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1.  Disease-related mutations among Caribbean Hispanics with familial dementia 
Pathogenic mutations in the three known genes – the amyloid precursor protein (APP), presenilin 1 (PSEN1), presenilin 2 (PSEN2) – are known to cause familial Alzheimer's disease (AD) and tend to be associated with early-onset AD. However, the frequency and risk associated with these mutations vary widely. In addition, mutations in the frontotemporal lobar degeneration (FTLD) genes – the microtubule-associated protein tau (MAPT), granulin (GRN) – have also been found to be associated with clinical AD. Here, we conducted targeted resequencing of the exons in genes encoding APP, PSEN1, PSEN2, GRN, and MAPT in 183 individuals from families with four or more affected relatives, presumed to be AD, and living in the Dominican Republic and Puerto Rico. We then performed linkage and family-based association analyses in carrier families, and genotyped 498 similarly aged unrelated controls from the same ethnic background. Twelve potentially pathogenic mutations were found to be associated with disease in 53 individuals in the five genes. The most frequently observed mutation was the p.Gly206Ala variant in PSEN1 present in 30 (57%) of those sequenced. In the combined linkage and association analyses several rare variants were associated with dementia. In Caribbean Hispanics with familial AD, potentially pathogenic variants were present in 29.2%, four were novel mutations, while eight had been previously observed. In addition, some family members carried variants in the GRN and MAPT genes which are associated with FTLD.
doi:10.1002/mgg3.85
PMCID: PMC4190878  PMID: 25333068
Alzheimer's disease; Caribbean Hispanics; familial dementia; mutations; next-generation sequencing
2.  Age-Specific Incidence Rates for Dementia and Alzheimer Disease in NIA-LOAD/NCRAD and EFIGA Families 
JAMA neurology  2014;71(3):315-323.
IMPORTANCE
Late-onset Alzheimer disease (LOAD), defined as onset of symptoms after age 65 years, is the most common form of dementia. Few reports investigate incidence rates in large family-based studies in which the participants were selected for family history of LOAD.
OBJECTIVE
To determine the incidence rates of dementia and LOAD in unaffected members in the National Institute on Aging Genetics Initiative for Late-Onset Alzheimer Disease/National Cell Repository for Alzheimer Disease (NIA-LOAD/NCRAD) and Estudio Familiar de Influencia Genetica en Alzheimer (EFIGA) family studies.
DESIGN, SETTING, AND PARTICIPANTS
Families with 2 or more affected siblings who had a clinical or pathological diagnosis of LOAD were recruited as a part of the NIA-LOAD/NCRAD Family Study. A cohort of Caribbean Hispanics with familial LOAD was recruited in a different study at the Taub Institute for Research on Alzheimer’s Disease and the Aging Brain in New York and from clinics in the Dominican Republic as part of the EFIGA study.
MAIN OUTCOMES AND MEASURES
Age-specific incidence rates of LOAD were estimated in the unaffected family members in the NIA-LOAD/NCRAD and EFIGA data sets. We restricted analyses to families with follow-up and complete phenotype information, including 396 NIA-LOAD/NCRAD and 242 EFIGA families. Among the 943 at-risk family members in the NIA-LOAD/NCRAD families, 126 (13.4%) developed dementia, of whom 109 (86.5%) met criteria for LOAD. Among 683 at-risk family members in the EFIGA families, 174 (25.5%) developed dementia during the study period, of whom 145 (83.3%) had LOAD.
RESULTS
The annual incidence rates of dementia and LOAD in the NIA-LOAD/NCRAD families per person-year were 0.03 and 0.03, respectively, in participants aged 65 to 74 years; 0.07 and 0.06, respectively, in those aged 75 to 84 years; and 0.08 and 0.07, respectively, in those 85 years or older. Incidence rates in the EFIGA families were slightly higher, at 0.03 and 0.02, 0.06 and 0.05, 0.10 and 0.08, and 0.10 and 0.07, respectively, in the same age groups. Contrasting these results with the population-based estimates, the incidence was increased by 3-fold for NIA-LOAD/NCRAD families (standardized incidence ratio, 3.44) and 2-fold among the EFIGA compared with the NIA-LOAD/NCRAD families (1.71).
CONCLUSIONS AND RELEVANCE
The incidence rates for familial dementia and LOAD in the NIA-LOAD/NCRAD and EFIGA families are significantly higher than population-based estimates. The incidence rates in all groups increase with age. The higher incidence of LOAD can be explained by segregation of Alzheimer disease–related genes in these families or shared environmental risks.
doi:10.1001/jamaneurol.2013.5570
PMCID: PMC4000602  PMID: 24425039
3.  Mental and Physical Health Consequences of the September 11, 2001 (9/11) Attacks in Primary Care: A Longitudinal Study 
Journal of traumatic stress  2013;26(1):45-55.
