Symptomatic herpes viruses were associated with several neurologic and cognitive features, however, not with Alzheimer’s disease processes, a longitudinal cohort study showed.
Among older adults who mainly were cognitively normal, herpes simplex virus infection was connected with accelerated tissue loss in brain white matter as time passes, particularly in the temporal lobe, in accordance with Keenan Walker, PhD, of the NIH National Institute on Aging in Baltimore, and colleagues.
However, there is no association between herpes simplex virus infection and changes in volumes of total brain, total gray matter, or in areas connected with Alzheimer’s disease, they reported in Neurology.
Infection was linked with accelerated longitudinal declines in attention and elevated plasma degrees of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes and neuroinflammation. It had been not connected with plasma amyloid-beta 42/40 ratios or neurofilament light (NfL) levels.
“We didn’t find evidence that herpetic infection is connected with measures of Alzheimer’s-specific disease processes, including brain volumes susceptible to atrophy in Alzheimer’s disease, verbal memory performance, and a way of measuring amyloid plaque burden,” Walker told MedPage Today.
Whether infections can trigger Alzheimer’s disease has been debated for a long time, and new research about herpes has fueled the controversy.
“An infectious origin of Alzheimer’s disease has received renewed attention, with a specific concentrate on human herpes viruses along with other inflammatory factors,” Walker noted. “However, the consequences of the viruses on brain structure and cognition as time passes remain poorly understood, as do their effects on Alzheimer’s and neurodegeneration biomarkers.”
Earlier studies have identified human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) in postmortem Alzheimer’s brain tissue samples at levels around doubly high as non-Alzheimer’s samples, leading researchers to take a position whether HHV-6A and HHV-7 DNA could regulate the expression of genes associated with Alzheimer’s.
Other investigators have proposed a combination of herpes virus 1 (HSV-1) and the APOE4 gene may increase Alzheimer’s risk. And earlier this month, a lab study suggested varicella zoster virus could are likely involved in Alzheimer’s by reactivating HSV-1.
Walker and colleagues evaluated 1,009 participants in the Baltimore Longitudinal Study of Aging (BLSA), 98% of whom were cognitively normal at baseline MRI. Comprehensive cognitive assessments started between 1984 and 1993 and 3T MRIs were initiated in 2009 and 2010. Plasma biomarkers were measured during the original MRI.
Study visits occurred biannually until 2005, then every 1 to 4 years based on age. Participants entered the analysis at differing times and had different follow-up periods. Serial brain MRIs occurred over 3.4 years and cognitive exams over 8.6 years, normally.
Health background reports were used to recognize herpes diagnoses. Participants with diagnostic codes that corresponded to chicken pox weren’t classified as having symptomatic herpes viruses in the analysis. There is no serological testing for human herpesviruses in the BLSA and the specificity of virus documentation cannot be independently verified.
Overall, 119 participants had an archive of symptomatic herpes infection. Having contamination was connected with longitudinal reductions in white matter volume (annual additional rate of change -0.34 cm3/year, P=0.035), notably in the temporal lobe. Contact with antiviral treatment attenuated declines in occipital white matter (P=0.04).
Although participants with a herpes diagnosis had higher cognitive scores at baseline, they showed greater longitudinal reductions in attention performance (annual additional rate of change -0.01 Z-score/year, P=0.008). Infected participants maintained elevated plasma degrees of GFAP, an indicator of reactive astrogliosis.
The analysis had several limitations, the researchers acknowledged. Inaccurate reporting or undiagnosed herpes simplex virus infection could have resulted in misclassifications. The observational time window to assess relationships with Alzheimer’s processes might have been too short, and unmeasured variables could have influenced results.
Despite its limitations, the analysis indicates that herpes simplex virus is connected with steeper declines in white matter volume and in attention, a cognitive domain particularly susceptible to disruptions in white matter integrity, Walker and colleagues noted. The outcomes provide evidence for a connection between herpes infection and GFAP.
“These findings highlight the neurobiological correlates of herpetic infection in older adults and suggest potential pathways where herpetic infection may influence dementia risk,” they wrote.
The analysis was supported by the National Institute on Aging Intramural Research Program.
Walker and co-authors disclosed no relationships with industry.