Marina Boziki

Neuropsychiatric syndromes in dementia - Results from the European Alzheimer Disease Consortium: Part I

Background/Aims: The aim of this study was to identify neuropsychiatric subsyndromes of the Neuropsychiatric Inventory in a large sample of outpatients with Alzheimer’s disease (AD). Methods: Cross-sectional data of 2,354 patients with AD from 12 centres from the European Alzheimer’s Disease Consortium were collected. Principal component analysis was used for factor analysis. Results: The results showed the presence of 4 neuropsychiatric subsyndromes: hyperactivity, psychosis, affective symptoms and apathy. The subsyndrome apathy was the most common, occurring in almost 65% of the patients. Conclusion: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD.

Consistency of Neuropsychiatric Syndromes across Dementias: Results from the European Alzheimer Disease Consortium

Background/Aims: The aim of this study was to determine the consistency of neuropsychiatric subsyndromes of the Neuropsychiatric Inventory across several clinical and demographic subgroups (e.g. dementia subtypes, dementia severity, medication use, age and gender) in a large sample of outpatients with dementia. Methods: Cross-sectional data of 2,808 patients with dementia from 12 centres from the European Alzheimer’s Disease Consortium were collected. Principal component analysis was used for factor analysis. Subanalyses were performed for dementia subtypes, dementia severity, medication use, age and gender. Results: The results showed the relatively consistent presence of the 4 neuropsychiatric subsyndromes ‘hyperactivity’, ‘psychosis’, ‘affective symptoms’ and ‘apathy’ across the subanalyses. The factor structure was not dependent on dementia subtypes, age and gender but was dependent on dementia severity and cholinesterase use. The factors hyperactivity and affective symptoms were present in all subanalyses, but the presence of the factors apathy and psychosis was dependent on use of cholinesterase inhibitors and dementia severity, respectively. Conclusion: The present study provided evidence of the relative consistency of neuropsychiatric subsyndromes across dementia subtypes, age and gender, thereby stressing the importance of thinking about neuropsychiatric subsyndromes instead of separate symptoms. However, the subsyndromes apathy and psychosis were dependent on use of cholinesterase inhibitors and dementia severity.

Relationship between Helicobacter pylori infection and Alzheimer disease

The authors investigated the association between Helicobacter pylori infection (Hp-I) and Alzheimer disease (AD) by using histology for diagnosis of Hp-I. Fifty patients with AD and 30 iron deficiency anemic control participants without AD were included. The histologic prevalence of Hp-I was 88% in patients with AD and 46.7% in controls (p < 0.001).

Five-year survival after Helicobacter pylori eradication in Alzheimer disease patients.

BackgroundAlzheimer disease (AD) is a progressive, fatal neurodegenerative condition. ObjectiveWe tested the hypothesis that eradication of Helicobacter pylori infection (Hp-I) could improve survival in a Greek cohort of AD patients, in a 5-year follow-up. MethodForty-six patients diagnosed with probable AD were enrolled in the analysis. Study population was classified into 3 groups: patients for whom Hp eradication treatment was successful; those for whom eradication of Hp had failed, they refused, and/or were noncompliant with eradication therapy; and those who were Hp negative at baseline. Cox proportional hazards model was built with all-cause mortality as the dichotomous outcome. ResultsDuring the 5-year follow-up [47.19±15.11 mo (range 12 to 60)], overall 21 patients died and 25 patients remained alive. Patients who died were older and exhibited lower mean MMSE score compared with the patients still alive. Successful eradication of Hp-I was associated with a significantly lower mortality risk [HR (95% CI)=0.287 (0.114-0.725), P=0.008]. The results were similar in adjusted and unadjusted models, for age and MMSE at baseline. ConclusionHp eradication regimen in AD patients is associated with a higher 5-year survival rate.

