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1.  Prevalence of Cognitive Impairment No Dementia in a Rural Area of Northern China 
Neuroepidemiology  2014;42(4):197-203.
Objective
Few data are available on the prevalence of cognitive impairment no dementia (CIND) in rural China. The aim of this study was to estimate the prevalence of CIND in individuals aged 60 years and older in a large rural community, and to analyze the associated risk factors.
Methods
A two-phase, door-to-door epidemiological study was used for residents aged 60 years and older in Ji County, a rural county near Tianjin in Northern China. In phase 1 of the study, the Mini-Mental State Examination and Clinical Dementia Rating were administered for screening purposes. In phase 2, the subjects who screened positive were further examined by neurologists. A total of 5,744 individuals underwent the home visit interview, where demographic variables and comorbidities were recorded; 5,550 individuals completed the two phases. CIND was diagnosed by the Aging, Demographics and Memory Study on CIND criteria. The odds ratio (OR) for each risk factor was calculated by logistic regression analysis.
Results
The prevalence of CIND among those aged 60 years and older was 23.3%. The prevalence of CIND was lower among those with a higher level of education or social involvement. CIND was more prevalent in fe males, older individuals, those with a past history of stroke, and those living without a partner. Significant risk factors were found by multivariate analyses: past history of stroke (OR = 1.889; 95% CI: 1.437–2.483); being female (OR = 1.546; 95% CI: 1.305–1.832); and having no partner (divorced, widowed or single; OR = 1.250; 95% CI: 1.042–1.499). In turn, level of education (OR = 0.560; 95% CI: 0.460–0.681) and engagement in social activities (OR = 0.339; 95% CI: 0.258–0.404) were protective factors.
Conclusions
This is the first large-scale community-based epidemiological study assessing the prevalence of cognitive loss in the rural Chinese population. The total prevalence of CIND observed was 23.3%, which was higher than in other studies in Western and Asian countries. Living without a partner, female gender and previous stroke increased the risk of CIND, whereas a higher level of education and engagement in social activities reduced the risk of CIND.
doi:10.1159/000360138
PMCID: PMC4074439  PMID: 24751796
Cognitive impairment no dementia; China; Prevalence
2.  Adiposity and Cognitive Decline in the Cardiovascular Health Study 
Neuroepidemiology  2013;40(4):274-281.
Background
Studies relating adiposity to cognition in the elderly show conflicting results, which may be explained by the choice of adiposity measures. Thus, we studied the longitudinal associations of different adiposity measures, fat mass by bioelectrical impedance analysis (BIA), body mass index (BMI) and waist circumference (WC), with cognitive performance in the Cardiovascular Health Study.
Methods
Cognitive performance was assessed with the modified Mini Mental State Examination (3MS), the Digit Symbol Substitution Test (DSST), and a composite of both. We used linear mixed models to estimate rates of change in cognitive function scores associated with adiposity measured at baseline.
Results
The final sample was comprised of 2,681 women (57.9%) and 1,949 men (42.1%) aged 73 ± 5.2 and 73.9 ± 5.6 years. Adiposity was associated with slower cognitive decline in most analyses. Results were similar for fat mass, BMI and WC. Higher fat-free mass was also related to slower cognitive decline. Results were similar in analyses excluding persons with cancer, smokers, and persons with short follow-up, poor self-reported health, or persons with cardiovascular disease.
Conclusions
Higher adiposity and higher fat-free mass in the elderly was related to better cognitive performance. This finding was not explained by confounding by pre-existing conditions.
doi:10.1159/000345136
PMCID: PMC4044822  PMID: 23445925
adiposity; fat mass; bioelectrical impedance; body mass index; waist circumference; cognition
3.  Age of Onset: Can We Rely on Essential Tremor Patients to Report This? Data from a Prospective, Longitudinal Study 
Neuroepidemiology  2012;40(2):93-98.
Background
Essential tremor (ET) is among the most prevalent neurological diseases. Age of onset, a key variable in neuroepidemiological and genetic research, is chiefly assessed by self-report rather than medical record review; the latter may be of little use. As a researcher, one wonders about the quality of this self-report. Is age of onset something which can be reproducibly self-reported by patients? There are few published data to aid researchers.
Methods
Age of onset was self-reported at two time points (baseline and follow-up) in 86 ET cases in a longitudinal epidemiological study in New York.
Results
The mean follow-up interval was 5.7 ± 2.5 (maximum = 14) years. Overall, agreement between the baseline and follow-up reports was high (ρ = 0.85, p < 0.001). Yet the difference (age of onset baseline − age of onset follow-up) ranged widely (from −47 to 32 years), and in one fifth of cases was ≥10 years. Greater agreement was associated with several clinical factors including age, medication use, embarrassment, depressive symptoms, cognitive test score and disease duration.
