A locus at 19q13.31 significantly reduces the ApoE ε4 risk for Alzheimer's Disease in African Ancestry.

African descent populations have a lower Alzheimer disease risk from ApoE ε4 compared to other populations. Ancestry analysis showed that the difference in risk between African and European populations lies in the ancestral genomic background surrounding the ApoE locus (local ancestry). Identifying the mechanism(s) of this protection could lead to greater insight into the etiology of Alzheimer disease and more personalized therapeutic intervention. Our objective is to follow up the local ancestry finding and identify the genetic variants that drive this risk difference and result in a lower risk for developing Alzheimer disease in African ancestry populations. We performed association analyses using a logistic regression model with the ApoE ε4 allele as an interaction term and adjusted for genome-wide ancestry, age, and sex. Discovery analysis included imputed SNP data of 1,850 Alzheimer disease and 4,331 cognitively intact African American individuals. We performed replication analyses on 63 whole genome sequenced Alzheimer disease and 648 cognitively intact Ibadan individuals. Additionally, we reproduced results using whole-genome sequencing of 273 Alzheimer disease and 275 cognitively intact admixed Puerto Rican individuals. A further comparison was done with SNP imputation from an additional 8,463 Alzheimer disease and 11,365 cognitively intact non-Hispanic White individuals. We identified a significant interaction between the ApoE ε4 allele and the SNP rs10423769_A allele, (ß = -0.54,SE = 0.12,p-value = 7.50x10-6) in the discovery data set, and replicated this finding in Ibadan (ß = -1.32,SE = 0.52,p-value = 1.15x10-2) and Puerto Rican (ß = -1.27,SE = 0.64,p-value = 4.91x10-2) individuals. The non-Hispanic Whites analyses showed an interaction trending in the "protective" direction but failing to pass a 0.05 significance threshold (ß = -1.51,SE = 0.84,p-value = 7.26x10-2). The presence of the rs10423769_A allele reduces the odds ratio for Alzheimer disease risk from 7.2 for ApoE ε4/ε4 carriers lacking the A allele to 2.1 for ApoE ε4/ε4 carriers with at least one A allele. This locus is located approximately 2 mB upstream of the ApoE locus, in a large cluster of pregnancy specific beta-1 glycoproteins on chromosome 19 and lies within a long noncoding RNA, ENSG00000282943. This study identified a new African-ancestry specific locus that reduces the risk effect of ApoE ε4 for developing Alzheimer disease. The mechanism of the interaction with ApoEε4 is not known but suggests a novel mechanism for reducing the risk for ε4 carriers opening the possibility for potential ancestry-specific therapeutic intervention.

Extended genome-wide association study employing the African genome resources panel identifies novel susceptibility loci for Alzheimer's disease in individuals of African ancestry.

INTRODUCTION: Despite a two-fold risk, individuals of African ancestry have been underrepresented in Alzheimer's disease (AD) genomics efforts. METHODS: Genome-wide association studies (GWAS) of 2,903 AD cases and 6,265 controls of African ancestry. Within-dataset results were meta-analyzed, followed by functional genomics analyses. RESULTS: A novel AD-risk locus was identified in MPDZ on chromosome (chr) 9p23 (rs141610415, MAF = 0.002, p = 3.68×10-9). Two additional novel common and nine rare loci were identified with suggestive associations (P < 9×10-7). Comparison of association and linkage disequilibrium (LD) patterns between datasets with higher and lower degrees of African ancestry showed differential association patterns at chr12q23.2 (ASCL1), suggesting that this association is modulated by regional origin of local African ancestry. DISCUSSION: These analyses identified novel AD-associated loci in individuals of African ancestry and suggest that degree of African ancestry modulates some associations. Increased sample sets covering as much African genetic diversity as possible will be critical to identify additional loci and deconvolute local genetic ancestry effects. HIGHLIGHTS: Genetic ancestry significantly impacts risk of Alzheimer's Disease (AD). Although individuals of African ancestry are twice as likely to develop AD, they are vastly underrepresented in AD genomics studies. The Alzheimer's Disease Genetics Consortium has previously identified 16 common and rare genetic loci associated with AD in African American individuals. The current analyses significantly expand this effort by increasing the sample size and extending ancestral diversity by including populations from continental Africa. Single variant meta-analysis identified a novel genome-wide significant AD-risk locus in individuals of African ancestry at the MPDZ gene, and 11 additional novel loci with suggestive genome-wide significance at p < 9×10-7. Comparison of African American datasets with samples of higher degree of African ancestry demonstrated differing patterns of association and linkage disequilibrium at one of these loci, suggesting that degree and/or geographic origin of African ancestry modulates the effect at this locus. These findings illustrate the importance of increasing number and ancestral diversity of African ancestry samples in AD genomics studies to fully disentangle the genetic architecture underlying AD, and yield more effective ancestry-informed genetic screening tools and therapeutic interventions.

