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Denis A Evans

Publications and source records attributed to Denis A Evans.

At least 19 recordsLinked to original sources
PubMed2025

Multi-ancestry genome-wide meta-analysis of 56,241 individuals identifies known and novel cross-population and ancestry-specific associations as novel risk loci for Alzheimer's disease.

BACKGROUND: Limited ancestral diversity has impaired our ability to detect risk variants more prevalent in ancestry groups of predominantly non-European ancestral background in genome-wide association studies (GWAS). We construct and analyze a multi-ancestry GWAS dataset in the Alzheimer's Disease Genetics Consortium (ADGC) to test for novel shared and population-specific late-onset Alzheimer's disease (LOAD) susceptibility loci and evaluate underlying genetic architecture in 37,382 non-Hispanic White (NHW), 6728 African American, 8899 Hispanic (HIS), and 3232 East Asian individuals, performing within ancestry fixed-effects meta-analysis followed by a cross-ancestry random-effects meta-analysis. RESULTS: We identify 13 loci with cross-population associations including known loci at/near CR1, BIN1, TREM2, CD2AP, PTK2B, CLU, SHARPIN, MS4A6A, PICALM, ABCA7, APOE, and two novel loci not previously reported at 11p12 (LRRC4C) and 12q24.13 (LHX5-AS1). We additionally identify three population-specific loci with genome-wide significance at/near PTPRK and GRB14 in HIS and KIAA0825 in NHW. Pathway analysis implicates multiple amyloid regulation pathways and the classical complement pathway. Genes at/near our novel loci have known roles in neuronal development (LRRC4C, LHX5-AS1, and PTPRK) and insulin receptor activity regulation (GRB14). CONCLUSIONS: Using cross-population GWAS meta-analyses, we identify novel LOAD susceptibility loci in/near LRRC4C and LHX5-AS1, both with known roles in neuronal development, as well as several novel population-unique loci. Reflecting the power of diverse ancestry in GWAS, we detect the SHARPIN locus with only 13.7% of the sample size of the NHW GWAS study (n = 409,589) in which this locus was first observed. Continued expansion into larger multi-ancestry studies will provide even more power for further elucidating the genomics of late-onset Alzheimer's disease.

Humans↗
PubMed2006

Black-white differences in health-related quality of life among older adults.

Very little information exists on racial differences in quality of life among older adults. In this paper, we examine black-white differences in health-related quality of life (HRQOL) and identify factors that may account for these differences. The participants were 5,986 community-dwelling persons age 65+ (62% black at baseline) from the Chicago Health and Aging Project. Poor HRQOL was defined as having 14 or more self-reported physically or mentally unhealthy days over the past 30 days. A higher proportion of blacks (11.0%) than whites (9.7%) reported poor HRQOL. After adjusting for age and sex, blacks had increased odds of reporting poor HRQOL compared with whites (odds ratio [OR] = 1.72; 95% CI: 1.50-1.98). The black-white differences in HRQOL tended to increase with age (p < 0.05) and were greater among females (p < 0.05). Lifetime socioeconomic status, summary measures of medical conditions, and cognitive function accounted for most of the black-white difference (OR = 1.06; 95% CI: 0.89-1.27). Our results suggest that racial differences in HRQOL are associated with the combined effects of social disadvantage, poor physical health, and lower cognitive function.

Black or African American↗
PubMed2006

Association of fecal incontinence with physical disability and impaired cognitive function.

