Global intervention in dementia – putting epidemiological findings into practice

Steady growth is predicted in cases of dementia over the next 40 years – both in high-, middle- and low-income countries.  Intervention to reduce its impact, therefore, requires identification of modifiable risk factors (RF). Here we review the progress that has been made in Latin America, Africa and Europe – regions at varying stages of this process.

AD risk can be lowered

A dementia prevention, intervention and case report identified 12 modifiable RF in high income countries during the course of a lifetime.1 Poor education in early life (</=45 years) (7% risk), hearing loss (8%), traumatic brain injury (3%), hypertension (2%), alcohol consumption (>21 units/week) (1%), obesity (1%) in mid-life (45-65 years) and smoking (5%), depression (4%), social isolation (4%), physical inactivity (2%), diabetes (1%) and air pollution (2%) in later life (>65 years). Thus, a potential risk reduction of 40% can be made in high income countries.

A potential risk reduction of 40% can be made in high income countries

 

Latin-America

Are these modifiable risk factors present in and at the same incidence in low- and middle-income countries Dr Ana Luisa Sosa-Ortiz, National Institute of Neurology and Neurosurgery, Mexico, asked? As a member of the 10/66 Group that systematically gathered epidemiological data on dementia and its risk factors across 8 low- and middle-income countries, including China, India and six Latin-American countries, she is in a good position to know.2

The 10/66 data were further analyzed to determine population modifiable RF.3 Considering just the six Latin-American countries, 9 modifiable RF were found which together give a 56% risk reduction of dementia if acted upon: Poor education in early life (11% risk), hearing loss (8%), hypertension (9%), obesity (8%) in mid-life and smoking (6%), depression (7%), social isolation (0.1%), physical inactivity (5%), and diabetes (3%) in later life.

A comparison with the high-income countries data - and the fact that socioeconomic deprivation e.g. malnutrition, serious infection are not included in assessments - suggests that dementia prevention potential is even greater in Latin-America.

Six Latin-American countries: 9 modifiable RF = 56% risk reduction of dementia

 

Fish – fact or fiction?

Some literature regarding depression, cardiovascular health and neuropsychiatric symptoms as dementia RF in Latin-American countries is available. Intriguingly, an additional RF has been identified in elderly Cubans: it appears that never consuming fish statistically significantly increased the risk of dementia.4

Never consuming fish statistically significantly increased the risk of dementia in elderly Cubans

 

Africa

As in Latin-America, so, too, are there limited data available on modifiable RF available in Africa. However, Adesola Ogunniyi, Ibadan, Nigeria, presented interesting findings from those that have been published.

A comparison of the presence of that APOE ε 4 allele and risk of AD and cognitive decline in African Americans and Yoruba Nigerians suggests that there are different genetic factors at play in these populations. Unlike in African American, in the Yoruba, only homozygosity for APOE ε4 was a significant risk factor for AD (p = 0.0002).5-6 Thus, APOE ε4 had a significant, but weaker, effect on incident AD in Yoruba than in African Americans. Professor Ogunniyi suggested this warrants further investigation in other African populations.

A recent systematic review and meta-analysis has also investigated the dominant and modifiable risk factors in sub-Saharan Africa.7 Lower educational attainment (32.5%) and poor pre-dementia cognitive functioning (20.5%) were the highest ranked modifiable RF identified. Thus, Dr Ogunniyi concluded targeting improvement in education was an important means in preventing dementia in Africa while the risk for novel risk factors continues.

Targeting improvement in education was an important means in preventing dementia in Africa

 

Europe – FINGER interventions

In Europe, the impetus has now moved to programs that intervene to reduce modifiable RF as Miia Kivipelto, Karolinska Institute, Stockholm. Sweden explained. In at-risk populations, the FINGER study is about ready to publish its 7 year findings.8 Follow-up after a 2-year intensive intervention suggests that there still appears to be good long-term adherence to the healthy diet and lifestyle component of the program, compared to controls, 5 years after the intervention ceased. Such beneficial effects are also becoming apparent in APOE ε4 carriers in the intervention group (P=0.012).

Other FINGER interventions are also being undertaken in the at-risk population including Met-FINGER – a lifestyle plus metformin intervention study – EU-FINGERS – a European multi-domain interventions study for dementia prevention and LatAm- FINGERS – a new Latin American intervention study.

 

Prodromal studies

Excitingly, two prodromal AD studies are also in place: MIND-AD and LipiDiDiet. MIND-AD targets prodromal AD with vascular and lifestyle interventions with or without medical food, compared to controls. It is almost fully recruited but its protocol is being adapted to enhance the important social component of the program. Thirty-six month data from the LipiDiDiet study – a multinutrient intervention – has reported broad and positive benefits on cognition.9

Thus, as Dr Kivipelto concluded, Can dementia and AD be prevented? Yes! A significant proportion of cases can be prevented and delayed. It’s never too late.

Can dementia and AD be prevented? Yes! It’s never too late.

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

References
  1. Livingstone G et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 2020;396:413-446.
  2. Prina M et al. Cohort profile: The 10/66 study. Int J Epidemiology 2017;406-406i
  3. Mukadam N et al. Population attributable fractions for risk factors for dementia in low-income and middle-income countries: an analysis using cross-sectional survey data. Lancet Global Health 2019;7:e596-603.
  4. Peeters G et al. Risk factors for incident dementia among older Cubans. Frontier in Public Health 2020;8:article 481
  5. Hall K. Cholesterol, APOE genotype and Alzheimer’s disease. Neurology 2006;66:223-227.
  6. Hendrie HC et al. APO ε4 and the risk for Alzheimer’s disease and cognitive decline in African Americans and Yoruba. Int Psychogeriatr 2014;26:977-985.
  7. Ojagbemi A et al. Dominant and modifiable risk factors for dementia in sub-Saharan Africa: a systematic review and meta-analysis. Frontiers in Neurology 2021; article 627761
  8. Ngandu T et al. A 2 year domain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled study.
  9. Soininen H et al. 36-month LipiDiDiet multinutrient trial in prodromal Alzheimer’s disease. Alzheimer’s and Dementia 2020;17:29-40.

Suggested reading

  1. Fratiglioni L et al. Ageing without dementia: can stimulating psychosocial and lifestyle experiences make a difference? Lancet Neurology 2020;19:P533-543
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