Several genes have been implicated in Alzheimer's, but the big one is the e4 allele of the ApoE gene (on chromosome 19). This variant is found in about a quarter of the population.
Having it doesn't mean you are foreordained to develop Alzheimer's, but it certainly increases the risk substantially. The risk goes up considerably more if both of your genes are the e4 variant (remember you inherit two: one from each parent).
It also increases if you have both the ApoE-e4 and the D10S1423 234-bp allele (found on chromosome 10). The combined risk of these two gene variants has been described as being greater than the increased risk of lung cancer caused by smoking1. Chromosome 10 has also been implicated in setting the age at which it begins, for both Alzheimer's and Parkinson's diseases, in those genetically disposed.
Another gene that has been linked to Alzheimer's is the KIBRA gene (on chromosome 5) — carriers of the T-allele have a 25% lower risk of developing Alzheimer's compared to those who carry the C-allele2.
It does seem that having the right, or wrong, genes is more important than we believed. Data from the Swedish Twin Registry3, involving nearly 12,000 people aged 65 and older, estimated that genetic influence accounted for 79% of Alzheimer's risk, with 95% probability of being within the range 67 to 88%.
But it's not just a matter of genes. Not everyone with the 'wrong' genes will develop dementia, and not everyone who develops dementia has the wrong genes. There are a number of lifestyle actions that affect it.
Even the genetic picture is not as simple as it sounds. One study4, for example, found indications that having a mother who had Alzheimer's is more significant than father's status. Data from the long-running Framingham Heart Study has found5 that cognitive impairment is more likely in those whose who have the ApoE ε4 gene — but only if they had a parent with dementia (particularly if it was Alzheimer's). There was no effect of parental dementia in those who didn’t have the ApoE ε4 gene.
For those who carry the “Alzheimer’s” APOE-4 gene, and those who later develop dementia, there is an association between smaller head size and lower educational achievement6. In other words, having both a small head size and low educational achievement in early life makes it more likely that a person will develop Alzheimer’s — probably because of their lack of cognitive reserve.
Cardiac & Blood Pressure Problems
A very large study7 found that those with atrial fibrillation, regardless of age, were 44% more likely to develop dementia, with those younger than 70 particularly at risk (130% more likely to develop dementia). Previous studies have connected atrial fibrillation with vascular dementia; this finding extends it to all dementia types.
Another, smaller, study8 (135 patients) found that memory declined significantly faster in those with high blood pressure or atrial fabrillation.
Atrial fibrillation, the most common heart rhythm problem, has a strong genetic link, and is also a risk factor for stroke.
A very large seven-year study9 found that older adults who smoked were 50% more likely to develop dementia than people who had never smoked or no longer smoked. Smoking did not increase the risk for those with the Alzheimer’s gene apolipoprotein E4, but for those without the gene, smoking increased the risk by nearly 70%. Another large study10 found that heavy smokers developed the disease 2.3 years sooner, while heavy drinkers developed Alzheimer’s nearly 5 years earlier than those who were not. Those with the APOE e4 gene developed the disease three years sooner than those without the gene variant. These three risk factors were additive — those with all three developed the disease 8.5 years earlier than those with none of the risk factors.
A large national study11 also found that exposure to second-hand smoke also increases your risk.
Depression, stress & anxiety
Several studies12 have found evidence that depression, high level of stress or anxiety, and even loneliness, increase the risk of later developing dementia.
Other Possible Risk Factors
Findings from a study13 using genetically engineered mice suggests that people genetically predisposed to Alzheimer's disease or with excessive amounts of beta amyloid in their brains are at increased risk of developing the disease earlier if they receive high concentrations of oxygen, for example during or after surgery.
A large long-running study14 has found that women with both the lowest and the highest levels of thyrotropin (a hormone secreted by the pituitary gland that helps regulate thyroid gland function) had more than double the risk of developing Alzheimer's disease. No such association was found in men.
- Zubenko, G.S., Hughes, H.B. III & Stiffler, J.S. 2001. D10S1423 identifies a susceptibility locus for Alzheimer's disease in a prospective, longitudinal, double-blind study of asymptomatic individuals. Molecular Psychiatry, 6 (4), 413-419.
- Corneveaux, J.J. et al. In press. Evidence for an association between KIBRA and late-onset Alzheimer's disease. Neurobiology of Aging.
