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Arterial stiffness is associated with cerebral small vessel disease
Oral O2-04: Vacular Factors profile. Experiment 2 investigated the mechanisms underlying the differential sensitivity of WM binding relative to traditional measures of hippocampal functions (e.g., associative learning). The recognition task and a paired associates learning task were given to carriers of the mutation and to controls. Carriers’ performance was found to be impaired in the WM binding task only. Conclusions: Processing feature bindings in WM appears to be sensitive to AD in its sporadic and familial variants. Relative to other neuropsychological functions currently measured in the standard assessment, WM binding is targeted by the disease earlier and through different mechanisms. WM binding appears to be a cognitive marker for AD. O2-03-08
LONGITUDINAL COGNITIVE AND BRAIN CHANGES IN ALZHEIMER’S DISEASE: EFFECTS OF AGE AND THE APOE-E4 GENOTYPE
Yu-Ling Chang1, Yu-Ling Chang1, Mark Bondi2, Nikki Stricker3, Christine Fennema-Notestine2, David Salmon2, Anders Dale2, 1National Taiwan University, Taipei, Taiwan; 2University of California, San Diego, La Jolla, Calif., United States; 3Boston VA, Jamaica Plain, Mass., United States. Background: The current study utilized age-appropriate samples of normally aging participants to derive standard scores for both neuropsychological and morphometric measures in order to (1) examine how cognitive decline and regional brain atrophy are differentially impacted in both Young-Old (YOAD) and Very-Old (VOAD) patients with Alzheimer’s disease (AD) cross-sectionally and longitudinally, and (2) determine whether APOE genotype differentially affects neuropsychological deficits and morphometric changes in these two AD cohorts. Methods: The total sample consisted of 227 participants: 83 YO Healthy Control (HC) participants, 64 YOAD, 40 VOHC, and 40 VOAD. The two AD groups were further divided into subgroups on the basis of the presence of at least one APOEe4 allele. Baseline and 12-month follow up neuropsychological and morphometric measures were included to investigate the cognitive and regional brain atrophy patterns in the YOAD versus the VOAD. Results: When patients were compared to their age-appropriate control groups, the severity of neuropsychological deficits associated with AD in the Very-Old was less severe than in the Young-Old at baseline. The YOAD also showed steeper declines over time on executive function, immediate and delayed memory, and language function relative to the VOAD. Moreover, the presence of an APOEe4 allele had a more deleterious effect in the YOAD than in the VOAD on cognition cross-sectionally and longitudinally. Relative to the VOAD, the YOAD showed greater cortical atrophy (relative to their age-appropriate controls) in parietal regions at baseline; the YOAD also showed greater annual atrophy in selective regions relative to the VOAD. Furthermore, the presence of an APOEe4 allele was associated with greater annual cortical atrophy rates in lateral temporal and parietal regions in the YOAD compared to the VOAD. Conclusions: The typical pattern of AD-related cognitive and morphometric changes seen in the YO appear to be less salient in the VO. Furthermore, APOE genotype appeared to further modify the cognitive and morphometric patterns observed in the two AD cohorts cross-sectionally and longitudinally, which suggest that a multi-faceted approach that integrates neuropsychological assessment, APOE genotyping, and neuroimaging technologies is needed to characterize the early and preclinical stages of AD. MONDAY, JULY 18, 2011 ORAL O2-04 VACULAR FACTORS O2-04-01
ARTERIAL CALCIFICATIONS IN RELATION TO COGNITIVE FUNCTION AND STRUCTURAL BRAIN CHANGES
Daniel Bos, Aad van der Lugt, Jacqueline Witteman, Gabriel Krestin, Albert Hofman, Meike Vernooij, Mohammad Ikram, Erasmus Medical Centre, Rotterdam, The Netherlands. Background: Atherosclerosis may play an important role in the etiology of cognitive decline and dementia. This study investigates associations be-
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tween atherosclerosis in four vessel beds outside the brain, with cognition and preclinical MRI-markers of dementia. Methods: From the general population, 863 participants (mean age 66.6 years) underwent non-enhanced CT of the coronaries, aortic arch, extracranial and intracranial carotid arteries to quantify calcification volume as a measure of atherosclerosis. Cognitive function was assessed with a neuropschycological test battery comprising the following domains: memory, executive function, information processing speed, global cognition and motor speed. On brain MRI, total brain volume (TBV), grey matter volume (GM), white matter volume (WM) and hippocampal volume were assessed. Associations between arterial calcifications (stratified by gender), cognition and brain tissue volumes were assessed with linear regression, adjusted for relevant confounders. Results: Higher CT-assessed calcification load in all vessel beds was associated with worse cognitive scores in all domains. Adjustment for total brain volume attenuated these associations, except for the associations between extracranial and intracranial carotid artery calcifications and motor speed in men. A higher load of extracranial carotid artery calcifications in men and intracranial carotid artery calcifications in women was significantly associated with smaller total brain volume and smaller white matter volume. In women, aortic calcifications were strongly associated with smaller grey matter volume. Calcifications in any vessel bed were not associated with hippocampal volume. Adjustment for cardiovascular risk factors or carotid plaque did not change these associations. Conclusions: A higher arterial calcification load is associated with worse cognitive function. Furthermore, calcification load in specific vessel beds is associated with smaller total brain volume, white matter volume and grey matter volume. The association between arterial calcification load and cognitive function is partly mediated by its effect on brain tissue volumes. O2-04-02
