Infectious diseases and cognition: do we have to worry?

Hernandez-Ruiz, Virgilio; Letenneur, Luc; Fülöp, Tamás; Helmer, Catherine; Roubaud-Baudron, C.; Avila-Funes, J Alberto; Amieva, Hélène

doi:10.1007/s10072-022-06280-9

Cited by 16 publications

(10 citation statements)

References 96 publications

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“…In a study of over one million Danish adults, infectious diseases-but not autoimmune disorders-were associated with a 1.5-fold increase in dementia risk later in life [127]. Similar findings have been documented in other settings [128,129], and across various classes of infectious diseases [130]. The antiinflammatory effects of antidepressants are often cited as desirable in the context of neuropsychiatric disorders associated with inflammation.…”

Section: Antidepressants and Infection: Immunosuppressive Effects?supporting

confidence: 56%

Resolving a paradox: antidepressants, neuroinflammation, and neurodegeneration

Rajkumar

2024

Explor Neuroprot Ther

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Depression is a known risk factor for dementia. Antidepressants are the most commonly used treatment for this condition, and are effective in at least half to two-thirds of cases. Extensive evidence from in vitro and animal models suggests that antidepressants have anti-inflammatory and neuroprotective properties. These effects have been shown to reduce the oxidative damage, amyloid aggregation, and expression of pro-inflammatory genes associated with animal models of neurodegenerative disorders. However, longitudinal research in humans has shown that antidepressants do not protect against dementia, and may even be associated with a risk of cognitive deterioration over time in older adults. The contrast between two sets of findings represents a paradox of significant clinical and public health significance, particularly when treating depression in late life. This review paper attempts to resolve this paradox by critically reviewing the medium- and long-term effects of antidepressants on peripheral immune-inflammatory responses, infection risk, gut microbiota, and neuroendocrine responses to stress, and how these effects may influence the risk of neurodegeneration. Briefly stated, it is possible that the peripheral actions of antidepressant medications may antagonize their beneficial effects against neuroinflammation. The implications of these findings are then explored with a particular focus on the development and testing of multimodal neuroprotective and anti-inflammatory treatments that could reduce the risk of Alzheimer’s and related dementias in patients suffering from depression.

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Section: Antidepressants and Infection: Immunosuppressive Effects?supporting

confidence: 56%

Resolving a paradox: antidepressants, neuroinflammation, and neurodegeneration

Rajkumar

2024

Explor Neuroprot Ther

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“…Finally, further investigation of a more chronic time course may reveal novel insights into the potential long-term consequences of TBI and infection, even if the infection is transient and contained. For example, patients who survive acute infections may be vulnerable to long-term complications including neurocognitive dysfunction [82,83]. In a mouse model of intranasal K. pneumoniae-induced pneumosepsis treated with ceftriaxone, even after the resolution of infection, surviving mice showed deficits in exploratory locomotor behavior associated with persistent brain inflammatory gene expression [64].…”

Section: Discussionmentioning

confidence: 99%

Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury

Shad,

Rewell,

Macowan

et al. 2024

J Neuroinflammation

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Pneumonia is a common comorbidity in patients with severe traumatic brain injury (TBI), and is associated with increased morbidity and mortality. In this study, we established a model of intratracheal Klebsiella pneumoniae administration in young adult male and female mice, at 4 days following an experimental TBI, to investigate how K. pneumoniae infection influences acute post-TBI outcomes. A dose-response curve determined the optimal dose of K. pneumoniae for inoculation (1 x 10^6 colony forming units), and administration at 4 days post-TBI resulted in transient body weight loss and sickness behaviors (hypoactivity and acute dyspnea). K. pneumoniae infection led to an increase in pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid at 24 h post-infection, in both TBI and sham (uninjured) mice. By 7 days, when myeloperoxidase + neutrophil numbers had returned to baseline in all groups, lung histopathology was observed with an increase in airspace size in TBI + K. pneumoniae mice compared to TBI + vehicle mice. In the brain, increased neuroinflammatory gene expression was observed acutely in response to TBI, with an exacerbated increase in Ccl2 and Hmox1 in TBI + K. pneumoniae mice compared to either TBI or K. pneumoniae alone. However, the presence of neuroinflammatory immune cells in the injured brain, and the extent of damage to cortical and hippocampal brain tissue, was comparable between K. pneumoniae and vehicle-treated mice by 7 days. Examination of the fecal microbiome across a time course did not reveal any pronounced effects of either injury or K. pneumoniae on bacterial diversity or abundance. Together, these findings demonstrate that K. pneumoniae lung infection after TBI induces an acute and transient inflammatory response, primarily localized to the lungs with some systemic effects. However, this infection had minimal impact on secondary injury processes in the brain following TBI. Future studies are needed to evaluate the potential longer-term consequences of this dual-hit insult.

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“…Surveying these historical perspectives reveals the gradual evolution of thoughts that led to recent considerations and investigations of this viral hypothesis in AD. During the mid-20th century, there were records by clinicians and researchers reporting peculiar associations between infectious events and cognitive decline generally [ 16 , 17 , 18 , 19 , 20 , 21 ]. Specifically, the persuasive work by Oskar Fischer in 1907 established AD pathology, and it was not until decades later, specifically during the 1980s, that infectious agents came under scrutiny for their potential influence on neurodegeneration.…”

Section: Historical Perspectives On Viral Links To Admentioning

confidence: 99%

Viral Infections, Are They a Trigger and Risk Factor of Alzheimer’s Disease?

Rippee-Brooks,

Wu,

Dong

et al. 2024

Pathogens

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Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe cute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD such as the lytic replication and axonal transport of HSV-1, the various mechanisms of ZIKV neurotropism through the human protein Musashi-1 (MSI1), and the spread of SARS-CoV-2 through the transfer of the virus through the BBB endothelial cells to glial cells and then to neurons via transsynaptic transfer. We will also explore beyond these mere associations by carefully analyzing the potential mechanisms by which these viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, the dysregulation of immune responses, and the impact on protein processing (Aβ42 and hyperphosphorylated tau). Controversies and challenges of the virus–AD relationship emerge as we tease out these potential mechanisms. Looking forward, we emphasize future directions, such as distinct questions and proposed experimentations to explore, that the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development while encouraging further discussion.

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Infectious diseases and cognition: do we have to worry?

Cited by 16 publications

References 96 publications

Resolving a paradox: antidepressants, neuroinflammation, and neurodegeneration

Resolving a paradox: antidepressants, neuroinflammation, and neurodegeneration

Modelling lung infection with Klebsiella pneumoniae after murine traumatic brain injury

Viral Infections, Are They a Trigger and Risk Factor of Alzheimer’s Disease?

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