The Next Generation of Evidence for Dementia Risk Reduction

The past 10-20 years have seen an exponential growth in the scientific literature on dementia, the identification of dementia risk factors, and the potential for risk reduction. We now benefit accordingly from a broad consensus as to the main modifiable and lifestyle factors that have been associated with an increased risk of developing dementia or cognitive decline (for a review, see Anstey et al. [1]).

However, despite our knowledge of the potential risk factors, the evidence for successful risk reduction has been slower to accrue. Given the evidence that multiple risk factors influence cognitive trajectories, the field has moved towards multifactorial interventions where several risk factors are tackled at once. Clinical trials using this approach are growing in popularity and prevalence [2-5] with protocols for two such trials reported in this supplemental issue [2,3]. Building on this, and in order to optimise the efficacy of risk reduction, we now need to drill down to the best evidence and to understand how this applies in different populations. The IRNDP supplemental issue [1-4,5-19] highlights how there remains an urgent need to build a more targeted risk reduction strategy. The issue includes new evidence on varied populations including aboriginal Australians, community dwelling Japanese elders, Malaysian, Portuguese, Brazilian, and Mozambican adults [7,8,17,18]. It reports on emerging risk factors such as air pollution, kidney disease, and chronic obstructive pulmonary disease [10-12] and on new analyses on the impact of modifiable and non-modifiable risk factors and changes in incidence over time [13-16]. In thoughtful editorials, Glymour and Whitmer [5] and Brayne and Richard [6] draw these findings together orientating us to both the potential but also to the gaps in the current epidemiology and trials-based approaches. Sexton and Yaffe [9] take this further highlighting the need for cultural awareness and the potential for locally-based risk reduction initiatives [18,19]. Overall the message from the research is that we need not only to continue to critically appraise and synthesize what we already know but also to develop new research to gather the more detailed information we currently lack.

Two key current unknowns for most if not all of the dementia risk factors include:

  1. gaps in the data on optimal risk factor exposure for the best protection of brain and cognitive health [6] and
  2. a lack of knowledge relating to the relative impact and relevance of the varied risk factors in different population groups [1]. Such population groups of course include sex and ethnicity but geographical, cultural, and genetic factors must also be considered, particularly if or rather when we design risk reduction messages targeted to such groups.

This supplemental issue of the Journal of Alzheimer’s Disease is sponsored by the International Research Network on Dementia Prevention (IRNDP) (see with a view to prompting thought and supporting discussion and scientific endeavour in this area.

The supplemental issue brings together a unique collection of dementia prevention related research that serves to highlight and starts to fill the gaps in our current knowledge of the area. This will help build the evidence base but we must not forget the importance of evaluating and testing the means and messages we use to communicate our dementia risk reduction information. This should be considered in parallel as we develop the literature to support the messaging, ensuring that we use appropriate and successful means to identify and reach those who need to hear them [7,9,18,19].

The dementia risk reduction field has come a long way in recent years but we have only painted in the broad-brush strokes so far. We know that living a healthy lifestyle, eating a healthy diet, physical activity, maintaining a healthy weight, taking appropriate clinical treatment to manage conditions such as hypertension, and staying socially and cognitively active are unlikely to harm and may protect brain health. We now need the information to be able to apply and tailor these messages to a global population to achieve the most robust and sustained benefit we can. This issue showcases some of the work that is taking us towards this goal.

