Rapid Eye Movement Sleep Behavior Disorder Symptoms Correlate with Domains of Cognitive Impairment in Parkinson's Disease

Background:

Rapid eye movement (REM) sleep behavior disorder (RBD) may be a risk factor for cognitive impairment in patients with Parkinson''s disease (PD). However, little is known regarding the relation between the severity of RBD and the different domains of cognitive impairment. The aim of this study was: (1) to investigate the domains of cognitive impairment in patients with PD and RBD, and (2) to explore risk factors for PD-mild cognitive impairment (PD-MCI) and the relationship between RBD severity and impairment in different cognitive domains in PD.

Methods:

The participants were grouped as follows: PD without RBD (PD-RBD; n = 42), PD with RBD (PD + RBD; n = 32), idiopathic RBD (iRBD; n = 15), and healthy controls (HCs; n = 36). All participants completed a battery of neuropsychological assessment of attention and working memory, executive function, language, memory, and visuospatial function. The information of basic demographics, diseases and medication history, and motor and nonmotor manifestations was obtained and compared between PD-RBD and PD + RBD groups. Particular attention was paid to the severity of RBD assessed by the RBD Questionnaire-Hong Kong (RBDQ-HK) and the RBD Screening Questionnaire (RBDSQ), then we further examined associations between the severity of RBD symptoms and cognitive levels via correlation analysis.

Results:

Compared to PD-RBD subjects, PD + RBD patients were more likely to have olfactory dysfunction and their Epworth Sleepiness Scale scores were higher (P < 0.05). During neuropsychological testing, PD + RBD patients performed worse than PD-RBD patients, including delayed memory function, especially. The MCI rates were 33%, 63%, 33%, and 8% for PD-RBD, PD + RBD, iRBD, and HC groups, respectively. RBD was an important factor for the PD-MCI variance (odds ratio = 5.204, P = 0.018). During correlation analysis, higher RBDSQ and RBDQ-HK scores were significantly associated with poorer performance on the Trail Making Test-B (errors) and Auditory Verbal Learning Test (delayed recall) and higher RBD-HK scores were also associated with Rey–Osterrieth complex figure (copy) results.

Conclusions:

When PD-RBD and PD + RBD patients have equivalent motor symptoms, PD + RBD patients still have more olfactory dysfunction and worse daytime somnolence. RBD is an important risk factor for MCI, including delayed memory. Deficits in executive function, verbal delayed memory, and visuospatial function were consistently associated with more severe RBD symptoms.     

The Natural Progression of Parkinson's Disease in a Small Cohort with 15 Drug-na?ve Patients

Background:

The studies of the natural progression of Parkinson''s disease (PD) in Chinese populations have been lacking. To address this issue and obtain a preliminary data, we conducted a PD progression assessment in 15 adults with de novo PD from a nutritional intervention trial (NIT) cohort in Lin County China.

Methods:

Using the Copiah County screening questionnaire and United Kingdom Parkinson''s Disease Society Brain Bank diagnostic criteria, we surveyed the available NIT cohort members in 2000 and diagnosed 86 patients as PD. In 2010, we resurveyed all PD patients and confirmed definite PD diagnosis in 15 cases with the rest of them being dead (54); having probable (10) PD or vascular Parkinsonism (3); refusing to participate (2); or being away (2). In both surveys, we used Hoehn and Yahr (HY) scale and assessed the disease progression. Unified Parkinson''s Disease Rating Scale (UPDRS) was added to the second survey.

Results:

In 2010, the average disease duration for 15 definite PD patients was 13.6 ± 7.3 years. Over a 10-year time span, 9 out of 15 patients remained at the same HY stage while the remaining 6 progressed. Rigidity (47% vs. 100%; P = 0.002) and postural instability (7% vs. 47%; P = 0.005) worsened significantly. The mean UPDRS motor scores in 2010 were 39.4 ± 23.7.

Conclusions:

Overall worsening of motor function in PD seems to be the rule in this untreated cohort, and their rate of progression seemed to be slower than those reported in the western populations.     

Investigation of Urination Disorder in Parkinson's Disease

Background:

Urination disorders are common in Parkinson''s disease (PD) and respond poorly to medication. This study aimed to analyze the risk factors for urination disorders in PD.

