Browsing by Author "Hendrie, Hugh C."
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Item A locus at 19q13.31 significantly reduces the ApoE ε4 risk for Alzheimer's Disease in African Ancestry(Public Library of Science, 2022-07-05) Rajabli, Farid; Beecham, Gary W.; Hendrie, Hugh C.; Baiyewu, Olusegun; Ogunniyi, Adesola; Gao, Sujuan; Kushch, Nicholas A.; Lipkin-Vasquez, Marina; Hamilton-Nelson, Kara L.; Young, Juan I.; Dykxhoorn, Derek M.; Nuytemans, Karen; Kunkle, Brian W.; Wang, Liyong; Jin, Fulai; Liu, Xiaoxiao; Feliciano-Astacio, Briseida E.; Alzheimer’s Disease Sequencing Project; Alzheimer’s Disease Genetic Consortium; Schellenberg, Gerard D.; Dalgard, Clifton L.; Griswold, Anthony J.; Byrd, Goldie S.; Reitz, Christiane; Cuccaro, Michael L.; Haines, Jonathan L.; Pericak-Vance, Margaret A.; Vance, Jeffery M.; Psychiatry, School of MedicineAfrican 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, (β = -0.54,SE = 0.12,p-value = 7.50x10-6) in the discovery data set, and replicated this finding in Ibadan (β = -1.32,SE = 0.52,p-value = 1.15x10-2) and Puerto Rican (β = -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 (β = -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.Item Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial(Wiley, 2017-07) Campbell, Noll L.; Perkins, Anthony J.; Gao, Sujuan; Skaar, Todd C.; Li, Lang; Hendrie, Hugh C.; Fowler, Nicole; Callahan, Christopher M.; Boustani, Malaz A.; Department of Medicine, IU School of MedicineBACKGROUND/OBJECTIVES: Post-marketing comparative trials describe medication use patterns in diverse, real-world populations. Our objective was to determine if differences in rates of adherence and tolerability exist among new users to acetylcholinesterase inhibitors (AChEI's). DESIGN: Pragmatic randomized, open label comparative trial of AChEI's currently available in the United States. SETTING: Four memory care practices within four healthcare systems in the greater Indianapolis area. PARTICIPANTS: Eligibility criteria included older adults with a diagnosis of possible or probable Alzheimer's disease (AD) who were initiating treatment with an AChEI. Participants were required to have a caregiver to complete assessments, access to a telephone, and be able to understand English. Exclusion criteria consisted of a prior severe adverse event from AChEIs. INTERVENTION: Participants were randomized to one of three AChEIs in a 1:1:1 ratio and followed for 18 weeks. MEASUREMENTS: Caregiver-reported adherence, defined as taking or not taking study medication, and caregiver-reported adverse events, defined as the presence of an adverse event. RESULTS: 196 participants were included with 74.0% female, 30.6% African Americans, and 72.9% who completed at least twelfth grade. Discontinuation rates after 18 weeks were 38.8% for donepezil, 53.0% for galantamine, and 58.7% for rivastigmine (P = .063) in the intent to treat analysis. Adverse events and cost explained 73.1% and 25.4% of discontinuation. No participants discontinued donepezil due to cost. Adverse events were reported by 81.2% of all participants; no between-group differences in total adverse events were statistically significant. CONCLUSIONS: This pragmatic comparative trial showed high rates of adverse events and cost-related non-adherence with AChEIs. Interventions improving adherence and persistence to AChEIs may improve AD management. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01362686 (https://clinicaltrials.gov/ct2/show/NCT01362686).Item Antidepressant Use in the Elderly Is Associated With an Increased Risk of Dementia(Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, 2016-04) Wang, Chenkun; Gao, Sujuan; Hendrie, Hugh C.; Kesterson, Joe; Campbell, Noll L.; Shekhar, Anantha; Callahan, Christopher M.; Biostatistics, School of Public HealthA 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.Item Antihypertensive Medication and Dementia Risk in Older Adult African Americans with Hypertension: A Prospective Cohort Study(Springer, 2018-04) Murray, Michael D.; Hendrie, Hugh C.; Lane, Kathleen A.; Zheng, Mengjie; Ambuehl, Roberta; Li, Shanshan; Unverzagt, Frederick W.; Callahan, Christopher M.; Gao, Sujuan; Psychiatry, School of MedicineBACKGROUND: 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.Item APOE ε4 and the risk for Alzheimer disease and cognitive decline in African Americans and Yoruba(Cambridge University Press, 2014-06) Hendrie, Hugh C.; Murrell, Jill; Baiyewu, Olusegun; Lane, Kathleen A.; Purnell, Christianna; Ogunniyi, Adesola; Unverzagt, Frederick W.; Hall, Kathleen; Callahan, Christopher M.; Saykin, Andrew J.; Gureje, Oye; Hake, Ann; Foroud, Tatiana; Gao, Sujuan; Department of Psychiatry, IU School of MedicineBackground There is little information on the association of the APOEe4 allele and AD risk in African populations. In previous analyses from the Indianapolis-Ibadan dementia project, we have reported that