Conclusions
Differences in reported age of onset in ET may vary widely, and in up to one fifth of patients may be substantial. Investigators should approach these self-reports with caution.
doi:10.1159/000341903
PMCID: PMC4035216  PMID: 23095658
Essential tremor; Epidemiology; Age of onset; Clinical factors; Genetics
4.  Familial Aggregation of Cranial Tremor in Familial Essential Tremor 
Neuroepidemiology  2013;41(1):48-53.
Background
Essential tremor (ET) is often familial and phenotypic features may be shared within families. Cranial (neck, voice, jaw) tremor is an important feature of ET. We examined whether cranial tremor aggregates in ET families, after controlling for other factors (age, tremor severity and duration).
Methods
Among ET probands and relatives enrolled in a genetic study at Columbia University (95 subjects in 28 families), we assessed the degree to which occurrence of cranial tremor in the proband predicted occurrence of cranial tremor in affected relatives.
Results
Forty-five (47.4%) subjects had cranial tremor on neurological examination (probands 66.7%, relatives 39.7%). Among 28 families, 23 (82.1%) contained individuals with and individuals without cranial tremor, indicating a high degree of within-family heterogeneity. In comparison to subjects without cranial tremor, those with cranial tremor had higher total tremor scores (p<0.001), were older (p=0.003), and had tremor of longer duration (p=0.01). In logistic regression models, the odds of cranial tremor in a relative was not related to occurrence of cranial tremor in the proband (p>0.24).
Conclusions
Cranial tremor did not aggregate in families with ET; the major predictor of this disease feature was tremor severity rather than presence of cranial tremor in another family member.
doi:10.1159/000348553
PMCID: PMC3770156  PMID: 23712245
essential tremor; genetics; familial; clinical; cranial tremor; head tremor
5.  APOE and Change in Episodic Memory in Blacks and Whites 
Neuroepidemiology  2013;40(3):211-219.
Background
APOE ε4 is related to faster decline in episodic memory in Whites but the relation is unknown in Blacks. The purpose of this study was to determine whether ε4 has a selective effect on decline in episodic memory in Blacks.
METHODS
Data are from two cohort studies with similar design. The sample consisted of 1,211 participants (28.4% Black, mean age = 78.6 (sd=7.4), education = 14.7 (sd=3.1)) without dementia at baseline, who underwent annual clinical evaluations for up to six years. Summary measures of five cognitive abililites were derived from 18 neuropsychological tests.
RESULTS
In mixed models that controlled for age, sex, education, and race, possession of ε4 (present in 32.9% of Blacks; 21.0% of Whites, p<.001) was related to faster decline in episodic memory and four other cognitive abilities (all p’s <.01). In separate models that examined the interaction of race and ε4 on decline, there was no significant difference between Blacks and Whites in the effect of ε4 on decline in episodic memory, perceptual speed, or visuospatial ability. By contrast, the effect of ε4 differed for semantic memory and working memory. Results were similar after adjusting for vascular conditions.
CONCLUSIONS
The results suggest that APOE ε4 is related to a faster rate of decline in episodic memory in Blacks similar to Whites. In addition, there were racial differences in the effect of ε4 in other cognitive abilities such that the ε4 allele was related to faster decline in semantic memory and working memory for Whites but not for Blacks.
doi:10.1159/000342778
PMCID: PMC3645297  PMID: 23364031
6.  Predicting Age of Onset in Familial Essential Tremor: How Much Does Age of Onset Run in Families? 
Neuroepidemiology  2013;40(4):269-273.
Background
The extent to which age of onset of essential tremor (ET) aggregates in families is unknown; hence it is unclear whether information about age of onset in one family member can be used to predict the age of onset in others.
Methods
ET probands and relatives were enrolled in a genetic study at Columbia University.
Results
Data from 26 probands and 52 relatives were analyzed. The probands’ age of onset correlated significantly with their relatives’ age of onset (r=0.50, p=0.001). In 57.7% of cases, the relative’s age of onset was within 10 years of the proband’s onset (i.e., a 20 year age range). The proportion of affected relatives with age at onset <20 years was 64.7% in the families of probands with onset younger than 20 years, but only 7.7% in the families of probands with onset ≥20 years, (p<0.001). There was little evidence for genetic anticipation; 9/18 (50.0%) children reported a younger age of onset than the proband.
