Relation between nicotine intake and Alzheimer's disease.

OBJECTIVE--To study the association between Alzheimer''s disease and nicotine intake through smoking. DESIGN--Population based case-control study. SETTING--City of Rotterdam and four northern provinces of The Netherlands. SUBJECTS--198 patients with early onset Alzheimer''s disease, 198 controls matched for age and sex, and families of 17 patients in whom Alzheimer''s disease was apparently inherited as an autosomal dominant disorder. MAIN OUTCOME MEASURES--Age of onset of dementia, relative risk of Alzheimer''s disease. RESULTS--89 of 193 patients with Alzheimer''s disease had a history of smoking compared with 102 of 195 controls. Among the patients and controls with a family history of dementia, smoking was significantly less common in those with dementia (40/95 with dementia v 55/96 controls; relative risk 0.35; 95% confidence interval 0.16 to 0.78). The risk of Alzheimer''s disease decreased with increasing daily number of cigarettes smoked before onset of disease (relative risk 0.3 in those smoking greater than 21/day v 1 in non-smokers). In six families in which the disease was apparently inherited as an autosomal dominant disorder, the mean age of onset was 4.17 years later in smoking patients than in non-smoking patients from the same family (p = 0.03). CONCLUSIONS--These findings suggest an inverse association between smoking and Alzheimer''s disease, although smoking cannot be advocated for other health reasons. We speculate that nicotine may have a role in the aetiology of both Alzheimer''s disease and Parkinson''s disease.     

Association of apolipoprotein E phenotypes with late onset Alzheimer's disease: population based study.

OBJECTIVE--To determine the association between the e4 allele of apolipoprotein E and Alzheimer''s disease in a randomly selected population sample. DESIGN--Cross sectional population based study. SUBJECTS--980 people aged 69 to 78 (349 men, 631 women). SETTING--Population of Kuopio, eastern Finland. MAIN OUTCOME MEASURES--Presence of e4 allele and diagnosis of Alzheimer''s disease by detailed neurological and neurophysiological evaluation. RESULTS--46 (4.7%) subjects were classified as having probable or possible Alzheimer''s disease. The frequency of the apolipoprotein E e4 allele was 0.359 in patients with Alzheimer''s disease and 0.165 subjects without dementia (P < 0.0001). The prevalence of Alzheimer''s disease was 2.9% in subjects with no e4 alleles, 7.6% in subjects with one e4 allele, and 21.4% in subjects with two e4 alleles of apolipoprotein E. CONCLUSIONS--Allele e4 of apolipoprotein is associated with Alzheimer''s disease in a dose-response fashion in a randomly selected elderly population.     

Apolipoprotein E genotype and association between smoking and early onset Alzheimer's disease.

OBJECTIVE--To investigate the hypothesis that differential survival between smokers and non-smokers leading to a decrease in the frequency of the e4 allele of the apolipoprotein E gene may explain the inverse relation between smoking history and early onset Alzheimer''s disease. DESIGN--A population based case-control study. SETTING--The four northern provinces of the Netherlands and metropolitan Rotterdam. SUBJECTS--175 patients with early onset Alzheimer''s disease and two independent control groups of 159 and 457 subjects. MAIN OUTCOME MEASURES--Frequencies of the apolipoprotein e4 allele and relative risk of early onset Alzheimer''s disease. RESULTS--The inverse association between smoking history and early onset Alzheimer''s disease could not be explained by a decrease in the frequency of the apolipoprotein e4 allele. Among carriers of this allele with a family history of dementia subjects with a history of smoking had a strongly reduced risk of early onset Alzheimer''s disease (odds ratio 0.10 (95% confidence interval 0.01 to 0.87)). CONCLUSIONS--The results suggest that the inverse relation between smoking history and early onset Alzheimer''s disease cannot be explained by an increased mortality in carriers of the apolipoprotein e4 allele who smoke. The association is strongly modified by the presence of the apolipoprotein e4 allele as well as by a family history of dementia.     

Association between features of the insulin resistance syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: cross sectional population based study.

