Interaction of Stress, Lead Burden, and Age on Cognition in Older Men: The VA Normative Aging Study

Junenette L. Peters; Marc G. Weisskopf; Avron Spiro III; Joel Schwartz; David Sparrow; Huiling Nie; Howard Hu; Robert O. Wright; Rosalind J. Wright


Environ Health Perspect. 2010;118(4):505-510. 

In This Article


A total of 811 participants in the NAS who completed the MMSE also had a lead measurement (blood, patella, or tibia) and at least one stress measure (self-report of the most stressful life event or the PSS). Table 1 summarizes participant characteristics as well as stress, cognition, and lead measures. In bivariate analyses, none of the lead measures or covariates were associated with either stress measure. This was also true for the relationship of the covariates with lead measures.

The differences between those with and without bone lead measurements have been reported elsewhere (Weisskopf et al. 2004; Wright et al. 2003). For those with a measure of their most stressful event versus those without, we noted no differences in any covariate or lead measure except for education (those who provided this stress measure had slightly higher education).

The most stressful life event measure was significantly associated with a 0.44 lower [95% confidence interval (CI), –0.77 to –0.10] MMSE score. This is equivalent to the effect of 6.4 years of age in our data. Higher PSS scores were also associated with a 0.20 lower MMSE score, although this did not quite reach statistical significance (95% CI, –0.43 to 0.03). No interaction was observed with age for either the most stressful event score or the PSS.

Both stress measures showed a trend toward negatively modifying the association of lead on cognition. Only the interaction between PSS and log blood lead was significant. Among men with higher PSS scores, an IQR increment in log blood lead was associated with a significant 0.57 lower (95% CI, –0.90 to –0.24) MMSE score, but among men with lower PSS scores, this same increase in log blood lead was associated with a nonsignificant 0.05 lower MMSE score (95% CI, –0.36 to 0.26), a –0.52 difference per IQR of log blood lead by stress (p-interaction = 0.02) (Table 2; Figure 1). A marginal negative interaction was also found between PSS and log patella lead (p-interaction = 0.06) (Table 2). In analyses of untransformed lead measurements excluding those identified as lead outliers (n = 7 for patella and n = 8 for blood) by the ESD procedure, we observed a stronger negative interaction between PSS and patella lead on the MMSE score (p-interaction = 0.02), although the interaction between PSS and blood lead was not significant (p-interaction = 0.23).

Figure 1.

The relationship of log blood lead to predicted MMSE by high PSS (A) and by low PSS (B).

Based on the positive two-way interaction with PSS, we investigated the association of the relationship with age for each of the PSS–lead categories: high stress–high lead, high stress–low lead, and low stress–high lead compared with low stress–low lead (Table 3). For blood lead and PSS, none of the groups (high stress–high lead, high stress–low lead, low stress–high lead) differed from each other, but they differed significantly from the low stress–low lead group in their interaction with age to predict MMSE score (Figure 2). For each year increase in age, we noted that the participants in these stress–lead categories showed a significantly greater reduction in the MMSE score than did those in the low stress–low lead group. For the PSS–lead categories for patella lead, only the low stress–high lead group showed significant interactions with age.

Figure 2.

Relationship between age and predicted MMSE scores (A) by combined high or low PSS and high or low blood lead categories with at least one high on either or both and (B) by low PSS and low blood lead.


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