- Email: [email protected]
Respiratory function in relation to white matter lesions and lacunar infarcts: A longitudinal population-based study in women
S78
Risk Factors / 1 (Suppl 1) (2005)
ing verbal and figural recognition memory tasks. Cholesterol profiles were examined with reference to accepted clinical criteria (i.e., Adult Treatment Panel III). BOLD imaging was performed on a 3 T GE Horizon LX Echospeed scanner. An event-related design was used with separate verbal and figural recognition memory tasks. Each task consisted of encoding, yes/no recognition, and yes/no matching conditions. Statistical Parametric Mapping (SPM) software was used to regress lipid levels onto activation maps obtained during recognition performance, with conservative extent and height thresholds (k ⫽ 30, p ⬍ .01). Results: Mean lipid levels were in the borderline high range. Total cholesterol and low-density lipoprotein (LDL) cholesterol were positively associated with activation in the right parahippocampal gyrus (PHG) and were negatively correlated with performance on the verbal recognition task (r ⫽ ⫺.48 and r ⫽ ⫺.37, p ⬍ .001, respectively). No similar effects were evident on the figural memory task. Conclusions: Increased activity in the PHG is observed in individuals with mild cognitive impairment and may reflect less efficient processing (Dickerson, 2004). Here we demonstrate for the first time that hyperlipidemia, a risk factor for dementia, is associated with increased PHG activation and decreased verbal memory performance at midlife. Total cholesterol was the strongest predictor, though LDL showed similar effects. These results suggest a need for further fMRI studies examining hyperlipidemia and risk for cognitive impairment. O1-01-03
RESPIRATORY FUNCTION IN RELATION TO WHITE MATTER LESIONS AND LACUNAR INFARCTS: A LONGITUDINAL POPULATIONBASED STUDY IN WOMEN
Xinxin Guo1, Michela Simoni2, Leonardo Pantoni2, Bo Palmertz3, Deborah Gustafson1, Ingmar Skoog1; 1Clinical Neurosciences, Sahlgrenska University Hospital, Go¨teborg, Sweden; 2Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy; 3Department of Radiology, Ostra Hospital, Go¨teborg, Sweden Background: Lower respiratory function increased risks of atherosclerosis, hypertension, and stroke. Only few studies have examined the relationship between respiratory function and white matter lesions (WMLs) and lacunar infarcts before, and are mainly cross-sectional. Objectives: To study whether lower respiratory function was related to WMLs and lacunar infarcts. Methods: As a part of a longitudinal population-based study in Gothenburg, the study sample included 359 women aged 50-72 years who were followed for 20 years. Respiratory function was measured by forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in 1980. Computerized tomographic (CT) scans of the brain was taken in 2000, and rated for presence and severity of WMLs as well as presence and number of lacunar infarcts. Results: Lower FVC and FEV1 in 1980 were associated with increased frequency and severity of WMLs and lacunar infarcts on CT in 2000. Per 1SD decrease of FVC, odds ratios (95% confidence intervals) were 1.42 (1.10-1.83) for presence of WMLs and 1.58 (1.21-2.07) for presence of lacunar infarcts, after adjustment for potential confounders. Per 1SD decrease of FEV1, adjusted odds ratios (95% confidence intervals) were 1.39 (1.07-1.82) for presence of WMLs and 1.49 (1.13-1.96) for presence of lacunar infarcts. The associations remained in non-smokers. Conclusions: Lower respiratory capacity increases risks of WMLs and lacunar infarcts. O1-01-04
TIME COURSE OF COGNITIVE DEFICITS IN PRECLINICAL ALZHEIMER’S DISEASE
Brent J. Small1, Laura Fratiglioni2, Lars Backman2; 1University of South Florida, Tampa, FL, USA; 2Karolinska Institute, Stockholm, Sweden Background: In recent years there has been a great deal of interest in describing the nature of changes in cognitive performance during preclinical Alzheimer’s disease (AD). A better understanding of the time course of these effects may aid in the early identification of persons at risk of AD. Objectives: In this presentation we examine whether the change in cog-