Conclusions
In families containing multiple individuals with ET, age at onset of probands and relatives was significantly correlated. Age of onset may be most tightly linked in families in which the proband had a young age of onset.
doi:10.1159/000345253
PMCID: PMC3718305  PMID: 23363932
essential tremor; genetics; familial; clinical; age of onset
7.  Interleukin 6 Plasma Concentration Associates with Cognitive Decline: The Northern Manhattan Study 
Neuroepidemiology  2013;40(4):253-259.
Background
Interleukin 6 (IL-6) is an inflammatory cytokine that has been associated with vascular disease and cognitive impairment, but few studies have examined these relationships in population-based studies that include Hispanic white and black people who often have a greater prevalence of vascular risk factors and are at elevated risk of dementia. We examined relative elevations of plasma IL-6 concentrations in relation to cognitive decline in a stroke-free race/ethnically diverse community-based sample from Northern Manhattan.
Methods
We used mixed effects models to measure the effect of IL-6 on change in performance on the Telephone Interview for Cognitive Status (TICS-m) measured annually in our cohort, adjusting for sociodemographic and vascular risk factors.
Results
There were 1224 participants with IL-6 levels (median 1.5 pg/mL, interquartile range (IQR) 0.83 – 2.57 pg/mL) and TICS-m data available (mean=31.6 points, SD 6.5). The mean age was 71 (SD 9.3; 64% women, 59% Hispanic, 19% Black, 19% White) with 3,406 person- and a median 3.0 years of follow-up (IQR 1.1 – 4.0). Participants with IL-6 levels above the median showed greater cognitive decline on the TICS-m compared to those with levels below the median, adjusting for sociodemographic and vascular factors (β= −0.17 points per year, p=0.02). Decline on the TICS-m among participants with IL-6 above the median differed by age (P for interaction <0.001). There was no interaction by race-ethnicity, vascular risk factors, C-reactive protein (CRP), APOE4 allele status, or the metabolic syndrome among non-diabetics.
Conclusions
Interleukin 6 associated with cognitive decline among older participants in this race/ethnically diverse sample independent of other vascular risk factors and CRP.
doi:10.1159/000343276
PMCID: PMC3725587  PMID: 23364322
cognitive decline; cohort studies; Interleukin-6; inflammation
8.  Poor Decision Making is Associated with an Increased Risk of Mortality Among Community-Dwelling Older Persons without Dementia 
Neuroepidemiology  2013;40(4):247-252.
Background
Decision making is thought to be an important determinant of health and well-being across the lifespan, but little is known about the association of decision making with mortality.
Methods
Participants were 675 older persons without dementia from the Rush Memory and Aging Project, a longitudinal cohort study of aging. Baseline assessments of decision making were used to predict the risk of mortality during up to 4 years of follow-up.
Results
The mean score on the decision making measure at baseline was 7.1 (SD=2.9, range: 0-12), with lower scores indicating poorer decision making. During up to 4 years of follow-up (mean=1.7 years), 40 (6% of 675) persons died. In a proportional hazards model adjusted for age, sex, and education, the risk of mortality increased by about 20% for each additional decision making error (HR=1.19, 95% CI 1.07, 1.32, p=0.002). Thus, a person who performed poorly on the measure of decision making (score=3, 10th percentile) was about four times more likely to die compared to a person who performed well (score=11, 90th percentile). Further, the association of decision making with mortality persisted after adjustment for the level of cognitive function.
Conclusion
Poor decision making is associated with an increased risk of mortality in old age even after accounting for cognitive function.
doi:10.1159/000342781
PMCID: PMC3760500  PMID: 23364306
9.  Carotid Artery Stenosis as a Cause of Stroke 
Neuroepidemiology  2012;40(1):36-41.
Background
Population-based studies have estimated that ≈15% of ischemic strokes are caused by large vessel cerebrovascular disease. We determined the types of large vessel atherosclerosis responsible for ischemic strokes in a population-based stroke study.
Methods
Patients with first-ever or recurrent ischemic stroke in the Greater Cincinnati area were identified during 2005 at all local hospitals. Study physicians assigned ischemic stroke subtypes. Overall event rates and incidence rates for first-ever events were calculated and age, race, and sex-adjusted to the 2000 US population.
Results
There were 2204 ischemic strokes, including 365 strokes of large vessel subtype (16.6% of all ischemic strokes). Extracranial internal carotid artery stenosis was associated with 8.0% of all ischemic strokes, while extracranial internal carotid artery occlusion and intracranial atherosclerosis were each associated with 3.5% of strokes. The annual rate of first-ever and recurrent stroke attributed to extracranial internal carotid stenosis was 13.4 (11.4–15.4) per 100,000 persons. We conservatively estimate that ≈ 41,000 strokes may be attributed to extracranial internal carotid artery stenosis annually in the United States.