OBJECTIVES: Fecal incontinence is a common health problem for older people and is associated with significant morbidity and cost. In this study, we report on the association of fecal incontinence with physical disability and impaired cognitive function in a large bi-racial population of individuals aged 65 yr and older. METHODS: Study subjects are participants of the Chicago Health and Aging Project (CHAP), an ongoing study of older Chicago residents. A total of 6,099 participants completed the baseline in-home interview and assessments used in this analysis. Physical disability was assessed using a performance-based measure of basic physical functions and three commonly used self-report measures. Impaired cognitive function was assessed using a global measure of the averaged scores of four cognitive tests. The question used to determine the presence of fecal incontinence was: "In the past few months have you ever lost control of your bowels when you didn't want to?" RESULTS: In multiple logistic regression models adjusted for age, sex, and race, fecal incontinence was correlated with the presence of physical disability and impaired cognitive function on every measure. For example, using the performance-based measure of physical function, the odds of prevalent fecal incontinence were higher by 20% (OR 1.20, 95% CI 1.2-1.2) for each additional unit higher on the performance score, indicating a lower physical performance. The prevalence odds ratio for fecal incontinence was decreased by 51% for each one-point increase in the global cognitive score, indicating higher cognitive function. We found a statistically significant interaction between both race and physical disability and race and impaired cognitive function, such that the associations were stronger in blacks than in non-blacks. These associations remained after further adjustment for diabetes and stroke, and the intake of psychoactive medications. CONCLUSION: In urban, community-dwelling, older adults, fecal incontinence may be more common among persons with physical disability and impaired cognitive function.

Aged↗
PubMed2006

Relative weight and mobility: a longitudinal study in a biracial population of older adults.

PURPOSE: We examined the association of relative weight with mobility and changes in mobility over time and whether these associations differed by race. METHODS: Data come from a prospective, population-based, observational study of adults aged 65 years or older. Mobility outcomes were assessed at baseline and two follow-up interviews at 3-year intervals. The study included 4195 participants with a mean age of 73.8 +/- 6.3 (SD) years; 61.4% were women, and 60.9% were black. Assessment of mobility included a brief self-report instrument and a performance-based walk test. Body mass index (BMI, kilograms per square meter) was used as a measure of relative weight. We used generalized estimating equation models to examine change in mobility outcomes over time as a function of BMI. RESULTS: Average BMI was 26.6 +/- 5.7 kg/m(2), with 34.0% overweight and 23.4% obese. BMI showed a significant curvilinear association with mobility outcomes at baseline (p < 0.001), but was not associated with change in mobility during follow-up. Maximum mobility levels occurred at a significantly higher level of BMI among blacks than whites. CONCLUSIONS: Higher levels of BMI may lead to mobility impairments earlier in life, but there is little evidence that they increase the rate of decline in mobility in older age itself.

Aged↗
PubMed2006

The relation of cigarette smoking to incident Alzheimer's disease in a biracial urban community population.

The relationship between smoking status and incident Alzheimer's disease (AD) was investigated in a random stratified sample of a biracial community in Chicago. Analyses are based on 1,064 persons (of 1,134 evaluated) who had data on smoking status, disease incidence, and key covariates such as apolipoprotein allele status. During a mean of about 4 years of follow-up, 170 persons met criteria for incident AD. Current smoking was associated with increased risk of incident AD (OR = 3.4, 95% CI = 1.4-8.0) compared to persons who never smoked. There was no apparent increase in risk of AD for former smokers compared to persons who never smoked (OR = 0.9, 95% CI = 0.5-1.7). Apolipoprotein E allele status modified this association in that former smokers with a upsilon4 allele were less likely to develop AD (p = 0.04) than those who never smoked. Former smokers also appeared to have a reduced risk of developing AD as their pack-years of smoking increased (p = 0.02)such that the odds of developing AD increased by 50% for every 10 years of smoking cessation (OR = 1.3, CI = 0.9-1.7). The results suggest that older people who currently smoke are more likely to develop AD compared to those who never smoked; the relation between those who used to smoke but quit and the risk of AD is complex and requires further research.

Black or African American↗
PubMed2006

Dietary copper and high saturated and trans fat intakes associated with cognitive decline.

