Aging and multiple sclerosis.

The life expectancy and average age of persons with multiple sclerosis (MS) have increased significantly during the last two decades. The introduction of disease-modifying therapies and a better delineation and understanding of the superimposed comorbidities often diagnosed in MS patients are probably the most important factors accountable for the increase in aging MS population worldwide. Healthcare teams must therefore address the problems arising due to advancing age superimposed on this chronic neurologic disease. In this review, we focus on the physiology of aging, its effects on MS disease course, and the pathological and immunological changes associated with aging and disease progression. Additionally, we discuss the common comorbidities that occur in aging persons with MS that may arise either as a result of the aging process or from relentless chronic MS disease progression as well as the challenges on differentiating the two processes for a more appropriate therapeutic approach.

Factors associated with benign multiple sclerosis in the New York State MS Consortium (NYSMSC).

BACKGROUND: This retrospective analysis explored prognostic factors associated with a benign multiple sclerosis (BMS) disease course at baseline and over the 4-year follow-up. METHODS: Patients from the centralized New York State Multiple Sclerosis Consortium registry were classified as having BMS according to 3 different criteria centered on disease duration and disability. Additional analyses explored prognostic factors associated with BMS using the most conservative disability criteria (Expanded Disability Status Scale ≤2 and disease duration ≥10 years). RESULTS: Among 6258 patients who fulfilled eligibility criteria, 19.8 % to 33.3 % were characterized as having BMS, at baseline depending on classification criteria used. Positive prognostic factors for BMS at baseline included female sex (p < 0.0001) and younger age at onset (p < 0.0001); negative prognostic factors included progressive-onset type of MS and African-American race. Of the 1237 BMS patients (per most conservative criteria), 742 were followed for a median of 4 years to explore effect of disease-modifying treatment (DMT) on benign status. DMT (p = 0.009) and longer disease duration (p = 0.007) were the only significant positive predictors of maintaining BMS at follow-up. The protective effect was stronger for patients taking DMT at both enrollment and follow-up (OR = 0.71; p = 0.006). CONCLUSIONS: There is a need for development of more reliable prognostic indicators of BMS. Use of DMT was significantly associated with maintaining a benign disease state.

Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset.

BACKGROUND: Growing evidence suggests an association between adolescent obesity and increased risk of multiple sclerosis (MS). OBJECTIVE: The objective of this paper is to investigate whether weight or body mass index (BMI) in adolescence and young adulthood was associated with age at MS symptom onset. METHODS: Our cohort is comprised of a sub-group of 184 women enrolled in the New York State MS Consortium registry. Individuals were asked to recall their weight at the time of first menstruation and at age 25. BMI was calculated accordingly for age 25. Regression analyses were carried out to investigate the association between weight or BMI and age at onset. RESULTS: Weight at menarche was significantly related to younger age at symptom onset (ß = -0.073, p = 0.001). These results were also found at age 25 for weight (ß = -0.080, p < 0.001) and BMI (ß = -0.448, p = 0.001). Significantly earlier disease onset (26.9 years ±9.9) was observed in individuals who were overweight at 25 compared to those who were not overweight (32.1 years ±9.2, p = 0.006). CONCLUSIONS: Women who reported higher weight in adolescence and BMI in early adulthood were younger at MS onset. Future research should investigate whether there is a causal link between body weight and MS, as prevention lifestyle and dietary interventions could be implemented.

MRI characteristics of familial and sporadic multiple sclerosis patients.

PURPOSE: To investigate the MRI characteristics in a large cohort of multiple sclerosis (MS) patients with and without a family history of MS. METHODS: Enrolled in this prospective study were 758 consecutive MS patients (mean age 46.2 ± 10.1 years, disease duration 13.6 ± 9.2 years and EDSS 3.4 ± 2.1), of whom 477 had relapsing-remitting, 222 secondary-progressive, and 30 primary-progressive disease courses and 29 had clinically isolated syndrome. One hundred and ninety-six patients (25.9%) had a positive family history of MS. Patients were assessed using measurements of lesions, brain atrophy, magnetization transfer ratio (MTR) and diffusion-weighted imaging. RESULTS: The familial MS group had greater T1-lesion volume (p=0.009) and a trend for lower MTR of T1-lesion volume (p=0.047) than the sporadic MS group. No clinical differences were found between familial versus sporadic group, or by a degree of affected relative subgroups. CONCLUSIONS: While familial MS was associated with more severe T1-lesion volume and its MTR characteristics, there were no clinical status differences between familial and sporadic MS patients. Therefore, a better understanding of the genetic and/or epigenetic influences causing these differences can advance the understanding and management of MS.