Methods:

Ninety-one patients with PD (aged 34–83 years old) were recruited. Patients were assessed with the Unified PD Rating Scale (UPDRS), Hoehn and Yahr stage, Pittsburgh Sleep Quality Index (PSQI), Hamilton Depression Rating Scale (HAMD), and Hamilton Anxiety Scale (HAMA). Micturition number was recorded, and Type B ultrasound was used to evaluate residual urine. Statistics was performed using binary logistic regression, bivariate correlations, and Chi-square and t-tests.

Results:

Of 91 patients, urinary dysfunction occurred in 55.0%. Among these, 49.5% suffered with nocturia, 47.3% with pollakiuria. Nocturia number had a positive linear relationship with HAMA score (odds ratio [OR] = 0.340, P = 0.001), HAMD score (OR = 0.323, P = 0.002), duration of L-dopa medication (OR = 0.328, P = 0.001), dose of L-dopa (OR = 0.273, P = 0.009), UPDRS-II (OR = 0.402, P = 0.000), UPDRS-III score (OR = 0.291, P = 0.005), and PSQI score (OR = 0.249, P = 0.017). Micturition number over 24 h was positively associated with HAMA (OR = 0.303, P = 0.004) and UPDRS-II scores (OR = 0.306, P = 0.003). Of patients with residual urine, 79.3% had a volume of residual urine <50 ml. Residual urine was present in 44.4% of the patients with nocturia, 46.5% of the patients with pollakiuria, and 80.0% of the patients with dysuria. More men than women had residual urine (35.2% male vs. 13.3% female; P = 0.002).

Conclusions:

Nocturia and pollakiuria were common micturition symptoms in our participants with PD. Nocturia was associated with depression, anxiety, sleep problems, and severity of PD. Pollakiuria was associated with anxiety and severity of PD. Male patients were more prone to residual urine and pollakiuria.     

Amplitude of Low-frequency Oscillations in Parkinson's Disease: A 2-year Longitudinal Resting-state Functional Magnetic Resonance Imaging Study

Background:

Neuroimaging studies have found that functional changes exist in patients with Parkinson''s disease (PD). However, the majority of functional magnetic resonance imaging (fMRI) studies in patients with PD are task-related and cross-sectional. This study investigated the functional changes observed in patients with PD, at both baseline and after 2 years, using resting-state fMRI. It further investigated the relationship between whole-brain spontaneous neural activity of patients with PD and their clinical characteristics.

Methods:

Seventeen patients with PD underwent an MRI procedure at both baseline and after 2 years using resting-state fMRI that was derived from the same 3T MRI. In addition, 20 age- and sex-matched, healthy controls were examined using resting-state fMRI. The fractional amplitude of low-frequency fluctuation (fALFF) approach was used to analyze the fMRI data. Nonlinear registration was used to model within-subject changes over the scanning interval, as well as changes between the patients with PD and the healthy controls. A correlative analysis between the fALFF values and clinical characteristics was performed in the regions showing fALFF differences.

Results:

Compared to the control subjects, the patients with PD showed increased fALFF values in the left inferior temporal gyrus, right inferior parietal lobule (IPL) and right middle frontal gyrus. Compared to the baseline in the 2 years follow-up, the patients with PD presented with increased fALFF values in the right middle temporal gyrus and right middle occipital gyrus while also having decreased fALFF values in the right cerebellum, right thalamus, right striatum, left superior parietal lobule, left IPL, left precentral gyrus, and left postcentral gyrus (P < 0.01, after correction with AlphaSim). In addition, the fALFF values in the right cerebellum were positively correlated with the Unified PD Rating Scale (UPDRS) motor scores (r = 0.51, P < 0.05, uncorrected) and the change in the UPDRS motor score (r = 0.61, P < 0.05, uncorrected).

Conclusions:

The baseline and longitudinal changes of the fALFF values in our study suggest that dysfunction in the brain may affect the regions related to cortico-striato-pallido-thalamic loops and cerebello-thalamo-cortical loops as the disease progresses and that alterations to the spontaneous neural activity of the cerebellum may also play an important role in the disease''s progression in patients with PD.     