nitive performance during preclinical AD represents a linear decline in functioning to the dementia diagnosis or whether a period of relative stability exists, followed by precipitous decline directly preceding the dementia diagnosis. Methods: Participants consisted of 528 very-old adults (M ⫽ 81.8 years) taken from the Kungsholmen Project, a longitudinal study of aging and dementia. Persons were measured on 4 occasions across a 7-year follow-up interval. At the final measurement point, 457 persons remained free of a dementia diagnosis, whereas 71 were newly diagnosed with AD and represent the incident AD cases. Cognitive performance was indexed with the Mini-Mental State Examination. In order to examine changes in cognitive performance, growth mixture modeling was applied to the longitudinal data. This technique, which is conceptually similar to random-effects models, allows for the extraction of sub-groups or classes of participants based upon differences in initial level, slope, or both. In the current study, we examined two statistical models, one specifying linear decline and the other incorporating a quadratic decline component to determine which model identified the most preclinical AD cases correctly. The results indicated that at baseline, 7-years prior to the dementia diagnosis, those who would go on to be diagnosed with AD scored significantly lower than persons who would remain free of dementia. Further, the growth mixture model that incorporated linear and quadratic decline provided the best statistical fit to the data, as well as generating the best sensitivity (61.9%) and specificity (94.3%) estimates. Conclusions: This analysis demonstrates that the decline in cognitive performance seen in preclinical AD is characterized by a period of relative stability followed by rapid declines just prior to the diagnosis of dementia. Further, the results illustrate the merits of this statistical approach to describe changes in cognitive functioning preclinically. O1-01-05
DIABETES MELLITUS AND RISK OF ALZHEIMER’S DISEASE IN THE CACHE COUNTY STUDY ON MEMORY, HEALTH, AND AGING
Gene Charoonruk1, Ronald Munger1, Heidi Wengreen1, Christopher Corcoran1, Kathleen Hayden2, Lori Bastian3, JoAnn Tschanz1, Maria Norton1, Kathleen Welsh-Bohmer3; 1Utah State University, Logan, UT, USA; 2Johns Hopkins University, Baltimore, MD, USA; 3Duke University, Durham, NC, USA Background: The role of diabetes mellitus in the etiology of Alzheimer’s disease (AD) is uncertain because some studies have reported a minimal or no association while others have observed a positive association. The relationship between diabetes and AD is of great public health interest because of the sharply rising prevalence of obesity and diabetes worldwide. Objective(s): To examine the association between diabetes mellitus and risk of incident AD. Methods: Characteristics of 5092 men and women aged 65 years or older in Cache County, Utah, were assessed at baseline in 1995. Diabetes was assessed at baseline using self-reports of a physician’s diagnosis. Incident AD was assessed in multi-stage screening and assessment protocols and clinical consensus conferences during follow-up examinations in 1998-99. Participants with dementia at baseline or dementia other than AD at follow-up were excluded from analyses. Logistic regression models were used to estimate the relative risk of AD while controlling for age, education, smoking, alcohol intake, APOE genotype, body mass index, and history of hypertension, hypercholesterolemia, stroke, and myocardial infarction. Conclusions: In the 3.5 year period of follow-up, nondiabetic women had a higher incidence of AD compared to non-diabetic men (4.0 vs. 1.7 percent); however among diabetics the incidence of AD was lower among women compared to men (3.1 vs. 4.0 percent). The multivariate-adjusted relative risk (RR) of AD in diabetics vs. non-diabetics was nearly 4-fold higher for men (RR ⫽ 3.71, 95% confidence interval (CI) ⫽ 1.54-8.58) but was not elevated for women (RR ⫽ 1.01, 95% CI ⫽ 0.35-2.48). In conclusion baseline history of diabetes was associated with a subsequent increase in risk of AD in men but not in women in Cache County, Utah. The interaction between diabetes, gender, and risk of AD should be explored further.