The magnitude of the September 11, 2001 (9/11) attacks was without precedent in the United States, but long-term longitudinal research on its health consequences for primary care patients is limited. We assessed the prevalence and exposure-related determinants of mental disorders, functioning, general medical conditions and service utilization, 1 and 4 years after the 9/11 attacks, in an urban primary care cohort (N = 444) in Manhattan. Although the prevalence of posttraumatic stress disorder (PTSD) and levels of functional impairment declined over time, a substantial increase in suicidal ideation and missed work was observed. Most medical outcomes and service utilization indicators demonstrated a short-term increase after the 9/11 attacks (mean change of +20.3%), followed by a minor decrease in the subsequent year (mean change of −3.2%). Loss of a close person was associated with the highest risk for poor mental health and functional status over time. These findings highlight the importance of longitudinal assessments of mental, functional, and medical outcomes in urban populations exposed to mass trauma and terrorism.
doi:10.1002/jts.21767
PMCID: PMC3685149  PMID: 23319335
4.  Gender Differences in Posttraumatic Stress Disorder Among Primary Care Patients After the World Trade Center Attack of September 11, 2001 
Gender medicine  2005;2(2):76-87.
Background
Debate surrounds the nature of gender differences in rates of posttraumatic stress disorder (PTSD).
Objective
The goal of this study was to quantify and explore the reasons for gender differences in rates of PTSD in low income, primary care patients after the World Trade Center (WTC) attack of September 11, 2001.
Methods
A survey was conducted at a large primary care practice in New York City 7 to 16 months after the WTC attack. The study involved a systematic sample of primary care patients aged 18 to 70 years. The main outcome measures were the Life Events Checklist, the Posttraumatic Stress Disorder Checklist–Civilian Version, and the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, all administered by a bilingual research staff.
Results
A total of 3807 patients were approached at the primary care clinic. Of the 1347 who met eligibility criteria, 1157 (85.9%) consented to participate. After the addition of the WTC/PTSD supplement to the study, the total number of patients was 992, of whom 982 (99.0%) completed the survey. Both sexes had high rates of direct exposure to the WTC attack and high rates of lifetime exposure to stressful life events. Overall, females had lower rates of exposure to the attack compared with males (P < 0.05). Hispanic females had the highest rate of PTSD in the full sample. Gender differences in rates of PTSD were largely accounted for by differences in marital status and education. The rate of current major depressive disorder (MDD) was higher in females than in males (P < 0.001), and the reverse was true for substance abuse (P < 0.001). Gender differences for MDD and substance abuse persisted even after adjustments for demographic differences between the sexes.
Conclusions
The increased rate of PTSD in women attending a primary care clinic was mediated by their social and economic circumstances, such as living alone without a permanent relationship and with little education or income. The increased rate of MDD in women appeared to be less dependent on these circumstances. These findings have implications for the treatment of women with PTSD in primary care and for research on gender differences in rates of psychiatric disorders.
PMCID: PMC3683844  PMID: 16115602
posttraumatic stress disorder; gender; World Trade Center; primary care
5.  Positive Screens for Psychiatric Disorders in Primary Care: A Long-Term Follow-Up of Patients Who Were Not in Treatment 
Objective
Screening for psychiatric disorders has gained acceptance in some general medical settings, but critics argue about its value. The purpose of this study was to determine the clinical utility of screening by conducting a long-term follow-up of patients who screened positive for psychiatric disorders but who were initially not in treatment.
Methods
A cohort of 519 low-income, adult primary care patients were screened for major depression and bipolar, anxiety, and substance use disorders and reassessed with the Structured Clinical Interview for DSM-IV after a mean of 3.7 years by a clinician blind to the initial screen. Data on treatment utilization was obtained through hospital records. The sample consisted of 348 patients who had not received psychiatric care in the year before screening.
Results
Among 39 patients who screened positive for major depression, 62% (95% confidence interval=45.5%–77.6%) met criteria for current major depressive disorder at follow-up. Those who screened positive reported significantly poorer mental and social functioning and worse general health at follow-up than the screen-negative patients and were more likely to have visited the emergency department for psychiatric reasons (12.1% and 3.0%, odds ratio [OR]=6.4) and to have major depression (OR=7.6). Generally similar results were observed for patients who screened positive for other disorders.
Conclusions
Commonly used screening methods identified patients with psychiatric disorders; about four years later, those not initially in treatment were likely to have enduring symptoms and to use emergency psychiatric services. Screening should be followed up by clinical diagnostic assessment in the context of available mental health treatment.
doi:10.1176/appi.ps.61.2.151
PMCID: PMC3670116  PMID: 20123820
6.  The Mental Health Consequences of Disaster-Related Loss: Findings from Primary Care One Year After the 9/11 Terrorist Attacks 
Psychiatry  2008;71(4):339-348.
