Neurology -- Correspondence for Ngandu et al., 69 (14) 1442-1450

Correspondence published:

Education and dementia: What lies behind the association?: Timo E. Strandberg, Kaisu H. Pitkala, Pentti J. Tienari, Reijo S. Tilvis (5 March 2008)

Reply from the authors: Tiia Ngandu, Miia Kivipelto (5 March 2008)

Education and dementia: What lies behind the association? 5 March 2008

Timo E. Strandberg,
Dept. of Public Health Science & General Practice University of Oulu & University Hospital
PO Box 5000, FIN-90014 OULUN YLIOPISTO, Finland,
Kaisu H. Pitkala, Pentti J. Tienari, Reijo S. Tilvis
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Re: Education and dementia: What lies behind the association?

timo.strandberg{at}oulu.fi Timo E. Strandberg, et al.

In their article, Ngandu et al. analyzed the association between low education and dementia. [1] They concluded that the findings provide evidence against the brain battering hypothesis. We present possible evidence to the contrary from our ongoing Drugs and Evidence Based Medicine in the Elderly (DEBATE) study. At baseline in 2000, this study involved 400 urban, home-dwelling elderly persons (average age at baseline 80 years, 65% women) with cardiovascular disease. [2]
We previously found that among the DEBATE participants, cognitive impairment was significantly associated with higher viral pathogen burden (seropositivity for herpes simplex virus type 1 [HSV-1], herpes simplex virus type 2 [HSV-2], or cytomegalovirus [CMV]). [2] These findings concur with other data concerning the connection between cognitive decline/Alzheimer disease and viral infection. [3,4] However, a relationship between socioeconomic position and immune response to latent infection was recently demonstrated. [5] We examined the association between viral seropositivity and education in our elderly population. Because ApoE4 carrier status was associated with cognitive decline, we also included ApoE status in the analyses.
We knew the type of education and viral burden of 380 participants (95%) in the DEBATE study. Education was dichotomized according to schooling: Finnish elementary school only (duration 6 to 8 years or less, n=142) vs. 9 or more years of education (n=238). Viral burden was defined as low (only one seropositivity, n=48), medium (two seropositivities, n=227) or high (three seropositivities, n=105). There was a significant inverse relationship (p=0.0001) between education and viral burden: 38.0% (n=54) and 21.4% (n=51) of those with low and higher education, respectively, had high viral burden.
There tended to be more ApoE4 carriers among those with low education, but nominal significance level was not reached (p=0.06). In multivariate analyses (adjusted for age, sex, diabetes, history of myocardial infarction, and cardiovascular risk factors) less schooling was significantly associated with ApoE4 (OR 1.59, 95% CI 1.01 to 2.52) and high viral burden (OR 2.14, 95% CI 1.37 to 3.35).
The relationship between viral disease and dementia has been controversial but we suggest that higher viral pathogen burden among individuals with less schooling may partially explain the association between education and dementia.
References
1. Ngandu T, von Strauss E, Helkala E-L, et al. Education and dementia. What lies behind the association? Neurology 2007;69:1442-1450.
2. Strandberg TE, Pitkala K, Eerola J, Tilvis R, Tienari PJ. Interaction of herpesviridae, APOE gene, and education in cognitive impairment. Neurobiol Aging. 2005;26:1001-1004.
3. Itzhaki RF, Wozniak MA. Herpes simplex virus type 1, apolipoprotein E, and cholesterol: a dangerous liaison in Alzheimer's disease and other disorders. Prog Lipid Res. 2006;45:73-90.
4. Aiello AE, Haan M, Blythe L, Moore K, Gonzalez JM, Jagust W. The influence of latent viral infection on rate of cognitive decline over 4 years. J Am Geriatr Soc 2006;54:1046-1054.
5. Dowd JB, Haan MN, Blythe L, Moore K, Aiello AE. Socioeconomic gradients in immune response to latent infection. Am J Epidemiol 2007 Sep 14; (Epub ahead of print).
Disclosure: The authors report no conflicts of interest.

Reply from the authors 5 March 2008

Tiia Ngandu,
Aging Research Center, Karolinska Institute
G�vlegatan 16, 11330 Stockholm, Sweden,
Miia Kivipelto
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Re: Reply from the authors

tiia.ngandu{at}ki.se Tiia Ngandu, et al.

We thank Professor Strandberg et al. for their interest in our recent article. [1] We showed that low education increases the risk of dementia despite various lifestyle and cardiovascular risk factors.
Strandberg et al. suggest that higher viral burden among people with low education might explain the association between education and dementia. While this is an interesting hypothesis, it was not demonstrated by the findings they mention from the DEBATE study. The authors showed a link between low education and high viral burden, but no evidence that viral burden would be the factor explaining the association between education and dementia.
Previous findings from the DEBATE showed that neither education nor viral burden on their own but in combination were associated with an increased prevalence of cognitive decline. [2] The findings are interesting but the small size of the population, the selective nature of the population, and cross-sectional study design must be considered.
In addition to the DEBATE study, there is some limited evidence linking viruses to AD pathologic changes in the brain or an increased risk of cognitive decline and dementia. [3-4] It will be interesting to see if the viral hypothesis can be confirmed by large scale, prospective, population-based studies or by experimental studies.

The authors report no conflicts of interest.