OBJECTIVE: To determine the association between features of the insulin resistance syndrome and Alzheimer''s disease. DESIGN: Cross sectional population based study. SUBJECTS: 980 people aged 69 to 78 (349 men, 631 women). SETTING: Population of Kuopio, eastern Finland. MAIN OUTCOME MEASURES: Presence of features of the insulin resistance syndrome and diagnosis of Alzheimer''s disease by detailed neurological and neuropsychological evaluation. RESULTS: 46 (4.7%) subjects were classified as having probable or possible Alzheimer''s disease. In univariate analyses, apolipoprotein E4 phenotype (odds ratio; 95% confidence interval 3.24: 1.77 to 5.92), age (1.16; 1.05 to 1.29), low level of education (0.82; 0.72 to 0.93), low total cholesterol concentration (0.77; 0.59 to 1.00), high systolic blood pressure (1.01; 1.00 to 1.03), high fasting and 2 hour plasma glucose concentrations (1.11; 1.01 to 1.23 and 1.08; 1.03 to 1.13, respectively), high fasting and 2 hour insulin concentrations (1.05; 1.02 to 1.08 and 1.003; 1.00 to 1.01, respectively), and abnormal glucose tolerance (1.86; 1.23 to 2.80) were significantly associated with Alzheimer''s disease. In multivariate analysis including apolipoprotein E4 phenotype, age, education, systolic blood pressure, total cholesterol concentration, fasting glucose concentration, and insulin concentration, apolipoprotein E4 phenotype, age, education, total cholesterol, and insulin were significantly associated with Alzheimer''s disease. In 532 non-diabetic subjects without the e4 allele hyperinsulinaemia was associated with an increased risk for Alzheimer''s disease (prevalence of disease 7.5% v 1.4% in normoinsulinaemic subjects, P = 0.0004). In contrast, in the 228 with the e4 allele hyperinsulinaemia had no effect on the risk of disease (7.0% v 7.1%, respectively). CONCLUSION: Features of the insulin resistance syndrome are associated with Alzheimer''s disease independently of apolipoprotein E4 phenotype.     

The Mini Mental State Examination at the Time of Alzheimer's Disease and Related Disorders Diagnosis,According to Age,Education, Gender and Place of Residence: A Cross-Sectional Study among the French National Alzheimer Database

The aim of this study

was firstly to describe the MMSE (Mini-Mental State Examination) score upon initial diagnosis of Alzheimer''s disease and related disorders among the French population, according to age. Secondly, education, gender and place of residence were studied as factors potentially associated with delayed Alzheimer''s disease diagnosis.

Design

we conducted a cross sectional analysis of the French National Alzheimer database (BNA). Data from 2008 to 2012 were extracted. Patients were selected at the moment of their first diagnosis of AD (n = 39,451).

Results

The MMSE score at initial diagnosis dropped significantly with increasing age. The test score increased with the degree of educational background regardless of age. Gender and place of residence were significantly related to the MMSE score, women and persons living in medical institutions having lower MMSE scores under the age of 90 years and at all educational levels.

Conclusions

Health care professionals should be aware of these risk factors in order to maximize chances of earliest possible diagnosis of Alzheimer''s disease and related disorders.     

基于BP神经网络和RBF神经网络预测老年痴呆症疾病进展的对比研究

目的:比较反向传播算法(BP)神经网络和径向基函数(RBF)神经网络预测老年痴呆症疾病进展的效果。方法:以老年痴呆症随访数据为研究对象,以性别、年龄、受教育程度、有无高血压、有无高胆固醇、有无心脏病、有无中风史、有无家族史8个指标作为输入变量,以五年随访的MMSE差值为输出变量,构建基于BP神经网络和RBF神经网络的老年痴呆症疾病进展预测模型。结果:与BP神经网络模型相比,RBF神经网络预测的结果更好,能够有效地预测老年痴呆症疾病进展。结论:神经网络模型将老年痴呆症疾病进展预测问题转化为随访数据中相关测量指标与MMSE差值的非线性问题,为复杂的老年痴呆症疾病进展预测提供了新思路。     

