Improved Clinical Functioning for Patients Receiving Fee Discounts That Reward Treatment Engagement.

OBJECTIVE: Financial incentives may have utility in promoting psychotherapy attendance and adherence, leading to improved clinical functioning. This study presents results from a novel application of financial incentives-a progressively lowered pay scale that rewards therapy attendance and adherence. METHOD: Overall, 110 outpatients participated; 56 patients (51%) were enrolled in the financial incentives condition and received a 5% fee discount-applied iteratively across sessions-if they followed defined criteria (e.g., completed homework). RESULTS: There were no statistically significant differences between groups in terms of the number of sessions attended, therapy duration, and number of no-shows and cancellations. However, adjusting for Global Assessment of Functioning (GAF) at intake, patients receiving the financial incentives had significantly higher GAF rating at termination compared with those who did not receive the intervention. CONCLUSIONS: Financial incentives that reward therapy attendance and adherence with discounted fees is associated with improved clinical functioning.

Longitudinal Study of Headache Trajectories in the Year After Mild Traumatic Brain Injury: Relation to Posttraumatic Stress Disorder Symptoms.

OBJECTIVE: To examine headache trajectories among persons with mild traumatic brain injury (MTBI) in the year after injury and the relation of headache trajectory to posttraumatic stress disorder (PTSD) at 1 year postinjury. DESIGN: Prospective, longitudinal study. SETTING: Participants were recruited through a university medical center and participated in follow-up assessments by telephone. PARTICIPANTS: Prospectively enrolled individuals (N=212) within 1 week of MTBI who were hospitalized for observation or other system injuries. Participants were assessed at baseline and 3, 6, and 12 months postinjury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants rated average headache pain intensity using the 0 to 10 numerical rating scale at each assessment period. The PTSD Checklist-Civilian Version was completed at 12 months postinjury. RESULTS: Latent class growth analysis produced a 4-trajectory group model, with groups labeled resolved, worsening, improving, and chronic. Multivariate regression modeling revealed that younger age and premorbid headache correlated with membership in the worse trajectory groups (worsening and chronic; P<.001). Univariate regression revealed a significant association between PTSD and membership in the worse trajectory groups (P<.001). CONCLUSIONS: Headache is common in the year after MTBI, with younger people, persons who previously had headaches, and persons with PTSD more likely to report chronic or worsening headache. Further research is needed to examine whether PTSD symptoms exacerbate headaches or whether problematic headache symptoms exacerbate PTSD.

Comorbidity of pain and depression among persons with traumatic brain injury.

OBJECTIVE: To assess the prevalence of pain, depression, and comorbid pain and depression among a civilian sample of persons with traumatic brain injury (TBI). DESIGN: Longitudinal survey design with 1-year follow-up. SETTING: Inpatient rehabilitation and the community. PARTICIPANTS: Participants (N=158) admitted to inpatient rehabilitation after moderate to severe TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Depression was assessed with the Patient Health Questionnaire-9 (PHQ-9); pain was assessed with a numerical rating scale from 0 (no pain) to 10 (worst pain). Participants who reported average pain ≥ 4 were classified as having pain, and participants with PHQ-9 scores ≥ 10 were classified as depressed. RESULTS: Both pain and depression were more prevalent at baseline assessment (pain: 70%; depression: 31%) than at year 1 (pain: 34%; depression: 22%). Comorbid pain and depression declined from 27% at baseline to 18% at year 1. Pain was significantly associated with depression at baseline (relative risk: 2.62, P=.003) and at year 1 (relative risk: 7.98, P<.001). CONCLUSIONS: Pain and depression are common and frequently co-occur in persons with TBI. Although their frequency declined over the first year after injury, the strength of their association increased. Assessment and treatment of both conditions simultaneously may lead to improved outcomes, both early after TBI and over time.

Psychometric properties of 3-meter backward walk test (3MBWT) in people with Parkinson disease.