Risk Factors / 1 (Suppl 1) (2005)
ing verbal and figural recognition memory tasks. Cholesterol profiles were examined with reference to accepted clinical criteria (i.e., Adult Treatment Panel III). BOLD imaging was performed on a 3 T GE Horizon LX Echospeed scanner. An event-related design was used with separate verbal and figural recognition memory tasks. Each task consisted of encoding, yes/no recognition, and yes/no matching conditions. Statistical Parametric Mapping (SPM) software was used to regress lipid levels onto activation maps obtained during recognition performance, with conservative extent and height thresholds (k ⫽ 30, p ⬍ .01). Results: Mean lipid levels were in the borderline high range. Total cholesterol and low-density lipoprotein (LDL) cholesterol were positively associated with activation in the right parahippocampal gyrus (PHG) and were negatively correlated with performance on the verbal recognition task (r ⫽ ⫺.48 and r ⫽ ⫺.37, p ⬍ .001, respectively). No similar effects were evident on the figural memory task. Conclusions: Increased activity in the PHG is observed in individuals with mild cognitive impairment and may reflect less efficient processing (Dickerson, 2004). Here we demonstrate for the first time that hyperlipidemia, a risk factor for dementia, is associated with increased PHG activation and decreased verbal memory performance at midlife. Total cholesterol was the strongest predictor, though LDL showed similar effects. These results suggest a need for further fMRI studies examining hyperlipidemia and risk for cognitive impairment. O1-01-03
RESPIRATORY FUNCTION IN RELATION TO WHITE MATTER LESIONS AND LACUNAR INFARCTS: A LONGITUDINAL POPULATIONBASED STUDY IN WOMEN
Xinxin Guo1, Michela Simoni2, Leonardo Pantoni2, Bo Palmertz3, Deborah Gustafson1, Ingmar Skoog1; 1Clinical Neurosciences, Sahlgrenska University Hospital, Go¨teborg, Sweden; 2Department of Neurological and Psychiatric Sciences, University of Florence, Florence, Italy; 3Department of Radiology, Ostra Hospital, Go¨teborg, Sweden Background: Lower respiratory function increased risks of atherosclerosis, hypertension, and stroke. Only few studies have examined the relationship between respiratory function and white matter lesions (WMLs) and lacunar infarcts before, and are mainly cross-sectional. Objectives: To study whether lower respiratory function was related to WMLs and lacunar infarcts. Methods: As a part of a longitudinal population-based study in Gothenburg, the study sample included 359 women aged 50-72 years who were followed for 20 years. Respiratory function was measured by forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) in 1980. Computerized tomographic (CT) scans of the brain was taken in 2000, and rated for presence and severity of WMLs as well as presence and number of lacunar infarcts. Results: Lower FVC and FEV1 in 1980 were associated with increased frequency and severity of WMLs and lacunar infarcts on CT in 2000. Per 1SD decrease of FVC, odds ratios (95% confidence intervals) were 1.42 (1.10-1.83) for presence of WMLs and 1.58 (1.21-2.07) for presence of lacunar infarcts, after adjustment for potential confounders. Per 1SD decrease of FEV1, adjusted odds ratios (95% confidence intervals) were 1.39 (1.07-1.82) for presence of WMLs and 1.49 (1.13-1.96) for presence of lacunar infarcts. The associations remained in non-smokers. Conclusions: Lower respiratory capacity increases risks of WMLs and lacunar infarcts. O1-01-04
TIME COURSE OF COGNITIVE DEFICITS IN PRECLINICAL ALZHEIMER’S DISEASE
Brent J. Small1, Laura Fratiglioni2, Lars Backman2; 1University of South Florida, Tampa, FL, USA; 2Karolinska Institute, Stockholm, Sweden Background: In recent years there has been a great deal of interest in describing the nature of changes in cognitive performance during preclinical Alzheimer’s disease (AD). A better understanding of the time course of these effects may aid in the early identification of persons at risk of AD. Objectives: In this presentation we examine whether the change in cog-