Long-Term In Vivo Imaging of Fibrillar Tau in the Retina of P301S Transgenic Mice

Tauopathies are widespread neurodegenerative disorders characterised by the intracellular accumulation of hyperphosphorylated tau. Especially in Alzheimer''s disease, pathological alterations in the retina are discussed as potential biomarkers to improve early diagnosis of the disease. Using mice expressing human mutant P301S tau, we demonstrate for the first time a straightforward optical approach for the in vivo detection of fibrillar tau in the retina. Longitudinal examinations of individual animals revealed the fate of single cells containing fibrillar tau and the progression of tau pathology over several months. This technique is most suitable to monitor therapeutic interventions aimed at reducing the accumulation of fibrillar tau. In order to evaluate if this approach can be translated to human diagnosis, we tried to detect fibrillar protein aggregates in the post-mortem retinas of patients that had suffered from Alzheimer''s disease or Progressive Supranuclear Palsy. Even though we could detect hyperphosphorylated tau, we did not observe any fibrillar tau or Aß aggregates. In contradiction to previous studies, our observations do not support the notion that Aβ or tau in the retina are of diagnostic value in Alzheimer''s disease.     

Relation between severity of Alzheimer's disease and costs of caring

BACKGROUND: Data from the Canadian Study of Health and Aging (CSHA) were used to examine the relation between severity of Alzheimer''s disease, as measured by the Mini-Mental State Examination (MMSE), and costs of caring. METHODS: The CSHA was a community-based survey of the prevalence of dementia, including subtypes such as Alzheimer''s disease, among elderly Canadians. Survey subjects with a diagnosis of possible or probable Alzheimer''s disease were grouped into disease severity levels of mild (MMSE score 21-26), mild to moderate (MMSE score 15-20), moderate (MMSE score 10-14) and severe (MMSE score below 10). Components of care available from the CSHA were use of nursing home care, use of medications, use of community support services by caregivers and unpaid caregiver time. Costs were calculated from a societal perspective and are expressed in 1996 Canadian dollars. RESULTS: The annual societal cost of care per patient increased significantly with severity of Alzheimer''s disease. The cost per patient was estimated to be $9451 for mild disease, $16,054 for mild to moderate disease, $25,724 for moderate disease and $36,794 for severe disease. Institutionalization was the largest component of cost, accounting for as much as 84% of the cost for people with severe disease. For subjects living in the community, unpaid caregiver time and use of community services were the greatest components of cost and increased with disease severity. INTERPRETATION: The societal cost of care of Alzheimer''s disease increases drastically with increasing disease severity. Institutionalization is responsible for the largest cost component.     

Prevalence of Alzheimer's disease and vascular dementia: association with education. The Rotterdam study.

OBJECTIVE--To estimate the prevalence of dementia and its subtypes in the general population and examine the relation of the disease to education. DESIGN--Population based cross sectional study. SETTING--Ommoord, a suburb of Rotterdam. SUBJECTS--7528 participants of the Rotterdam study aged 55-106 years. RESULTS--474 cases of dementia were detected, giving an overall prevalence of 6.3%. Prevalence ranged from 0.4% (5/1181 subjects) at age 55-59 years to 43.2% (19/44) at 95 years and over. Alzheimer''s disease was the main subdiagnosis (339 cases; 72%); it was also the main cause of the pronounced increase in dementia with age. The relative proportion of vascular dementia (76 cases; 16%), Parkinson''s disease dementia (30; 6%), and other dementias (24; 5%) decreased with age. A substantially higher prevalence of dementia was found in subjects with a low level of education. The association with education was not due to confounding by cardiovascular disease. CONCLUSIONS--The prevalence of dementia increases exponentially with age. About one third of the population aged 85 and over has dementia. Three quarters of all dementia is due to Alzheimer''s disease. In this study an inverse dose-response relation was found between education and dementia--in particular, Alzheimer''s disease.     