Equol status modifies the association of soy intake and mammographic density in a sample of postmenopausal women.

Only 30% to 50% of people produce the daidzein-metabolite equol after eating soy. We conducted a cross-sectional study of the associations between equol status, intake of soy foods, and mammographic density in a sample of postmenopausal women recruited at a radiology clinic near Buffalo, New York. Participants were 48 to 82 years old, had no history of cancer or breast reduction/augmentation, and no recent use of antibiotics or hormones. Percent density was measured by computer-assisted analysis of digitized images of craniocaudal films. Equol status was assessed using a soy-challenge protocol and usual soy intake by questionnaire. General linear models were used to assess independent and joint effects of equol status and intake of soy on multivariate adjusted percent density (covariates included age, body mass index, parity, age at first birth, and ever use of combined hormone therapy). Of 325 enrolled, 232 (71%) participants completed study assessments and are included in the present analysis. Mean percent density was 34% (+/-18%). Seventy-five (30%) participants were producers of equol. Forty-three (19%) participants reported regularly eating >1 soy food or supplement/wk. There were no significant independent associations of equol status or soy intake with percent density, but the interaction between these factors was significant (P < 0.01). Among equol producers, those with weekly soy intake had lower percent density (30.7% in weekly consumers of soy versus 38.9% in others; P = 0.08); among nonproducers, weekly soy intake was associated with higher percent density (37.5% in weekly soy consumers versus 30.7% in others; P = 0.03). Results suggest that equol producers and nonproducers may experience different effects of dietary soy on breast tissue.

Fatigue and Mood States in Nursing Home and Nonambulatory Home-Based Patients with Multiple Sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic, progressively disabling condition of the central nervous system. We sought to evaluate and compare mood states in patients with MS with increased disability residing in nursing homes and those receiving home-based care. METHODS: We conducted a cross-sectional analysis of the New York State Multiple Sclerosis Consortium to identify patients with MS using a Kurtzke Expanded Disability Status Scale (EDSS) score of 7.0 or greater. The nursing home group was compared with home-based care patients regarding self-reported levels of loneliness, pessimism, tension, panic, irritation, morbid thoughts, feelings of guilt, and fatigue using independent-samples t tests and χ2 tests. Multivariate logistic regression analyses were used to investigate risk-adjusted differences in mood states. RESULTS: Ninety-four of 924 patients with EDSS scores of at least 7.0 lived in a nursing home (10.2%). Nursing home patients were less likely to use disease-modifying therapy and had higher mean EDSS scores compared with home-based patients. However, nursing home patients were less likely than home-based patients to report fatigue (odds ratio [OR] for no fatigue, 3.8; 95% CI, 2.1-7.2), feeling tense (OR for no tension, 1.7; 95% CI, 1.1-2.7), and having feelings of pessimism (OR for no pessimism, 1.8; 95% CI, 1.2-2.8). CONCLUSIONS: The nursing home patients with MS were less likely to report fatigue, pessimism, and tension than those receiving home-based care. Further studies should examine ways of facilitating a greater degree of autonomy and decision-making control in MS patients receiving home-based care.

Disease modifying therapies use associated with comorbid autoimmune diseases in multiple sclerosis patients.

