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A Positive Test for Lyme Disease Is Not Associated with Neuropsychiatric Disorders

Article In Brief

In a longitudinal study, researchers found no significant association between previous exposure (seropositivity) to the Lyme bacterium and incidental neuropsychiatric outcomes such as cognitive decline, dementia, depression, and disability in older adults.

Being exposed to a Lyme disease bacterium does not increase the risk of developing depression or dementia in older people, according to a paper published in the September 27 online issue of JAMA Neurology.

“The main message of the study was that just having a positive serological status for Borrelia burgdorferi is not a risk factor for cognitive decline, depressive symptoms, or functional decline. Laboratory or serological tests should always be performed to support a thorough clinical history or to corroborate a diagnosis when manifestations of disease are suspected,” lead investigator Virgilio Hernández Ruiz, MD, a geriatrician and attending physician in the department of geriatrics at the National Institute of Medical Sciences and Nutrition-Salvador Zubirán in Mexico City, told Neurology Today in an email.

This is one of a few longitudinal studies to examine the association between previous exposure to the Lyme bacterium and neuropsychiatric disorders, Dr. Ruiz said, noting that most previous studies were cross-sectional and lacked controls for confounding factors.

Study Design

To investigate the association, researchers from Mexico and France conducted a prospective six-year study of retired French farmworkers in rural southwestern France. The subjects—689 older adults (mean age 75.8; 62.2 percent men)—agreed to submit a blood sample and were randomly recruited from the Farmer's Health Insurance. All were participating in the Aging Multidisciplinary Investigation study cohort, an ongoing epidemiological prospective study of aging initiated in 2007.

“Being close to a rural environment (or a wooded area), the participants were thought to be more easily exposed to the etiologic agent of Lyme disease than participants of other epidemiologic studies mainly composed of urban populations,” said Dr. Ruiz.

The researchers sought to determine the relationship between previous exposure (seropositivity) to the Lyme bacterium and incidental neuropsychiatric outcomes such as cognitive decline, dementia, depression, and disability in older adults. At baseline, 6.5 percent of the sample tested positive for the Lyme bacterium and that group tended to be older, male, with more long-term diseases, and fewer depressive symptoms.

Clinicians assessed participants repeatedly between 2007 and 2016. A geriatrician performed the clinical examination, and a nurse took blood samples and obtained medical information. A trained psychologist used a battery of tests to assess cognitive decline, depressive symptoms, dementia, followed by a clinical evaluation and a review by an independent committee of neurologists. The investigators also assessed disability using tests for activities such as shopping and managing finances and basic activities of daily living such as bathing and eating.

The data analysis showed no significant statistical difference on the four neuropsychiatric outcomes between the participants that tested positive and those who tested negative.

Dr. Ruiz said they didn't draw any conclusion about the clinical manifestations of the disease because they didn't know when the participants were exposed to Lyme bacterium or if they received treatment. “Instead, we restricted our interpretation of the results to the association between the serological status and the studied outcomes. Indeed, for most of the cases, adequate detection and treatment of Lyme disease should limit its consequences.”

He also cautioned against generalizing the results from a specific cohort to a wider population and suggested that future studies include a clinical history of the disease and treatment status.

Expert Commentary

The lack of a meaningful signal indicating the presence of neuropsychiatric disease in people who tested positive for Lyme disease is consistent with previous systematic studies, including a large population-based study from Denmark published online October 9 in the journal Clinical Infectious Diseases. “Such studies have consistently found no long-term risk of dementia or other neuropsychiatric disease in Lyme positive patients”, said John J. Halperin, MD, FAAN, chair of the department of neurosciences at Overlook Medical Center, and professor of neurology and medicine at Sidney Kimmel Medical College of Thomas Jefferson University.

“Although the study can't address causality, nonetheless, the findings add further reassurance for patients with dementia who may have feared their cognitive decline was due to past exposure to Lyme disease and wished they had been tested earlier and treated for Lyme disease,” said Dr. Halperin.