Chinese Medicine for Idiopathic Parkinson's Disease: A Meta Analysis of Randomized Controlled Trials

Objective:To evaluate the efficacy of Chinese medicine(CM) adjunct to conventional medications for idiopathic Parkinson's disease(PD).Methods:Electronic English and Chinese databases including PubMed,Cochrane Library,Web of Science,Chinese Medical Current Contents,China National Knowledge Infrastructure,China Science and Technology Journal Database,Wanfang Med Database,and Traditional Chinese Medical Database System were used for key words searching in a highly sensitive search strategy.The extracted data was analyzed by the Review Manager 5.0.Results:Twelve trials involving 869 participants were included in the meta-analysis.Unified PD Rating Scale(UPDRS) I,Ⅱ,Ⅲ,Ⅳ scores and UPDRS Ⅰ-Ⅳ total scores were used to be the primary outcomes,Parkinson Disease Question-39(PDQ-39) and Scores of Chinese Medical Symptoms were the secondary outcomes.CM adjunct therapy had greater improvement in UPDRS Ⅰ[2 trials;standardized mean difference(SMD)-0.40,95%confidence interval(CI)-0.71 to-0.09;Z=2.49(P=0.01)],Ⅱ[5 trials;SMD-0.47,95%CI-0.69 to-0.25;Z=4.20(P0.01)],Ⅲ[5 trials;SMD-0.35,95%CI-0.57 to-0.13;Z=3.16(P=0.002)],Ⅳ scores[3 trials;SMD-0.32,95%CI-0.60 to-0.03;Z=2.17(P=0.03)],UPDRS Ⅰ-Ⅳ total scores[7 trials;SMD-0.36,95%CI-0.53 to-0.20;Z=4.24(P0.05)].PDQ-39 and Chinese medical symptoms compared to the conventional medication only.Conclusion:CM adjunct therapy has potential therapeutic benefits by decreasing UPDRS scores and reducing adverse effect.     

Long-term Efficacy of Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A 5-year Follow-up Study in China

Background:

Subthalamic nucleus deep brain stimulation (STN DBS) is effective against advanced Parkinson''s disease (PD), allowing dramatic improvement of Parkinsonism, in addition to a significant reduction in medication. Here we aimed to investigate the long-term effect of STN DBS in Chinese PD patients, which has not been thoroughly studied in China.

Methods:

Ten PD patients were assessed before DBS and followed up 1, 3, and 5 years later using Unified Parkinson''s Disease Rating Scale Part III (UPDRS III), Parkinson''s Disease Questionnatire-39, Parkinson''s Disease Sleep Scale-Chinese Version, Mini-mental State Examination, Montreal Cognitive Assessment, Hamilton Anxiety Scale and Hamilton Depression Scale. Stimulation parameters and drug dosages were recorded at each follow-up. Data were analyzed using the ANOVA for repeated measures.

Results:

In the “off” state (off medication), DBS improved UPDRS III scores by 35.87% in 5 years, compared with preoperative baseline (P < 0.001). In the “on” state (on medication), motor scores at 5 years were similar to the results of preoperative levodopa challenge test. The quality of life is improved by 58.18% (P < 0.001) from baseline to 3 years and gradually declined afterward. Sleep, cognition, and emotion were mostly unchanged. Levodopa equivalent daily dose was reduced from 660.4 ± 210.1 mg at baseline to 310.6 ± 158.4 mg at 5 years (by 52.96%, P < 0.001). The average pulse width, frequency and amplitude at 5 years were 75.0 ± 18.21 μs, 138.5 ± 19.34 Hz, and 2.68 ± 0.43 V, respectively.

Conclusions:

STN DBS is an effective intervention for PD, although associated with a slightly diminished efficacy after 5 years. Compared with other studies, patients in our study required lower voltage and medication for satisfactory symptom control.     

Dopamine Agonists Exert Nurr1-inducing Effect in Peripheral Blood Mononuclear Cells of Patients with Parkinson's Disease

Background:

Nurr1 plays an essential role in the development, survival, and function maintenance of midbrain dopaminergic (DA) neurons, and it is a potential target for Parkinson''s disease (PD). Nurr1 mRNA can be detected in peripheral blood mononuclear cells (PBMCs), but whether there is any association of altered Nurr1 expression in PBMC with the disease and DA drug treatments remains elusive. This study aimed to measure the Nurr1 mRNA level in PBMC and evaluate the effect of Nurr1 expression by DA agents in vivo and in vitro.

Methods:

The mRNA levels of Nurr1 in PBMC of four subgroups of 362 PD patients and 193 healthy controls (HCs) using real-time polymerase chain reaction were measured. The nonparametric Mann-Whitney U-test and Kruskal-Wallis test were performed to evaluate the differences between PD and HC, as well as the subgroups of PD. Multivariate linear regression analysis was used to evaluate the independent association of Nurr1 expression with Hoehn and Yahr scale, age, and drug treatments. Besides, the Nurr1 expression in cultured PBMC was measured to determine whether DA agonist pramipexole affects its mRNA level.