Understanding the healthcare experiences and needs of African immigrants in the United States: a scoping review.

BACKGROUND: Africans immigrants in the United States are the least-studied immigrant group, despite the research and policy efforts to address health disparities within immigrant communities. Although their healthcare experiences and needs are unique, they are often included in the "black" category, along with other phenotypically-similar groups. This process makes utilizing research data to make critical healthcare decisions specifically targeting African immigrants, difficult. The purpose of this Scoping Review was to examine extant information about African immigrant health in the U.S., in order to develop lines of inquiry using the identified knowledge-gaps. METHODS: Literature published in the English language between 1980 and 2016 were reviewed in five stages: (1) identification of the question and (b) relevant studies, (c) screening, (d) data extraction and synthesis, and (e) results. Databases used included EBSCO, ProQuest, PubMed, and Google Scholar (hand-search). The articles were reviewed according to title and abstract, and studies deemed relevant were reviewed as full-text articles. Data was extracted from the selected articles using the inductive approach, which was based on the comprehensive reading and interpretive analysis of the organically emerging themes. Finally, the results from the selected articles were presented in a narrative format. RESULTS: Culture, religion, and spirituality were identified as intertwined key contributors to the healthcare experiences of African immigrants. In addition, lack of culturally-competent healthcare, distrust, and complexity, of the U.S. health system, and the exorbitant cost of care, were identified as major healthcare access barriers. CONCLUSION: Knowledge about African immigrant health in the U.S. is scarce, with available literature mainly focusing on databases, which make it difficult to identify African immigrants. To our knowledge, this is the first Scoping Review pertaining to the healthcare experiences and needs of African immigrants in the U.S.

Perspective on the "African American participation in Alzheimer disease research: Effective strategies" workshop, 2018.

The Washington University School of Medicine Knight Alzheimer Disease Research Center's "African American Participation in Alzheimer Disease Research: Effective Strategies" Workshop convened to address a major limitation of the ongoing scientific progress regarding Alzheimer's disease and related dementias (ADRD): participants in most ADRD research programs overwhelmingly have been limited to non-Hispanic white persons, thus precluding knowledge as to how ADRD may be represented in non-white individuals. Factors that may contribute to successful recruitment and retention of African Americans into ADRD research were discussed and organized into actionable next steps as described within this report.

Antihypertensive Medication and Dementia Risk in Older Adult African Americans with Hypertension: A Prospective Cohort Study.

BACKGROUND: African Americans are especially at risk of hypertension and dementia. Antihypertensive medications reduce the risk of cardiovascular events, but may also reduce the risk of dementia. OBJECTIVE: To assess the longitudinal effects of antihypertensive medications and blood pressure on the onset of incident dementia in a cohort of African Americans. DESIGN: Prospective cohort. PARTICIPANTS: 1236 community-dwelling patients from an inner-city public health care system, aged 65 years and older, with a history of hypertension but no history of dementia, and who had at least three primary care visits and a prescription filled for any medication. MAIN MEASURES: Blood pressure was the average of three seated measurements. Dementia was diagnosed using a two-stage design, with a screening evaluation every 2 to 3 years followed by a comprehensive in-home clinical evaluation for those with a positive screen. Laboratory, inpatient and outpatient encounter data, coded diagnoses and procedures, and medication records were derived from a health information exchange. KEY RESULTS: Of the 1236 hypertensive participants without dementia at baseline, 114 (9%) developed incident dementia during follow-up. Individuals prescribed any antihypertensive medication (n = 816) were found to have a significantly reduced risk of dementia (HR = 0.57, 95% CI 0.37-0.88, p = 0.0114) compared to untreated hypertensive participants (n = 420). When this analysis was repeated including a variable indicating suboptimally treated blood pressure (> 140 mmHg systolic or >90 mmHg diastolic), the effect of antihypertensive medication was no longer statistically significant (HR = 0.65, 95% CI 0.32-1.30, p = 0.2217). CONCLUSIONS: Control of blood pressure in older adult African American patients with hypertension is a key intervention for preventing dementia, with similar benefits from most of the commonly available antihypertensive medications.