Ruth Peters and Kaarin Anstey

[1] Anstey KJ, Ee N, Eramudugolla R, Jagger C, Peters R (2019) A systematic review of meta-analyses that evaluate risk factors for dementia to evaluate the quantity, quality and global representativeness of evidence. J Alzheimers Dis 70 (Suppl 1), S165-S186.
[2] Yaffe K, Barnes DE, Rosenberg D, Dublin S, Kaup AR, Ludman EJ, Vittinghoff E, Peltz CB, Renz AD, Adams KJ, Larson EB (2019) Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT): study protocol. J Alzheimers Dis 70 (Suppl 1), S207-S220.
[3] Heffernan M, Andrews G, Fiatarone Singh MA, Valenzuela M, Anstey KJ, Maeder A, McNeil J, Jorm L, Lautenschlager N, Sachdev P, Ginige A, Hobbs M, Boulamatsis C, Chau T, Cobiac L, Cox K, Daniel K, Flood VM, Guerrero Y, Gunn J, Jain N, Kochan NA, Lampit A, Mavros Y, Meiklejohn J, Noble Y, O'Leary F, Radd-Vagenas S, Walton C, Brodaty H (2019) Maintain Your Brain: protocol of a 3-year randomized controlled trial of a personalized multi-modal digital health intervention to prevent cognitive decline among community dwelling 55 to 77 year olds. J Alzheimers Dis 70 (Suppl 1), S221-S237.
[4] Ngandu T, Lehtisalo J, Solomon A, Levälahti E, Ahtiluoto S, Antikainen R, Bäckman L, Hänninen T, Jula A, Laatikainen T, Lindström J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M (2015) 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.
[5] Brayne C, Richard E (2019) Prevention of cognitive decline: a goal in sight? J Alzheimers Dis 70 (Suppl 1), S11-S14.
[6] Glymour MM, Whitmer RA (2019) Using cross-cultural studies to improve evidence on dementia prevention: lessons from the special issue sponsored by the International Research Network on Dementia Prevention (IRNDP). J Alzheimers Dis 70 (Suppl 1), S5-S10.
[7] Oliveira D, Jun Otuyama L, Mabunda D, Mandlate F, Gonçalves-Pereira M, Xavier M, Laks J, Ferri CP (2019) Reducing the number of people with dementia through primary prevention in Mozambique, Brazil, and Portugal: an analysis of population-based data. J Alzheimers Dis 70 (Suppl 1), S283-S291.
[8] Radford K, Lavrencic LM, Delbaere K, Draper B, Cumming R, Daylight G, Mack HA, Chalkley S, Bennett H, Garvey G, Hill TY, Lasschuit D, Broe GA (2019) Factors associated with the high prevalence of dementia in older Aboriginal Australians. J Alzheimer Dis 70 (Suppl 1), S75-S85.
[9] Sexton CA, Yaffe K (2019) Population-based approaches to dementia prevention. J Alzheimers Dis 70 (Suppl 1), S15-S17.
[10] Peters R, Ee N, Peters J, Booth A, Mudway I, Anstey KJ (2019) Air pollution and dementia: a systematic review. J Alzheimers Dis 70 (Suppl 1), S145-S163.
[11] Sacre JW, Magliano DJ, Zimmet PZ, Polkinghorne KR, Chadban SJ, Anstey KJ, Shaw JE (2019) Associations of chronic kidney disease markers with cognitive function: a 12-year follow-up study. J Alzheimers Dis 70 (Suppl 1), S19-S30.
[12] Cherbuin N, Walsh EI, Prina AM (2019) Chronic obstructive pulmonary disease and risk of dementia and mortality in lower to middle income countries. J Alzheimers Dis 70 (Suppl 1), S63-S73.
[13] McFall GP, McDermott KL, Dixon RA (2019) Modifiable risk factors discriminate memory trajectories in non-demented aging: precision factors and targets for promoting healthier brain aging and preventing dementia? J Alzheimers Dis 70 (Suppl 1), S101-S118.
[14] Derby CA, Katz MJ, Rozner S, Lipton RB, Hall CB (2019) A birth cohort analysis of amnestic mild cognitive impairment incidence in the Einstein Aging Study (EAS) cohort. J Alzheimers Dis 70 (Suppl 1), S271-S281.
[15] Deckers K, Nooyens A, van Boxtel M, Verhey F, Verschuren M, Köhler S (2019) Gender and educational differences in the association between lifestyle and cognitive decline over 10 years: The Doetinchem Cohort Study. J Alzheimers Dis 70 (Suppl 1), S31-S41.
[16] Peters R, Peters J, Booth A, Anstey KJ (2019) Trajectory of blood pressure, body mass index, cholesterol and incident dementia. A systematic review. Br J Psychiatry, doi: 10.1192/bjp.2019.156.
[17] Vanoh D, Shahar S, Razali R, Ali NM, Manaf ZA, Noah SAM, Nur AM (2019) The effectiveness of a web-based health education tool, WESIHAT 2.0, among older adults: a randomized controlled trial. J Alzheimers Dis 70 (Suppl 1), S255-S270.
[18] Meguro K, Dodge HH (2019) Vascular mild cognitive impairment: identifying disease in community-dwelling older adults, reducing risk factors, and providing support. The Osaki-Tajiri and Kurihara Projects. J Alzheimers Dis 70 (Suppl 1), S293-S302.
[19] Collins R, Silarova B, Clare L (2019) Dementia primary prevention policies and strategies and their local implementation: a scoping review using England as a case study. J Alzheimers Dis 70 (Suppl 1), S303-S318.