Racial differences in retinal neurodegeneration as a surrogate marker for cortical atrophy in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) has both an inflammatory and a neurodegenerative component, with gray matter (GM) atrophy being an important contributor to disability. Optical coherence tomography (OCT) may serve as a prognostic tool for neuroaxonal health by measuring ganglion cell inner plexiform layer (GCIPL) thickness. There is a paucity of literature regarding the effects of race on pathobiology of MS, as racial minorities are underrepresented in research studies. OBJECTIVE: The aim of this paper is to compare the correlation between GM fraction (GMF) and GCIPL thickness in Caucasian Americans with MS (CAMS) and African Americans with MS (AAMS). METHODS: Fifty-nine patients with relapsing-remitting multiple sclerosis (RRMS) were included. Using a cross-sectional design, we compared the OCT (GCIPL thickness) and MRI (GMF) data of 32 CAMS and 27 AAMS patients. RESULTS: No significant correlation was observed between GMF and GCIPL in our study group (p = 0.127, r = 0.148). CAMS exhibited a significant correlation between these measures (p = 0.0004, r = 0.434), while in AAMS these measures did not correlate significantly (p = 0.187, r = -0.201). CONCLUSION: GCIPL might be a sensitive biomarker predicting GM atrophy and disability in CAMS, but not in AAMS. Larger studies are needed to investigate reliable biomarkers across races. Inclusion of AAMS in research studies is necessary to shed more light on the pathobiology of MS.

Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study.

On average, African Americans with multiple sclerosis demonstrate higher inflammatory disease activity, faster disability accumulation, greater visual dysfunction, more pronounced brain tissue damage and higher lesion volume loads compared to Caucasian Americans with multiple sclerosis. Neurodegeneration is an important component of multiple sclerosis, which in part accounts for the clinical heterogeneity of the disease. Brain atrophy appears to be widespread, although it is becoming increasingly recognized that regional substructure atrophy may be of greater clinical relevance. Patient race (within the limitations of self-identified ancestry) is regarded as an important contributing factor. However, there is a paucity of studies examining differences in neurodegeneration and brain substructure volumes over time in African Americans relative to Caucasian American patients. Optical coherence tomography is a non-invasive and reliable tool for measuring structural retinal changes. Recent studies support its utility for tracking neurodegeneration and disease progression in vivo in multiple sclerosis. Relative to Caucasian Americans, African American patients have been found to have greater retinal structural injury in the inner retinal layers. Increased thickness of the inner nuclear layer and the presence of microcystoid macular pathology at baseline predict clinical and radiological inflammatory activity, although whether race plays a role in these changes has not been investigated. Similarly, assessment of outer retinal changes according to race in multiple sclerosis remains incompletely characterized. Twenty-two African Americans and 60 matched Caucasian Americans with multiple sclerosis were evaluated with brain MRI, and 116 African Americans and 116 matched Caucasian Americans with multiple sclerosis were monitored with optical coherence tomography over a mean duration of 4.5 years. Mixed-effects linear regression models were used in statistical analyses. Grey matter (-0.9%/year versus -0.5%: P =0.02), white matter (-0.7%/year versus -0.3%: P =0.04) and nuclear thalamic (-1.5%/year versus -0.7%/year: P =0.02) atrophy rates were approximately twice as fast in African Americans. African Americans also exhibited higher proportions of microcystoid macular pathology (12.1% versus 0.9%, P =0.001). Retinal nerve fibre layer (-1.1% versus -0.8%: P =0.02) and ganglion cell+ inner plexiform layer (-0.7%/year versus -0.4%/year: P =0.01) atrophy rates were faster in African versus Caucasian Americans. African Americans on average exhibited more rapid neurodegeneration than Caucasian Americans and had significantly faster brain and retinal tissue loss. These results corroborate the more rapid clinical progression reported to occur, in general, in African Americans with multiple sclerosis and support the need for future studies involving African Americans in order to identify individual differences in treatment responses in multiple sclerosis.

Cerebral structural changes in diabetic kidney disease: African American-Diabetes Heart Study MIND.