Lysosomal Dysfunction Promotes Cleavage and Neurotoxicity of Tau In Vivo

Expansion of the lysosomal system, including cathepsin D upregulation, is an early and prominent finding in Alzheimer''s disease brain. Cell culture studies, however, have provided differing perspectives on the lysosomal connection to Alzheimer''s disease, including both protective and detrimental influences. We sought to clarify and molecularly define the connection in vivo in a genetically tractable model organism. Cathepsin D is upregulated with age in a Drosophila model of Alzheimer''s disease and related tauopathies. Genetic analysis reveals that cathepsin D plays a neuroprotective role because genetic ablation of cathepsin D markedly potentiates tau-induced neurotoxicity. Further, generation of a C-terminally truncated form of tau found in Alzheimer''s disease patients is significantly increased in the absence of cathepsin D. We show that truncated tau has markedly increased neurotoxicity, while solubility of truncated tau is decreased. Importantly, the toxicity of truncated tau is not affected by removal of cathepsin D, providing genetic evidence that modulation of neurotoxicity by cathepsin D is mediated through C-terminal cleavage of tau. We demonstrate that removing cathepsin D in adult postmitotic neurons leads to aberrant lysosomal expansion and caspase activation in vivo, suggesting a mechanism for C-terminal truncation of tau. We also demonstrate that both cathepsin D knockout mice and cathepsin D–deficient sheep show abnormal C-terminal truncation of tau and accompanying caspase activation. Thus, caspase cleavage of tau may be a molecular mechanism through which lysosomal dysfunction and neurodegeneration are causally linked in Alzheimer''s disease.     

Epidemiology of Alzheimer's presenile dementia in Scotland, 1974-88.

OBJECTIVE--To describe the epidemiology of presenile Alzheimer''s disease in Scotland from 1974 to 1988. DESIGN--Retrospective review of hospital records of patients aged less than 73 years admitted to psychiatric hospital with various diagnoses of dementia. Diagnoses were classified by National Institute for Communicative Disorders and Stroke and Alzheimer''s Disease and Related Disorders Association Criteria and the Hachinski score. Completeness of the study sample was evaluated by scrutiny of neurology outpatient and general hospital records. SETTING--All general psychiatric hospitals in Scotland. SUBJECTS--All patients with onset of dementia aged 40-64. MAIN OUTCOME MEASURES--Probable and broad Alzheimer''s disease, sex of patient, age at onset. RESULTS--5874 psychiatric hospital records, 129 neurology outpatient records, and 89 records from non-psychiatric hospitals were examined. 317 patients met criteria for probable Alzheimer''s disease, 569 met criteria for broad Alzheimer''s disease, and 267 met those for multi-infarct dementia. Minimal incidences per 100,000 population aged 40-64 years were 22.6 (95% confidence interval, 20.2 to 25.2) and 40.5 (38.9 to 42.3) per 100,000 for probable and broad Alzheimer''s disease. In the 1981 census year the annual incidence of probable Alzheimer''s disease was 1.6 (1.0 to 2.6). Women were at greater risk with incidence rates for probable Alzheimer''s disease of 28.2 (24.5 to 32.4) per 100,000 compared with 16.5 (13.8 to 19.8) per 100,000 for men. The incidence per 100,000 for multi-infarct dementia was greater in men (25.1, 23.3 to 27.1) than women (13.4, 12.1 to 14.8). CONCLUSION--Female sex seems to be positively associated with development of Alzheimer''s disease before age 65 years.     

Smoking and dementia in male British doctors: prospective study

ObjectiveTo assess the possible association between smoking and dementia.DesignProspective study.SettingCohort of British male doctors followed up since 1951.Subjects34 439 male British doctors, with 24 133 deaths recorded.ResultsFor all types of dementia combined the relative risk was 0.96 (95% confidence interval 0.78 to 1.18), based on 473 deaths at a mean age of 81 years. For probable or definite Alzheimer''s disease, the relative risk in continuing smokers was 0.99 (0.78 to 1.25), based on 370 deaths at a mean age of 82 years. In aggregate, however, the other prospective studies indicate a direct, although not clearly significant, association between smoking and the onset of dementia in general and of Alzheimer''s disease in particular. ConclusionsContrary to previous suggestions persistent smoking does not substantially reduce the age specific onset rate of Alzheimer''s disease or of dementia in general. If anything, it might increase rather than decrease the rate, but any net effect on severe dementia cannot be large in either direction.     