Results:

The relative Nurr1 mRNA levels in DA agonists treated subgroup were significant higher than those in recent-onset cases without any anti-PD treatments (de novo) (P < 0.001) and HC groups (P < 0.010), respectively. Furthermore, the increase in Nurr1 mRNA expression was seen in DA agonist and L-dopa group. Multivariate linear regression showed DA agonists, L-dopa, and DA agonists were independent predictors correlated with Nurr1 mRNA expression level in PBMC. In vitro, in the cultured PBMC treated with 10 μmol/L pramipexole, the Nurr1 mRNA levels were significantly increased by 99.61%, 71.75%, 73.16% in 2, 4, and 8 h, respectively (P < 0.001).

Conclusions:

DA agonists can induce Nurr1 expression in PBMC, and such effect may contribute to DA agonists-mediated neuroprotection on DA neurons.     

Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson's Disease

Objective:

This review examines the evidence that deep brain stimulation (DBS) has extensive impact on nonmotor symptoms (NMSs) of patients with Parkinson''s disease (PD).

Data Sources:

We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus internus (GPi), subthalamic nucleus (STN), and ventral intermediate thalamic nucleus.

Study Selection:

We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances. For psychological symptoms and cognitive impairment, we tried to use more reliable proofs: Random, control, multicenter, large sample sizes, and long period follow-up clinical studies. We categorized the NMSs into four groups: those that would improve definitively following DBS; those that are not significantly affected by DBS; those that remain controversial on their surgical benefit; and those that can be worsened by DBS.

Results:

In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results; Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS; The impact of DBS on behavioral addictions and dysphagia is still uncertain.

Conclusions:

As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients.     

Mitochondrial DNA Haplogroups and the Risk of Sporadic Parkinson's Disease in Han Chinese

Background:

Mitochondrial dysfunction is linked to the pathogenesis of Parkinson''s disease (PD). However, the precise role of mitochondrial DNA (mtDNA) variations is obscure. On the other hand, mtDNA haplogroups have been inconsistently reported to modify the risk of PD among different population. Here, we try to explore the relationship between mtDNA haplogroups and sporadic PD in a Han Chinese population.

Methods:

Nine single-nucleotide polymorphisms, which define the major Asian mtDNA haplogroups (A, B, C, D, F, G), were detected via polymerase chain reaction-restriction fragment length polymorphism or denaturing polyacrylamide gel electrophoresis in 279 sporadic PD patients and 510 matched controls of Han population.

Results:

Overall, the distribution of mtDNA haplogroups did not show any significant differences between patients and controls. However, after stratification by age at onset, the frequency of haplogroup B was significantly lower in patients with early-onset PD (EOPD) compared to the controls (odds ratio [OR] =0.225, 95% confidence interval [CI]: 0.082–0.619, P = 0.004), while other haplogroups did not show significant differences. After stratification by age at examination, among subjects younger than 50 years of age: Haplogroup B also showed a lower frequency in PD cases (OR = 0.146, 95% CI: 0.030–0.715, P = 0.018) while haplogroup D presented a higher risk of PD (OR = 3.579, 95% CI: 1.112–11.523, P = 0.033), other haplogroups also did not show significant differences in the group.

Conclusions:

Our study indicates that haplogroup B might confer a lower risk for EOPD and people younger than 50 years in Han Chinese, while haplogroup D probably lead a higher risk of PD in people younger than 50 years of age. In brief, particular Asian mtDNA haplogroups likely play a role in the pathogenesis of PD among Han Chinese.     

ApaI,BsmI, FokI,and TaqI Polymorphisms in the Vitamin D Receptor Gene and Parkinson's Disease

Background:

The vitamin D receptor (VDR) gene has been identified as a candidate gene for susceptibility to Parkinson''s disease (PD), but results from genetic association studies to date are inconsistent. Here, we conducted a meta-analysis of published case-control studies to evaluate the association of the extensively studied VDR ApaI (G/T), BsmI (G/A), FokI (C/T), and TaqI (T/C) gene polymorphisms with risk of PD.

Methods:

Electronic search at PubMed, EMBASE, EBSCO, China National Knowledge Infrastructure, Weipu database, and Wanfang database was conducted to identify all relevant studies. Odds ratio (OR) with 95% confidence interval (CI) values was applied to evaluate the strength of the association.