This study examines the long-term psychiatric consequences, pain interference in daily activities, work loss, and functional impairment associated with 9/11-related loss among low-income, minority primary care patients in New York City. A systematic sample of 929 adult patients completed a survey that included a sociodemographic questionnaire, the PTSD Checklist, the PRIME-MD Patient Health Questionnaire, and the Medical Outcomes Study Short Form-12 (SF-12).
Approximately one-quarter of the sample reported knowing someone who was killed in the attacks of 9/11, and these patients were sociodemographically similar to the rest of the sample. Compared to patients who had not experienced 9/11-related loss, patients who experienced loss were roughly twice as likely (OR = 1.97, 95%; CI = 1.40, 2.77) to screen positive for at least one mental disorder, including major depressive disorder (MDD; 29.2%), generalized anxiety disorder (GAD; 19.4%), and posttraumatic stress disorder (PTSD; 17.1%). After controlling for pre-9/11 trauma, 9/11-related loss was significantly related to extreme pain interference, work loss, and functional impairment. The results suggest that disaster-related mental health care in this clinical population should emphasize evidence-based treatments for mood and anxiety disorders.
doi:10.1521/psyc.2008.71.4.339
PMCID: PMC3653136  PMID: 19152283
7.  Trauma exposure and posttraumatic stress disorder among primary care patients with bipolar spectrum disorder 
Bipolar disorders  2008;10(4):503-510.
Objective
To examine relationships between exposure to trauma, bipolar spectrum disorder (BD) and posttraumatic stress disorder (PTSD) in a sample of primary care patients.
Methods
A systematic sample (n = 977) of adult primary care patients from an urban general medicine practice were interviewed with measures including the Mood Disorders Questionnaire, the PTSD Checklist–Civilian Version, and the Medical Outcomes Study 12-Item Short Form Health Survey.
Results
Compared with patients who screened negative for BD (n = 881), those who screened positive (n = 96) were 2.6 times [95% confidence interval (CI): 1.6–4.2] as likely to report physical or sexual assault, and 2.9 times (95% CI: 1.6–5.1) as likely to screen positive for current PTSD. Among those screening positive for BD, comorbid PTSD was associated with significantly worse social functioning. These results controlled for selected background characteristics, current major depressive episode, and current alcohol/drug use disorder.
Conclusion
In an urban general medicine setting, trauma exposure was related to BD, and the frequency of PTSD among patients with BD appears to be common and clinically significant. These results suggest an unmet need for mental health care in this specific population and are especially important in view of available treatments for BD and PTSD.
doi:10.1111/j.1399-5618.2008.00589.x
PMCID: PMC3633108  PMID: 18452446
bipolar disorder; posttraumatic stress disorder; primary care; trauma exposure
8.  Posttraumatic stress disorder in primary care one year after the 9/11 attacks☆ 
General hospital psychiatry  2006;28(3):213-222.
Objective
To screen for posttraumatic stress disorder (PTSD) in primary care patients 7–16 months after 9/11 attacks and to examine its comorbidity, clinical presentation and relationships with mental health treatment and service utilization.
Method
A systematic sample (n = 930) of adult primary care patients who were seeking primary care at an urban general medicine clinic were interviewed using the PTSD Checklist: the Primary Care Evaluation of Mental Disorders (PRIME-MD) Patient Health Questionnaire and the Medical Outcome Study 12-Item Short Form Health Survey (SF-12). Health care utilization data were obtained by a cross linkage to the administrative computerized database.
Results
Prevalence estimates of current 9/11-related probable PTSD ranged from 4.7% (based on a cutoff PCL-C score of 50 and over) to 10.2% (based on the DSM-IV criteria). A comorbid mental disorder was more common among patients with PTSD than patients without PTSD (80% vs. 30%). Patients with PTSD were more functionally impaired and reported increased use of mental health medication as compared to patients without PTSD (70% vs. 18%). Among patients with PTSD there was no increase in hospital and emergency room (ER) admissions or outpatient care during the first year after the attacks.
Conclusions
In an urban general medicine setting, 1 year after 9/11, the frequency of probable PTSD appears to be common and clinically significant. These results suggest an unmet need for mental health care in this clinical population and are especially important in view of available treatments for PTSD.
doi:10.1016/j.genhosppsych.2006.02.002
PMCID: PMC3622521  PMID: 16675364
Primary care; Posttraumatic stress disorder; 9/11 attacks
9.  Familial Aggregation of Dementia With Lewy Bodies 
Archives of Neurology  2011;68(1):90-93.
Background
Familial aggregation of dementia with Lewy bodies (DLB) remains unclear.
Objectives
To determine the degree of family aggregation of DLB by comparing DLB risk between siblings of probands with clinically diagnosed DLB and siblings of probands with clinically diagnosed Alzheimer disease in a cohort of Caribbean Hispanic families and to explore the degree of aggregation of specific clinical manifestations (ie, cognitive fluctuations, visual hallucinations, and parkinsonism) in DLB.
Design
Familial cohort study.