BACKGROUND: Evidence from prospective epidemiologic studies and animal models suggests that intakes of dietary fats and copper may be associated with neurodegenerative diseases. OBJECTIVE: To examine whether high dietary copper intake is associated with increased cognitive decline among persons who also consume a diet high in saturated and trans fats. DESIGN: Community-based prospective study. SETTING: Chicago, Ill. Patients Chicago residents 65 years and older. MAIN OUTCOME MEASURES: Cognitive function was assessed using 4 cognitive tests administered during in-home interviews at 3-year intervals for 6 years. Dietary assessment was performed with a food frequency questionnaire. Dietary intakes of copper and fats were related to change in global cognitive score (the mean of the 4 tests) among 3718 participants. RESULTS: Among persons whose diets were high in saturated and trans fats, higher copper intake was associated with a faster rate of cognitive decline. In multiple-adjusted mixed models, the difference in rates for persons in the highest (median, 2.75 mg/d) vs lowest (median, 0.88 mg/d) quintiles of total copper intake was -6.14 standardized units per year (P<.001) or the equivalent of 19 more years of age. There was also a marginally statistically significant association (P = .07) with the highest quintile of food intake of copper (median, 1.51 mg/d) and a strong dose-response association with higher copper dose in vitamin supplements. Copper intake was not associated with cognitive change among persons whose diets were not high in these fats. CONCLUSION: These data suggest that high dietary intake of copper in conjunction with a diet high in saturated and trans fats may be associated with accelerated cognitive decline.

Aged↗
PubMed2006

Cognitive decline and survival in Alzheimer's disease.

OBJECTIVE: To test the association of rate of cognitive decline, an indicator of the severity of the underlying disease process, with risk of death in Alzheimer's disease (AD). METHODS: A total of 472 persons with clinically diagnosed AD were recruited from a memory disorders clinic and day care centers in the Chicago area. They completed a uniform clinical evaluation at baseline and a battery of nine cognitive tests at six-month intervals for a mean of about three years. A previously established measure of global cognition was derived from the nine tests. RESULTS: During follow-up, 168 persons (36%) died. In a proportional hazards model that controlled for age, sex, race, education, and baseline level of cognition, individual rate of global cognitive decline, estimated with least squares regression, was linearly related to mortality risk. Thus, a person declining minimally (increase of 0.04 unit per year, 90th percentile) was 2.7 times less likely to die during the study period than a person declining rapidly (decrease of 0.76 unit per year, 10th percentile). Controlling for baseline disability did not substantially affect results. The association of cognitive decline with mortality was substantially stronger for white persons compared to African Americans and in those with less compared to more education. CONCLUSION: The results indicate that the rate at which cognition declines in AD is robustly related to survival.

Adult↗
PubMed2006

Is lower cognitive function in one spouse associated with depressive symptoms in the other spouse?

This study examines whether lower cognitive function in one spouse is associated with depressive symptoms in the other spouse. The subjects were 528 community-dwelling spouse pairs aged 65+ who participated in the Chicago Health and Aging Project (CHAP), an ongoing longitudinal, bi-racial, population-based study of risk factors for incident Alzheimer's disease and other age-related chronic conditions. CHAP participants were assessed at 3-year intervals over a period of nearly ten years. The results show a cross-sectional association of wives' lower cognitive function at baseline with depressive symptoms in husbands; however, husbands' cognitive function was not associated with wives' depressive symptoms. There was no longitudinal association of cognitive function at baseline with increased depressive symptoms over time. Furthermore, change in cognitive function over time had no effect on depressive symptoms in either spouse. The relationship between cognitive function and depressive symptoms in spouse pairs is complex. Our findings suggest that husbands may be particularly psychologically vulnerable to the negative effects of their wives' cognitive impairment. This vulnerability may have a range of long-term health and caregiving implications.

Activities of Daily Living↗
PubMed2006

Blood pressure and lower limb function in older persons.

BACKGROUND: Factors contributing to gait difficulties in elderly persons are considered to be multifactorial and are not well understood. The purpose of this study was to examine the association of blood pressure (BP) with change in lower limb function in older persons. METHODS: Eight hundred eighty-eight older Catholic clergy members without baseline dementia or Parkinson's disease were recruited from about 40 groups across the United States. At baseline, BP was measured, the presence of vascular diseases and diabetes was recorded, cognitive function was assessed, and medications were inspected. At baseline and subsequent annual visits, gait and balance were assessed using performance-based tasks from which a previously established composite measure of lower limb function was derived. RESULTS: In a general estimating equation analysis controlling for age, education, and gender, a 10 mmHg increment in systolic blood pressure (SBP) was associated with greater decline in lower limb function (estimate of interaction = -6.35 x 10(-3), standard error = 2.49 x 10(-3), p =.011). Thus, on average, lower limb function declined 28.7% faster in persons with an SBP of 160 mmHg than in persons with an SBP of 120 mmHg. This effect was unchanged after controlling for baseline vascular diseases, diabetes, or cognition. However, censoring individuals who developed stroke during the study made the relationship between SBP and change in lower limb function nonsignificant. CONCLUSIONS: SBP may be associated with decline in lower limb function in older persons.