Population Neuroscience: Dementia Epidemiology Serving Precision Medicine and Population Health.

Over recent decades, epidemiology has made significant contributions to our understanding of dementia, translating scientific discoveries into population health. Here, we propose reframing dementia epidemiology as "population neuroscience," blending techniques and models from contemporary neuroscience with those of epidemiology and biostatistics. On the basis of emerging evidence and newer paradigms and methods, population neuroscience will minimize the bias typical of traditional clinical research, identify the relatively homogenous subgroups that comprise the general population, and investigate broader and denser phenotypes of dementia and cognitive impairment. Long-term follow-up of sufficiently large study cohorts will allow the identification of cohort effects and critical windows of exposure. Molecular epidemiology and omics will allow us to unravel the key distinctions within and among subgroups and better understand individuals' risk profiles. Interventional epidemiology will allow us to identify the different subgroups that respond to different treatment/prevention strategies. These strategies will inform precision medicine. In addition, insights into interactions between disease biology, personal and environmental factors, and social determinants of health will allow us to measure and track disease in communities and improve population health. By placing neuroscience within a real-world context, population neuroscience can fulfill its potential to serve both precision medicine and population health.

Targeting Functional Decline in Alzheimer Disease: A Randomized Trial.

BACKGROUND: Alzheimer disease results in progressive functional decline, leading to loss of independence. OBJECTIVE: To determine whether collaborative care plus 2 years of home-based occupational therapy delays functional decline. DESIGN: Randomized, controlled clinical trial. (ClinicalTrials.gov: NCT01314950). SETTING: Urban public health system. PATIENTS: 180 community-dwelling participants with Alzheimer disease and their informal caregivers. INTERVENTION: All participants received collaborative care for dementia. Patients in the intervention group also received in-home occupational therapy delivered in 24 sessions over 2 years. MEASUREMENTS: The primary outcome measure was the Alzheimer's Disease Cooperative Study Group Activities of Daily Living Scale (ADCS ADL); performance-based measures included the Short Physical Performance Battery (SPPB) and Short Portable Sarcopenia Measure (SPSM). RESULTS: At baseline, clinical characteristics did not differ significantly between groups; the mean Mini-Mental State Examination score for both groups was 19 (SD, 7). The intervention group received a median of 18 home visits from the study occupational therapists. In both groups, ADCS ADL scores declined over 24 months. At the primary end point of 24 months, ADCS ADL scores did not differ between groups (mean difference, 2.34 [95% CI, -5.27 to 9.96]). We also could not definitively demonstrate between-group differences in mean SPPB or SPSM values. LIMITATION: The results of this trial are indeterminate and do not rule out potential clinically important effects of the intervention. CONCLUSION: The authors could not definitively demonstrate whether the addition of 2 years of in-home occupational therapy to a collaborative care management model slowed the rate of functional decline among persons with Alzheimer disease. This trial underscores the burden undertaken by caregivers as they provide care for family members with Alzheimer disease and the difficulty in slowing functional decline. PRIMARY FUNDING SOURCE: National Institute on Aging.

Changes of glucose levels precede dementia in African-Americans with diabetes but not in Caucasians.

INTRODUCTION: Changes in glucose levels may represent a powerful metabolic indicator of dementia in African-Americans with diabetes. It is unclear whether these changes also occur in Caucasians. METHODS: A secondary data analysis using electronic medical records from 5228 African-Americans and Caucasians aged ≥65 years was carried out. Mixed effects models with repeated serum glucose measurements were used to compare changes in glucose levels between African-Americans and Caucasian patients with and without incident dementia. RESULTS: African-Americans and Caucasians with diabetes had significantly different changes in glucose levels by dementia status (P < .0001). African-Americans experienced a significant decline in glucose levels before the dementia diagnosis (estimated glucose decline 1.3421 mg/dL per year, P < .0001) than those who did not develop dementia. Caucasians with and without dementia showed stable glucose levels over time (P = .3071). DISCUSSION: Significant changes in glucose levels precede dementia in African-American patients with diabetes but not in Caucasians.

Categorizing Health Outcomes and Efficacy of mHealth Apps for Persons With Cognitive Impairment: A Systematic Review.

