-
[show abstract]
[hide abstract]
ABSTRACT: This study investigated the hypothesis that vascular risk factors are amyloidogenic. Participants were 43 persons, most with normal cognition or mild cognitive impairment. Vascular risk was quantified using the Framingham Coronary Risk Profile (FCRP) score. Cerebral amyloid was measured by [(11)C]Pittsburgh compound B (PIB) positron emission tomography (PET) and quantified with a Global PIB index, which is the average of distribution volume ratios in selected cortical regions of interest. In a bivariate model FCRP accounted for 16% of the variance in PIB index (p < 0.008) and the positive association remained significant controlling for age and sex. The effect of FCRP was independent of apolipoprotein E (APOE) genotype, which was also associated as expected with PIB. Carotid intima-media thickness was not associated with PIB index. Effects of individual FCRP component risk factors, cholesterol, and glycemic status on PIB index were all nonsignificant, suggesting an aggregate effect of risk factors. Although this is a correlational observation it may represent a causal relationship as there are multiple, plausible, amyloidogenic mechanisms of vascular risk factors.
Neurobiology of aging 11/2011; 33(9):1979-87. · 5.94 Impact Factor
-
Helena C Chui,
Chris Zarow,
Wendy J Mack,
William G Ellis,
Ling Zheng,
William J Jagust,
Dan Mungas,
Bruce R Reed,
Joel H Kramer, Charles C Decarli,
Michael W Weiner,
Harry V Vinters
[show abstract]
[hide abstract]
ABSTRACT: To assess the interactions among three types of pathology (ie, cerebrovascular disease, hippocampal sclerosis [HS], and Alzheimer's disease [AD]), cognitive status, and apolipoprotein E genotype.
We report clinicopathological correlations from 79 autopsy cases derived from a prospective longitudinal study of subcortical ischemic vascular disease and AD.
Thirty percent of the cases had significant cerebrovascular parenchymal pathology scores (CVDPS), 54% had significant AD pathology, and 18% had HS. In an ordinal logistic regression analysis that included interaction terms to assess the effects of each pathological variable when the other variables are interpolated to zero, each of the three pathology variables contributed independently to cognitive status: Braak and Braak stage odds ratio (OR) = 2.84 (95% confidence interval, 1.81-4.45), HS score OR = 2.43 (95% confidence interval, 1.01-5.85), and CVDPS OR = 1.02 (95% confidence interval, 1.00-1.04). Only Braak and Braak stage contributed to a global neuropsychological measure of cognitive impairment. Apolipoprotein E4 genotype was associated with Braak and Braak stage (OR, 1.31 [95% confidence interval, 1.03-1.68]), but not CVDPS or HS scores.
In this convenience sample enriched for subcortical ischemic vascular disease, HS was a common unsuspected neuropathological finding. Apolipoprotein E4 genotype was associated with cerebral amyloid angiopathy, but not HS or arteriosclerosis. When Braak and Braak stage was interpolated to zero, both CVDPS and HS contributed to cognitive impairment. However, advancing stages of AD pathology overwhelmed the effects of CVDPS and HS, to become the major determinant of dementia.
Annals of Neurology 01/2007; 60(6):677-87. · 11.09 Impact Factor
-
Helena C. Chui MD,
Chris Zarow PhD,
Wendy J. Mack PhD,
William G. Ellis MD,
Ling Zheng MD,
William J. Jagust MD,
Dan Mungas PhD,
Bruce R. Reed PhD,
Joel H. Kramer PhD, Charles C. DeCarli MD,
Michael W. Weiner MD,
Harry V. Vinters MD
[show abstract]
[hide abstract]
ABSTRACT: Objective
To assess the interactions among three types of pathology (ie, cerebrovascular disease, hippocampal sclerosis [HS], and Alzheimer's disease [AD]), cognitive status, and apolipoprotein E genotype.Methods
We report clinicopathological correlations from 79 autopsy cases derived from a prospective longitudinal study of subcortical ischemic vascular disease and AD.ResultsThirty percent of the cases had significant cerebrovascular parenchymal pathology scores (CVDPS), 54% had significant AD pathology, and 18% had HS. In an ordinal logistic regression analysis that included interaction terms to assess the effects of each pathological variable when the other variables are interpolated to zero, each of the three pathology variables contributed independently to cognitive status: Braak and Braak stage odds ratio (OR) = 2.84 (95% confidence interval, 1.81–4.45), HS score OR = 2.43 (95% confidence interval, 1.01–5.85), and CVDPS OR = 1.02 (95% confidence interval, 1.00–1.04). Only Braak and Braak stage contributed to a global neuropsychological measure of cognitive impairment. Apolipoprotein E4 genotype was associated with Braak and Braak stage (OR, 1.31 [95% confidence interval, 1.03–1.68]), but not CVDPS or HS scores.InterpretationIn this convenience sample enriched for subcortical ischemic vascular disease, HS was a common unsuspected neuropathological finding. Apolipoprotein E4 genotype was associated with cerebral amyloid angiopathy, but not HS or arteriosclerosis. When Braak and Braak stage was interpolated to zero, both CVDPS and HS contributed to cognitive impairment. However, advancing stages of AD pathology overwhelmed the effects of CVDPS and HS, to become the major determinant of dementia. Ann Neurol 2006;60:677–687
Annals of Neurology 11/2006; 60(6):677 - 687. · 11.09 Impact Factor
