Eradication of Helicobacter pylori may be beneficial in the management of Alzheimer’s disease. J Neurol

Department of Gastroenterology, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.
Journal of Neurology (Impact Factor: 3.38). 03/2009; 256(5):758-67. DOI: 10.1007/s00415-009-5011-z
Source: PubMed


Infectious agents have been proposed as potential causes of Alzheimer's disease (AD). Recently, we documented a high prevalence of Helicobacter pylori (Hp) infection in patients with AD. We aim to access the effect of Hp eradication on the AD cognitive (MMSE: Mini Mental State Examination and CAMCOG: Cambridge Cognitive Examination for the Elderly) and functional (FRSSD: Functional Rating Scale for Symptoms of Dementia) status parameters. In the first part of the study, a total of 50 consecutive patients with AD and 30 age-matched anaemic controls underwent an upper gastrointestinal endoscopy, and gastric mucosal biopsies were obtained to detect the presence of Hp infection by histologic analysis and rapid urease test. Serum anti-Hp-specific IgG level was analysed by enzyme-linked immunosorbent assay. In the second part, Hp-positive AD patients received a triple eradication regimen (omeprazole, clarithromycin and amoxicillin), and all patients were followed up for 2 years, while under the same treatment with cholinesterase inhibitors. Hp was detected in 88% of AD patients and in 46.7% of controls (P < 0.001). Hp eradication was successful in 84.8% of treated patients. At the 2-year clinical endpoint, cognitive and functional status parameters improved in the subgroup of patients where Hp eradication was successful (P < 0.001 and P = 0.049 for MMSE and CAMCOG, respectively; P < 0.001 for FRSSD), but not in the other patients. Hp eradication may positively influence AD manifestations, suggesting a possible common link between Hp and AD.

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    • "Using some histological studies it was found that there is an association between H. pylori and AD [111]. Furthermore, eradication of H. pylori from AD patients positively influences cognitive and functional status of patient [119]. In a recent study it has been reported that H. pylori infection triggers accumulation of AD lesions and neuroinflammation hence is a significant risk factor for developing AD [120]. "
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    ABSTRACT: Alzheimer disease (AD) is a degenerative disease of brain that is associated with dementia, brain atrophy, accumulation of hyperphosphorylated tau protein and amyloid-beta peptide in hippocampus and cortex region of the brain. The development of AD is a multifactorial process that may also involve infection with bacterial pathogens. Recent studies suggest that bacteria including spirochetes have potential to initiate cascade of events leading to inflammatory condition of central nervous system. Bacteria and spirochetes are activators of proinflammatory cytokines, generate free radicals, nitric oxide and further induction of apoptosis. Infection with these microbes may be considered as a risk factor for pathophysiology of AD or to cognitive changes. Recent studies have revealed that exposure to these microorganisms induces Aβ accumulation and tau protein phosphorylation and chronic infection with these pathogenic bacteria can possibly contribute to progression of AD. In this article, we update and review the role of bacteria in the pathogenesis of AD resulting from initiation of cascade events in chronic inflammations and amyloidogenesis. By controlling these chronic infections with antibacterial or anti-inflammatory drugs will allow preventing inflammation, a risk factor for AD.
    CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) 09/2014; 13(7). DOI:10.2174/1871527313666140917115741 · 2.63 Impact Factor
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    • "AD patients have a higher prevalence of H. pylori than controls (Kountouras et al., 2006); increased levels of H. pylori antibodies are detected both in plasma and cerebrospinal fluid of AD patients (Malaguarnera et al., 2004; Kountouras et al., 2009a). AD patients infected by H. pylori tend to be more cognitively impaired (Roubaud-Baudron et al., 2012), and H. pylori eradication therapy has a beneficial effect on AD patients with H. pylori infection (Kountouras et al., 2009b, 2010). However, all these investigations are based on clinical observation, till now the direct laboratory evidence link H. pylori infection and AD is still lacking. "
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    ABSTRACT: Helicobacter pylori (H. pylori) infection is related with a high risk of Alzheimer's disease (AD), but the intrinsic link between H. pylori infection and AD development is still missing. In the present study, we explored the effect of H. pylori infection on cognitive function and β-amyloid production in rats. We found that intraperitoneal injection of H. pylori filtrate induced spatial learning and memory deficit in rats with a simultaneous retarded dendritic spine maturation in hippocampus. Injection of H. pylori filtrate significantly increased Aβ42 both in the hippocampus and cortex, together with an increased level of presenilin-2 (PS-2), one key component of γ-secretase involved in Aβ production. Incubation of H. pylori filtrate with N2a cells which over-express amyloid precursor protein (APP) also resulted in increased PS-2 expression and Aβ42 overproduction. Injection of Escherichia coli (E.coli) filtrate, another common intestinal bacterium, had no effect on cognitive function in rats and Aβ production in rats and cells. These data suggest a specific effect of H. pylori on cognition and Aβ production. We conclude that soluble surface fractions of H. pylori may promote Aβ42 formation by enhancing the activity of γ-secretase, thus induce cognitive impairment through interrupting the synaptic function.
    Frontiers in Aging Neuroscience 07/2014; 6(4):66. DOI:10.3389/fnagi.2014.00066 · 4.00 Impact Factor
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    • "Interestingly, H. pylori infection was recently linked with increased likelihood of Alzheimer disease [28] and mild cognitive impairment in older adults [29]. It was suggested that H. pylori eradication therapy might be beneficial to cognitive and functional status among such patients [30]. This association was explained by a cascade of events, starting with H. pylori-gastritis, resulting in reduced absorption of vitamin B12 and folate which lead to accumulation of homocysteine levels, which is considered a risk factor of cognitive impairment in adults [29,31]. "
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    ABSTRACT: H. pylori infection has been linked to iron deficiency anemia, a risk factor of diminished cognitive development. The hypothesis on an association between H. pylori infection and cognitive function was examined in healthy children, independently of socioeconomic and nutritional factors. A community-based study was conducted among 200 children aged 6-9 years, from different socioeconomic background. H. pylori infection was examined by an ELISA kit for detection of H. pylori antigen in stool samples. Cognitive function of the children was blindly assessed using Stanford-Benit test 5th edition, yielding IQ scores. Data on socioeconomic factors and nutritional covariates were collected through maternal interviews and from medical records. Multivariate linear regression analysis was performed to obtain adjusted beta coefficients. H. pylori infection was associated with lower IQ scores only in children from a relatively higher socioeconomic community; adjusted beta coefficient -6.1 (95% CI -11.4, -0.8) (P = 0.02) for full-scale IQ score, -6.0 (95% CI -11.1, -0.2) (P = 0.04) for non-verbal IQ score and -5.7 (95% CI -10.8, -0.6) (P = 0.02) for verbal IQ score, after controlling for potential confounders. H. pylori infection might be negatively involved in cognitive development at early school age. Further studies in other populations with larger samples are needed to confirm this novel finding.
    BMC Pediatrics 05/2011; 11(1):43. DOI:10.1186/1471-2431-11-43 · 1.93 Impact Factor
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