OBJECTIVE: Albuminuria and reduced kidney function are associated with cognitive impairment. Relationships between nephropathy and cerebral structural changes remain poorly defined, particularly in African Americans (AAs), a population at higher risk for both cognitive impairment and diabetes than European Americans. We examined the relationship between urine albumin:creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), and cerebral MRI volumes in 263 AAs with type 2 diabetes. RESEARCH DESIGN AND METHODS: Cross-sectional associations between renal parameters and white matter (WM), gray matter (GM), hippocampal, and WM lesion (WML) volumes were assessed using generalized linear models adjusted for age, education, sex, BMI, hemoglobin A1c (HbA1c) level, and hypertension. RESULTS: Participants had a mean (SD) age of 60.2 years (9.7 years), and 62.7% were female. Mean diabetes duration was 14.3 years (8.9 years), HbA1c level was 8.2% (2.2%; 66 mmol/mol), eGFR was 86.0 mL/min/1.73 m(2) (23.2 mL/min/1.73 m(2)), and UACR was 155.8 mg/g (542.1 mg/g; median 8.1 mg/g). Those with chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m(2) or UACR >30 mg/g) had smaller GM and higher WML volumes. Higher UACR was significantly associated with higher WML volume and greater atrophy (larger cerebrospinal fluid volumes), and smaller GM and hippocampal WM volumes. A higher eGFR was associated with larger hippocampal WM volumes. Consistent with higher WML volumes, participants with CKD had significantly poorer processing speed and working memory. These findings were independent of glycemic control. CONCLUSIONS: We found albuminuria to be a better marker of cerebral structural changes than eGFR in AAs with type 2 diabetes. Relationships between albuminuria and brain pathology may contribute to poorer cognitive performance in patients with mild CKD.

Associations of a PTPN11 G/A polymorphism at intron 3 with Helicobactor pylori seropositivity, gastric atrophy and gastric cancer in Japanese.

BACKGROUND: Previous studies have revealed the significance of Helicobacter pylori (H. pylori) infection as a risk factor of gastric cancer. Cytotoxin-associated gene A (cagA) positivity has been demonstrated to determine the clinical outcome of H. pylori infection in the presence of SHP-2 (src homology 2 domain-containing protein tyrosine phosphatase-2). This study aimed to examine the formerly reported association of G/A PTPN11 (protein-tyrosine phosphatase, nonreceptor-type 11) polymorphism (rs2301756) with gastric atrophy, as well as the association with gastric cancer in a Japanese population using a large sample size. METHODS: Study subjects were 583 histologically diagnosed patients with gastric cancer (429 males and 154 females) and age- and sex-frequency-matched 1,636 non-cancer outpatients (1,203 males and 433 females), who visited Aichi Cancer Center Hospital between 2001-2005. Serum anti-H. pylori IgG antibody and pepsinogens were measured to evaluate H. pylori infection and gastric atrophy, respectively. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by a logistic model. RESULTS: Among H. pylori seropositive non-cancer outpatients, the age- and sex-adjusted OR of gastric atrophy was 0.82 (95% CI 0.62-1.10, P = 0.194) for G/A, 0.84 (95% CI 0.39-1.81, P = 0.650) for A/A, and 0.83 (95% CI 0.62-1.09, P = 0.182) for G/A+A/A, relative to G/G genotype, and that of severe gastric atrophy was 0.70 (95% CI 0.47-1.04, P = 0.079), 0.56 (95% CI 0.17-1.91, P = 0.356), and 0.68 (95% CI 0.46-1.01, P = 0.057), respectively. Among H. pylori infected subjects (H. pylori seropositive subjects and seronegative subjects with gastric atrophy), the adjusted OR of severe gastric atrophy was further reduced; 0.62 (95% CI 0.42-0.90, P = 0.012) for G/A+A/A. The distribution of the genotype in patients with gastric cancer was not significantly different from that for H. pylori infected subjects without gastric atrophy. CONCLUSION: Our study results revealed that those with the A/A genotype of PTPN11 rs2301756 polymorphism are at lower risk of severe gastric atrophy, but are not associated with a decreased risk of gastric cancer, which partially supported our previous finding that the polymorphism in the PTPN11 gene encoding SHP-2 was associated with the gastric atrophy risk in H. pylori infected Japanese. The biological roles of this PTPN11 polymorphism require further investigation.

Macroscopic extent of gastric mucosal atrophy: increased risk factor for esophageal squamous cell carcinoma in Japan.

BACKGROUND: We aimed to estimate whether the macroscopic extent of gastric mucosal atrophy is associated with a risk for esophageal squamous cell carcinoma using a case-control study in Japanese subjects, a population known to have a high prevalence of CagA-positive H. pylori infection. METHODS: Two hundred and fifty-three patients who were diagnosed as having esophageal squamous cell carcinoma, and 253 sex- and age-matched controls were enrolled in the present study. The macroscopic extent of gastric mucosal atrophy was evaluated based on the Kimura and Takemoto Classification. A conditional logistic regression model with adjustment for potential confounding factors was used to assess the associations. RESULTS: Body gastritis, defined endoscopically, was independently associated with an increased risk for esophageal squamous cell carcinoma. CONCLUSION: Our findings suggest that macroscopic body gastritis may be a risk factor for esophageal squamous cell carcinoma in Japan. Further studies are needed to confirm these findings.

Brain volumes in Guam dementia vs Parkinson dementia complex vs aging Chamorro adults.