BACKGROUND AND PURPOSE: The purpose of this study was to investigate the 3-meter backward walk test (3MBWT) in individuals with Parkinson Disease (PD) to determine the following: (1) concurrent validity with other gait velocity measures and (2) interrater and intrarater reliability of in-person and video assessment. METHODS: A convenience sample of 25 people with PD participated. Forward gait velocity was measured using a computerized walkway (Zeno Walkway System), the 10-meter walk test (10MWT), and 4-meter walk test (4MWT). Backward gait velocity was measured using the 3MBWT. Concurrent validity was assessed using Pearson's correlations. Reliability was assessed using intra-class correlation coefficients (ICC(2,1)). RESULTS: All relationships between the 3MBWT and gait outcome measures were significant. The 3MBWT demonstrated strong correlations with the 4MWT dual task (r = .795, p=<.001) and moderate correlations with 4MWT comfortable walking speed (r = .658, p < .001), 4MWT fast walking speed (r = .601,p=.002), 10MWT comfortable walking speed (r = .512, p = .009), and 10MWT dual task (r = .535, p = .006). A low yet significant correlation was noted with the 10MWT fast walking speed (r = .398, p = .049). Association between the 3MBWT and the Zeno Walkway System revealed moderate correlations. All reliability tests were significant at p < .001. Interrater reliability ICC(2,1) values were very high for 3MBWT (ICC(2,1) = 0.93, [0.83-0.91]). Intrarater reliability was also very high (ICC(2,1) = 0.96 [0.90-0.98]). CONCLUSION: The 3MBWT demonstrates validity and reliability as a tool for assessing gait speed in the posterior direction in people with PD.

A longitudinal study of differences in late- and early-onset geriatric depression: depressive symptoms and psychosocial, cognitive, and neurological functioning.

OBJECTIVES: Studies suggest early-onset depression (EOD) is associated with a more severe course of the depressive disorder, while late-onset depression (LOD) is associated with more cognitive and neuroimaging changes. This study examined if older adults with EOD, compared with those with LOD, would exhibit more severe symptoms of depression and, consistent with the glucocorticoid cascade hypothesis, have more hippocampal volume loss. A second goal was to determine if LOD, compared with EOD, would demonstrate more cognitive and neuroimaging changes. METHOD: At regular intervals over a four-year period non-demented, older, depressed adults were assessed on the Mini-Mental Status Examination and the Montgomery-Asberg Depression Rating Scale. They were also assessed on magnetic resonance imaging. RESULTS: Compared with LOD, EOD had more depressive symptoms, more suicidal thoughts, and less social support. Growth curve analyses indicated that EOD demonstrated higher levels of residual depressive symptoms over time. The LOD group exhibited a greater decrement in cognitive scores. Contrary to the glucocorticoid cascade hypothesis, participants with EOD lost right hippocampal volume at a slower rate than did participants with LOD. Right cerebrum gray matter was initially smaller among participants with LOD. CONCLUSIONS: EOD is associated with greater severity of depressive illness. LOD is associated with more severe cognitive and neurological changes. These differences are relevant to understanding cognitive impairment in geriatric depression.

Quadriceps Strain and TKA: Contribution of the Tourniquet and Intramedullary Rod to Postoperative Thigh Pain: A Randomized Controlled Trial.

BACKGROUND: Thigh pain is relatively common after total knee arthroplasty (TKA) and has been attributed to compression of the thigh muscles by the tourniquet used during surgery. Thigh pain that occurs after a TKA that was performed without a tourniquet may be due to a strain of the quadriceps muscle or insertion of the intramedullary (IM) rod. The purpose of the present study was to determine the cause of thigh pain after TKA in a randomized controlled trial evaluating tourniquet use, IM rod use, and quadriceps strain. METHODS: This prospective randomized controlled trial enrolled 97 subjects undergoing primary knee arthroplasty into 4 groups according to tourniquet use (yes or no) and IM rod use (yes or no). Quadriceps strain was evaluated with magnetic resonance imaging (MRI) on postoperative day 1 (POD 1). Data collected preoperatively, intraoperatively, and postoperatively until the 6-week clinical visit included pain levels for the knee and thigh (recorded separately) and knee range of motion. RESULTS: Regardless of tourniquet or IM rod use, 73 (75%) of the 97 patients reported thigh pain on POD 1. Thigh pain at 2 weeks postoperatively was indicative of a quadriceps strain. Use of a tourniquet and patient-reported thigh pain at 2 weeks increased the odds of a quadriceps strain, whereas IM rod use did not significantly contribute to thigh pain. CONCLUSIONS: The etiology of thigh pain after TKA may be multifactorial; however, an iatrogenic quadriceps strain is one source of thigh pain after TKA, especially if the pain persists 2 weeks after surgery. LEVEL OF EVIDENCE: Prognostic Level I . See Instructions for Authors for a complete description of levels of evidence.

Depressed older patients with the atypical features of interpersonal rejection sensitivity and reversed-vegetative symptoms are similar to younger atypical patients.