Association between Helicobacter pylori infection and mild cognitive impairment

The association of Helicobacter pylori infection and Alzheimers disease (AD) has recently been addressed, but no relative data exist regarding mild cognitive impairment (MCI), a prodromal phase of AD. The aim of this prospective study was to evaluate H. pylori infection, by histology in a Greek MCI cohort. Sixty‐three consecutive patients with amnestic MCI and 35 normal controls underwent upper gastrointestinal endoscopy, histologic and serological examinations. The prevalence of H. pylori infection was 88.9% (56/63) in MCI patients and 48.6% (17/35) in anaemic controls, as confirmed by biopsy (P < 0.001, odds ratio: 8.47, 95% CI: 3.03–23.67). Mean serum anti‐H. pylori IgG concentration and plasma total homocysteine (Hcy) titre were higher in MCI patients than controls (74.86 ± 57.22 vs. 17.37 ± 9.30 U/ml; and 16.03 ± 4.28 vs. 13.5 ± 1.20 μmol/l; P < 0.001 and P = 0.015, respectively). When compared with the anaemic participants, MCI patients exhibited more often multifocal (body and antral) gastritis (92.1% vs. 68.6%; P = 0.03); in H. pylori positive MCI patients cognitive state correlated with serum anti‐H. pylori IgG concentration. In conclusion, H. pylori prevalence was significantly higher in MCI patients than controls. This infection might contribute, at least in part, to the pathophysiology of MCI, possibly through induction of chronic atrophic gastritis and elevated Hcy consequences.

Increased Cerebrospinal Fluid Helicobacter Pylori Antibody in Alzheimer’s Disease

Background: Helicobacter pylori (H. pylori) infection may play a role in Alzheimers disease (AD). Aim: A prospective, nonrandomized, comparative study was car- ried out to examine the levels of anti-H. pylori-specific IgG antibodies in the cerebrospinal fluid (CSF) and serum of AD patients, compared with those of age-matched cognitively normal controls. Patients: CSF was aspirated from 27 AD patients and 27 age-matched cognitively normal patients with prostate hyperplasia or long-bone fractures necessitating surgery after epidural anesthesia. Serum samples were obtained from AD patients and the day before surgery from controls. Methods: CSF and serum anti-H. pylori IgG concentrations were measured by means of an enzyme-linked immunosorbent assay. Results: The mean concentration of anti-H. pylori-specific IgG was significantly greater in (a) the CSF of AD patients (10.53 ± 12.54 U/mL) than in controls (8.63 ± 8.01 U/mL, p = 0.047), and (b) the serum of AD patients (30.44 ± 33.94 U/mL) than in controls (16.24 ± 5.77 U/mL, p = 0.041). CSF anti-H. pylori IgG antibodies correlated with the degree of severity of the disease. Conclusion: H. pylori-specific IgG antibody levels are significantly increased in CSF and serum of AD; its titer in CSF might reflect the AD severity, thereby supporting a role for this common infection in the pathobiology of the disease.

Familial prevalence of autoimmune disorders in multiple sclerosis in Northern Greece.

