Prevention
The failure during the last two decades of all experimental treatments led to the idea that treatments should be directed to prodromal or asymptomatic phases of the disease 1-3 , making prevention AD a major objective in the AD Health strategy. As a matter of fact, AD prevention is the second major wave of preventive efforts in the field of neurology, after stroke.

Key opinion leaders have suggested that AD should be treated the same way as other pathological conditions such as stroke, diabetes, cancer, were treated in the past, where prevention initiatives had led to significant reductions in the prevalence of these diseases.

Identification of people at risk is key for the effectiveness of preventative measures and consequently, APOE ε4 carriers were defined as a priority population where preventative treatments should be directed 4,5. Accordingly, several ongoing, prevention clinical trials include APOE ɛ4 as an inclusion factor (NCT02565511, NCT03131453, NCT02569398) and large-scale screening programs are being established to identify APOE ɛ4 carriers for AD preventive clinical trials6.

e4Risk®, due to its simplicity, ease of use and cost-effective can be very useful as a screening test for AD clinical trials, where APOE ε4 carriers can be selected in a fast and inexpensive manner.

Intensive efforts are being place to define effective strategies to prevent or delay AD. Recently, it has been shown that multimodal intervention of modifiable vascular and life-style risk factors could improve or maintain cognitive functioning in at-risk elderly people7. Interestingly, this multimodal intervention consisting in diet, exercise, cognitive training and vascular risk monitoring has been shown effective also in APOE ɛ4 carriers8, suggesting that early detection of APOE ɛ4 carriers could be relevant for reducing AD prevalence through adoption of these vascular and life-style recommendations.

1.Sperling, R. in 14th Annual Mild Cognitive Impairment Symposium (Miami Beach Resort, Miami. Florida; 2016).
2.Livingston, G. et al. Dementia prevention, intervention, and care. Lancet (2017).
3.Crous-Bou, M., Minguillon, C., Gramunt, N. & Molinuevo, J.L. Alzheimer’s disease prevention: from risk factors to early intervention. Alzheimer’s research & therapy 9, 71 (2017).
4.Reiman, E.M. et al. Alzheimer’s Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments. Journal of Alzheimer’s disease : JAD 26 Suppl 3, 321-329 (2011).
5.Solomon, A. et al. Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain Lifestyle Intervention: A Subgroup Analysis of a Randomized Clinical Trial. JAMA neurology (2018).
6.Langbaum, J.B. et al. GeneMatch: A novel recruitment registry using at-home APOE genotyping to enhance referrals to Alzheimer’s prevention studies. Alzheimer’s & dementia : the journal of the Alzheimer’s Association (2019).
7.Ngandu, T. et al. A 2 year multidomain 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 trial. Lancet 385, 2255-2263 (2015).
8.Rosenberg, A. et al. Multidomain lifestyle intervention benefits a large elderly population at risk for cognitive decline and dementia regardless of baseline characteristics: The FINGER trial. Alzheimer’s & dementia : the journal of the Alzheimer’s Association 14, 263-270 (2018).

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