OBJECTIVES: The atypical depression (AD) subtype has rarely been examined in older patients. However, younger AD patients have been characterized as having more severe and chronic symptoms of depression compared with non-AD patients. DESIGN: Secondary data analysis by using analyses of variance and Growth Curve Modeling. SETTING: Clinical Research Center for the study of depression in later life. PARTICIPANTS: Depressed older patients (N = 248) followed over 2 years. METHOD: In a longitudinal study, we examined depression severity and chronicity in patients with major depression with some features of AD, specifically rejection sensitivity and reversed-vegetative symptoms (e.g., hyperphagia and hypersomnia), or leaden paralysis, and compared them to non-AD patients. The Diagnostic Interview Schedule (DIS) was used to assess depressive symptoms and history. Depression severity and chronicity were assessed every 3 months by using the Montgomery Asberg Depression Rating Scale. RESULTS: The AD symptom group reported more DIS depressive symptoms, more thoughts about wanting to die, earlier age of onset, poorer social support, and double the number of lifetime episodes than non-AD patients. Growth curve analyses revealed that, compared with non-AD patients, the AD symptom group had more residual symptoms of depression during the first year of follow-up but not during the second year. CONCLUSION: Characteristics of older patients with features of AD are similar to younger patients. Assessment of atypical symptoms, in particular, rejection sensitivity and reversed-vegetative symptoms, is essential and should be considered in treatment plans.

Depression, hippocampal volume changes, and cognitive decline in a clinical sample of older depressed outpatients and non-depressed controls.

OBJECTIVE: The aim of this study was to develop and test a model of depression, hippocampal changes, and cognitive decline. METHOD: Participants were 248 community-dwelling, depressed patients and 147 healthy, non-depressed individuals 60 years and older. Participants received a structured interview assessing current depressive symptoms and past depressive episodes, completed cognitive testing with the Mini Mental State Examination (MMSE), and underwent structural Magnetic Resonance Imaging (MRI) of the brain. For up to 10 years, assessment of depressive symptoms and MMSE administration was repeated at least annually, and MRI was repeated every two years. RESULTS: Regression analyses demonstrated that depression diagnosis at baseline predicted decrease in right (but not left) hippocampal volume over a four-year period. Analyses using structural equation modeling demonstrated that a decrease in left and right hippocampal volumes predicted decrease in MMSE score over four years. CONCLUSION: Results provide some evidence for relationships between depression and decrease in right hippocampal volume, and between hippocampal volume and MMSE score. This would be consistent with depression as a causal factor in subsequent cognitive decline. Plausible biological mechanisms include a glucocorticoid cascade or a facilitating effect of depression on amyloid-beta plaque formation. Future studies should examine the relationship between hippocampal volume and specialized memory measures, as well as between depression diagnosis and volume of other brain structures.

Race as a Predictor of Recurrence and Complications After Urethroplasty in Men With Urethral Stricture Disease.

OBJECTIVE: To determine the role of race in surgical outcomes of and complications after urethroplasty. METHODS: A single institution, retrospective review was conducted from 2011 to 2019 on male patients ≥18 years of age who underwent urethroplasty. Exclusion criteria included previous urethral cancer, lack of follow up, or revision urethroplasty. Failure of urethroplasty was defined as requiring revision surgery or recurrence on imaging or cystoscopy. Risk factors for recurrence were determined using descriptive statistics, Wilcoxon comparisons, and multivariate logistic regression. RESULTS: Three hundred and seven patients were identified with 234 patients meeting inclusion criteria. 63.2% identified as White/Caucasian (CA), 32.5% Black/African American (AA), and 4.3% other race. Mean age was 49.4 years. Between CA and AA patients, there was no difference in mean age, body mass index, smoking status, prior urethroplasty, or prior dilation/DVIU. CAs were more likely to have a fossa navicularis stricture compared to AAs (P = .0094), but there were no significant differences in bulbar, penile, or posterior stricture rates (all P >.05) or length (P = .32). The overall stricture recurrence rate was 15.8% with a median of 242 days to recurrence and no significant difference by race for either outcome (P = .83, P = .64). The only predictor of stricture recurrence was prior dilation/DVIU (P = .0404, OR 2.3, 95% CI 1.0, 5.6). Overall complication rate was 17.5%, with no difference between CA and AAs rates (P = .83) or complication type (P = .62). CONCLUSION: There was no significant difference in the rate of surgical failure for urethral stricture repair based on race. The only predictor of surgical failure was having a prior urethral dilation/DVIU.