Detection of Alzheimer's disease and dementia in the preclinical phase: population based cohort study

ObjectivesTo evaluate a simple three step procedure to identify people in the general population who are in the preclinical phase of Alzheimer''s disease and dementia.DesignThree year population based cohort study.SettingKungsholmen cohort, Stockholm, Sweden.Participants1435 people aged 75-95 years without dementia.AssessmentsSingle question asking about memory complaints, assessment by mini-mental state examination, and neuropsychological testing.ResultsNone of the three instruments was sufficiently predictive of Alzheimer''s disease and dementia when administered separately. After participants had been screened for memory complaints and global cognitive impairment, specific tests of word recall and verbal fluency had positive predictive values for dementia of 85-100% (95% confidence intervals range from 62% to 100%). However, only 18% of future dementia cases were identified in the preclinical phase by this three step procedure. Memory complaints were the most sensitive indicator of Alzheimer''s disease and dementia in the whole population, but only half the future dementia cases reported memory problems three years before diagnosis.ConclusionThis three step procedure, which simulates what might occur in clinical practice, has a high positive predictive value for dementia, although only a small number of future cases can be identified.

What is already known on this topic

Alzheimer''s disease is characterised by a preclinical phase, during which cognitive deficits are seen before diagnosisElderly people with subjective memory complaints and objective global cognitive impairment have a high risk of developing Alzheimer''s disease and dementia

What this study adds

This three step procedure (self report of memory complaints, test of global cognitive functioning, and then domain specific cognitive tests) has a positive predictivity of 85-100% for Alzheimer''s disease and dementia at three yearsHowever, only 18% of people in the preclinical phase can be identified using this procedureAbout half of the people in the preclinical phase of Alzheimer''s disease and dementia do not report problems with their memory three years before diagnosis     

La enfermedad de Alzheimer antes de la demencia. Beneficios del diagnóstico precoz

Given population aging and the rise in the number of persons with Alzheimer's disease, measures that aim not only to delay but also to prevent the development of this disease are increasingly required. Advances in the diagnosis of Alzheimer's disease support the need for a review of current clinical standards for mildcognitive impairment and provide new goals in the early treatment of this disease. The current diagnostic process should be refocussed toward the pathological substrate of this disease rather than symptoms in order to initiate therapeutic measures as soon as possible without waiting for clinical manifestations to appear. Such an approach is essential in patients with greater cognitive reserve, in whom the lesions are usually more severe at diagnosis and treatment is less effective.To identify disease-modifying therapies to delay the onset of the clinical symptoms of Alzheimer's disease in cognitively intact persons at high risk, biomarkers for this disease must be validated. A single biomarker is unlikely to provide the required diagnostic accuracy and therefore a multimodal approach, incorporating biochemical, neuropathological and anatomical and metabolic neuroimaging methods, should be employed. To optimize the results of drugs under investigation, a combination of biomarkers should be used to select appropriate participants in the earliest phases of the disease, and disease progression should be followedup.Early diagnosis might clarify essential questions in the care of patients with Alzheimer's disease, such as the possibility of distinguishing among various subtypes, thus encouraging the development of optimal treatments for each.The ultimate goal is to develop disease-modifying treatments that could be initiated early, while patients are asymptomatic or only minimally symptomatic, to maintain their quality of life.     

Parkinson's disease and Alzheimer's disease as disorders of the isodendritic core.