Conclusions
Large vessel atherosclerosis is an important cause of stroke, with extracranial internal carotid artery stenosis significantly more common than extracranial internal carotid artery occlusion or intracranial atherosclerotic disease.
doi:10.1159/000341410
PMCID: PMC3626492  PMID: 23075828
carotid stenosis; carotid atherosclerosis; intracranial atherosclerosis; stroke; stroke etiology; epidemiology; carotid occlusion
10.  Antiphospholipid Antibodies, Brain Infarcts, and Cognitive and Motor Decline in Aging (ABICMA): Design of a Community-based, Longitudinal, Clinical-pathological Study 
Neuroepidemiology  2012;40(2):73-84.
The overall goal of the Antiphospholipid antibodies, Brain Infarcts, and Cognitive and Motor decline in Aging study (ABICMA) is to test the hypothesis that antiphospholipid antibodies (aPL) are associated with an increased risk of pathologically-proven brain infarcts and related to cognitive and motor decline in aging. Putative biologic mechanisms underlying the association of aPL with infarcts and the relation of aPL with clinical outcomes of cognitive and motor impairment, including vascular and other processes, will be examined. The design of this longitudinal, clinical-pathologic study involves quantifying four aPL assays, and relating these to brain infarcts, and to cognitive and motor decline. Vascular mechanisms assessed using ante-mortem magnetic resonance neuroimaging and postmortem neuropathology, as well as non-vascular mechanisms of inflammation and blood-brain barrier permeability alterations will be examined as plausible mediators of the relation of aPL to cognitive and motor impairment. We will take advantage of ante-mortem biologic specimens (longitudinally-collected sera and plasma from which aPL, annexins, C-reactive protein, and matrix metalloproteinases will be quantified), and clinical, neuroimaging, and postmortem neuropathologic data from about 800 older, community-dwelling women and men who have agreed to brain autopsy at time of death, participating in one of two ongoing studies of aging: the Religious Orders Study and the Memory and Aging Project.
doi:10.1159/000342761
PMCID: PMC3638838  PMID: 23095514
11.  Association between physical activity and risk of stroke subtypes: The Atherosclerosis Risk in Communities (ARIC) Study 
Neuroepidemiology  2012;40(2):109-116.
Background
The relationship between stroke subtypes and physical activity is unclear.
Methods
Using data from 13,069 men and women aged 45-64 years who participated in the Atherosclerosis Risk in Communities (ARIC) Study, physical activity was assessed by self-report using the Baecke questionnaire at baseline (1987-1989). The American Heart Association’s (AHA) ideal cardiovascular health guidelines served as basis for the calculation of three physical activity categories: poor, intermediate, and ideal. Stroke and its subtypes were ascertained from physician review of medical records. Multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models.
Results
During a median follow-up of 18.8 years, a total of 648 incident ischemic strokes occurred. Significant inverse associations were found between physical activity categories and total, total ischemic, and nonlacunar stroke in adjusted models (age, sex, race-center, education, cigarette-years). Compared with poor physical activity, the adjusted HR (95% CI) for ideal physical activity were 0.78 (0.62, 0.97) for total, 0.76 (0.59, 0.96) for total ischemic, 0.85 (0.51, 1.40) for lacunar, 0.77 (0.47, 1.27) for cardioembolic, and 0.71 (0.51, 0.99) for nonlacunar stroke. Additional adjustments for waist-to-hip ratio, systolic blood pressure, antihypertensive medication, diabetes, left ventricular hypertrophy and laboratory parameters attenuated the HR. Further sex- and race-specific analysis revealed that the association was predominantly observed among males and among African-Americans.
Conclusion
These data suggest a tendency toward a reduced risk of total, total ischemic, and nonlacunar stroke with higher levels of physical activity.
doi:10.1159/000342151
PMCID: PMC3641888  PMID: 23095721
cerebrovascular disease; stroke subtypes; exercise; epidemiology; prevention
13.  Cognition and Incident Dementia Hospitalization: Results from the Atherosclerosis Risk in Communities (ARIC) Study 
Neuroepidemiology  2012;40(2):117-124.
Background/Aims
Cognitive decline is a defining feature of dementia. We sought to determine if a single baseline cognitive test score or change in test score over time is more strongly associated with risk of dementia hospitalization. We also sought to compare short- and long-term dementia risk.
Methods
Prospective cohort study of 9,399 individuals from the Atherosclerosis Risk in Communities (ARIC) Study (median 10 years follow-up). Cognition was assessed at two time points (6 years apart) using three tests: Delayed Word Recall (DWRT), Digit Symbol Substitution (DSST), and Word Fluency (WFT). Dementia hospitalizations were determined using ICD-9 codes.