Progress with RNA Interference for the Treatment of Primary Hyperoxaluria.

Over the last few years, US Food and Drug Administration-approved drugs using RNA interference have come to the market. Many have treated liver-specific diseases utilizing N-acetyl galactosamine conjugation because of its effective delivery and limited off-target effects. The autosomal recessive disorder primary hyperoxaluria, specifically type 1, has benefited from these developments. Primary hyperoxaluria arises from mutations in the enzymes involved in endogenous oxalate synthesis. The severity of disease varies but can result in kidney failure and systemic oxalosis. Until recently, the treatment options were limited and focused primarily on supportive treatments, pyridoxine use in a subset of patients with primary hyperoxaluria type 1, and liver-kidney transplants in those who progressed to kidney failure. Two genes have been targeted with RNA interference; lumasiran targets glycolate oxidase and nedosiran targets lactate dehydrogenase A. Lumasiran was recently approved in the treatment of primary hyperoxaluria type 1 and nedosiran is in the approval process. Unfortunately, despite initial hopes that nedosiran may also be a treatment option for primary hyperoxaluria types 2 and 3, initial data suggest otherwise. The use of RNA interference liver-specific targeting for the treatment of primary hyperoxaluria type 1 will likely transform the natural history of the disease.

The moderating effect of the APOE [small element of] 4 allele on the relationship between hippocampal volume and cognitive decline in older depressed patients.

OBJECTIVE: the apolipoprotein E epsilon-4 (APOE [small element of] 4) allele and depression are independently associated with increased risk for cognitive decline (CD). The authors have reported that depressed elders with an APOE [small element of]4 allele had greater CD compared with depressed elders without the allele. Depression affects the hippocampus, and reduced hippocampal volume has been associated with CD. This study sought to examine in depressed patients the relationships between hippocampal volume, the APOE [small element of] 4 allele, and their interaction on CD. Analyses were performed to examine the influence of baseline hippocampal volume, the APOE [small element of] 4 allele, and their interactions on change in cognitive functioning overtime. DESIGN: secondary data analysis using linear regression analyses. SETTING: clinical Research Center for the Study of Depression in Later Life conducted at Duke University. PARTICIPANTS: depressed older patients (N = 61) followed up for 4 years. MEASURES: At baseline, cognitive functioning (assessed by the Mini-Mental State Examination), left and right hippocampal volume (assessed by magnetic resonance imaging), and APOE genotype were obtained. At 4-year follow-up, cognitive functioning was reassessed. RESULTS: the APOE [small element of] 4 allele and left hippocampal volume, but not right hippocampal volume, were independently associated with CD. Importantly, the authors found the APOE [small element of]4 allele to moderate the effects of left hippocampal volume on CD. The APOE [small element of]4 allele seemed to have little effect among those with larger left hippocampal volumes, whereas the allele influenced CD among those with smaller hippocampal volumes. CONCLUSION: future studies of cognitive impairment and decline should examine both individual and conjoint effects of putative risk factors.

The recombinational anatomy of a mouse chromosome.

Among mammals, genetic recombination occurs at highly delimited sites known as recombination hotspots. They are typically 1-2 kb long and vary as much as a 1,000-fold or more in recombination activity. Although much is known about the molecular details of the recombination process itself, the factors determining the location and relative activity of hotspots are poorly understood. To further our understanding, we have collected and mapped the locations of 5,472 crossover events along mouse Chromosome 1 arising in 6,028 meioses of male and female reciprocal F1 hybrids of C57BL/6J and CAST/EiJ mice. Crossovers were mapped to a minimum resolution of 225 kb, and those in the telomere-proximal 24.7 Mb were further mapped to resolve individual hotspots. Recombination rates were evolutionarily conserved on a regional scale, but not at the local level. There was a clear negative-exponential relationship between the relative activity and abundance of hotspot activity classes, such that a small number of the most active hotspots account for the majority of recombination. Females had 1.2x higher overall recombination than males did, although the sex ratio showed considerable regional variation. Locally, entirely sex-specific hotspots were rare. The initiation of recombination at the most active hotspot was regulated independently on the two parental chromatids, and analysis of reciprocal crosses indicated that parental imprinting has subtle effects on recombination rates. It appears that the regulation of mammalian recombination is a complex, dynamic process involving multiple factors reflecting species, sex, individual variation within species, and the properties of individual hotspots.

Problems meeting basic needs moderate the association between the APOE epsilon4 allele and cognitive decline.

