Herpes Viruses in the Baltimore Longitudinal Study of Aging:Associations with Brain Volumes, Cognitive Performance and Plasma Biomarkers

Abstract

AbstractBackgroundAlthough an infectious etiology of Alzheimer’s Disease (AD) has received renewed attention, the longitudinal effects of symptomatic herpes viruses (sHHV) infection on brain structure and cognition remain poorly understood, as does the effect of sHHV on AD/neurodegeneration biomarkers.MethodUsing data from the Baltimore Longitudinal Study of Aging (BLSA), we characterize the association of sHHV diagnoses – defined using ICD‐9 classification – with longitudinal changes in total and regional brain volumes obtained from 3T magnetic resonance imaging (MRI), and cognitive performance across five cognitive domains. Additionally, we relate sHHV to plasma biomarkers of AD (Ab42/40), astrogliosis (glial fibrillary acidic protein [GFAP]) and neurodegeneration (neurofilament light [NfL]). The study design is illustrated in Figure 1.ResultA total of 1,009 participants were included in the primary MRI analysis, 98% of whom were cognitively normal at baseline MRI. Having a sHHV diagnosis (N = 119) was associated with longitudinal reductions in white matter volume (annual additional rate of change ‐0.34 cm3; p = 0.035), particularly in the temporal cortex; however, there was no association between sHHV and change in total brain, total gray matter, or AD signature region volume (Table 1; Figure 2). Among the 119 participants with sHHV infection, exposure to antiviral treatment attenuated declines in occipital white matter (annual reduction in rate of change 0.10 cm3; p = 0.036). Although the sHHV group (N = 290) had higher cognitive scores on certain cognitive domains at baseline, sHHV diagnosis was associated with accelerated longitudinal declines in attention (annual additional rate of change ‐0.01 Z‐score; p = 0.008) (Figure 3). In cross‐sectional analyses, sHHV diagnosis (N = 83) was associated with elevated plasma GFAP (Figure 4). However, sHHV was unrelated to plasma Ab42/40 and NfL levels.ConclusionThese findings suggest an association of sHHV infection with white matter volume loss, attentional decline, and astrogliosis. Although the findings link sHHV to several neurocognitive features, the results do not support an association between sHHV and AD‐specific disease processes.