BACKGROUND: Use of mobile health (mHealth) apps is growing at an exponential rate in the United States and around the world. Mild cognitive impairment (MCI), Alzheimer disease, and related dementias are a global health problem. Numerous mHealth interventions exist for this population, yet the effect of these interventions on health has not been systematically described. OBJECTIVE: The aim of this study is to catalog the types of health outcomes used to measure effectiveness of mHealth interventions and assess which mHealth interventions have been shown to improve the health of persons with MCI, Alzheimer disease, and dementia. METHODS: We searched 13 databases, including Ovid MEDLINE, PubMed, EMBASE, the full Cochrane Library, CINAHL, PsycINFO, Ei Compendex, IEEE Xplore, Applied Science & Technology Source, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar from inception through May 2017 for mHealth studies involving persons with cognitive impairment that were evaluated using at least one quantitative health outcome. Proceedings of the Annual ACM Conferences on Human Factors in Computing Systems, the ACM User Interface Software and Technology Symposium, and the IEEE International Symposium on Wearable Computers were searched in the ACM Digital Library from 2012 to 2016. A hand search of JMIR Publications journals was also completed in July 2017. RESULTS: After removal of duplicates, our initial search returned 3955 records. Of these articles, 24 met final inclusion criteria as studies involving mHealth interventions that measured at least one quantitative health outcome for persons with MCI, Alzheimer disease, and dementia. Common quantitative health outcomes included cognition, function, mood, and quality of life. We found that 21.2% (101/476) of the fully reviewed articles were excluded because of a lack of health outcomes. The health outcomes selected were observed to be inconsistent between studies. For those studies with quantitative health outcomes, more than half (58%) reported postintervention improvements in outcomes. CONCLUSIONS: Results showed that many mHealth app interventions targeting those with cognitive impairment lack quantitative health outcomes as a part of their evaluation process and that there is a lack of consensus as to which outcomes to use. The majority of mHealth app interventions that incorporated health outcomes into their evaluation noted improvements in the health of persons with MCI, Alzheimer disease, and dementia. However, these studies were of low quality, leading to a grade C level of evidence. Clarification of the benefits of mHealth interventions for people with cognitive impairment requires more randomized controlled trials, larger numbers of participants, and trial designs that minimize bias. TRIAL REGISTRATION: PROSPERO Registration: PROSPERO 2016:CRD42016033846; http://www.crd.york.ac.uk/PROSPERO/ display_record.asp?ID=CRD42016033846 (Archived by WebCite at http://www.webcitation.org/6sjjwnv1M).

Glucose level decline precedes dementia in elderly African Americans with diabetes.

INTRODUCTION: High blood glucose levels may be responsible for the increased risk for dementia in diabetic patients. METHODS: A secondary data analysis merging electronic medical records (EMRs) with data collected from the Indianapolis-Ibadan Dementia project (IIDP). Of the enrolled 4105 African Americans, 3778 were identified in the EMR. Study endpoints were dementia, mild cognitive impairment (MCI), or normal cognition. Repeated serum glucose measurements were used as the outcome variables. RESULTS: Diabetic participants who developed incident dementia had a significant decrease in serum glucose levels in the years preceding the diagnosis compared to the participants with normal cognition (P = .0002). They also had significantly higher glucose levels up to 9 years before the dementia diagnosis (P = .0367). DISCUSSION: High glucose levels followed by a decline occurring years before diagnosis in African American participants with diabetes may represent a powerful presymptomatic metabolic indicator of dementia.

Antidepressant Use in the Elderly Is Associated With an Increased Risk of Dementia.

A retrospective cohort study was conducted including 3688 patients age 60 years or older without dementia enrolled in a depression screening study in primary care clinics. Information on antidepressant use and incident dementia during follow-up was retrieved from electronic medical records. The Cox proportional hazard models were used to compare the risk for incident dementia among 5 participant groups: selective serotonin re-uptake inhibitors (SSRI) only, non-SSRI only (non-SSRI), mixed group of SSRI and non-SSRI, not on antidepressants but depressed, and not on antidepressants and not depressed. SSRI and non-SSRI users had significantly higher dementia risk than the nondepressed nonusers (hazard ratio [HR]=1.83, P=0.0025 for SSRI users and HR=1.50, P=0.004 for non-SSRI users). In addition, SSRIs users had significantly higher dementia risk than non-users with severe depression (HR=2.26, P=0.0005). Future research is needed to confirm our results in other populations and to explore potential mechanism underlying the observed association.

Dementia incidence declined in African-Americans but not in Yoruba.