Setting
Academic research.
Patients
We separately compared risks of possible DLB, probable DLB, and clinical core features of DLB (cognitive fluctuations, visual hallucinations, and parkinsonism) between siblings of probands with clinically diagnosed DLB (n=344) and siblings of probands with clinically diagnosed Alzheimer disease (n=280) in 214 Caribbean Hispanic families with extended neurologic and neuropsychological assessment.
Main Outcome Measures
We applied general estimating equations to adjust for clustering within families. In these models, age and proband disease status were independent variables, and disease status of siblings was the measure of disease risk and the dependent variable.
Results
Compared with siblings of probands having clinically diagnosed Alzheimer disease, siblings of probands having clinically diagnosed DLB had higher risks of probable DLB (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.04–5.04) and visual hallucinations (2.32; 1.16–4.64). They also had increased risks of possible DLB (OR, 1.51; 95% CI, 0.97–2.34) and cognitive fluctuations (1.55; 0.95–2.53).
Conclusions
Dementia with Lewy bodies and core features of DLB aggregate in families. Compared with siblings of probands having clinically diagnosed AD, siblings of probands having clinically diagnosed DLB are at increased risks of DLB and visual hallucinations. These findings are an important step in elucidating the genetic risk factors underlying DLB and in delineating DLB from other neurodegenerative diseases, such as Alzheimer disease.
doi:10.1001/archneurol.2010.319
PMCID: PMC3268781  PMID: 21220678
10.  Identification of Novel Loci for Alzheimer Disease and Replication of CLU, PICALM, and BIN1 in Caribbean Hispanic Individuals 
Archives of Neurology  2010;68(3):320-328.
Objectives
To identify novel loci for late-onset Alzheimer disease (LOAD) in Caribbean Hispanic individuals and to replicate the findings in a publicly available data set from the National Institute on Aging Late-Onset Alzheimer’s Disease Family Study.
Design
Nested case-control genome-wide association study.
Setting
The Washington Heights–Inwood Columbia Aging Project and the Estudio Familiar de Influencia Genetica de Alzheimer study.
Participants
Five hundred forty-nine affected and 544 unaffected individuals of Caribbean Hispanic ancestry.
Intervention
The Illumina HumanHap 650Y chip for genotyping.
Main Outcome Measure
Clinical diagnosis or pathologically confirmed diagnosis of LOAD.
Results
The strongest support for allelic association was for rs9945493 on 18q23 (P=1.7 × 10−7), but 22 additional single-nucleotide polymorphisms (SNPs) had a P value less than 9 × 10−6 under 3 different analyses: unadjusted and stratified by the presence or absence of the APOE ε4 allele. Of these SNPs, 5 SNPs (rs4669573 and rs10197851 on 2p25.1; rs11711889 on 3q25.2; rs1117750 on 7p21.1; and rs7908652 on 10q23.1) were associated with LOAD in an independent cohort from the National Institute on Aging Late-Onset Alzheimer’s Disease Family Study. We also replicated genetic associations for CLU, PICALM, and BIN1.
Conclusions
Our genome-wide search of Caribbean Hispanic individuals identified several novel genetic variants associated with LOAD and replicated these associations in a white cohort. We also replicated associations in CLU, PICALM, and BIN1 in the Caribbean Hispanic cohort.
doi:10.1001/archneurol.2010.292
PMCID: PMC3268783  PMID: 21059989
11.  Medicare payments, healthcare service use, and telemedicine implementation costs in a randomized trial comparing telemedicine case management with usual care in medically underserved participants with diabetes mellitus (IDEATel) 
Objective
To determine whether a diabetes case management telemedicine intervention reduced healthcare expenditures, as measured by Medicare claims, and to assess the costs of developing and implementing the telemedicine intervention.
Design
We studied 1665 participants in the Informatics for Diabetes Education and Telemedicine (IDEATel), a randomized controlled trial comparing telemedicine case management of diabetes to usual care. Participants were aged 55 years or older, and resided in federally designated medically underserved areas of New York State.
Measurements
We analyzed Medicare claims payments for each participant for up to 60 study months from date of randomization, until their death, or until December 31, 2006 (whichever happened first). We also analyzed study expenditures for the telemedicine intervention over six budget years (February 28, 2000– February 27, 2006).
Results
Mean annual Medicare payments (SE) were similar in the usual care and telemedicine groups, $9040 ($386) and $9669 ($443) per participant, respectively (p>0.05). Sensitivity analyses, including stratification by censored status, adjustment by enrollment site, and semi-parametric weighting by probability of dropping-out, rendered similar results. Over six budget years 28 821 participant/months of telemedicine intervention were delivered, at an estimated cost of $622 per participant/month.
