The influence of latent viral infection on rate of cognitive decline over 4 years

OBJECTIVES: To examine whether cytomegalovirus (CMV) and herpes simplex virus type-1 (HSV-1) are associated with cognitive decline over a 4-year period and to assess whether C-reactive protein (CRP) modifies these relationships. DESIGN: Prospective cohort study over a 4-year period. SETTING: Community-dwelling elderly population. PARTICIPANTS: The sample was a subset (1,204/1,789) of participants in the Sacramento Area Latino Study on Aging (SALSA) aged 60 to 100. MEASUREMENTS: Participants were screened annually over a 4-year period for cognitive function and episodic memory. Cognitive function was assessed using the modified Mini-Mental State Examination, and episodic memory was assessed using a word list-learning test of delayed recall. Baseline serum samples were assayed for levels of immunoglobulin G antibodies to CMV and HSV-1 and for levels of CRP. RESULTS: There was a significantly higher rate of cognitive decline over the 4-year period in subjects with the highest CMV antibody levels at baseline than in individuals with the lowest levels (beta = -0.053, standard error = 0.018; P = .003), after controlling for age, sex, education, income, and chronic health conditions. There was no association between HSV-1 antibody levels and cognitive decline. CRP did not modify the relationship between viral antibody levels and cognitive decline. CONCLUSION: This is the first study to show that individuals with higher levels of antibody to CMV experience a more-rapid rate of cognitive decline than those with lower levels. Understanding the mechanisms by which CMV influences cognition may aid development of intervention strategies targeting infection, viral reactivation, and immune response over the life course.