Results
Baseline cognitive test scores were associated with both short-term and long-term risk of dementia. The association of 6-year change in cognitive test score with dementia risk was stronger than that of individual test scores at a single visit (change from highest to lowest tertile, DWRT: HR=6.45 (1.80, 23.08), DSST: HR=10.94 (3.07, 38.97)).
Conclusions
In this community-based population, 6-year changes in cognitive scores were more strongly associated with risk of incident dementia hospitalization than baseline scores, although single DWRT and DSST scores at were predictive. Our findings support the contention that cognitive changes may precede clinical dementia by a decade or more.
doi:10.1159/000342308
PMCID: PMC3642775  PMID: 23095770
Cognition; Dementia; Hospitalizations; Cognitive Function; Cognitive Decline
14.  A Systematic Review of Randomized, Double-Blind, Placebo-Controlled Trials Examining the Clinical Efficacy of Vitamin D in Multiple Sclerosis 
Neuroepidemiology  2012;40(3):147-153.
Background
An association between multiple sclerosis (MS) prevalence as well as MS mortality and vitamin D nutrition has led to the hypothesis that high levels of vitamin D could be beneficial for MS. The purpose of this systematic review is to establish whether there is evidence for or against vitamin D in the treatment of MS.
Methods
Systematic literature searches were performed to locate randomized, placebo-controlled, double-blind trials measuring the clinical effect of vitamin D on MS in human participants. Data were extracted in a standardized manner and methodological quality was assessed by the Jadad score.
Results
Five trials were located meeting the selection criteria. Of the five trials, four showed no effect of vitamin D on any outcome, and one showed a significant effect, namely upon reduction in the number of T1 enhancing lesions on brain magnetic resonance imaging. Three studies commented on adverse effects of vitamin D, with gastrointestinal adverse effects being the most frequently reported. The literature is limited by small study sizes (studies size ranged from 23 to 68 patients) and heterogeneity of dosing, form of vitamin D tested (vitamin D3 in four trials, and vitamin D2 in one), and outcome clinical measures. Therefore, a meta-analysis was not performed.
Conclusions
The evidence for vitamin D as a treatment for MS is inconclusive. Larger studies are warranted to assess the effect of vitamin D on clinical outcomes in patients with MS. We further encourage researchers to also test the effect of vitamin D on the health-related quality of life experienced by patients and their families.
doi:10.1159/000345122
PMCID: PMC3649517  PMID: 23257784
Multiple sclerosis; treatment; systematic review; vitamin D
15.  Cross-sectional association between polyfluoroalkyl chemicals and cognitive limitation in the National Health and Nutrition Examination Survey (NHANES) 
Neuroepidemiology  2012;40(2):125-132.
Background/Aims
Our limited understanding of how polyflouoroalkyl chemicals (PFCs) may impact human health suggests the potential for a protective impact on brain health. This study was designed to explore the association between PFCs and cognitive ability in older adults.
Methods
We assessed the association between four PFCs, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), and self-reported limitation due to difficulty remembering or periods of confusion using data from participants aged 60–85 from the 1999–2000 and 2003–2008 National Health and Nutrition Examination Surveys. We also considered whether diabetic status or diabetic medication use modifies this association in light of in vitro evidence that PFCs may act on the same receptors as some diabetic medications.
Results
In multivariable adjusted models, point estimates suggest a protective association between PFCs and self-reported cognitive limitation (OR (95% CI) for a doubling in PFOS, 0.90 (0.78, 1.03); PFOA, 0.92 (0.78, 1.09); PFNA, 0.91 (0.79, 1.04); PFHxS, 0.93 (0.82, 1.06)). The protective association was concentrated in diabetics, with strong, significant protective associations in non-medicated diabetics.
Conclusions
This cross-sectional study suggests that there may be a protective association between exposure to PFCs and cognition in older adults, particularly diabetics.
doi:10.1159/000342310
PMCID: PMC3658136  PMID: 23095808
NHANES; National Health and Nutrition Examination Survey; CDC; Centers for Disease Control; cognitive function; polyfluoroalkyl chemicals; PFCs; epidemiology; risk factor
16.  Can a screening questionnaire accurately identify Mild Parkinsonian Signs? 
Neuroepidemiology  2012;39(3-4):171-175.
Background
Mild Parkinsonian Signs (MPS) are early features that, when present, increase risk of neurodegenerative disease and mortality. Current methods to identify MPS are limited to neurological examination. Our objective was to assess the ability of a 9-item Parkinson’s Disease Screening Questionnaire (PDSQ), which has high sensitivity in the detection of overt Parkinson’s disease (PD), to detect Mild Parkinsonian Signs.