Conclusion
Telemedicine case management was not associated with a reduction in Medicare claims in this medically underserved population. The cost of implementing the telemedicine intervention was high, largely representing special purpose hardware and software costs required at the time. Lower implementation costs will need to be achieved using lower cost technology in order for telemedicine case management to be more widely used.
doi:10.1136/jamia.2009.002592
PMCID: PMC3000788  PMID: 20190064
Diabetes; informatics; telemedicine
12.  Costs and Cost Effectiveness of a Health Care Provider–Directed Intervention to Promote Colorectal Cancer Screening 
Journal of Clinical Oncology  2009;27(32):5370-5375.
Purpose
Colorectal cancer (CRC) screening remains underutilized in the United States. Prior studies reporting the cost effectiveness of randomized interventions to improve CRC screening have not been replicated in the setting of small physician practices. We recently conducted a randomized trial evaluating an academic detailing intervention in 264 small practices in geographically diverse New York City communities. The objective of this secondary analysis is to assess the cost effectiveness of this intervention.
Methods
A total of 264 physician offices were randomly assigned to usual care or to a series of visits from trained physician educators. CRC screening rates were measured at baseline and 12 months. The intervention costs were measured and the incremental cost-effectiveness ratio (ICER) was derived. Sensitivity analyses were based on varying cost and effectiveness estimates.
Results
Academic detailing was associated with a 7% increase in CRC screening with colonoscopy. The total intervention cost was $147,865, and the ICER was $21,124 per percentage point increase in CRC screening rate. Sensitivity analyses that varied the costs of the intervention and the average medical practice size were associated with ICERs ranging from $13,631 to $36,109 per percentage point increase in CRC screening rates.
Conclusion
A comprehensive, multicomponent academic detailing intervention conducted in small practices in metropolitan New York was clinically effective in improving CRC screening rates, but was not cost effective.
doi:10.1200/JCO.2008.20.6458
PMCID: PMC2773222  PMID: 19826133
13.  Barriers, Enablers, and Incentives for Research Participation: A Report from the Ambulatory Care Research Network (ACRN) 
Introduction
Supported by a supplement to our Clinical and Translational Science Award, we studied the feasibility of implementing clinical research in Northern Manhattan community practices that primarily serve Hispanic patients.
Methods
We applied a mixed methods approach (surveys, focus groups, interviews) based upon the PRECEDE-PROCEED model to determine the level of interest in clinical research among community clinicians (Practice-based Research Network (PBRN) and non-PBRN members), the perceived barriers that hamper participation in clinical research, and the perceived facilitators for conducting research in such practices.
Results
Survey and qualitative data indicated strong interest in clinical research among current and potential PBRN members if it was relevant to improving quality of care in their practice or community. They also identified important perceived barriers (lack of time, inadequate training in research methods, lack of collaborators and support staff, institutional review board hurdles, and community distrust of research) and the necessary requirements for overcoming barriers to conducting research in busy clinical settings: collaborators, mentors, research support staff, and trusting patient-clinician relationship.
Conclusion
It is feasible to conduct clinical research studies in urban community medical practices if the topics are relevant to the community and appropriate enabling structures and processes are put into place.
doi:10.3122/jabfm.2009.04.090017
PMCID: PMC2744643  PMID: 19587259
14.  Age-At-Onset Linkage Analysis in Caribbean Hispanics with Familial Late-Onset Alzheimer’s Disease 
Neurogenetics  2007;9(1):51-60.
The aim of the study was to identify chromosomal regions containing putative genetic variants influencing age-at-onset in familial late-onset Alzheimer’s disease. Data from a genome-wide scan that included genotyping of APOE was analyzed in 1,161 individuals from 209 families of Caribbean Hispanic ancestry with a mean age-at-onset of 73.3 years multiply affected by late-onset Alzheimer’s disease. Two-point and multipoint analyses were conducted using variance component methods from 376 microsatellite markers with an average inter-marker distance of 9.3 cM. Family-based test of association were also conducted for the same set of markers. Age-at-onset of symptoms among affected individuals was used as the quantitative trait. Our results showed that the presence of APOE-ε4 lowered the age-at-onset by three years. Using linkage analysis strategy, the highest LOD scores were obtained using a conservative definition of LOAD at 5q15 (LOD 3.1) 17q25.1 (LOD=2.94) and 14q32.12 (LOD=2.36) and 7q36.3 (LOD=2.29) in covariate adjusted models that included APOE-ε4. Both linkage and family-based association identified 17p13 as a candidate region. In addition, family-based association analysis showed markers at 12q13 (p=0.00002), 13q (p=0.00043) and 14q23 (p=0.00046) to be significantly associated with age at onset. The current study supports the hypothesis that there are additional genetic loci that could influence age-at-onset of late onset Alzheimer’s disease. The novel loci at 5q15, 17q25.1, 13q and 17p13, and the previously reported loci at 7q36.3, 12q13, 14q23 and 14q32 need further investigation.
doi:10.1007/s10048-007-0103-3
PMCID: PMC2701253  PMID: 17940814
Alzheimer’s disease; age-at-onset; linkage analysis; family-based association analysis; APOE
15.  The Association Between Genetic Variants in SORL1 and Alzheimer’s Disease in an Urban, Multiethnic, Community-Based Cohort 
Archives of neurology  2007;64(4):501-506.
