BACKGROUND AND PURPOSE:

• Due to an aging population, approximately 50 million people worldwide have dementia, projected to increase to 75 million by 2030 and to 132 million by 2050
• Symptoms occur late in life but pathology begins early
• Delay in onset of 1 year could prevent more than 9 million cases of dementia by 2050
  • Delay in onset by 5 years could reduce worldwide prevalence by 50%
• Livingston et al., under the auspices of The Lancet Commission (Lancet, 2017) investigated the most current evidence regarding diagnosis and treatment of dementia and cognitive impairment
  • As part of this comprehensive review, the Lancet Commission also assessed the evidence related to the impact of modifiable risk factors on dementia, including risk reducing interventions

METHODS:

• The authors reviewed guidelines and literature to assess modifiable risk factors and interventions
• ‘All cause’ dementia was used rather than cause-specific dementia because more data was available
• International studies were included so that results could be more generalizable
• The authors focused on estimating the ‘Population Attributable Fraction’ (PAF), which is the percentage reduction in new cases over a given time if a particular risk factor is eliminated

RESULTS:

The Lancet Commission identified the following modifiable risk factors for dementia (PAF scores are weighted to provide the unique, relative contribution of each risk factor to the overall PAF):

• Age < 18 years
  • Education no greater than primary school (PAF=7.5%): relative risk 1.6 (95% CI 1.26-2.01)
• Age 45-65 years
  • Hypertension (PAF=2.0%): relative risk 1.6 (95% CI 1.16-2.24)
  • Obesity (PAF=0.8%): relative risk 1.6 (95% CI 1.34-1.92)
  • Hearing loss (PAF=9.1%): relative risk 1.9 (95% CI 1.38-2.73)
• Age > 65 years
  • Smoking (PAF=5.5%): relative risk 1.6 (95% CI 1.15-2.20)
  • Depression (PAF=4.0%): relative risk 1.9 (95% CI 1.55-2.33)
  • Physical inactivity (PAF=2.6%): relative risk 1.4 (95% CI 1.16-1.67)
  • Social isolation (PAF=5.9%): relative risk 1.6 (95% CI 1.32-1.85)
  • Diabetes (PAF=1.2%): relative risk 1.5 (95% CI 1.33-1.79)

KEY POINTS:

Risk Factor Prevention

• An unexpected decline in dementia has been reported in the US, UK, Canada, Sweden and Netherlands but increased in China and Japan while stable in Nigeria
  • US reported decreased age-specific prevalence was associated with an increase in education
  • While certain lifestyle factors may be improving, concern remains around increasing mid-life rates of obesity
• Age remains an unmodifiable factor, with 80% of dementias occurring in individuals ≥ 75 years
• Concept of ‘resilience’ and ‘cognitive reserve’: more brain reserve can tolerate more neuropathology
  • Reserve related to brain anatomical substrate or adaptability of cognition
  • In theory, less reserve leads to earlier onset dementia
    • May explain benefit of education/learning, exercise, blood pressure control
• Hearing loss: No studies available as to whether hearing aids may delay dementia
• Physical Activity: Observational studies demonstrate that exercise has a protective effect against cognitive decline, dementia and Alzheimer’s disease
  • RCTs are conflicting regarding effects and type of physical activity
  • Multiple benefits in older people including improved balance, mood, reduced mortality and improved function
• Validated large scale dementia prevention programs are not yet available
  • Research into multimodal strategies is ongoing

Interventions to Prevent Dementia

• Mediterranean diet
  • RCTs suggest that this diet may help with decline in cognition but not dementia (although benefit may be underestimated due to issues related to the study)
• Cognitive interventions
  • There is data to support engaging in cognitively stimulating activities to improve cognition and reduce dementia
  • Commercial brain training tools have been promoted but not validated
• Social engagement
  • Data suggests social engagement will delay onset of dementia but no evidence for prevention
  • Living alone, never married, divorced, or widowed have an increased risk of all-cause dementia
  • Dementia risk elevated for those with little social activity but data insufficient to confirm causation
• Trials do not support the following interventions to prevent dementia:
  • NSAIDs
  • Rosiglitazone
  • Estrogen hormone therapy
  • Statins
  • Vitamins
  • Ginkgo biloba extract

CONCLUSION:

• The Lancet Commission concludes that interventions for modifiable risk factors have the potential to delay or prevent a third of dementia cases
• The authors suggest that while caution in interpreting PAF is advisable,

There is good evidence that treatment of hypertension reduces dementia incidence and preliminary evidence that modification of several risk factors has a beneficial effect on cognition. The interventions most likely to be beneficial (increasing education in early life, increasing physical activity and social engagement, reducing smoking, treating hypertension, diabetes, and hearing impairment) are safe and confer other health benefits.

Learn More – Primary Sources:

Commissions from the Lancet Journals: Dementia prevention, intervention, and care

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