BACKGROUND: The relation between the use of disease modifying therapies (DMT׳s) and the occurrence of comorbid autoimmune diseases (AID׳s) in multiple sclerosis (MS) patients is still unclear. OBJECTIVE: To investigate the difference in duration from MS symptom onset to first reported AID in subjects using DMT׳s vs. DMT naïve. Type and prevalence of comorbid AID׳s was also investigated. METHODS: Data was extracted from the New York State MS Consortium (NYSMSC) registry and comprised of MS patients with a minimum of 5 years follow-up. After exclusion, 1792 patients were enrolled in the study, 1478 had no AID, and 314 patients had comorbid AID׳s that developed after the initial enrollment. Patients who had an AID were divided into two groups: those with an AID after DMT initiation (n=281) and patients with an AID who were DMT naïve (n=33). Logistic regression analysis was used to test differences in duration between MS symptom onset and the development of AID between the two groups while adjusting for confounders RESULTS: DMT use did not change the frequency of self-reported AID (17.2 vs. 20.4%). However, the duration between first MS symptom onset and the initial reported occurrence of a comorbid AID was significantly shorter in the DMT user group (192 months±115) compared to the DMT naïve group (262 months±107, p=.002). CONCLUSION: There were no group differences between DMT users vs. DMT naïve subjects with regards to AID frequency. The DMT user group reported the development of an AID earlier than the DMT naïve group. Further studies that can identify patients with higher risk for developing AID׳s is warranted.

Estrogen metabolism and mammographic density in postmenopausal women: a cross-sectional study.

BACKGROUND: Prospective studies have consistently found that postmenopausal breast cancer risk increases with circulating estrogens; however, findings from studies of estrogens and mammographic density (MD), an intermediate marker of breast cancer risk, have been inconsistent. We investigated the cross-sectional associations of urinary estrogens, and their 2-, 4-, and 16-hydroxylated metabolites with MD. METHODS: Postmenopausal women without breast cancer (n = 194), ages 48 to 82 years, and reporting no current menopausal hormone therapy use were enrolled at a clinic in Western NY in 2005. Urinary estrogens and estrogen metabolites were measured using mass spectrometry. Percent MD and dense area (cm(2)) were measured using computer-assisted analyses of digitized films. Linear regression models were used to estimate associations of log-transformed estrogen measures with MD while adjusting for age, body mass index (BMI), parity, and past hormone therapy use. RESULTS: Urinary concentrations of most individual estrogens and metabolites were not associated with MD; however, across the interdecile range of the ratio of parent estrogens (estrone and estradiol) to their metabolites, MD increased by 6.8 percentage points (P = 0.02) and dense area increased by 10.3 cm(2) (P = 0.03). Across the interdecile ranges of the ratios of 2-, 4-, and 16-hydroxylation pathways to the parent estrogens, MD declined by 6.2 (P = 0.03), 6.4 (P = 0.04), and 5.7 (P = 0.05) percentage points, respectively. All associations remained apparent in models without adjustment for BMI. CONCLUSION: In this study of postmenopausal women, less extensive hydroxylation of parent estrogens was associated with higher MD. IMPACT: Hydroxylation of estrogens may modulate postmenopausal breast cancer risk through a pathway involving MD.

Risk of ovarian cancer associated with BMI varies by menopausal status.

Obesity has been linked to increased risk of several malignancies, but the role of obesity in the etiology of ovarian cancer remains unclear. Therefore, a hospital-based case-control study was conducted to investigate the association between body size and risk of ovarian cancer. Participants included 427 women with primary, incident ovarian cancer and 854 cancer-free controls. All participants received medical services at Roswell Park Cancer Institute in Buffalo, NY between 1982 and 1998 and completed a comprehensive epidemiological questionnaire. The instrument included questions regarding height and usual wt prior to survey. Participants were classified as underweight/normal (BMI < or = 24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), or obese (BMI > or = 30.0 kg/m2). Compared with underweight/normal participants, being overweight (adjusted odds ratio [OR] = 1.02; 95% CI 0.77-1.36) or obese (adjusted OR = 1.17; 95% CI 0.84-1.65) was not significantly associated with an elevated risk of ovarian cancer. After stratification by menopausal status, BMI showed no significant association to ovarian cancer risk among postmenopausal women (> or = 50 y old). However, among premenopausal women (<50 y old), those classified as obese had a significantly increased risk (adjusted OR = 2.19; 95% CI 1.19-4.04) compared with women classified as normal/underweight. These findings suggest a potential influence of menopausal status on the total endogenous hormonal environment, including estrogens, androgens, and insulin-like growth factors, when considering the association between body size and ovarian cancer risk. In light of the fact that obesity is a modifiable risk factor, further investigation on this topic is warranted.