OBJECTIVES: The ApolipoproteinE epsilon4 (APOE epsilon4) allele influences cognitive decline (CD) in some but not in all individuals. The purpose of this study was to investigate whether problems meeting basic needs (BN) (e.g., having enough money to meet needs, having enough money for emergencies, having adequate housing, and having enough heat) influences the relationship between the APOE epsilon4 allele and CD. We predicted that problems meeting BN would have a greater influence on CD among those with the APOE epsilon4 allele than those without the allele. METHODS: Participants consisted of community-dwelling older adults from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). Data were drawn from Waves 1 and 2, which were 3 years apart. Cognitive functioning was assessed at both waves so that change in cognitive status was examined over time, and cognitive status was controlled at baseline. Genotyping, however, was not obtained until Wave 3. RESULTS: The APOE epsilon4 allele and problems meeting BN independently predicted CD. Importantly, the influence of BN on CD was greater for individuals with the APOE epsilon4 allele compared to those without the allele. Other indicators of socioeconomic status (e.g., education, income) did not interact with the APOE epsilon4 allele in predicting CD. CONCLUSIONS: There is a synergistic effect of perceived problems meeting BN and the APOE epsilon4 allele on jointly influencing cognitive functioning. Although genetic risk factors are not easily modifiable, resource deprivation may be more amenable to interventions, which may reduce risk for CD.

APOE epsilon4 allele carriers: Biological, psychological, and social variables associated with cognitive impairment.

OBJECTIVE: The apolipoprotein (APOE) epsilon4 allele genotype is a risk factor for dementia, but not all people with the APOE epsilon4 allele develop cognitive impairment (CI). Among participants with the APOE epsilon4 allele (N = 664), we identified biological, psychological, and social variables that discriminate between participants who develop CI from those who do not. We then determined if these variables predicted CI in noncarriers (N = 1421). In the sample as a whole we then determined if each of these identified variables moderate the relationship between the APOE epsilon4 allele and CI. METHODS: We used data from a biracial community-dwelling sample of older adults. Data were collected at four time points over a 10-year period. Cognitive functioning was assessed at each wave, using the Short Portable Mental Status Questionnaire (SPMSQ). APOE genotyping was performed at Wave 3. RESULTS: Among APOE epsilon4 allele carriers, but not noncarriers, variables associated with CI included white race, female gender, low BMI, number of negative life events, and health problems (high blood pressure, heart disease, and stroke). In analyses testing for moderate effects and including the entire sample, significant interactions with APOE epsilon4 allele and predictor variables revealed that white race, low BMI, stroke, heart disease, and negative life events had a greater effect on CI among those with the APOE epsilon4 allele compared to those without the allele. CONCLUSION: There are biological, psychological, and social variables associated with increased risk for CI among individuals with the APOE epsilon4 allele.

The long-term impact of childhood abuse on internalizing disorders among older adults: the moderating role of self-esteem.

OBJECTIVES: First, to determine if childhood experiences of abuse have an impact on internalizing disorders (e.g., anxiety and depressive disorders) among older adults. Second, we wish to determine if self-esteem plays a role in explaining the relationship between abuse and internalizing disorders. METHOD: First, we conducted an analysis on a population sample of participants aged 50 years or older (mean age = 67 years; SD = 10.3) assessed at two time points, three years apart (Wave 1, N = 1460; Wave 2, N = 1090). We examined the relationship between reports of childhood abuse (physical, emotional, and sexual) and internalizing disorders. Second, we determined the role self-esteem played in explaining the relationship. RESULTS: We found that childhood experiences of abuse assessed at Wave 1 predicted the number of DSM-IV internalizing disorders occurring three years later. Demonstrating the specificity of self-esteem; we found self-esteem, but not emotional reliance, to moderate the relationship between abuse and internalizing disorders such that childhood abuse had more negative effects on those with low self-esteem compared to those with higher self-esteem. Contrary to prediction, self-esteem did not mediate the relationship between abuse and internalizing disorders. CONCLUSION: The negative effects of childhood abuse persist for many years, even into older adulthood. However, contrary to the findings in younger adults, self-esteem was not correlated with childhood abuse in older adults. Moreover, childhood abuse only had a negative effect on those who had low self-esteem. It may be through the process of lifespan development that some abused individuals come to separate out the effects of abuse from their self-concept.

Appendiceal Interposition for Ureteral Stricture Disease: Technique and Surgical Outcomes.