Results:

A total of seven studies with 2034 PD cases and 2432 controls were included in the meta-analysis following the inclusion and exclusion criteria. Overall, no significant association between ApaI, BsmI, and TaqI gene polymorphisms and PD susceptibility in all four genetic models was found (T vs. G: OR = 1.00, 95% CI: 0.89–1.12, P = 0.97; A vs. G: OR = 0.94, 95% CI: 0.77–1.15, P = 0.53; C vs. T: OR = 1.03, 95% CI: 0.85–1.25, P = 0.77) while a significant association between FokI (C/T) and PD risk was observed (C vs. T: OR = 1.41, 95% CI: 1.14–1.75, P = 0.001; CC vs. TT: OR = 2.45, 95% CI: 1.52–3.93, P = 0.0002; CT vs. TT: OR = 2.21, 95% CI: 1.38–3.52, P = 0.0009, CC vs. CT+TT: OR = 2.32, 95% CI: 1.49–3.61, P = 0.0002).

Conclusions:

Polymorphisms of ApaI, BsmI, and TaqI may not be associated with the susceptibility to PD while the FokI (C/T) polymorphism is possibly associated with increased PD risk. However, conclusions should be cautiously interpreted due to the relatively small number of studies included.     

Hyperbaric Oxygen and Ginkgo Biloba Extract Ameliorate Cognitive and Memory Impairment via Nuclear Factor Kappa-B Pathway in Rat Model of Alzheimer's Disease

Background:

Hyperbaric oxygen (HBO) and Ginkgo biloba extract (e.g., EGB 761) were shown to ameliorate cognitive and memory impairment in Alzheimer''s disease (AD). However, the exact mechanism remains elusive. The aim of the present study was to investigate the possible mechanisms of HBO and EGB 761 via the function of nuclear factor kappa-B (NF-κB) pathway.

Methods:

AD rats were induced by injecting β-amyloid 25–35 into the hippocampus. All animals were divided into six groups: Normal, sham, AD model, HBO (2 atmosphere absolute; 60 min/d), EGB 761 (20 mg·kg⁻¹·d⁻¹), and HBO/EGB 761 groups. Morris water maze tests were used to assess cognitive, and memory capacities of rats; TdT-mediated dUTP Nick-End Labeling staining and Western blotting were used to analyze apoptosis and NF-κB pathway-related proteins in hippocampus tissues.

Results:

Morris water maze tests revealed that EGB 761 and HBO significantly improved the cognitive and memory ability of AD rats. In addition, the protective effect of combinational therapy (HBO/EGB 761) was superior to either HBO or EGB 761 alone. In line, reduced apoptosis with NF-κB pathway activation was observed in hippocampus neurons treated by HBO and EGB 761.

Conclusions:

Our results suggested that HBO and EGB 761 improve cognitive and memory capacity in a rat model of AD. The protective effects are associated with the reduced apoptosis with NF-κB pathway activation in hippocampus neurons.     

Vascular disease burden in Indian subjects with vascular dementia

Background

Vascular disease factors like hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease contribute to the development of vascular dementia. As comorbidity of vascular disease factors in vascular dementia is common, we investigated the vascular disease burden in subjects with vascular dementia.

Aims

To investigate the vascular disease burden due to four vascular disease factors: hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease in Indian subjects with vascular dementia.

Methods

In this study, 159 subjects with probable vascular dementia (as per NINDS-AIREN criteria) attending the memory clinic at a tertiary care hospital were assessed for the presence of hypertension, diabetes mellitus, dyslipidaemia, and ischaemic heart disease using standardised operational definitions and for severity of dementia on the Clinical Dementia Rating (CDR) scale. The data obtained was subjected to appropriate statistical analysis.

Results

Dyslipidaemia (79.25 per cent) was the most common vascular disease factor followed by hypertension (73.58 per cent), ischaemic heart disease (58.49 per cent), and diabetes mellitus (40.80 per cent). Most subjects (81.1 per cent) had two or more vascular disease factors. Subjects with more severe dementia had more vascular disease factors (sig 0.001).

Conclusion

People with moderate to severe dementia have a significantly higher vascular disease burden; therefore, higher vascular disease burden may be considered as a poor prognostic marker in vascular dementia. Subjects with vascular dementia and their caregivers must manage cognitive impairment and ADL alongside managing serious comorbid vascular diseases that may worsen the dementia.     