Methods
Measures including the PDSQ, Unified Parkinson’s Disease Rating Scale and University of Pennsylvania Smell Identification Test were administered to 267 participants without neurodegenerative disease. Two published definitions of MPS were used to classify cases.
Results
PDSQ scores were higher for cases compared to controls (p < 0.001 for the first case definition and 0.07 for the second). However, the questionnaire had low sensitivity (47 and 59%) and specificity (62 and 63%) in the detection of MPS. Adding factors such as age, gender, and smell test score to the questionnaire in a predictive model only marginally improved the test characteristics.
Conclusion
The results show the screening questionnaire does not accurately identify Mild Parkinsonian Signs. More accurate tests are needed to improve detection of this early syndrome which can lead to motor disability, neurodegenerative disease and mortality.
doi:10.1159/000341409
PMCID: PMC3513756  PMID: 22948126
Mild Parkinsonian Signs; screening questionnaire; validity; sensitivity; specificity
17.  Predictors of Survival Among Pediatric and Adult Ependymoma Cases: A Study Using Surveillance, Epidemiology, and End Results Data from 1973–2007 
Neuroepidemiology  2012;39(2):116-124.
Background
Despite previous research, prognostic factors for ependymoma remain relatively controversial. The purpose of our study was to examine demographic, clinical, and tumor attributes as potential predictors of survival using Surveillance, Epidemiology, and End Results (SEER) program data (1973–2007).
Methods
All ependymoma (ICD-O-3 code 9391) and anaplastic ependymoma cases (ICD-O-3 code 9392) with complete data (n=2369 and n=319, respectively) were included from SEER. Predictive Cox regression models were built separately among pediatric and adult cases. Recursive partitioning was used to corroborate results from regression models.
Results
Among pediatric cases, tumor characteristics with a significantly increased mortality risk were anaplastic histology (vs. low grade, HR: 1.51, 95% CI: 1.04–2.19) and infratentorial tumor location (vs. spinal cord, HR: 3.86, 95% CI: 1.17–12.77). Among adults, supratentorial tumors were associated with higher mortality hazard (vs. spinal cord tumors) than infratentorial tumors (HR: 4.83, 95% CI: 3.49–6.68 & HR: 2.41, 95% CI: 1.79–3.25, respectively). Complete surgical resection of the tumor conferred the most protection among pediatric and adult patients.
Conclusion
Our results indicate that treatment type and tumor characteristics are important prognostic factors in patients with ependymoma. However, there may be key differences between pediatric and adult cases regarding how these factors influence survival.
doi:10.1159/000339320
PMCID: PMC3470871  PMID: 22846789
18.  A random change point model for cognitive decline in Alzheimer’s disease and mild cognitive impairment 
Neuroepidemiology  2012;39(2):73-83.
Background
We present a random change point model to characterize decline in cognition among community-based elderly who developed Alzheimer’s disease (AD) or amnestic mild cognitive impairment (MCI), and to examine how decline varies with age, sex, education, and APOE status.
Methods
Using longitudinal cohort data on cognitive function, we fit a piecewise linear trajectory with a random change point that allows different rates of cognitive decline before and after the change point. We estimated the change point that signals the onset of cognitive impairment, and examined the association of risk factors with the location of the change point as well as the rates of decline before and after the change point.
Results
Among participants who were dementia free at enrollment and developed incident AD, the change point occurred on average 5.7 years after enrollment and the rate of cognitive decline after the change point nearly quadrupled. Age, education, and APOE status play important but different roles in the timing of the onset of cognitive impairment and in the rates of decline before and after its onset. Results were similar among participants who were cognitively unimpaired at enrollment but later developed amnestic MCI or AD.
Conclusions
The random change point model provides a more comprehensive understanding of the relation of risk factors with the onset of cognitive impairment and rates of decline before and after its onset.
doi:10.1159/000339365
PMCID: PMC3484884  PMID: 22814083
Change point model; cognitive decline; Alzheimer’s disease; amnestic mild cognitive impairment
19.  Fasting Plasma Insulin, C-Peptide and Cognitive Change in Older Men without Diabetes: Results from the Physicians’ Health Study II 
Neuroepidemiology  2010;34(4):200-207.
Background
Type 2 diabetes has been associated with diminished late-life cognition; less is known about relations of insulin levels and insulin secretion to cognitive change among persons without diabetes. We examined prospectively relations of fasting insulin levels and insulin secretion to cognitive decline among healthy, community-dwelling older men without diabetes.