Objective: The objective of this study was to evaluate for up to 7 years the prevalence of autoimmune disorders among naïve (untreated) multiple sclerosis family members compared with a contemporary general control population in Northern Greece, in a prospective case-control study, and to examine the possible relationship between immunomodulatory treatment and the appearance of additional autoimmune disorders. Methods: The patients and controls enrolled comprised 1383 patients with definite MS and 4392 relatives in their families and a total of 452 controls families with 1652 members. Results: At baseline, 891 multiple sclerosis families with 3112 members (73 multiplex multiple sclerosis families with 292 members and 818 simplex families with 2820 members) and 355 control families with 1580 members were examined regarding whether they had any of 12 autoimmune diseases. The baseline affected multiplex plus simplex multiple sclerosis families, the family members and the coexistent additional autoimmune disorders were higher compared with controls. There was an increase in longitudinally affected multiple sclerosis families, multiple sclerosis family members and coexistent additional autoimmune disorders compared with respective findings at the baseline observation. Comparison analysis between two time point observations (after a mean 7.1 ± 2.2 years) for each autoimmune disorder in overall multiple sclerosis family members revealed increased rates for longitudinal autoimmune Hashimoto’s thyroiditis, Graves’ disease, insulin-dependent diabetes mellitus, psoriasis and vitiligo (p = 0.02, p = 0.006, p = 0.0004, p = 0.05, and p = 0.05, respectively). Some 145 newly developed, longitudinally definite autoimmune cases were recognized in multiplex plus simplex multiple sclerosis families; 116 (80%) of these disorders were observed in patients with multiple sclerosis treated with immunomodulatory medications, and 68 of these 116 (58.6%) cases exhibited baseline positive autoreactive antibodies. Binary logistic regression analysis revealed that immunotherapy predisposes to autoimmunity (odds ratio 2.8, p < 0.001) independently of the presence of baseline autoantibodies and patients’ gender. Conclusions: There is a longitudinally increased frequency of additional autoimmune disorders among multiple sclerosis family members, probably related to immunomodulatory therapy.

Impact of reactive oxygen species generation on Helicobacter pylori-related extragastric diseases: a hypothesis.

Abstract Helicobacter pylori (H. pylori) induces reactive oxygen species (ROS) production that contribute to pathogenesis of a variety of H. pylori-related gastric diseases, as shown in animal and human studies. Helicobacter pylori infection is also associated with variety of systemic extragastric diseases in which H. pylori-related ROS production might also be involved in the pathogenesis of these systemic conditions. We proposed that Hp-related ROS may play a crucial role in the pathophysiology of Hp-related systemic diseases including Alzheimer’s disease, multiple sclerosis, glaucoma and other relative neurodegenerative diseases, thereby suggesting introduction of relative ROS scavengers as therapeutic strategies against these diseases which are among the leading causes of disability and are associated with a large public health global burden. Moreover, we postulated that H. pylori-related ROS might also be involved in the pathogenesis of extragastric common malignancies, thereby suggesting that H. pylori eradication might inhibit the development or delay the progression of aforementioned diseases. However, large-scale future studies are warranted to elucidate the proposed pathophysiological mechanisms, including H. pylori-related ROS, involved in H. pylori-associated systemic and malignant conditions.

Helicobacter pylori induced cognitive dysfunction might be associated with falls and fractures in cirrhosis

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Association between Helicobacter pylori infection and Alzheimer’s disease in Japan

We read with interest the paper by Shiota et al. [1], who reported that older age and male sex were significantly associated with Alzheimer’s disease. Moreover, the authors reported a lack of association between Helicobacter pylori infection (Hp-I) status and Alzheimer’s disease in their Japanese cohort, suggesting that their findings might be explained by the much higher prevalence of Hp-I in the general Japanese than in the European population. We herein wish to emphasize two essential concerns regarding the methodological limitations which may render the results of this study highly debatable. The first is that both age and sex, found to be associated with Alzheimer’s disease, were not matched in the two study groups (p \ 0.001 and p = 0.01, respectively), and thus comparisons between the two study groups (i.e., Alzheimer’s disease patients and controls) cannot be expected to establish any firm conclusions. The second concern is that the very high Hp-I prevalence in the general Japanese population around 70 years old, reported by the authors, and, deductively, in the control group of the study, renders the study underpowered, meaning it requires probably thousands of participants in order to prove whether an association between Alzheimer’s disease and Hp-I can be established or excluded; it requires a very large population to be screened to prove or not a statistical difference in Hp-I among patients with Alzheimer’s disease and the general Japanese population. In view of the aforementioned methodological limitations, we deduce that this study can neither confirm the lack of association between the Hp-I status and Alzheimer’s disease in the Japanese population, nor is it comparable with the European studies indicating such an association [2–4].