiveness estimate for donanemab is 5 to 6 times above what NICE normally considers an acceptable use of NHS resources.”

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?

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Outline

  1. The Public Health Lens
  2. Example 1: Risk Reduction
  3. Example 2: Amyloid Immunotherapies

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Research

Research Output

Enduring Impact

Research

Research Output

Research

Research Output

Research

Research Output

Research

Research Output

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Final Thoughts

  • The Public Health Lens brings added, and unique, value alongside clinical and other perspectives.
    • It can directly inform the design of studies
    • It can be a lens through which any study can be examined for its representativeness and likely impact at the population-level
  • There are tensions between targeting interventions and universalism
  • We must find positive and dynamic ways to explain Public Health, why it matters, and to emotionally engage the public in it.

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With thanks to

Twitter: @seb_walsh

Contact: sjw261@cam.ac.uk