Parkinson''s disease and Alzheimer''s disease may represent two parts of a spectrum of disease characterised by a primary loss of cells of the isodendritic core. Secondary cell loss from the striatum and cerebral cortex therefore occurs as a consequence of the loss of ascending projections from the isodendritic cells. The anatomy of this system should provide a unique opportunity for therapeutic intervention. Neurotransmitter replacement treatment may be provided either by enhancing transmitter release by any remaining neurones or by direct agonists. The wide dispersal of the isodendritic projection systems affected in Parkinson''s and Alzheimer''s disease and the possibility that they are tonically active create an opportunity for neurotransmitter replacement treatment. Animal studies should be able to show whether such treatment can delay secondary cell loss, and, together with human postmortem studies, whether the hypothesis that the primary lesion is a loss of isodendritic cells is correct.     

A Clinical Index to Predict Progression from Mild Cognitive Impairment to Dementia Due to Alzheimer's Disease

Background

Mild cognitive impairment is often a precursor to dementia due to Alzheimer''s disease, but many patients with mild cognitive impairment never develop dementia. New diagnostic criteria may lead to more patients receiving a diagnosis of mild cognitive impairment.

Objective

To develop a prediction index for the 3-year risk of progression from mild cognitive impairment to dementia relying only on information that can be readily obtained in most clinical settings.

Design and Participants

382 participants diagnosed with amnestic mild cognitive impairment enrolled in the Alzheimer''s Disease Neuroimaging Initiative (ADNI), a multi-site, longitudinal, observational study.

Main Predictors Measures

Demographics, comorbid conditions, caregiver report of participant symptoms and function, and participant performance on individual items from basic neuropsychological scales.

Main Outcome Measure

Progression to probable Alzheimer''s disease.

Key Results

Subjects had a mean (SD) age of 75 (7) years and 43% progressed to probable Alzheimer''s disease within 3 years. Important independent predictors of progression included being female, resisting help, becoming upset when separated from caregiver, difficulty shopping alone, forgetting appointments, number of words recalled from a 10-word list, orientation and difficulty drawing a clock. The final point score could range from 0 to 16 (mean [SD]: 4.2 [2.9]). The optimism-corrected Harrell''s c-statistic was 0.71(95% CI: 0.68–0.75). Fourteen percent of subjects with low risk scores (0–2 points, n = 124) converted to probable Alzheimer''s disease over 3 years, compared to 51% of those with moderate risk scores (3–8 points, n = 223) and 91% of those with high risk scores (9–16 points, n = 35).

Conclusions

An index using factors that can be obtained in most clinical settings can predict progression from amnestic mild cognitive impairment to probable Alzheimer''s disease and may help clinicians differentiate between mild cognitive impairment patients at low vs. high risk of progression.     

Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal,population based study

Objective To examine the relation of midlife raised blood pressure and serum cholesterol concentrations to Alzheimer''s disease in later life.Design Prospective, population based study.SettingPopulations of Kuopio and Joensuu, eastern Finland.ParticipantsParticipants were derived from random, population based samples previously studied in a survey carried out in 1972, 1977, 1982, or 1987. After an average of 21 years'' follow up, a total of 1449 (73%) participants aged 65-79 took part in the re-examination in 1998.Results People with raised systolic blood pressure (⩾160 mm Hg) or high serum cholesterol concentration (⩾6.5 mmol/l) in midlife had a significantly higher risk of Alzheimer''s disease in later life, even after adjustment for age, body mass index, education, vascular events, smoking status, and alcohol consumption, than those with normal systolic blood pressure (odds ratio 2.3, 95% confidence interval 1.0 to 5.5) or serum cholesterol (odds ratio 2.1, 1.0 to 4.4). Participants with both of these risk factors in midlife had a significantly higher risk of developing Alzheimer''s disease than those with either of the risk factors alone (odds ratio 3.5, 1.6 to 7.9). Diastolic blood pressure in midlife had no significant effect on the risk of Alzheimer''s disease.Conclusion Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increase the risk of Alzheimer''s disease in later life.