INTRODUCTION: To compare dementia incidence of African-American and Yoruba cohorts aged ≥70 years enrolled in 1992 and 2001. METHODS: African-Americans residing in Indianapolis and Yoruba in Ibadan, Nigeria without dementia were enrolled in 1992 and 2001 and evaluated every 2-3 years until 2009. The cohorts consist of 1440 African-Americans, 1774 Yoruba in 1992 and 1835 African-Americans and 1895 Yoruba in the 2001 cohorts aged ≥70 years. RESULTS: In African-Americans, dementia and Alzheimer's disease (AD) incidence rates were significantly lower in 2001 than 1992 for all age groups except the oldest group. The overall standardized annual dementia incidence rates were 3.6% (95% confidence interval [CI], 3.2%-4.1%) in the 1992 cohort and 1.4% (95% CI, 1.2%-1.7%) in the 2001 cohort. There was no significant difference in dementia or AD incidence between the Yoruba cohorts. DISCUSSION: Future research is needed to explore the reasons for the differential changes in incidence rates in these two populations.

Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk.

INTRODUCTION: African-American (AA) individuals have a higher risk for late-onset Alzheimer's disease (LOAD) than Americans of primarily European ancestry (EA). Recently, the largest genome-wide association study in AAs to date confirmed that six of the Alzheimer's disease (AD)-related genetic variants originally discovered in EA cohorts are also risk variants in AA; however, the risk attributable to many of the loci (e.g., APOE, ABCA7) differed substantially from previous studies in EA. There likely are risk variants of higher frequency in AAs that have not been discovered. METHODS: We performed a comprehensive analysis of genetically determined local and global ancestry in AAs with regard to LOAD status. RESULTS: Compared to controls, LOAD cases showed higher levels of African ancestry, both globally and at several LOAD relevant loci, which explained risk for AD beyond global differences. DISCUSSION: Exploratory post hoc analyses highlight regions with greatest differences in ancestry as potential candidate regions for future genetic analyses.

Errors in self-reports of health services use: impact on alzheimer disease clinical trial designs.

BACKGROUND: Most Alzheimer disease clinical trials that compare the use of health services rely on reports of caregivers. The goal of this study was to assess the accuracy of self-reports among older adults with Alzheimer disease and their caregiver proxy respondents. This issue is particularly relevant to Alzheimer disease clinical trials because inaccuracy can lead both to loss of power and increased bias in study outcomes. METHODS: We compared respondent accuracy in reporting any use and in reporting the frequency of use with actual utilization data as documented in a comprehensive database. We next simulated the impact of underreporting and overreporting on sample size estimates and treatment effect bias for clinical trials comparing utilization between experimental groups. RESULTS: Respondents self-reports have a poor level of accuracy with κ-values often below 0.5. Respondents tend to underreport use even for rare events such as hospitalizations and nursing home stays. In analyses simulating underreporting and overreporting of varying magnitude, we found that errors in self-reports can increase the required sample size by 15% to 30%. In addition, bias in the reported treatment effect ranged from 3% to 18% due to both underreporting and overreporting errors. CONCLUSIONS: Use of self-report data in clinical trials of Alzheimer disease treatments may inflate sample size needs. Even when adequate power is achieved by increasing sample size, reporting errors can result in a biased estimate of the true effect size of the intervention.

Statin Use, Incident Dementia and Alzheimer Disease in Elderly African Americans.

OBJECTIVE: To investigate the association between statin use, incident dementia, and Alzheimer disease (AD) in a prospective elderly African American cohort. DESIGN: Two stage design with a screening interview followed by a comprehensive in-home assessment conducted over an eight-year period. Diagnoses of incident AD and dementia were made by consensus. Statin use was collected at each evaluation. Measurements of low-density lipoprotein cholesterol (LDL), C-reactive protein (CRP) and APOE genotype were obtained from baseline blood samples. Logistic regression models were used to test the association of statin use on incident dementia and AD and its possible association with lipid and CRP levels. SETTING: Indianapolis, Indiana. PARTICIPANTS: From an original cohort of 2629 participants, a subsample of 974 African Americans aged >70 years with normal cognition, at least one follow up evaluation, complete statin information, and biomarker availability were included. MAIN OUTCOME MEASURES: Incident dementia and incident AD. RESULTS: After controlling for age at diagnosis, sex, education level, presence of the APOE ε4 allele and history of stroke for the incident dementia model, baseline use of statins was associated with a significantly decreased risk of incident dementia (OR=.44, P=.029) and incident AD (OR=.40, P=.029). The significant effect of statin use on reduced AD risk and trend for dementia risk was found only for those participants who reported consistent use over the observational period (incident AD: P=.034; incident dementia: P=.061). Additional models found no significant interaction between baseline statin use, baseline LDL, or CRP level and incident dementia/AD. CONCLUSIONS: Consistent use of statin medications during eight years of follow-up resulted in significantly reduced risk for incident AD and a trend toward reduced risk for incident dementia.

