Postherpetic Neuralgia After Herpes Zoster and Incident Dementia Risk

NCT07399288 | Completed

• 1 other identifier: CMUH114-REC3-226
• Study Type: observational
• Target: 68,786
• Locations: 1 country
• Sites: 1

Brief Summary

This retrospective observational cohort study uses de-identified electronic health record data from the TriNetX Global Collaborative Network to evaluate whether postherpetic neuralgia after herpes zoster is associated with an increased risk of incident dementia. Adults aged 40 to 120 years with incident herpes zoster between 1 October 2015 and 31 December 2024 are identified using diagnostic codes. Postherpetic neuralgia is defined by International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) codes B02.22 or B02.29 recorded between 90 and 365 days after the index herpes zoster date, and comparators have no such codes within 365 days after index. The primary analysis uses 1:1 propensity score matching and a 365-day landmark design, including only individuals alive and free of dementia at the landmark. Time-to-event analyses estimate hazard ratios for incident dementia and related outcomes.

Conditions

Herpes Zoster; Dementia; Postherpetic Neuralgia (PHN)

Keywords

Landmark analysis; Propensity score matching; TriNetX; Alzheimer disease; Vascular dementia; Zoster vaccination; Negative control outcome

Outcome Measures

Primary Outcomes (1)

• Incident all-cause dementia

  Incident all-cause dementia is identified using ICD-10-CM codes F01, F02, F03, or G30. Individuals with any record of dementia before the 365-day landmark are excluded from the risk set.

  From the 365-day landmark after the index herpes zoster date to the earliest of the first record of dementia, death, loss to follow-up, or 31 December 2024.

Secondary Outcomes (6)

• Alzheimer disease

  From the 365-day landmark after the index herpes zoster date to the earliest of the first record of Alzheimer disease, death, loss to follow-up, or 31 December 2024.

• Vascular dementia

  From the 365-day landmark after the index herpes zoster date to the earliest of the first record of vascular dementia, death, loss to follow-up, or 31 December 2024.

• Other or unspecified dementia

  From the 365-day landmark after the index herpes zoster date to the earliest of the first record of other or unspecified dementia, death, loss to follow-up, or 31 December 2024.

• All-cause mortality

  From the 365-day landmark after the index herpes zoster date to the earliest of death, loss to follow-up, or 31 December 2024.

• Ischaemic stroke

  From the 365-day landmark after the index herpes zoster date to the earliest of the first record of ischaemic stroke, death, loss to follow-up, or 31 December 2024.

Other Outcomes (1)

• Acute appendicitis (negative control outcome)

  From the 365-day landmark after the index herpes zoster date to the earliest of the first record of acute appendicitis, death, loss to follow-up, or 31 December 2024.

Study Arms (2)

Postherpetic neuralgia (PHN)

Adults aged 40 to 120 years with incident herpes zoster between 1 October 2015 and 31 December 2024 who had a recorded postherpetic neuralgia diagnosis (ICD-10-CM B02.22 or B02.29) between 90 and 365 days after the index herpes zoster date. Follow-up begins at a 365-day landmark after index among individuals alive and free of dementia at the landmark.

Other: Exposure: postherpetic neuralgia

Non-PHN comparator

Adults aged 40 to 120 years with incident herpes zoster between 1 October 2015 and 31 December 2024 with no recorded postherpetic neuralgia diagnosis (ICD-10-CM B02.22 or B02.29) within 365 days after the index herpes zoster date. Follow-up begins at a 365-day landmark after index among individuals alive and free of dementia at the landmark.

Interventions

Exposure: postherpetic neuralgia OTHER

This is an observational study and no treatment is assigned by the investigators. The intervention of interest is exposure status defined by recorded diagnoses of postherpetic neuralgia after herpes zoster, based on ICD-10-CM codes B02.22 or B02.29 within 90 to 365 days after the index herpes zoster date.

Postherpetic neuralgia (PHN)

Eligibility Criteria

• Age: 40 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The study population comprises adults aged 40 to 120 years with incident herpes zoster identified in the TriNetX Global Collaborative Network from 1 October 2015 to 31 December 2024. Exposure groups are defined by the presence or absence of recorded postherpetic neuralgia diagnoses within 90 to 365 days after the index herpes zoster date. Follow-up for outcomes starts at a 365-day landmark after index among individuals alive and free of the outcome at the landmark. Replication analyses are performed in the TriNetX Asia Pacific (APAC) network.

You may qualify if:

• Adults aged 40 to 120 years with an incident herpes zoster diagnosis recorded between 1 October 2015 and 31 December 2024 in the TriNetX network.
• A 3-year washout period with no recorded herpes zoster diagnosis before the index date.
• Eligible for analysis at the 365-day landmark after the index date, defined as being alive and free of the specified outcome at the landmark.

You may not qualify if:

• Any record of the specified outcome before the 365-day landmark.
• Missing data elements required to define exposure status within the prespecified time window.

Sponsors & Collaborators

• China Medical University Hospital: lead

Study Sites (1)

China Medical University Hospital

Taichung, Taichung City, 40447, Taiwan

Location

Related Publications (3)

• Stein E, Huser M, Amirian ES, Palchuk MB, Brown JS. TriNetX Dataworks-USA: Overview of a Multi-Purpose, De-Identified, Federated Electronic Health Record Real-World Data and Analytics Network and Comparison to the US Census. Pharmacoepidemiol Drug Saf. 2025 Sep;34(9):e70198. doi: 10.1002/pds.70198.

  PMID: 40915660 BACKGROUND

• Warren-Gash C, Williamson E, Shiekh SI, Borjas-Howard J, Pearce N, Breuer JM, Smeeth L. No evidence that herpes zoster is associated with increased risk of dementia diagnosis. Ann Clin Transl Neurol. 2022 Mar;9(3):363-374. doi: 10.1002/acn3.51525. Epub 2022 Feb 16.

  PMID: 35170873 BACKGROUND

• Forbes HJ, Thomas SL, Smeeth L, Clayton T, Farmer R, Bhaskaran K, Langan SM. A systematic review and meta-analysis of risk factors for postherpetic neuralgia. Pain. 2016 Jan;157(1):30-54. doi: 10.1097/j.pain.0000000000000307.

  PMID: 26218719 BACKGROUND

Related Links

• TriNetX: Real-world data for the life sciences and healthcare

MeSH Terms

Conditions

Herpes Zoster; Dementia; Neuralgia, Postherpetic; Alzheimer Disease; Dementia, Vascular

Condition Hierarchy (Ancestors)

Varicella Zoster Virus Infection; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders; Neuralgia; Peripheral Nervous System Diseases; Neuromuscular Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Tauopathies; Neurodegenerative Diseases; Cerebrovascular Disorders; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Leukoencephalopathies; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• En-Bo Wu, MD

  China Medical University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2026
• First Posted: February 10, 2026
• Study Start: October 1, 2015
• Primary Completion: December 31, 2024
• Study Completion: December 31, 2024
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)