Aged↗
PubMed2006

Dietary folate and vitamins B-12 and B-6 not associated with incident Alzheimer's disease.

CONTEXT: It is currently not known whether dietary intakes of folate and vitamins B12 and B6, co-factors in the methylation of homocysteine, protect against Alzheimer's disease. OBJECTIVE: To examine the association between risk of incident Alzheimer's disease and dietary intakes of folate, vitamin B-12, and vitamin B-6. DESIGN: Prospective cohort study. SETTING: Geographically defined biracial Chicago community. PARTICIPANTS: 1,041 residents, aged 65 years and older, initially free of Alzheimer's disease and followed a median 3.9 years for the development of incident disease. MAIN OUTCOME MEASURE: Probable Alzheimer's disease identified through structured clinical neurological evaluation using standardized criteria. RESULTS: A total of 162 persons developed incident Alzheimer's disease during follow-up. In logistic regression models adjusted for age, sex, race, education, cognitive activities, APOE-epsilon4, and dietary intakes of vitamin E in food and total niacin, there was no association between risk of developing Alzheimer's disease and quintiles of folate intake or of vitamin B-12 intake. The adjusted odds ratio was 1.6 (95% confidence interval: 0.5, 5.2) for persons in the highest quintile of total folate intake (median of 752.7 microg/d) compared with persons in the lowest quintile of intake (median, 202.8 microg/d). Compared with persons in the first quintile of total vitamin B-12 intake (median, 3.1 microg/d) the odds ratio was 0.6 (95% confidence interval: 0.2, 1.6) for persons in the fifth quintile of intake (median, 20.6 microg/d). Intake of vitamin B-6 was not associated with incident Alzheimer's disease after control for dietary intakes of vitamin E and total niacin. CONCLUSION: Dietary intakes of folate, vitamin B-12, or vitamin B-6 do not appear to be associated with the development of Alzheimer's disease.

Aged↗
PubMed2005

Change in cognitive function in Alzheimer's disease in African-American and white persons.

Few studies have examined the association of race with change in cognitive function in Alzheimer's disease (AD). We studied the rate of decline in global and specific measures of cognitive function in a cohort of 410 older African-Americans and whites with clinically diagnosed AD. Persons were examined annually for an average of 3.5 years, and follow-up participation among survivors exceeded 90%. In mixed-effects models that controlled for age, gender, education, and premorbid reading activity, African-Americans scored lower than whites at baseline on a composite measure of global cognition and on specific measures of visuoconstruction and naming. However, they experienced less rapid decline in episodic memory (p < 0.01), with similar but not quite significant effects for global cognition (p = 0.06), perceptual speed (p = 0.07) and naming (p = 0.08). The results suggest that the rate of cognitive decline in AD is slower in African-Americans compared with whites, particularly for episodic memory.

Aged↗
PubMed2005

Relation of blood pressure to risk of incident Alzheimer's disease and change in global cognitive function in older persons.