Context
Variants in 3′ and 5′ regions of SORL1, the neuronal sorting protein-related receptor, were recently found to be associated with late onset familial and sporadic Alzheimer’s disease in several datasets that were selected for familial aggregation or were ethnically diverse or clinic-based selected series.
Objective
To investigate the association between Alzheimer’s disease and variant alleles in SORL1 using a series of single nucleotide polymorphisms (SNPs) in an urban, multiethnic community-based population.
Design & Setting
We used a nested case-control analysis in a population-based, prospective study of aging and dementia in Medicare recipients, 65 years and older, residing in northern Manhattan.
Participants
There were 296 patients with probable Alzheimer’s disease and 428 healthy elderly controls. The participants were of African American (34%), Caribbean Hispanic (51%) or non-Hispanic whites (15%).
Main Outcome Measures
We genotyped all 29 SNPs in SORL1 that were examined in the earlier report. We assessed allelic association with AD using standard case-control methods which included APOE genotype as a covariate.
Results
Several individual SNPs and SNP haplotypes were significantly associated with AD in this prospectively collected community-based cohort, confirming the previously reported positive association of SORL1 with Alzheimer’s disease. SNP 12 near the 5′ region was associated with AD in African-Americans and Hispanics. Two SNPs in the 3′ region were also associated with AD in African-Americans (SNP 26) and Whites (SNP 20). A single haplotype in the 3′ region was associated with AD in Hispanics. However, several different haplotypes were associated with AD in the African-Americans and Whites, including the “TTC” haplotypes at SNPs 23–25 (p=0.035) that was significantly associated with AD in the North European Whites in the previous report.
Conclusions
This study confirms the association between genetic variants in SORL1 and AD. While the associations observed in these datasets overlap with those previously reported, the finding of novel SNP and haplotype associations suggest that there may be extensive allelic heterogeneity in SORL1. Broad regions of the SORL1 gene will therefore need to be scrutinized for functional pathogenic variants.
doi:10.1001/archneur.64.4.501
PMCID: PMC2639214  PMID: 17420311
SORL1; Alzheimer’s disease; sporadic; African American; Caribbean Hispanic
16.  Familial Alzheimer Disease in Latinos: Interaction Between APOE, Stroke and Estrogen Replacement 
Neurology  2006;66(1):35-40.
Background
Factors that modify risk related to APOE variants have been examined primarily in unrelated patients and controls, but seldom in family-based studies. Stroke, vascular risk factors, estrogen replacement therapy (ERT), head injury (HI) and smoking have been reported to influence risk of sporadic but not familial AD.
Objectives
To examine the potential relationship between these risk factors and APOE, we used a family study design in a population in which the APOE-ε4 variant is strongly associated with risk of AD.
Methods
Latino families primarily from the Caribbean Islands in which two or more living relatives had dementia were identified in the New York City metropolitan area, the Dominican Republic and Puerto Rico. 1,498 participants from 350 families underwent a clinical interview, medical and neurological examinations, neuropsychological testing and APOE genotyping. Diagnosis was made by consensus using research criteria for AD.
Results
APOE-ε4 was associated with a nearly two-fold increased risk of AD. A history of stroke was also associated with a four-fold increased risk. A statistical interaction between APOE-ε4 and stroke was observed. Women with an APOE-ε4 who took ERT did not have an increased risk of AD, but in women with a history of stroke ERT was a deleterious effect modifier.
Conclusions
APOE-ε4 and stroke independently increase risk of familial AD among Latinos, and may interact to further increase AD risk. Among women, the risk of AD associated with APOE-ε4 may be attenuated by a history of ERT.
doi:10.1212/01.wnl.0000191300.38571.3e
PMCID: PMC2639210  PMID: 16401842
Alzheimer disease; estrogen; stroke; APOE
17.  Further Examination of the Candidate Genes in Chromosome 12p13 Locus for Late-Onset Alzheimer Disease 
Neurogenetics  2008;9(2):127-138.