Reduction of Glucose Metabolism in Olfactory Bulb is an Earlier Alzheimer's Disease-related Biomarker in 5XFAD Mice

Background:

Early diagnosis assumes a vital role in an effective treatment of Alzheimer''s disease (AD). Most of the current studies can only make an AD diagnosis after the manifestation of typical clinical symptoms. The present study aimed to investigate typical and other biomarkers of AD to find a possible early biomarker.

Methods:

A total of 14 5XFAD mice (at 3 and 6 months old), with 14 age-matched wild-type (WT) mice as control, were enrolled in this case-control study. Morris water maze test was performed to evaluate the cognitive function; buried food pellet test and olfactory maze test were employed to investigate the olfactory function; immunofluorescence to detect amyloid deposition and positron emission tomography to examine 2-deoxy-2-(¹⁸ F) fluoro-D-glucose ([¹⁸ F]-FDG) uptake in the hippocampus and cerebral cortex.

Results:

With the increasing age, cognitive performance (P = 0.0262) and olfactory function were significantly deteriorated (day 1 P = 0.0012, day 2 P = 0.0031, day 3 P = 0.0160, respectively) and the (¹⁸ F)-FDG uptake was markedly decreased in multi-cerebral regions including the olfactory bulb (P < 0.0001), hippocampus (P = 0.0121), and cerebral cortex (P < 0.0001). Of note, in 3-month-old 5XFAD mice, a significant decline of (¹⁸ F)-FDG uptake in the olfactory bulb was found when compared with that of age-matched WT mice (P = 0.023) while no significant difference was present when the uptakes in other cerebral regions were compared.

Conclusions:

The decline of (¹⁸ F)-FDG uptake in the olfactory bulb occurs earlier than other incidents, serving as an earlier in vivo biological marker of AD in 5XFAD mice and making early diagnosis of AD possibly.     

Discriminating Potential of Extraintestinal Systemic Manifestations and Colonoscopic Features in Chinese Patients with Intestinal Beh?et's Disease and Crohn's Disease

Background:

The distinction between intestinal Behçet''s disease (BD) and Crohn''s disease (CD) is always challenging due to many overlapping clinical features. We conducted a retrospective study to reveal valuable strategies for the differential diagnosis between intestinal BD and CD in Chinese patients based on their clinical and colonoscopic features.

Methods:

Thirty-five intestinal BD patients and 106 CD patients hospitalized from January 1983 to January 2010, who had ulcerative lesions in the terminal ileum or colon under colonoscopy and no history of gastrointestinal operation except appendectomy before admission, were enrolled. Univariate and multivariate logistic regression analyses were conducted to find discriminating predictors among demographic data, clinical manifestations, and colonoscopic findings.

Results:

Based on univariate analysis, massive gastrointestinal hemorrhage, fever, and extraintestinal systemic manifestations were more common in intestinal BD patients (P = 0.022, 0.048 and 0.001, respectively), while diarrhea, intestinal obstruction, and perianal lesions were more common in CD patients (P = 0.002, 0.010, and 0.027 respectively). Based on colonoscopy, focal involvement, ileocecal valve deformity, solitary ulcers, large ulcers (ulcer size > 2 cm), and circumferential ulcers were more common in intestinal BD patients (P = 0.003, 0.003, 0.014, 0,013, and 0.003, respectively), while segmental involvement, longitudinal ulcers, a cobblestone or nodular appearance, and pseudo-polyps were more common in CD patients (P = 0.003, 0.008, 0.023, and 0.002, respectively). Based on multivariate logistic regression analysis, diarrhea, extraintestinal manifestations, ulcer distribution, size, and type, and pseudo-polyps were independent discriminating predictors between the two groups (P = 0.048, 0.008, 0.006, 0.021, 0.002, and 0.041, respectively). The discriminating algorithm composed of the above independent predictors had the highest area under the curve of 0.987 for distinguishing between the two diseases.

Conclusions:

Extraintestinal systemic manifestations and the characteristic colonoscopic features, such as ulcer distribution, size and type, helped to distinguish intestinal BD from CD.     

Memory Dysfunction in Type 2 Diabetes Mellitus Correlates with Reduced Hippocampal CA1 and Subiculum Volumes

Background:

Little attention has been paid to the role of subcortical deep gray matter (SDGM) structures in type 2 diabetes mellitus (T2DM)-induced cognitive impairment, especially hippocampal subfields. Our aims were to assess the in vivo volumes of SDGM structures and hippocampal subfields using magnetic resonance imaging (MRI) and to test their associations with cognitive performance in T2DM.