PURPOSE: To examine the relation of systolic and diastolic blood pressure to incident Alzheimer's disease (AD) and rate of cognitive change. METHODS: Longitudinal cohort study with annual clinical evaluations. At baseline, blood pressure was measured, apolipoprotein E (APOE) genotyping was performed, and medications were reviewed. RESULTS: 824 older Catholic clergy members without baseline dementia were recruited from across the United States. During a mean of about 6 years of observation, 151 persons developed AD. In a proportional hazards model adjusted for age, sex and education, neither systolic (relative risk = 0.995; 95% CI: 0.986, 1.004, p = 0.249) nor diastolic (relative risk = 1.000; 95% CI: 0.985, 1.015, p = 0.975) blood pressure was related to AD incidence. In mixed effects models, neither systolic nor diastolic blood pressure was related to level or to annual rate of change on a global measure of cognition. These results did not change in subsequent models that accounted for the use of medications with antihypertensive properties or for the possession of an APOE epsilon4 allele. CONCLUSIONS: In a cohort of older persons with a majority taking medications with antihypertensive properties, we did not find a relationship between blood pressure and risk of AD or cognitive decline.

Aged↗
PubMed2005

Fish consumption and cognitive decline with age in a large community study.

BACKGROUND: Dietary intake of fish and the omega-3 fatty acids have been associated with lower risk of Alzheimer disease and stroke. OBJECTIVE: To examine whether intakes of fish and the omega-3 fatty acids protect against age-related cognitive decline. DESIGN: Prospective cohort study. SETTING: Geographically defined Chicago, Ill, community. PARTICIPANTS: Residents, 65 years and older, who participated in the Chicago Health and Aging Project. MAIN OUTCOME MEASURE: Change in a global cognitive score estimated from mixed models. The global score was computed by summing scores of 4 standardized tests. In-home cognitive assessments were performed 3 times over 6 years of follow-up. RESULTS: Cognitive scores declined on average at a rate of 0.04 standardized units per year (SU/y). Fish intake was associated with a slower rate of cognitive decline in mixed models adjusted for age, sex, race, education, cognitive activity, physical activity, alcohol consumption, and total energy intake. Compared with a decline rate in score of -0.100 SU/y among persons who consumed fish less than weekly, the rate was 10% slower (-0.090 SU/y) among persons who consumed 1 fish meal per week and 13% slower (-0.088 SU/y) among persons who consumed 2 or more fish meals per week. The fish association was not accounted for by cardiovascular-related conditions or fruit and vegetable consumption but was modified after adjustment for intakes of saturated, polyunsaturated, and trans fats. There was little evidence that the omega-3 polyunsaturated fatty acids were associated with cognitive change. CONCLUSIONS: Fish consumption may be associated with slower cognitive decline with age. Further study is needed to determine whether fat composition is the relevant dietary constituent.

Age Factors↗
PubMed2005

Early life socioeconomic status and late life risk of Alzheimer's disease.

The authors examined the relation of early life socioeconomic status to incident Alzheimer's disease (AD), level of cognition and rate of cognitive decline in old age. For up to 10 years, 859 older Catholic clergy members without dementia at baseline completed annual clinical evaluations as part of the Religious Orders Study. The evaluations included clinical classification of AD and detailed cognitive testing. At baseline, indicators of early life household socioeconomic level (e.g., parental education) and the county of birth were ascertained. Socioeconomic features of the birth county (e.g., literacy rate) were estimated with data from the 1920 US Census. Composite measures of early life household and community socioeconomic level were developed. In analyses that controlled for age, sex and education, higher household and community socioeconomic levels in early life were associated with higher level of cognition in late life but not with risk of AD or rate of cognitive decline. The results suggest that early life socioeconomic level is related to level of cognition in late life but not to rate of cognitive decline or risk of AD.

Aged↗
PubMed2005

Physical activity, cognitive activity, and cognitive decline in a biracial community population.

BACKGROUND: Findings from studies investigating whether physical activity reduces the risk of cognitive decline in old age have been inconsistent. OBJECTIVE: To examine whether participation in physical activity by older adults reduces the rate of cognitive decline after accounting for participation in cognitively stimulating activities. DESIGN: A prospective population study conducted from August 1993 to January 2003, with an average follow-up of 6.4 years. SETTING: A biracial community population on the south side of Chicago. PARTICIPANTS: Participants were 4055 community-dwelling adults 65 years and older who were able to walk across a small room and had participated in at least 2 of the 3 follow-up assessments. MAIN OUTCOME MEASURE: Annual rate of cognitive change as measured by a global cognitive score, which consisted of averaged standardized scores from 4 cognitive tests. RESULTS: In a mixed model adjusted for age, sex, race, and education, each additional physical activity hour per week was associated with a slower rate of cognitive decline by 0.0007 U/y (P = .04). However, with further adjustments (1) for participation in cognitive activities (beta = .0006, P = .10), (2) for depression and vascular diseases (beta = .0005, P = .19), and (3) by excluding participants whose global cognitive score at baseline was at or below the 10th percentile (beta = .0002, P = .45), the coefficients were smaller and no longer statistically significant. CONCLUSION: These data do not support the hypothesis that physical activity alone protects against cognitive decline among older adults.