A broad region on chromosome 12p13 has been intensely investigated for novel genetic variants associated with Alzheimer disease (AD). We examined this region with 23 microsatellite markers using 124 North European (NE) families and 209 Caribbean Hispanic families with late-onset AD (FAD). Significant evidence for linkage was present in a 5 cM interval near 20 cM in both the NE FAD (LOD=3.5) and the Caribbean Hispanic FAD (LOD=2.2) datasets. We further investigated these families and an independent NE case-control dataset using 14 single nucleotide polymorphisms (SNPs). The initial screening of the region at ~20 cM in the NE case-control dataset revealed significant association between AD and seven SNPs in several genes, with the strongest result for rs2532500 in TAPBPL (p=0.006). For rs3741916 in GAPDH, the C allele, rather than the G allele as was observed by Li and colleagues (2004), was the risk allele. When the two family datasets were examined, none of the SNPs were significant in NE families, but two SNPs were associated with AD in Caribbean Hispanics: rs740850 in NCAPD2 (p=0.0097) and rs1060620 in GAPDH (p=0.042). In a separate analysis combining the Caribbean Hispanic families and NE cases and controls, rs740850 was significant after correcting for multiple testing (empirical p=0.0048). Subsequent haplotype analyses revealed that two haplotype sets -- haplotype C-A at SNPs 6-7 within NCAPD2 in Caribbean Hispanics, and haplotypes containing C-A-T at SNPs 8-10 within GAPDH in Caribbean Hispanic family and NE case-control datasets -- were associated with AD. Taken together, these SNPs may be in linkage disequilibrium with a pathogenic variant(s) on or near NCAPD2 and GAPDH.
doi:10.1007/s10048-008-0122-8
PMCID: PMC2635895  PMID: 18340469
Alzheimer disease; GAPDH; NCAPD2; linkage; association
18.  Comparison of Clinical Manifestation in Familial Alzheimer's disease and Dementia with Lewy Bodies 
Archives of neurology  2008;65(12):1634-1639.
Background
The clinical delineation of Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) remains unclear.
Objective
To compare the neuropsychological profiles of patients with clinically diagnosed Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).
Methods
We first compared measures of memory, orientation, language, executive, visual perception and visual construction function between persons with DLB and AD in two Caribbean Hispanic cohorts, including a family dataset (DLB =89; AD: n=118) and an epidemiologic dataset (DLB: n=70; AD: n=157). DLB in the family sample was further divided into i) families with two or more affected family members (DLB), or ii) one affected family member (DLB). To determine whether observed differences in cognitive profiles were driven by heritable factors, we then repeated the analyses in the epidemiologic cohort excluding all familial cases. We applied general linear models adjusting for age, sex, education, disease duration, and APOE-ε4 genotype.
Results
Persons with DLB were in both cohorts more severely impaired in orientation, visual construction and non verbal reasoning after controlling for potential confounders. Persons with 2 or more DLB cases per family had the most severe impairment in episodic and semantic memory, followed by those with one DLB case per family, then by those with AD. When familial AD and DLB cases were excluded from the analysis in the epidemiologic cohort, the differences between the AD and DLB groups persisted but were attenuated.
Conclusions
Compared to persons with AD, persons with DLB are more severely impaired in various cognitive domains, particularly orientation, visual perception and visual construction. The difference appears strong in familial rather than sporadic DLB. Whether this divergence in cognitive functions is caused by gene-gene or gene-environmental interactions remains unclear.
doi:10.1001/archneur.65.12.1634
PMCID: PMC2633487  PMID: 19064751
19.  Implementing academic detailing for breast cancer screening in underserved communities 
Background
African American and Hispanic women, such as those living in the northern Manhattan and the South Bronx neighborhoods of New York City, are generally underserved with regard to breast cancer prevention and screening practices, even though they are more likely to die of breast cancer than are other women. Primary care physicians (PCPs) are critical for the recommendation of breast cancer screening to their patients. Academic detailing is a promising strategy for improving PCP performance in recommending breast cancer screening, yet little is known about the effects of academic detailing on breast cancer screening among physicians who practice in medically underserved areas. We assessed the effectiveness of an enhanced, multi-component academic detailing intervention in increasing recommendations for breast cancer screening within a sample of community-based urban physicians.
Methods
Two medically underserved communities were matched and randomized to intervention and control arms. Ninety-four primary care community (i.e., not hospital based) physicians in northern Manhattan were compared to 74 physicians in the South Bronx neighborhoods of the New York City metropolitan area. Intervention participants received enhanced physician-directed academic detailing, using the American Cancer Society guidelines for the early detection of breast cancer. Control group physicians received no intervention. We conducted interviews to measure primary care physicians' self-reported recommendation of mammography and Clinical Breast Examination (CBE), and whether PCPs taught women how to perform breast self examination (BSE).
Results
Using multivariate analyses, we found a statistically significant intervention effect on the recommendation of CBE to women patients age 40 and over; mammography and breast self examination reports increased across both arms from baseline to follow-up, according to physician self-report. At post-test, physician involvement in additional educational programs, enhanced self-efficacy in counseling for prevention, the routine use of chart reminders, computer- rather than paper-based prompting and tracking approaches, printed patient education materials, performance targets for mammography, and increased involvement of nursing and other office staff were associated with increased screening.