Methods
Fasting plasma insulin and C-peptide (insulin secretion) levels were measured in 1,353 nondiabetic men, aged 60–92 years (mean = 71.3 years), in the Physicians’ Health Study II, who participated in cognitive testing an average of 3.3 years later. Two assessments were administered 2 years apart (range = 1.5–4.0 years) using telephone-based tests (general cognition, verbal memory and category fluency). Primary outcomes were the Telephone Interview for Cognitive Status (TICS), global cognition (averaging all tests) and verbal memory (averaging 4 verbal tests). Multivariable linear regression models were used to estimate the relations of insulin and C-peptide to cognitive decline.
Results
Higher fasting insulin was associated with a greater decline on all tests, after adjustment. Findings were statistically significant for the TICS and category fluency, e.g. the multivariable-adjusted mean difference (95% CI) in decline for men with the highest versus lowest insulin levels was −0.62 (−1.15, −0.09) points on the TICS (p for trend = 0.04); this difference was similar to that between men 7 years apart in age. Similarly, there was a greater decline across all tests with increasing C-peptide, but the findings were statistically significant only for the global score (p for trend = 0.03).
Conclusions
Higher fasting insulin and greater insulin secretion in older men may be related to overall cognitive decline, even in the absence of diabetes.
doi:10.1159/000289351
PMCID: PMC2883838  PMID: 20197703
Insulin; C-Peptide; Cognitive decline; Dementia; Diabetes
21.  Fasting plasma insulin, c-peptide and cognitive change in older men without diabetes: results from the Physicians’ Health Study II 
Neuroepidemiology  2010;34(4):200-207.
Background
Type 2 diabetes has been associated with diminished late-life cognition; less is known about relations of insulin levels and insulin secretion to cognitive change among persons without diabetes. We examined prospectively relations of fasting insulin levels and insulin secretion to cognitive decline, among healthy, community-dwelling older men without diabetes.
Methods
Fasting plasma insulin and c-peptide (insulin secretion) levels were measured in 1,353 non-diabetic men, aged 60–92 years (mean=71.3), in the Physicians’ Health Study II who participated in cognitive testing an average of 3.3 years later. Two assessments were administered 2 years apart (range=1.5–4.0) using telephone-based tests (general cognition, verbal memory, and category fluency). Primary outcomes were the Telephone interview for Cognitive Status (TICS), global cognition (averaging all tests) and verbal memory (averaging four verbal tests). Multivariable linear regression models were used to estimate relations of insulin and c-peptide to cognitive decline.
Results
Higher fasting insulin was associated with worse decline on all tests, after adjustment. Findings were statistically significant for the TICS and category fluency: e.g., the multivariable-adjusted mean difference (95% CI) in decline for men with the highest vs. lowest insulin levels was −0.62 (−1.15, −0.09) points on the TICS (p-trend=0.04); this difference was similar to that between men 7 years apart in age. Similarly, there was worse decline across all tests with increasing c-peptide, but findings were statistically significant only for global score (p-trend=0.03).
Conclusions
Higher fasting insulin and greater insulin secretion in older men may be related to overall cognitive decline, even in the absence of diabetes.
doi:10.1159/000289351
PMCID: PMC2883838  PMID: 20197703
insulin; c-peptide; cognitive decline; dementia; diabetes
22.  Mediterranean Diet and Essential Tremor 
Neuroepidemiology  2007;29(3-4):170-177.
Background
Higher adherence to the Mediterranean diet (MeDi) has been related to lower Alzheimer’s disease risk. Some dietary factors have been studied in patients with essential tremor (ET), but the MeDi’s effect has not been investigated.
Methods
Adherence to the MeDi was calculated from a food frequency questionnaire administered in a case-control study of environmental epidemiology of ET in the New York Tri-State area. Logistic regression models were used to examine whether adherence to the MeDi predicted ET (vs. control) outcome. The models adjusted for age, gender, ethnicity, education, caloric intake, body mass index, smoking, ethanol consumption, coffee intake and blood harmane concentrations.
Results
148 ET cases adhered less to MeDi (0–9 scale with higher scores indicating higher adherence) than 250 controls (mean 4.3 ± 1.7 vs. 4.7 ± 1.7; p = 0.03). Higher adherence to MeDi was associated with lower odds for ET [0.78 (0.61–0.99); p = 0.042]. As compared to subjects at the lowest MeDi adherence tertile, those at the middle tertile had lower ET odds [0.41 (0.16–1.05)], while subjects at the highest tertile had an even lower ET odds [0.29 (0.10–0.82); p for trend 0.021].