- Gatz, M. et al. 2006. Role of Genes and Environments for Explaining Alzheimer Disease. Archives of General Psychiatry, 63, 168-174.
- Mosconi, L. et al. 2007. Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism. PNAS, 104, 19067-19072.
- Debette, S. et al. 2009. Parental Dementia and Alzheimer Disease Are Associated with Poorer Memory in Middle-Aged Adults: The Framingham Offspring Study. Presented April 29 at the American Academy of Neurology's 61st Annual Meeting in Seattle, Washington.
- Mortimer, J,A., Snowdon, D.A. & Markesbery, W.R. 2008. Small Head Circumference is Associated With Less Education in Persons at Risk for Alzheimer Disease in Later Life. Alzheimer Disease & Associated Disorders, 22(3), 249-254.
- Bunch, T.J. et al. 2009. Atrial Fibrillation is Independently Associated with Senile, Vascular, and Alzheimer's Dementia. Presented Friday, May 15, at "Heart Rhythm 2009," the annual scientific sessions of the Heart Rhythm Society in Boston.
- Mielke, M.M. et al. 2007. Vascular factors predict rate of progression in Alzheimer disease. Neurology, 69, 1850-1858.
- Reitz, C., den Heijer, T., van Duijn, C., Hofman, A. & Breteler, M.M.B. 2007. Relation between smoking and risk of dementia and Alzheimer disease: The Rotterdam Study. Neurology, 69, 998-1005.
- Harwood, D. et al. 2008. Impact of Alcohol Use, Smoking and Apolipoprotein-E Epsilon 4 Allele (APOE 4) on Age of Onset of Late Onset Alzheimers Disease (LOAD). Presented at the American Academy of Neurology 60th Annual Meeting in Chicago, April 16.
- Llewellyn, D.J. et al. 2009. Exposure to secondhand smoke and cognitive impairment in non-smokers: national cross sectional study with cotinine measurement. British Medical Journal, 338, 462. Full text available here.
- Peavy, G.M. et al. 2007. The Effects of Prolonged Stress and APOE Genotype on Memory and Cortisol in Older Adults. Biological Psychiatry, 62 (5), 472-478.
Rapp, M.A. et al. 2006. Increased Hippocampal Plaques and Tangles in Patients With Alzheimer Disease With a Lifetime History of Major Depression. Archives of General Psychiatry, 63,161-167.
Wang, H. -X. et al. 2009. Personality and lifestyle in relation to dementia incidence. Neurology, 72, 253-259.
Wilson, R.S., Arnold, S.E., Beck, T.L., Bienias, J.L. & Bennett, D.A. 2008. Change in Depressive Symptoms During the Prodromal Phase of Alzheimer Disease. Archives of General Psychiatry, 65(4), 439-445.
Wilson, R.S., Schneider, J.A., Boyle, P.A., Arnold, S.E., Tang, Y. & Bennett, D.A. 2007. Chronic distress and incidence of mild cognitive impairment. Neurology, 68, 2085-2092.
Wilson, R.S., Krueger, K.R., Arnold, S.E., Schneider, J.A., Kelly, J.F., Barnes, L.L., Tang, Y. & Bennett, D.A. 2007. Loneliness and Risk of Alzheimer Disease. Archives of General Psychiatry, 64, 234-240.
Wilson, R.S., Evans, D.A., Bienias, J.L., Mendes de Leon, C.F., Schneider, J.A. & Bennett, D.A. 2003. Proneness to psychological distress is associated with risk of Alzheimer’s disease. Neurology, 61, 1479-1485.
Wilson, R.S., Barnes, L.L., de Leon, C.F.M., Aggarwal, N.T., Schneider, J.S., Bach, J., Pilat, J., Beckett, L.A., Arnold, S.E., Evans, D.A. & Bennett, D.A. 2002. Depressive symptoms, cognitive decline, and risk of AD in older persons. Neurology, 59, 364-370.
- Arendash, G.W. et al. 2009. Oxygen treatment triggers cognitive impairment in Alzheimer's transgenic mice. NeuroReport, 20 (12), 1087-1092.
- Tan, Z.S. et al. 2008. Thyroid Function and the Risk of Alzheimer Disease: The Framingham Study. Archives of Internal Medicine, 168(14), 1514-1520.