Conclusion
We found some evidence of improvement in breast cancer screening practices due to enhanced academic detailing among primary care physicians practicing in urban underserved communities.
doi:10.1186/1748-5908-2-43
PMCID: PMC2266776  PMID: 18086311
20.  Intraurban influences on physician colorectal cancer screening practices. 
BACKGROUND: Community social and economic resources influence colorectal (CRC) screening decisions by physicians and patients. The aim of this study is to systematically assess the differences in screening recommendations of primary care physicians within two urban communities that are distinct in socioeconomic characteristics. METHODS: Two-hundred-sixty-four primary care community (i.e., not hospital-based) physicians were stratified by community. Using self-report questionnaires, we examined primary care physicians' CRC screening practices, knowledge of risk factors and perceived physician and patient barriers to screening, Physicians practicing in upper-socioeconomic status (SES) communities were compared with those of participants practicing in lower SES communities. RESULTS: Physicians practicing in low-SES urban communities were significantly more likely to screen with fecal occult blood test than were physicians in upper-SES areas. Alternatively, upper-SES physicians were significantly more likely to recommend screening colonoscopy than were lower-SES physicians. The number of physicians (N=11) who screened for CRC using the double-contrast barium enema were few. CONCLUSIONS: Community-level SES influences physician cancer screening practices. Further understanding of these relationships may guide the development of interventions targeted to specific neighborhoods within urban areas.
PMCID: PMC2575938  PMID: 18229773
21.  A Randomized Trial Comparing Telemedicine Case Management with Usual Care in Older, Ethnically Diverse, Medically Underserved Patients with Diabetes Mellitus 
Background: Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions who experience barriers to access to care or a high burden of illness.
Methods: The authors conducted a randomized, controlled trial comparing telemedicine case management to usual care, with blinding of those obtaining outcome data, in 1,665 Medicare recipients with diabetes, aged 55 years or greater, and living in federally designated medically underserved areas of New York State. The primary endpoints were HgbA1c, blood pressure, and low-density lipoprotein (LDL) cholesterol levels.
Results: In the intervention group (n = 844), mean HgbA1c improved over one year from 7.35% to 6.97% and from 8.35% to 7.42% in the subgroup with baseline HgbA1c ≥7% (n = 353). In the usual care group (n = 821) mean HgbA1c improved over one year from 7.42% to 7.17%. Adjusted net reductions (one-year minus baseline mean values in each group, compared between groups) favoring the intervention were as follows: HgbA1c, 0.18% (p = 0.006), systolic and diastolic blood pressure, 3.4 (p = 0.001) and 1.9 mm Hg (p < 0.001), and LDL cholesterol, 9.5 mg/dL (p < 0.001). In the subgroup with baseline HgbA1c ≥7%, net adjusted reduction in HgbA1c favoring the intervention group was 0.32% (p = 0.002). Mean LDL cholesterol level in the intervention group at one year was 95.7 mg/dL. The intervention effects were similar in magnitude in the subgroups living in New York City and upstate New York.
Conclusion: Telemedicine case management improved glycemic control, blood pressure levels, and total and LDL cholesterol levels at one year of follow-up.
doi:10.1197/jamia.M1917
PMCID: PMC1380195  PMID: 16221935
22.  Depression and Glycemic Control in Hispanic Primary Care Patients with Diabetes 
Context
Maintaining optimal glycemic control is an important goal of therapy in patients with diabetes mellitus. Patients of Hispanic ancestry have been shown to have high rates of diabetes and poor glycemic control (PGC). Although depression is common in adults with diabetes, its relationship to glycemic control remains unclear, especially among Hispanics.
Objective
To assess the association of depression with PGC in Hispanics.
Design
Data from a cross-sectional mental health survey in primary care were crosslinked to the hospital's computerized laboratory database.
Setting
Urban general medicine practice at a teaching hospital.
Patients
Two hundred and nine patients (mean [standard deviation] age, 57.1 [10.3] years; 68% females) with recent International Classification of Diseases, Ninth Revision (ICD-9) codes for diabetes mellitus, and 1 or more hemoglobin A1c (HbA1c) tests.
Main Outcome Measure
Probability of PGC (HbA1c≥8%).
Results
Probability for PGC steadily increased with severity of depression. Thirty-nine (55.7%) of the 70 patients with major depression had HbA1c≥8%, compared with 39/92 (42.4%) in the minimal to mild depression group, and 15/47 (31.9%) in the no depression group (Ptrend=.01; adjusted odds ratio, 3.27; 95% confidence interval, 1.23 to 8.64, for moderate or severe depression vs no depression). Only 29 (41.4%) of the patients with major depression received mental health treatment in the previous year.
Conclusions
In this primary care sample of Hispanic patients with diabetes, we found a significant association between increasing depression severity and PGC. Yet, less than one half of the patients with moderate or severe depression received mental health treatment in the previous year. Improving identification and treatment of depression in this high-risk population might have favorable effects on diabetic outcomes.
doi:10.1111/j.1525-1497.2005.30003.x
PMCID: PMC1490114  PMID: 15963173
glycemic control; depression; diabetes; hispanics; primary care

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