We sought to determine if Chamorro individuals with a family history of Guam dementia (GD) or Parkinson dementia complex (PDC) exhibit presymptomatic brain MRI changes. Sixty-six Chamorro subjects had neurocognitive assessment and volumetric MRI. MRI brain volumes differed between diagnostic groups (GD, PDC, control) and according to family history. Chamorros with a family history of PDC or dementia may have increased brain atrophy, suggesting a hereditary susceptibility to neurodegenerative disorders.

Noninvasive versus histologic detection of gastric atrophy in a Hispanic population in North America.

BACKGROUND & AIMS: Cancer risk is directly correlated with the severity and extent of mucosal atrophy, making identification of atrophy a goal in cancer prevention programs. The aim of this study was to compare targeted histology with noninvasive testing for the identification of antral and/or corpus atrophy in North America. METHODS: In a cross-sectional study of a random sample of households, 8 gastric biopsy specimens were obtained from defined locations in the antrum and corpus. Biopsies were scored for the presence of Helicobacter pylori and gastric atrophy (defined as loss of normal glandular components). Atrophy was scored by using the Sydney system and a system based on the number and location of corpus biopsies with atrophy. Patients' sera were examined for pepsinogen I, pepsinogen II, and gastrin-17 (fasting and stimulated). RESULTS: One hundred eighty volunteers, approximately 30 per age group and ranging in age from 18-82 years, participated. There were 76 men. The overall weighted prevalence of a corpus atrophy was 4.7% (95% confidence interval, 2.3-7.0). There was a significant inverse relationship between the grade of corpus atrophy and the pepsinogen I/pepsinogen II ratio (R = -0.31, P < .01). We failed to confirm the usefulness of the proposed algorithm by using gastrin-17, H. pylori serology, and serum pepsinogens to categorize the gastric histology. The Sydney system underestimated the prevalence of corpus atrophy by approximately 25%. CONCLUSION: Noninvasive testing is both possible and practical by using pepsinogen assays for the identification of the precancerous condition of moderate to severe corpus atrophy in North American Hispanic patients.

Comparison of precancerous conditions: atrophy and intestinal metaplasia in Helicobacter pylori gastritis among Chinese and Dutch patients.

AIM-Atrophy and intestinal metaplasia (IM) as precancerous conditions consistently begin in the antrum and are most severe along the lesser curvature. The aim of this study was to investigate discrepancies in the prevalence, the severity of atrophy, and IM in antral mucosa of Helicobacter pylori infected gastritis and difference in age of onset among Chinese and Dutch patients. METHODS-Two hundred and sixty five Chinese patients and 261 Dutch patients with H pylori infection were enrolled. The degrees of atrophy and IM were graded according to the updated Sydney system. RESULTS-The overall prevalences of atrophy and IM were lower in Dutch patients (42% and 26%, respectively) than in Chinese patients (52% and 32%, respectively). Only the difference in atrophy reached significance (p = 0.028). However, in both Chinese and Dutch patients, the degrees of atrophy and IM were low and severe degrees were rare. The mean ages of Chinese and Dutch patients with atrophy and IM were higher than those without atrophy and IM (with atrophy (Chinese patients): mean, 42.12; SD, 9.80; with IM (Chinese patients): mean, 42.56; SD, 9.96; with atrophy (Dutch patients): mean, 55.16; SD, 12.20; with IM (Dutch patients): mean, 57.79; SD, 11.13; without atrophy (Chinese patients): mean, 39.71; SD, 10.16; without IM (Chinese patients): mean, 40.19; SD, 9.99; without atrophy (Dutch patients): mean, 45.70; SD, 12.44; without IM (Dutch patients): mean, 46.89; SD, 12.68). Atrophy and IM occurred earlier and were more severe in Chinese patients, with both reaching a peak value in patients over 60 years. CONCLUSIONS-There are geographical differences in the prevalence and severity of H pylori infected gastritis, in particular with respect to atrophy and IM, which suggests that infection with H pylori occurs earlier in life and has a higher prevalence in CHINA:

Racial differences in the prevalence of atrophic-appearing macular lesions between black and white patients with retinitis pigmentosa.

We compared the prevalence of atrophic-appearing macular lesions between black and white patients with isolated or various genetic types of retinitis pigmentosa to determine if an appreciable difference existed between these two groups. The study included 720 patients of whom 138 (19.2%) were black patients from 115 families and 582 (80.8%) were white patients from 478 families. A logistic regression analysis combining isolated and all genetic types but randomly selecting one patient per family showed a statistically significant difference in the prevalence of atrophic-appearing macular lesions between black and white patients for the right eye (P = .0012) and left eye (P = .002). When considering either all patients or one patient per family, the estimated odds ratios were approximately 2.0 for blacks relative to whites. Our findings indicate that black patients with retinitis pigmentosa are approximately twice as likely as white patients to develop an atrophic-appearing macular lesion. This observation has implications for the prognosis of central visual function in such patients.