Conclusions
Compared to controls, ET cases adhered less to MeDi. The gradual reduction in ET odds with higher MeDi adherence tertiles suggests a possible dose-response effect. The mechanisms that underlie this association merit further study.
doi:10.1159/000111579
PMCID: PMC3030195  PMID: 18043001
Essential tremor; Epidemiology; Mediterranean diet
23.  Factor Analysis of Motor and Nonmotor Signs in Essential Tremor: Are These Signs All Part of the Same Underlying Pathogenic Process? 
Neuroepidemiology  2009;33(1):41-46.
Essential tremor (ET) has traditionally been viewed as monosymptomatic. However, there is an emerging appreciation of an expanded number of motor manifestations as well as a new awareness of nonmotor manifestations. The current goal, through factor analyses, was to determine how these diverse signs relate to one another and shed light on their pathogenic bases. One hundred and thirty-eight ET patients had detailed neurological examinations. In these analyses, three separate factors emerged, explaining 58.7% of the variance. Factor I was comprised of the hallmark feature of ET, action tremor. It also included intention tremor, which is generally viewed as a sign of cerebellar dysfunction, and tremor duration. Factor II was comprised of cognitive test scores and age, and factor III, of rest tremor. Cognitive test scores did not fall into the same domain as motor features or tremor duration. These results suggest that: (1) the process that underlies cognitive dysfunction in ET is distinct from that which is responsible for action and intention tremors and their progression over time, and (2) cognitive dysfunction in ET is not likely due to cerebellar degeneration. Age loaded with cognitive test scores, further raising the possibility that age-related processes (e.g. Alzheimer-type changes) could underlie cognitive changes in ET.
doi:10.1159/000211952
PMCID: PMC2684569  PMID: 19365141
Essential tremor; Cerebellar degeneration; Parkinsonism; Dementia
24.  Increased Mortality for Neurological and Mental Diseases following Early Bilateral Oophorectomy 
Neuroepidemiology  2009;33(1):32-40.
Background
The effects of oophorectomy on brain aging remain uncertain.
Methods
We conducted a cohort study with long-term follow-up of women in Olmsted County, Minn., USA, who underwent either unilateral or bilateral oophorectomy before the onset of menopause from 1950 through 1987. Each member of the oophorectomy cohort was matched by age to a referent woman from the same population who had not undergone any oophorectomy. We studied underlying and contributory causes of death in 1,274 women with unilateral oophorectomy, 1,091 women with bilateral oophorectomy, and 2,383 referent women.
Results
Mortality for neurological or mental diseases was increased in women who underwent bilateral oophorectomy before age 45 years compared with referent women (hazard ratio = 5.24; 95% confidence interval = 2.02–13.6; p < 0.001). Within this age stratum, mortality was similar in women who were or were not treated with estrogen from the time of oophorectomy through age 45 years, and in women who had bilateral oophorectomy for prophylaxis or for treatment of a benign ovarian condition. Mortality was also increased in women who underwent unilateral oophorectomy before age 45 years without concurrent hysterectomy.
Conclusions
Bilateral oophorectomy performed before age 45 years is associated with increased mortality for neurological or mental diseases.
doi:10.1159/000211951
PMCID: PMC2697609  PMID: 19365140
Oophorectomy; Neurological diseases; Mental diseases; Mortality; Cohort study
25.  Prevalence of Essential Tremor in a Multiethnic, Community-Based Study in Northern Manhattan, New York, N.Y. 
Neuroepidemiology  2009;32(3):208-214.
Background
Our aims were to: (1) estimate the prevalence of essential tremor (ET) in a community-based study in northern Manhattan, New York, N.Y., USA; (2) compare prevalence across ethnic groups, and (3) provide prevalence estimates for the oldest old.
Methods
This study did not rely on a screening questionnaire. Rather, as part of an in-person neurological evaluation, each participant produced several handwriting samples, from which ET diagnoses were assigned.
Results
There were 1,965 participants (76.7 ± 6.9 years, range = 66–102 years); 108 had ET [5.5%, 95% confidence interval (CI) = 4.5–6.5%]. Odds of ET were robustly associated with Hispanic ethnicity versus white ethnicity [odds ratio (OR) = 2.19, 95% CI = 1.03–4.64, p = 0.04] and age (OR = 1.14, 95% CI = 1.03–1.26, p = 0.01), i.e. with every 1 year advance in age, the odds of ET increased by 14%. Prevalence reached 21.7% among the oldest old (age ≥95 years).
Conclusions
This study reports a significant ethnic difference in the prevalence of ET. The prevalence of ET was high overall (5.5%) and rose markedly with age so that in the oldest old, more than 1 in 5 individuals had this disease.
doi:10.1159/000195691
PMCID: PMC2744469  PMID: 19169043
Essential tremor; Epidemiology; Prevalence; Ethnicity; Clinical

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