Aged↗
PubMed2005

Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons.

BACKGROUND: Deficiencies in folate and vitamin B12 have been associated with neurodegenerative disease. OBJECTIVE: To examine the association between rates of age-related cognitive change and dietary intakes of folate and vitamin B12. DESIGN: Prospective study performed from 1993 to 2002. SETTING: Geographically defined biracial community in Chicago, Ill. PARTICIPANTS: A total of 3718 residents, 65 years and older, who completed 2 to 3 cognitive assessments and a food frequency questionnaire. MAIN OUTCOME MEASURE: Change in cognitive function measured at baseline and 3-year and 6-year follow-ups, using the average z score of 4 tests: the East Boston Tests of immediate and delayed recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test. RESULTS: High folate intake was associated with a faster rate of cognitive decline in mixed models adjusted for multiple risk factors. The rate of cognitive decline among persons in the top fifth of total folate intake (median, 742 microg/d) was more than twice that of those in the lowest fifth of intake (median, 186 microg/d), a statistically significant difference of 0.02 standardized unit per year (P = .002). A faster rate of cognitive decline was also associated with high folate intake from food (P for trend = .04) and with folate vitamin supplementation of more than 400 microg/d compared with nonusers (beta = -.03, P<.001). High total B12 intake was associated with slower cognitive decline only among the oldest participants. CONCLUSIONS: High intake of folate may be associated with cognitive decline in older persons. These unexpected findings call for further study of the cognitive implications of high levels of dietary folate in older populations.

Age Factors↗
PubMed2005

Sex differences in the clinical manifestations of Alzheimer disease pathology.

CONTEXT: Sex differences in risk of clinically diagnosed Alzheimer disease (AD) have been studied extensively, but little is known about the relation of the pathologic indices of AD to the clinical manifestations of the disease in men compared with women. OBJECTIVE: To test whether the relation of AD pathology to the clinical manifestations of the disease differs in men and women. DESIGN: Longitudinal, clinicopathologic cohort study. PARTICIPANTS AND SETTING: Analyses were conducted on 141 older Catholic clergy members who underwent detailed annual clinical evaluations and brain autopsy at death. The number of neuritic plaques, diffuse plaques, and neurofibrillary tangles in a 1-mm2 area sampled from 4 cortical regions was counted, and a global measure of AD pathology (range, 0-2.98 U) and specific measures of each pathology were derived. MAIN OUTCOME MEASURES: Clinical diagnosis of probable AD and level of global cognitive function at the last evaluation before death. RESULTS: Women had more global AD pathology than did men (P = .04), due primarily to more neurofibrillary tangles (P = .02). At the last evaluation before death, 57 persons met clinical criteria for probable AD (34 [60%] of them women). In logistic regression models, sex was not related to odds of clinical AD (odds ratio [OR], 1.35; 95% confidence interval [CI], 0.56-3.25), but the relation of global AD pathology to clinical diagnosis differed for men and women. Each additional unit of AD pathology was associated with a nearly 3-fold increase in the odds of clinical AD in men (OR, 2.82; 95% CI, 1.03-7.65) compared with a more than 20-fold increase in the odds of clinical AD in women (OR, 22.67; 95% CI, 5.11-100.53). Results were unchanged after controlling for potential confounders or using level of cognition as the outcome. CONCLUSION: These data suggest that AD pathology is more likely to be clinically expressed as dementia in women than in men.

Aged↗