Effect of a 24-Month Physical Activity Intervention vs Health Education on Cognitive Outcomes in Sedentary Older Adults: The LIFE Randomized Trial.

IMPORTANCE: Epidemiological evidence suggests that physical activity benefits cognition, but results from randomized trials are limited and mixed. OBJECTIVE: To determine whether a 24-month physical activity program results in better cognitive function, lower risk of mild cognitive impairment (MCI) or dementia, or both, compared with a health education program. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial, the Lifestyle Interventions and Independence for Elders (LIFE) study, enrolled 1635 community-living participants at 8 US centers from February 2010 until December 2011. Participants were sedentary adults aged 70 to 89 years who were at risk for mobility disability but able to walk 400 m. INTERVENTIONS: A structured, moderate-intensity physical activity program (n = 818) that included walking, resistance training, and flexibility exercises or a health education program (n = 817) of educational workshops and upper-extremity stretching. MAIN OUTCOMES AND MEASURES: Prespecified secondary outcomes of the LIFE study included cognitive function measured by the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale (score range: 0-133; higher scores indicate better function) and the revised Hopkins Verbal Learning Test (HVLT-R; 12-item word list recall task) assessed in 1476 participants (90.3%). Tertiary outcomes included global and executive cognitive function and incident MCI or dementia at 24 months. RESULTS: At 24 months, DSC task and HVLT-R scores (adjusted for clinic site, sex, and baseline values) were not different between groups. The mean DSC task scores were 46.26 points for the physical activity group vs 46.28 for the health education group (mean difference, -0.01 points [95% CI, -0.80 to 0.77 points], P = .97). The mean HVLT-R delayed recall scores were 7.22 for the physical activity group vs 7.25 for the health education group (mean difference, -0.03 words [95% CI, -0.29 to 0.24 words], P = .84). No differences for any other cognitive or composite measures were observed. Participants in the physical activity group who were 80 years or older (n = 307) and those with poorer baseline physical performance (n = 328) had better changes in executive function composite scores compared with the health education group (P = .01 for interaction for both comparisons). Incident MCI or dementia occurred in 98 participants (13.2%) in the physical activity group and 91 participants (12.1%) in the health education group (odds ratio, 1.08 [95% CI, 0.80 to 1.46]). CONCLUSIONS AND RELEVANCE: Among sedentary older adults, a 24-month moderate-intensity physical activity program compared with a health education program did not result in improvements in global or domain-specific cognitive function. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01072500.

Health outcomes and cost of care among older adults with schizophrenia: a 10-year study using medical records across the continuum of care.

OBJECTIVES: The population of older patients with schizophrenia is increasing. This study describes health outcomes, utilization, and costs over 10 years in a sample of older patients with schizophrenia compared with older patients without schizophrenia. METHODS: An observational cohort study of 31,588 older adults (mean age: 70.44 years) receiving care from an urban public health system, including a community mental health center, during 1999-2008. Of these, 1,635 (5.2%) were diagnosed with schizophrenia and 757 (2.4%) had this diagnosis confirmed in the community mental health center. Patients' electronic medical records were merged with Medicare claims, Medicaid claims, the Minimum Dataset, and the Outcome and Assessment Information Set. Information on medication use was not available. MEASUREMENTS: Rates of comorbid conditions, healthcare utilization, costs, and mortality. RESULTS: Patients with schizophrenia had significantly higher rates of congestive heart failure (45.05% versus 38.84%), chronic obstructive pulmonary disease (52.71% versus 41.41%), and hypothyroidism (36.72% versus 26.73%) than the patients without schizophrenia (p <0.001). They had significantly lower rates of cancer (30.78% versus 43.18%) and significantly higher rates of dementia (64.46% versus 32.13%). The patients with schizophrenia had significantly higher mortality risk (hazard ratio: 1.25, 95% confidence interval: 1.07-1.47) than the patients without schizophrenia. They also had significantly higher rates of healthcare utilization. The mean costs for Medicare and Medicaid were significantly higher for the patients with schizophrenia than for the patients without schizophrenia. CONCLUSIONS: The management of older adult patients with schizophrenia is creating a serious burden for our healthcare system, requiring the development of integrated models of healthcare.