APOE ε4 increased the risk for Alzheimer’s disease (AD) in African Americans but not in Yoruba. This study represents a replication of this earlier work using enriched cohorts and extending the analysis to include cognitive decline. Methods In this longitudinal study of two community dwelling cohorts of elderly Yoruba and African Americans, APOE genotyping was conducted from blood samples taken on or before 2001 (1,871 African Americans & 2,200 Yoruba). Mean follow up time was 8.5 years for African Americans and 8.8 years for Yoruba. The effects of heterozygosity or homozygosity of ε4 and of the possession of e4 on time to incident AD and on cognitive decline were determined using Cox’s proportional hazards regression and mixed effects models. Results After adjusting for covariates, one or two copies of the APOE ε4 allele were significant risk factors for incident AD (p < 0.0001) and cognitive decline in the African-American population (p < 0001). In the Yoruba, only homozygosity for APOE ε4 was a significant risk factor for AD (p = 0.0002) but not for cognitive decline (p = 0.2346), however, possession of an e4 allele was significant for both incident AD (p = 0.0489) and cognitive decline (p = 0.0425). Conclusions In this large longitudinal comparative study, APOE ε4 had a significant, but weaker, effect on incident AD and on cognitive decline in Yoruba than in African Americans. The reasons for these differences remain unclear.Item Assessing Psychological Well-Being: Self-Report Instruments for the NIH Toolbox(Springer International Publishing, 2014-02) Salsman, John M.; Lai, Jin-Shei; Hendrie, Hugh C.; Butt, Zeeshan; Zill, Nicholas; Pilkonis, Paul A.; Peterson, Christopher; Stoney, Catherine M.; Brouwers, Pim; Cella, David; Department of Medicine, IU School of MedicineObjective— Psychological well-being (PWB) has a significant relationship with physical and mental health. As part of the NIH Toolbox for the Assessment of Neurological and Behavioral Function, we developed self-report item banks and short forms to assess PWB. Study Design and Setting— Expert feedback and literature review informed the selection of PWB concepts and the development of item pools for Positive Affect, Life Satisfaction, and Meaning and Purpose. Items were tested with a community-dwelling U.S. internet panel sample of adults aged 18 and above (N=552). Classical and item response theory (IRT) approaches were used to evaluate unidimensionality, fit of items to the overall measure, and calibrations of those items, including differential item function (DIF). Results— IRT-calibrated item banks were produced for Positive Affect (34 items), Life Satisfaction (16 items), and Meaning and Purpose (18 items). Their psychometric properties were supported based on results of factor analysis, fit statistics, and DIF evaluation. All banks measured the concepts precisely (reliability ≥0.90) for more than 98% of participants. Conclusion— These adult scales and item banks for PWB provide the flexibility, efficiency, and precision necessary to promote future epidemiological, observational, and intervention research on the relationship of PWB with physical and mental health.Item The Association of Early Life Factors and Declining Incidence Rates of Dementia in an Elderly Population of African Americans(Oxford University Press, 2018-04-16) Hendrie, Hugh C.; Smith-Gamble, Valerie; Lane, Kathleen A.; Purnell, Christianna; Clark, Daniel O.; Gao, Sujuan; Psychiatry, School of MedicineObjectives: To explore the possible association of childhood residence, education levels, and occupation with declining incidence rates of dementia in 2 cohorts of elderly African Americans. Methods: African Americans residing in Indianapolis without dementia were enrolled in 1992 and 2001 and evaluated every 2-3 years. The cohorts consist of 1,440 participants in 1992 and 1,835 participants in 2001 aged 70 years and older. Cox proportional hazard regression models were used to compare cohort differences in dementia and Alzheimer's disease (AD) risk. Results: The 2001 cohort had significantly decreased risk of both incident dementia and AD (hazard ratio [HR]: 0.62/0.57 for dementia/AD). Years of education was associated with decreased risk of dementia (HR = 0.93; p = .0011). A significant interaction (p = .0477) between education and childhood rural residence was found for the risk of AD that higher education level is significantly associated with reduced AD risk (HR = 0.87) in participants with childhood rural residence, but no association in those with urban upbringing. The cohort difference for dementia rates were attenuated by adjusting for the 3 risk factors but remained significant (HR = 0.75; p = .04). Discussion: These results emphasize the importance of early life factors including rural residence and education for the risk for dementia later in life.Item Changes of glucose levels precede dementia in African Americans with diabetes but not in Caucasians(Elsevier, 2018-12) Hendrie, Hugh C.; Zheng, Mengjie; Lane, Kathleen A.; Ambuehl, Roberta; Purnell, Christianna; Li, Shanshan; Unverzagt, Frederick W.; Murray, Michael D.; Balasubramanyam, Ashok; Callahan, Chris M.; Gao, Sujuan; Psychiatry, School of MedicineINTRODUCTION Changes in glucose levels may represent a powerful metabolic indicator for 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 65 years and older. 