nitive performance during preclinical AD represents a linear decline in functioning to the dementia diagnosis or whether a period of relative stability exists, followed by precipitous decline directly preceding the dementia diagnosis. Methods: Participants consisted of 528 very-old adults (M ⫽ 81.8 years) taken from the Kungsholmen Project, a longitudinal study of aging and dementia. Persons were measured on 4 occasions across a 7-year follow-up interval. At the final measurement point, 457 persons remained free of a dementia diagnosis, whereas 71 were newly diagnosed with AD and represent the incident AD cases. Cognitive performance was indexed with the Mini-Mental State Examination. In order to examine changes in cognitive performance, growth mixture modeling was applied to the longitudinal data. This technique, which is conceptually similar to random-effects models, allows for the extraction of sub-groups or classes of participants based upon differences in initial level, slope, or both. In the current study, we examined two statistical models, one specifying linear decline and the other incorporating a quadratic decline component to determine which model identified the most preclinical AD cases correctly. The results indicated that at baseline, 7-years prior to the dementia diagnosis, those who would go on to be diagnosed with AD scored significantly lower than persons who would remain free of dementia. Further, the growth mixture model that incorporated linear and quadratic decline provided the best statistical fit to the data, as well as generating the best sensitivity (61.9%) and specificity (94.3%) estimates. Conclusions: This analysis demonstrates that the decline in cognitive performance seen in preclinical AD is characterized by a period of relative stability followed by rapid declines just prior to the diagnosis of dementia. Further, the results illustrate the merits of this statistical approach to describe changes in cognitive functioning preclinically. O1-01-05
DIABETES MELLITUS AND RISK OF ALZHEIMER’S DISEASE IN THE CACHE COUNTY STUDY ON MEMORY, HEALTH, AND AGING
Gene Charoonruk1, Ronald Munger1, Heidi Wengreen1, Christopher Corcoran1, Kathleen Hayden2, Lori Bastian3, JoAnn Tschanz1, Maria Norton1, Kathleen Welsh-Bohmer3; 1Utah State University, Logan, UT, USA; 2Johns Hopkins University, Baltimore, MD, USA; 3Duke University, Durham, NC, USA Background: The role of diabetes mellitus in the etiology of Alzheimer’s disease (AD) is uncertain because some studies have reported a minimal or no association while others have observed a positive association. The relationship between diabetes and AD is of great public health interest because of the sharply rising prevalence of obesity and diabetes worldwide. Objective(s): To examine the association between diabetes mellitus and risk of incident AD. Methods: Characteristics of 5092 men and women aged 65 years or older in Cache County, Utah, were assessed at baseline in 1995. Diabetes was assessed at baseline using self-reports of a physician’s diagnosis. Incident AD was assessed in multi-stage screening and assessment protocols and clinical consensus conferences during follow-up examinations in 1998-99. Participants with dementia at baseline or dementia other than AD at follow-up were excluded from analyses. Logistic regression models were used to estimate the relative risk of AD while controlling for age, education, smoking, alcohol intake, APOE genotype, body mass index, and history of hypertension, hypercholesterolemia, stroke, and myocardial infarction. Conclusions: In the 3.5 year period of follow-up, nondiabetic women had a higher incidence of AD compared to non-diabetic men (4.0 vs. 1.7 percent); however among diabetics the incidence of AD was lower among women compared to men (3.1 vs. 4.0 percent). The multivariate-adjusted relative risk (RR) of AD in diabetics vs. non-diabetics was nearly 4-fold higher for men (RR ⫽ 3.71, 95% confidence interval (CI) ⫽ 1.54-8.58) but was not elevated for women (RR ⫽ 1.01, 95% CI ⫽ 0.35-2.48). In conclusion baseline history of diabetes was associated with a subsequent increase in risk of AD in men but not in women in Cache County, Utah. The interaction between diabetes, gender, and risk of AD should be explored further.