OBJECTIVE: To report our initial experience with ureteral appendiceal interposition (UAI) in a series of adult patients undergoing ureteral reconstruction for ureteral stricture. METHODS: We retrospectively collected data of patients who underwent UAI for ureteral stricture disease from December 2015 to March of 2020. Success of surgery was defined as one that required no subsequent procedural intervention for recurrent ureteral stricture disease, or loss of kidney function. RESULTS: Eleven patients underwent UAI for ureteral stricture. Etiologies for stricture disease included radiation exposure, nephrolithiasis, and iatrogenic injury. Median follow-up was 363 days. Three patients had Clavien-Dindo class III complications during their hospitalization. No patient required repeat intervention due to recurrent ureteral stricture disease. On imaging, 9 patients had no obstruction on Lasix renal scan postoperatively, or improvement in hydronephrosis on CT scan. Two patients with poor renal function preop continued to show poor function after surgery. CONCLUSION: The use of the appendix is a safe and feasible option for ureteral reconstruction in appropriately selected adult patients when primary ureteral repair is not possible.

Depressive symptoms moderate the influence of the apolipoproteine epsilon4 allele on cognitive decline in a sample of community dwelling older adults.

OBJECTIVES: The apolipoproteinE epsilon4 (APOE epsilon4) allele and a history of depression are each separate risk factors for cognitive decline (CD). However, little research has investigated whether a history of depression influences the relationship between APOE epsilon4 and CD. The present study examined whether depressive symptoms had greater influence on subsequent CD among participants with APOE epsilon4 than those without the allele. DESIGN: Prospective 6-year longitudinal study. SETTING: Community in-home interviews. PARTICIPANTS: A biracial sample of community dwelling older adults (N = 1,992) from the Duke Established Populations for Epidemiologic Studies of the Elderly (EPESE). MEASUREMENTS: Data were drawn from Waves 1 to 3 of the EPESE, which were conducted 6 years apart. Cognitive functioning and depressive symptoms were assessed at both waves, and APOE genotyping was completed during the Wave 3 assessment. RESULTS: Regression analyses revealed that depressive symptoms and the APOE epsilon4 allele independently predicted CD. Importantly, the influence of depressive symptoms on CD was greater for individuals with the APOE epsilon4 allele compared with those without the allele. CONCLUSION: Depressive symptoms and the APOE epsilon4 allele are independent contributors to CD. Moreover, the influence of depressive symptoms on CD is greater among individuals with the APOE epsilon4 allele. Depression and the APOE epsilon4 allele may act together in disrupting neurological functioning, which may in turn lower an individual's cognitive reserve capacity. Given the efficacious treatments currently available for depression, future research should investigate the extent to which interventions for depression may reduce the risk for subsequent CD.

Racial differences in the influence of the APOE epsilon 4 allele on cognitive decline in a sample of community-dwelling older adults.

BACKGROUND: Most, but not all, past studies have suggested that the APOE genotype is a risk factor for dementia in whites but not African Americans. This paper first describes explanations as to why some studies may have failed to detect the effect of APOE genotype in African American samples. Briefly, studies have been limited by various methodological problems including small sample sizes, dichotomous measures of cognitive functioning (which tend to be less sensitive to change), and racial bias in assessing demented status. OBJECTIVE: This paper suggests methods for increasing the likelihood that genuine racial differences will be identified when examining genetic risk factors. Further, we test our model of racial differences in the relationship of APOE genotype and cognitive decline (CD) in a large prospective community sample. METHODS: Building on the work of Fillenbaum and colleagues [J Am Geriatr Soc 2001;49:1148-1155], we used data from the Duke EPESE study collected in four waves over a 10-year period (n = 2,076) to illustrate methods which may better assess racial differences in the influence of the APOE epsilon 4 allele on CD. We used multilevel models for repeated measures to examine racial differences in participants' increase in errors on a continuous measure of cognitive functioning as they aged. RESULTS: We found the APOE epsilon 4 allele to predict CD for both African Americans and whites. Having at least one epsilon 4 allele predicted more cognitive errors at wave 1 and a faster rate of decline for both African Americans and whites over time. While African Americans experienced a faster rate of CD than whites, there was no additional increase in CD from being both African American and a carrier of the epsilon 4 allele. CONCLUSION: The study points to several common methodological issues that arise when examining racial differences in genetic influences on health-related outcomes. Further, the study's results highlight the importance of including both African Americans and Caucasians in research concerning the contribution of APOE genotype to CD.