Methods:

A total of 80 T2DM patients and 80 neurologically unimpaired healthy controls matched by age, sex and education level was enrolled in this study. We assessed the volumes of the SDGM structures and seven hippocampal subfields on MRI using a novel technique that enabled automated volumetry. We used Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores as measures of cognitive performance. The association of glycosylated hemoglobin (HbA1c) with SDGM structures and neuropsychological tests and correlations between hippocampal subfields and neuropsychological tests were assessed by partial correlation analysis in T2DM.

Results:

Bilaterally, the hippocampal volumes were smaller in T2DM patients, mainly in the CA1 and subiculum subfields. Partial correlation analysis showed that the MoCA scores, particularly those regarding delayed memory, were significantly positively correlated with reduced hippocampal CA1 and subiculum volumes in T2DM patients. Additionally, higher HbA1c levels were significantly associated with poor memory performance and hippocampal atrophy among T2DM patients.

Conclusions:

These data indicate that the hippocampus might be the main affected region among the SDGM structures in T2DM. These structural changes in the hippocampal CA1 and subiculum areas might be at the core of underlying neurobiological mechanisms of hippocampal dysfunction, suggesting that degeneration in these regions could be responsible for memory impairments in T2DM patients.     

Seroprevalence of helicobacter pylori in human immunodeficiency virus-positive Patients and it's correlation with CD4+ Lymphocyte Count

Background:

This study assessed the seroprevalence of Helicobacter pylori antibodies among Iranian patients with human immunodeficiency virus (HIV) infection. It also examines whether anti H. pylori seroprevalence was associated with the severity of the HIV infection or the antiretroviral treatment.

Material and Methods:

A total of 114 HIV-infected patients and 114 age and sex-matched controls, without symptoms referable to upper gastrointestinal tract were recruited. Blood samples were obtained from all subjects. Serum IgG and IgA against H. pylori measured using the enzyme-linked immunosorbent assay (ELISA).

Results:

The rate of anti H. pylori IgG seropositivity was 57.9% in HIV-infected patients and 28.95% in controls (P < 0.001), while the rate of IgA seropositivity was 2.64% in HIV patients and 31.57% in controls (P < 0.001). Although there was an increasing trend of higher IgG and IgA titre by increasing CD4 cell count in HIV-positive patients, it was not reach statistical significance. There was no statistical difference in the serology of anti H. pylori IgG and IgA between patients receiving antiretroviral therapy comparing untreated HIV patients.

Conclusions:

This study showed higher seroprevalence of H. pylori IgG along with lower seroprevalence of H. pylori IgA in HIV-positive patients compared matched controls.     

Dipstick urinalysis findings in children with Plasmodium falciparum in the South Tongu District: A case-control study

Background:

Malaria ranks among the major health and developmental challenges facing some of the poorest countries in tropical and sub-tropical regions across the globe. We determined urinary abnormalities and its relationship with parasite density in children ≤12 years with Plasmodium falciparum infection.

Materials and Methods:

From December 2013 to March 2014, we randomly recruited 116 participants comprising 58 malaria patients (cases) and 58 healthy controls from the Comboni Mission and the Sogakope District Hospitals both in the South Tongu district. Blood was collected for the estimation of hemoglobin and total white blood cells; thick and thin blood films were used for the determination of malaria parasite density. Urine was collected for the measurement of the various biochemical components using the automated urine analyzer. A pretested questionnaire was used to obtain demographic and clinical data.

Results:

Urine protein (P < 0.001), blood (P < 0.001), bilirubin (P < 0.001), urobilinogen (P < 0.001), and ketones (P = 0.001) were significantly higher in individuals with P. falciparum infection than in healthy controls. Proteinuria (P = 0.247; r = 0.155), hematuria (P = 0.142; r = 0.195), bilirubinuria (P = 0.001; r = 0.438), urobilinogenuria (P = 0.876; r = 0.021), and ketonuria (P = 0.136; r = 0.198) were positively correlated with malaria parasite density; however, only bilirubinuria was significantly higher at higher parasitemia.

Conclusion:

Malaria has a significant effect on the chemical composition of urine with bilirubin positively correlated with parasite density. Dipstick urinalysis can be used together with light microscopy in resource-limited malaria-endemic areas to accurately diagnose falciparum malaria infection.     

Visual function and vision-related quality of life in presbyopic adult population of Northwestern Nigeria

Purpose:

To determine the impact of uncorrected presbyopia on vision-related quality of life (QoL) and visual function (VF) among adults 40 years and older in Bungudu local government area (LGA) of Zamfara State, Nigeria.