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<0.0001). African Americans experienced a significant decline in glucose levels before the dementia diagnosis (estimated glucose decline 1.3421 mg/dL per year, p<0.0001) than those who did not develop dementia. Caucasians with and without dementia showed stable glucose levels over time (p=0.3071). DISCUSSION Significant changes in glucose levels precede dementia in African American patients with diabetes but not in Caucasians.Item The changing prevalence and incidence of dementia over time — current evidence(Nature, 2017) Wu, Yu-Tzu; Beiser, Alexa S.; Breteler, Monique M. B.; Fratiglioni, Laura; Helmer, Catherine; Hendrie, Hugh C.; Honda, Hiroyuki; Ikram, M. Arfan; Langa, Kenneth M.; Lobo, Antonio; Matthews, Fiona E.; Ohara, Tomoyuki; Pérès, Karine; Qiu, Chengxuan; Seshadri, Sudha; Sjölund, Britt-Marie; Skoog, Ingmar; Brayne, Carol; Psychiatry, School of MedicineDementia is an increasing focus for policymakers, civil organizations and multidisciplinary researchers. The most recent descriptive epidemiological research into dementia is enabling investigation into how the prevalence and incidence are changing over time. To establish clear trends, such comparisons need to be founded on population-based studies that use similar diagnostic and research methods consistently over time. This narrative Review synthesizes the findings from 14 studies that investigated trends in dementia prevalence (nine studies) and incidence (five studies) from Sweden, Spain, the UK, the Netherlands, France, the USA, Japan and Nigeria. Besides the Japanese study, these studies indicate stable or declining prevalence and incidence of dementia, and some provide evidence of sex-specific changes. No single risk or protective factor has been identified that fully explains the observed trends, but major societal changes and improvements in living conditions, education and healthcare might have favourably influenced physical, mental and cognitive health throughout an individual's life course, and could be responsible for a reduced risk of dementia in later life. Analytical epidemiological approaches combined with translational neuroscientific research could provide a unique opportunity to explore the neuropathology that underlies changing occurrence of dementia in the general population.Item Comorbidity Profile and Health Care Utilization in Elderly Patients with Serious Mental Illnesses(Elsevier, 2013-12) Hendrie, Hugh C.; Hay, Don; Lane, Kathleen A.; Gao, Sujuan; Purnell, Christianna; Munger, Stephanie; Smith, Faye; Dickens, Jeanne; Boustani, Malaz A.; Callahan, Christopher M.; Department of Psychiatry, IU School of MedicineObjectives Patients with serious mental illness are living longer. Yet there remain few studies that focus on health care utilization and its relationship to comorbidities in these elderly mentally ill patients. Design Comparative study. Information on demographics, comorbidities and health care utilization were taken from an electronic medical record system. Setting Wishard Health Services senior care and community mental health clinics. Participants Patients age 65 years and over-255 patients with serious mental illness (schizophrenia, major recurrent depression and bipolar illness) attending a mental health clinic and a representative sample of 533 non-demented patients without serious mental illness attending primary care clinics. Results Patients having serious mental illness had significantly higher rates of medical emergency room visits (p=0.0027) and significantly longer lengths of medical hospitalizations (p<0.0001) than did the primary care control group. The frequency of medical comorbidities such as diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, thyroid disease, and cancer were not significantly different between the groups. Hypertension was lower in the mentally ill group (p<0.0001). Reported falls (p<0.0001), diagnoses of substance abuse (p=0.02), and alcoholism (p=0.0016) were higher in the seriously mentally ill. The differences in health care utilization between the groups remained significant after adjusting for comorbidity levels, lifestyle factors, and attending primary care. Conclusions Our findings of higher rates of emergency care, longer hospitalizations, and increased frequency of falls, substance abuse, and alcoholism suggest the elderly seriously mentally ill remain a vulnerable population requiring an integrated model of health care.