Moreover, some doctors and patients believe that patients with dementia should be routinely tested for Lyme disease. “This study argues against such routine testing, unless there's another good reason to do so, such as a likely history of tick exposure, consistent skin rash, or more typical joint or neurologic symptoms,” said Dr. Halperin.

The study's strengths were its prospective design and unbiased sample. The limitations were the relatively small sample size and the lack of clinical information about exposure and treatment. “Even if someone unknowingly contracted Lyme disease, and subsequently took amoxicillin for something else, inadvertently curing the Lyme disease, it is difficult to imagine a way the fully treated Lyme disease would go on to cause dementia.”

Gary Wormser, MD, chief of infectious diseases and vice-chair of the department of medicine at New York Medical College, found the findings reassuring. “This is a further piece of evidence collected in a systematic way that shows that Lyme disease is not a cause of unexplained dementia or certain psychiatric disorders.”

He and his colleagues have studied whether early Lyme disease was associated with depression. Although at baseline before antibiotic therapy, Lyme disease patients had significantly higher depression scores on the Beck Depression Inventory than matched controls, there was no difference at six or 12 months. “We think the higher scores at baseline reflected somatic symptoms from being acutely ill from Lyme disease.”

He added: “There's an amazing amount of confusion surrounding Lyme disease—many activists and some physicians have a different perspective on Lyme disease than mainstream medical practitioners. This has led to the concept that Lyme disease is responsible for a large variety of medical symptoms and conditions including dementia, without convincing scientific evidence to support these contentions.”

Some of the confusion surrounding the disease is based on a misunderstanding of Lyme serologic testing. For a variety of reasons, background seropositivity rates can be as high as 9 percent in asymptomatic populations in certain geographic areas in the United States, according to Dr. Wormser.

Background seropositivity can occur from false-positive tests or from having been infected with Borrelia burgdorferi in the past “that was either purposefully or inadvertently treated with antibiotics, or alternatively, that self-resolved. Therefore, just because a person has a positive test, it does not mean that the patient's illness is in any way related to this test result,” said Dr. Wormser.

To diagnose the Lyme rash, laboratory testing isn't useful because this manifestation typically occurs before antibodies develop. “On the other hand, the vast majority of patients with non-cutaneous manifestations should test positive; indeed, 100 percent of patients with Lyme arthritis should have antibodies to the bacteria that cause Lyme disease, because it is a late manifestation of the illness,” said Dr. Wormser.

Serologic testing is expected to remain positive for a substantial period of time, extending to years in some cases after antibiotic treatment and resolution of the patient's symptoms. “Therefore, serologic testing should not be used as a test-of-cure,” said Dr. Wormser.


Dr. Ruiz had no disclosures. Dr. Halperin is a chapter author for UpToDate and Medlink and has received royalties from books on encephalitis and the book, Lyme Disease: An Evidence-Based Approach. Dr. Wormser reports receiving research grants from Immunetics, Inc., Institute for Systems Biology, Rarecyte, Inc., and Quidel Corporation. He owns equity in Abbott/AbbVie, has been an expert witness in malpractice cases involving Lyme disease, and is an unpaid board member of the American Lyme Disease Foundation.

Link Up for More Information

• Ruiz VH, Edjolo A, Roubaud-Baudron C, et al. Association of seropositivity to Borrelia burgdorferi with the risk of neuropsychiatric disorders and functional decline in older adults the Aging Multidisciplinary Investigation Study JAMA Neurology 2019; Epub 2019 Sep 27.
    • Haahr R, Tetens MM, Dessau RB, et al Risk of neurological disorders in patients with European Lyme neuroborreliosis. A nationwide population-based cohort study Clin Infect Dis 2019; Epub 2019 Oct 9.
      • Wormser GP, Park K, Madison C, et al. Evaluation of prospectively followed adult patients with erythema migrans using the Beck Depression Inventory Second Edition Am J Med 2019; 132:519–524.
        • Wormser GP, Strle F, Shapiro ED, et al. A critical appraisal of the mild axonal peripheral neuropathy of late neurologic Lyme disease Diagn Microbiol Infect Dis 2017;87: 163–167.