Materials and Methods:

A population-based cross-sectional study in Bungudu LGA of Zamfara State Nigeria was conducted in 2012. Six-hundred and fifty persons at least 40 years of age were examined using a two-stage cluster random sampling-based on probability proportional to size. Presbyopia was defined as the inability to read N8 at 40 cm in an indoor illumination using LogMAR E-chart. Demographic information comprising of age, sex, occupation, and educational level among others was obtained from a pilot tested VF-14 and modified vision-related QoL questionnaire by trained interviewer.

Results:

Out Of the 650 subjects enumerated 635 were examined given a response rate of 97.7%. The mean age of participants was 53.59 years (95% confidence interval:52.75%-54.43%). The crude prevalence of presbyopia was 30.4%, (95% CI: 26.8%-34.1%). The mean VF score of persons with presbyopia was 85.09, (95% CI: 83.09%-87.09%) and being female was strongly associated with high VF scores (P = 0.003). The VFs most impaired were the ability to read, write, use mobile phones, and thread needles. The higher the degree of presbyopia the lower the mean VF score (P = 0.00).

Conclusion:

Uncorrected presbyopia is associated with functional visual impairment and reduce QoL especially in the ability to read, write, and usage of mobile cell phones among adults 40 years and older in Bungudu District.     

Knowledge of diabetes and its associated ocular manifestations by diabetic patients: A study at Korle-Bu Teaching Hospital,Ghana

Background:

Diabetes mellitus is a significant cause of visual impairment, hence adequate knowledge on this condition and its ocular manifestations is of immense importance to diabetic patients.

Aim:

To assess the knowledge of diabetic patients on the disorder and its ocular manifestations, and their attitude towards ocular examinations.

Materials and Methods:

A cross-sectional survey involving the use of a structured interview was conducted among diabetic patients attending the Diabetic Clinic of the Korle-Bu Teaching Hospital. Using Fishers Exact Chi-square (χ²) and Odds Ratios (ORs), data obtained was analyzed.

Results:

Only 103 (26.4%) patients knew the type of diabetes mellitus they were suffering from. Knowledge on ocular effects of diabetes mellitus was low and only 15 (3.8%) knew that it could affect the ocular refraction with no patient mentioning that diabetes mellitus could cause cataract or diabetic retinopathy. Attitude to routine eye examination was poor. As much as 135 (34.6%) had never had an eye examination since being diagnosed of diabetes. Knowledge of the type of diabetes mellitus the individual had or any ocular complication of this disorder was significantly related (OR: 4.22; P < 0.001 and OR: 2.55; P < 0.001) respectively to their attitude to seeking eye care.

Conclusion:

Diabetic patients’ knowledge on diabetes mellitus and its ocular manifestations, and the attitude of diabetic patients towards eye examination were poor. Intensive health education by diabetes care givers and leaders of the Ghana Diabetic Association for diabetic patient is therefore required to improve attitude towards eye care to prevent visual impairment.     

Targeted Genes Sequencing Identified a Novel 15 bp Deletion on GJA8 in a Chinese Family with Autosomal Dominant Congenital Cataracts

Background:

Congenital cataract (CC) is the leading cause of visual impairment or blindness in children worldwide. Because of highly genetic and clinical heterogeneity, a molecular diagnosis of the lens disease remains a challenge.

Methods:

In this study, we tested a three-generation Chinese family with autosomal dominant CCs by targeted sequencing of 45 CC genes on next generation sequencing and evaluated the pathogenicity of the detected mutation by protein structure, pedigree validation, and molecular dynamics (MD) simulation.

Results:

A novel 15 bp deletion on GJA8 (c.426_440delGCTGGAGGGGACCCT or p. 143_147delLEGTL) was detected in the family. The deletion, concerned with an in-frame deletion of 5 amino acid residues in a highly evolutionarily conserved region within the cytoplasmic loop domain of the gap junction channel protein connexin 50 (Cx50), was in full cosegregation with the cataract phenotypes in the family but not found in 1100 control exomes. MD simulation revealed that the introduction of the deletion destabilized the Cx50 gap junction channel, indicating the deletion as a dominant-negative mutation.

Conclusions:

The above results support the pathogenic role of the 15 bp deletion on GJA8 in the Chinese family and demonstrate targeted genes sequencing as a resolution to molecular diagnosis of CCs.