Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections—a Nationwide, Population-Based Cohort Study in Taiwan

Tzeng, Nian Sheng; Chung, Chi Hsiang; Lin, Fu Huang; Chiang, Chien Ping; Yeh, Chin Bin; Huang, San Yuan; Lu, Ru Band; Chang, Hsin‐An; Kao, Yu Chen; Yeh, Hui Wen; Chiang, Wei Shan; Chou, Yu Ching; Tsao, Chang Huei; Wu, Yung-Fu; Chien, Wu Chien

doi:10.1007/s13311-018-0611-x

Cited by 271 publications

(270 citation statements)

References 60 publications

(70 reference statements)

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“…The re-emergence of HHV-6A in this new dataset provides an encouraging consistency in viral signal. In combination with the findings of many other investigators 3,4,6,7,13,[15][16][17][18][19][20][21] these new data also support the utility of a systematic, coordinated effort to characterize the brain microbiome in AD.…”

Section: Introductionsupporting

confidence: 72%

“…These reports have accelerated even further recently, including reports of Herpesviridae induced seeding of Aβ fibrillation in transgenic AD mouse and 3D organoid model systems 3 . In a population-based cohort study in Taiwan, Tzeng et al 4 observed an increased dementia risk following HSV-1 infection. These authors reported that the dementia risk in this cohort post HSV-1 infection appeared to be almost completely abolished by antiviral use.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Further evidence of increased human Herpesvirus in Alzheimer’s disease

Readhead

Haure‐Mirande

Ehrlich

et al. 2019

Preprint

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The recent coordination of scientific and political efforts within the field of Alzheimer's disease (AD) research coupled with the rapid evolution of molecular profiling technologies has enabled the generation of unprecedented repositories of biological sequence data available for investigation by the scientific community. Next-generation sequences (NGS) represent complex readouts of cellular transcriptomic and genomic states, and hold the potential to illuminate disease biology via unexpected applications of collected data. We recently reported a multiomic study of the Alzheimer's associated brain virome, leveraging NGS data to understand the potential relevance of viral activity to AD. We observed increased abundance of human herpesvirus 6A (HHV-6A), HHV-7, and herpes simplex virus 1 (HSV-1) genomes in banked postmortem brains from subjects with AD compared with controls.These results were replicated in two additional, independent and geographically dispersed cohorts. Although these findings might be of general interest to the field, such analyses present novel methodological challenges that have not been well characterized. The viral abundances that we detected were generally quite low, and, in many samples, no virome was detected. We sought to understand whether such sparsity might be associated with the spurious detection of differential abundance. Herein, we employ a simulation approach, which indicates that sparsity in abundance actually biases against the detection of significant differences between AD and control subjects. We also report new results based on previously unpublished whole genome sequences that show increases in both abundance and prevalence of HHV-6A in AD, consistent with our previously reported results. These findings, as well as reports from many other groups employing a variety of approaches, support the dedication of a coordinated effort toward a comprehensive characterization of the microbiome of the brain affected by AD. Such studies should advance our understanding of the potential clinical relevance of these observations.

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Section: Introductionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

Further evidence of increased human Herpesvirus in Alzheimer’s disease

Readhead

Haure‐Mirande

Ehrlich

et al. 2019

Preprint

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“…Most recently, a 16-year long study involving over 33,000 patients found HSV1 infection increases AD risk 2.5 fold (Tzeng et al, 2018). Moreover, long-term administration of anti-herpetic medications appears to reduce AD risk for HSV1 infected patients.…”

Section: Discussionmentioning

confidence: 99%

Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection

Eimer

Kumar

Shanmugam

et al. 2018

Neuron

517

371

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SUMMARY Amyloid-β peptide (Aβ) fibrilization and deposition as β-amyloid are hallmarks of Alzheimer’s disease (AD) pathology. We recently reported Aβ is an innate immune protein that protects against fungal and bacterial infections. Fibrilization pathways mediate Aβ antimicrobial activities. Thus, infection can seed and dramatically accelerate β-amyloid deposition. Here, we show Aβ oligomers bind herpesvirus surface glycoproteins, accelerating β-amyloid deposition and leading to protective viral entrapment activity in 5XFAD mouse and 3D human neural cell culture infection models against neurotropic herpes simplex virus 1 (HSV1) and human herpesvirus 6A and B. Herpesviridae are linked to AD, but it has been unclear how viruses may induce β-amyloidosis in brain. These data support the notion that Aβ might play a protective role in CNS innate immunity, and suggest an AD etiological mechanism in which herpesviridae infection may directly promote Aβ amyloidosis.

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“…8 Recent studies carried out on genital herpes infections have been linked to dementia. 10 Other population-based studies have also shown that viral diseases of the skin, such as herpes simplex or herpes zoster infections, were associated with the increased risk of dementia, [11][12][13][14][15][16] and some studies have observed that treatment with antiherpetic antiviral medications could attenuate the risk of developing dementia in patients with herpetic virus infection. 17,18 Several studies have shown that HPV may be detected in neurological diseases, for example, in the brains of patients with pediatric epilepsy 19,20 and Rasmussen's encephalitis.…”

Section: Introductionmentioning

confidence: 99%

Increased risk of dementia in patients with genital warts: A nationwide cohort study in Taiwan

Lin

Chien

Chung

et al. 2020

The Journal of Dermatology

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Genital warts are a common sexually transmitted disease caused by human papillomavirus (HPV) infections. The prevalence of dementia is 4-8% in those aged 65 years or older in Taiwanese community studies, with a high social and economic burden for patients, family caregivers, the community and society. Previous studies have shown that viral infections such as herpes simplex and herpes zoster were associated with dementia. This study aimed to investigate the association between dementia and HPV infections. A population-based cohort study using data from Taiwan's National Health Insurance Research Database was conducted. Fine and Grays's survival analysis was employed to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the association between genital warts and dementia. From all of the potential participants aged 50 years or more, a total of 16 116 patients were enrolled, including 4029 genital warts-infected patients, with 12 087 sex-, age-and indexed date-matched controls (1:3). The cumulative incidences of dementia were 10.72 per 10 3 person-years and 6.43 per 10 3 person-years in the genital warts and control group, respectively. There were 475 dementia cases from the genital warts cohort during the follow-up period of 15 years. The adjusted HR for dementia was 1.485 (95% CI, 1.321-1.668; P < 0.001) for genital warts patients after adjusting for all of the covariates. Our study indicates that genital warts infection may increase the risk of dementia.

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Anti-herpetic Medications and Reduced Risk of Dementia in Patients with Herpes Simplex Virus Infections—a Nationwide, Population-Based Cohort Study in Taiwan

Cited by 271 publications

References 60 publications

Further evidence of increased human Herpesvirus in Alzheimer’s disease

Further evidence of increased human Herpesvirus in Alzheimer’s disease

Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection

Increased risk of dementia in patients with genital warts: A nationwide cohort study in Taiwan

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