Dementia: Protective factors

Knowledge gaps

Thus far, no pharmaceutical agents have been shown to delay or prevent conversion to dementia, although mentally stimulating activities are showing promise. Agents that interfere with the production of insoluble amyloid fragments in the brain, or accelerate their clearance, are being actively pursued. Despite previous disappointments, it is possible that a vaccine may eventually be found. With regard to genetic risk factors, new susceptibility genes for late-onset Alzheimer’s disease continue to be found with increasing regularity.

This review highlights significant gaps in our current knowledge of risk factors for Alzheimer disease. Although we now know much about individual risk factors for dementia, we do not know how they interact or which risk factors account for what proportion of dementia cases. Also lacking is a clear picture of which specific interventions can lower this risk, and at what age and in whom they need to be implemented. Large (and expensive) longitudinal intervention studies are needed to
define the optimal preventive strategies.

In multivariate-adjusted longitudinal studies, the incidence of dementia independently increased with pre-existing cardiovascular disease, the metabolic syndrome, skinfold thickness, body mass index, hypercholesterolemia, diabetes mellitus, hyperhomocysteinemia, smoking, and/or high-sensitivity C-reactive protein, whereas higher education, more exercise at middle age, and moderate alcohol consumption were protective.

Source: http://hyper.ahajournals.org/cgi/reprint/49/3/389

Forette F et al, Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial. Lancet. 1998;352:1347–1351.


Although there is insufficient evidence to make a firm recommendation for the primary prevention of dementia, physicians may advocate for appropriate levels of education and strategies to retain students in appropriate learning environments [grade C recommendation, level 2 evidence; new recommendation].

Intellectually challenging activity of various types has been associated with a reduced risk of dementia in longitudinal studies. Daily mental activities were associated with a decreased risk of all-cause dementia (relative risk 0.59) in the Kungsholmen study.(1) Similarly, the Washington Heights Study (New York) showed a reduced risk of all-cause dementia (relative risk 0.62) among participants who engaged in a higher level of leisure activity (self-reported participation in > 6 of 13 activities v. < 6 activities [low level] in the previous month).(2)

There is emerging evidence that cognitive training, especially involving novel or unfamiliar tasks, may delay cognitive decline. A recently published follow-up study of a randomized controlled trial of cognitive training appeared to show sustained improvement in specific cognitive performance up to 5 years after the intervention.(2) Whether this type of endeavour translates into a reduced risk of dementia remains to be proven.


Early case–control studies had suggested that tobacco smoking actually reduced the risk of dementia, but longitudinal cohort studies have identified a significantly increased risk of all-cause dementia and Alzheimer disease among tobacco smokers.




(1) Wang H-X, Karp A, Winblad B, et al. Late-life engagement in social and leisure activities is associated with a decreased risk of dementia: a longitudinal study from the Kungsholmen Project. Am J Epidemiol 2002;155:1081-7.
(2) Scarmeas N, Levy G, Tang M-X, et al. Influence of leisure activity on the incidence of Alzheimer’s disease. Neurology 2001;57:2236-42.
(3) Willis SL, Tennstedt SL, Marsiske M, et al. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA 2006;296:2805-14.


Source: Chris Patterson, Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease;http://www.cmaj.ca/cgi/reprint/178/5/548





Those participants who had at least one APOE4 allele had 3.28 times the risk of Alzheimer’s disease compared with those who had two ε3 alleles. Of the antecedent or coexisting chronic conditions included in the risk factor questionnaire, only arthritis was significantly related to a reduced risk of Alzheimer’s disease. No statistically significant relation was observed between Alzheimer’s disease risk and high blood pressure, stroke, heart disease, depression, head trauma, diabetes, thyroid condition, cancer (any type), or stomach ulcer.