What is already known on this topic

Vascular risk factors may play an important part as risk factors for Alzheimer''s diseaseNo population based studies have evaluated prospectively the impact of both midlife blood pressure and cholesterol concentration in both men and women on the subsequent development of Alzheimer''s disease

What this study adds

Raised systolic blood pressure and high serum cholesterol concentration, and in particular the combination of these risks, in midlife increased the risk of Alzheimer''s disease in later lifeRaised systolic blood pressure and hypercholesterolaemia may have a role in the pathogenesis of Alzheimer''s disease; more emphasis should be placed on identification and appropriate treatment of these conditions     

L’imagerie TEP-traceurs des plaques amyloïdes : le point de vue du clinicien

The purpose of this article is to summarize the main elements of clinician point of view concerning the contribution of amyloid neuroimaging in the diagnostic approach of the Alzheimer's disease. The main pathological characteristics of the Alzheimer's disease are established by two types of protein aggregates: the extracellular plaques (containing Aβ aggregates) and neurofibrillary tangles (composed of aggregates of tau-protein). At present, the use of biomarkers is more and more included in the diagnostic approach of Alzheimer's disease. The possibility to highlight in vivo cortical amyloid deposits through the amyloid neuroimaging can allow the realization of an earlier diagnosis. However, the amyloid imaging is a “physiopathological” biomarker and is not correlated with the clinical evaluation. It is still difficult to differentiate the Alzheimer's disease of the other neurodegenerative diseases.     

Review: Impact of Helicobacter pylori on Alzheimer's disease: What do we know so far?

Background

Helicobacter pylori has changed radically gastroenterologic world, offering a new concept in patients' management. Over time, more medical data gave rise to diverse distant, extragastric manifestations and interactions of the “new” discovered bacterium. Special interest appeared within the field of neurodegenerative diseases and particularly Alzheimer's disease, as the latter and Helicobacter pylori infection are associated with a large public health burden and Alzheimer's disease ranks as the leading cause of disability. However, the relationship between Helicobacter pylori infection and Alzheimer's disease remains uncertain.

Methods

We performed a narrative review regarding a possible connection between Helicobacter pylori and Alzheimer's disease. All accessible relevant (pre)clinical studies written in English were included. Both affected pathologies were briefly analyzed, and relevant studies are discussed, trying to focus on the possible pathogenetic role of this bacterium in Alzheimer's disease.

Results

Data stemming from both epidemiologic studies and animal experiments seem to be rather encouraging, tending to confirm the hypothesis that Helicobacter pylori infection might influence the course of Alzheimer's disease pleiotropically. Possible main mechanisms may include the bacterium's access to the brain via the oral‐nasal‐olfactory pathway or by circulating monocytes (infected with Helicobacter pylori due to defective autophagy) through disrupted blood‐brain barrier, thereby possibly triggering neurodegeneration.

Conclusions

Current data suggest that Helicobacter pylori infection might influence the pathophysiology of Alzheimer's disease. However, further large‐scale randomized controlled trials are mandatory to clarify a possible favorable effect of Helicobacter pylori eradication on Alzheimer's disease pathophysiology, before the recommendation of short‐term and cost‐effective therapeutic regimens against Helicobacter pylori‐related Alzheimer's disease.     

Porphyrin derivatives as inhibitors for acetylcholinesterase from Drosophila melanogaster

The cure for Alzheimer''s disease (AD) is still unknown. According to Cholinergic hypothesis, Alzheimer''s disease is caused by the reduced synthesis of the neurotransmitter, Acetylcholine. Regional cerebral blood flow can be increased in patients with Alzheimer''s disease by Acetylcholinesterase (AChE) inhibitors. In this regard, Tetraphenylporphinesulfonate (TPPS), 5,10,15,20- Tetrakis (4-sulfonatophenyl) porphyrinato Iron(III) Chloride (FeTPPS) and 5,10,15,20-Tetrakis (4-sulfonatophenyl) porphyrinatoIron(III) nitrosyl Chloride (FeNOTPPS) were investigated as candidate compounds for inhibition of Acteylcholinesterase of Drosophila melanogaster (DmAChE) by use of Molecular Docking. The results show that FeNOTPPS forms the most stable complex with DmAChE.