ARTERIAL STIFFNESS IS ASSOCIATED WITH CEREBRAL SMALL VESSEL DISEASE
Mohammad Ikram, Keren Zaccai, Mari€elle Poels, Germaine Verwoert, Meike Vernooij, Jacqueline Witteman, Aad van der Lugt, Francesco Mattace-Raso, Monique Breteler, Erasmus Medical Center, Rotterdam, The Netherlands. Background: Arterial stiffness, as measured by aortic Pulse Wave Velocity (aPWV), is a novel marker of cardiovascular damage and has been associated with cardiovascular disease. Recent studies have also investigated the association with cerebral small vessel disease. However, because most studies were conducted in small samples or pre-selected populations, the results have been inconsistent. In a large cohort study of community-dwelling elderly we investigated the association between arterial stiffness and cerebral small vessel disease. Methods: From the Rotterdam Study 1460 participants (45 years of age and older) underwent aPWV measurement and a brain MRI scan. We calculated aPWV by measuring time differences and distances between pulse waves in the carotid and femoral arteries. Using automated MRI analysis we obtained volumes of grey matter, white matter and white matter lesions. Brain infarcts (cortical or lacunar) and microbleeds (lobar or deep) were rated visually according to location. We used linear and logistic regression models to investigate the association between aPWV and brain MRI markers. All analyses were adjusted for age, sex, mean arterial pressure and heart-rate and additionally for relevant cardiovascular risk factors. Subsequently, we stratified the analyses by presence or absence of hypertension. Results: In the total population, higher aPWV was associated with a smaller grey matter volume, and larger white matter lesion volume, but not with brain infarcts or microbleeds. In contrast, after stratification by hypertension we found that higher aPWV was significantly associated with larger white matter lesion volume (difference in standardized volume per SD increase in aPWV 0.12 [95%CI0.02;0.22]), and higher prevalence of lacunar infarcts (OR per SD increase in aPWV 1.54 [1.00-2.36] and deep microbleeds (OR 1.83 [1.11;3.02]). Among persons without hypertension we did not find any significant associations with brain infarcts or microbleeds. Conclusions: We found that arterial stiffness is associated with markers of cerebral small vessel disease; the associations were most pronounced in persons with hypertension.
LONGITUDINAL COGNITIVE AND BRAIN CHANGES IN ALZHEIMER’S DISEASE: EFFECTS OF AGE AND THE APOE-E4 GENOTYPE
Yu-Ling Chang1, Yu-Ling Chang1, Mark Bondi2, Nikki Stricker3, Christine Fennema-Notestine2, David Salmon2, Anders Dale2, 1National Taiwan University, Taipei, Taiwan; 2University of California, San Diego, La Jolla, Calif., United States; 3Boston VA, Jamaica Plain, Mass., United States. Background: The current study utilized age-appropriate samples of normally aging participants to derive standard scores for both neuropsychological and morphometric measures in order to (1) examine how cognitive decline and regional brain atrophy are differentially impacted in both Young-Old (YOAD) and Very-Old (VOAD) patients with Alzheimer’s disease (AD) cross-sectionally and longitudinally, and (2) determine whether APOE genotype differentially affects neuropsychological deficits and morphometric changes in these two AD cohorts. Methods: The total sample consisted of 227 participants: 83 YO Healthy Control (HC) participants, 64 YOAD, 40 VOHC, and 40 VOAD. The two AD groups were further divided into subgroups on the basis of the presence of at least one APOEe4 allele. Baseline and 12-month follow up neuropsychological and morphometric measures were included to investigate the cognitive and regional brain atrophy patterns in the YOAD versus the VOAD. Results: When patients were compared to their age-appropriate control groups, the severity of neuropsychological deficits associated with AD in the Very-Old was less severe than in the Young-Old at baseline. The YOAD also showed steeper declines over time on executive function, immediate and delayed memory, and language function relative to the VOAD. Moreover, the presence of an APOEe4 allele had a more deleterious effect in the YOAD than in the VOAD on cognition cross-sectionally and longitudinally. Relative to the VOAD, the YOAD showed greater cortical atrophy (relative to their age-appropriate controls) in parietal regions at baseline; the YOAD also showed greater annual atrophy in selective regions relative to the VOAD. Furthermore, the presence of an APOEe4 allele was associated with greater annual cortical atrophy rates in lateral temporal and parietal regions in the YOAD compared to the VOAD. Conclusions: The typical pattern of AD-related cognitive and morphometric changes seen in the YO appear to be less salient in the VO. Furthermore, APOE genotype appeared to further modify the cognitive and morphometric patterns observed in the two AD cohorts cross-sectionally and longitudinally, which suggest that a multi-faceted approach that integrates neuropsychological assessment, APOE genotyping, and neuroimaging technologies is needed to characterize the early and preclinical stages of AD. MONDAY, JULY 18, 2011 ORAL O2-04 VACULAR FACTORS O2-04-01
ARTERIAL CALCIFICATIONS IN RELATION TO COGNITIVE FUNCTION AND STRUCTURAL BRAIN CHANGES
Daniel Bos, Aad van der Lugt, Jacqueline Witteman, Gabriel Krestin, Albert Hofman, Meike Vernooij, Mohammad Ikram, Erasmus Medical Centre, Rotterdam, The Netherlands. Background: Atherosclerosis may play an important role in the etiology of cognitive decline and dementia. This study investigates associations be-
S295
tween atherosclerosis in four vessel beds outside the brain, with cognition and preclinical MRI-markers of dementia. Methods: From the general population, 863 participants (mean age 66.6 years) underwent non-enhanced CT of the coronaries, aortic arch, extracranial and intracranial carotid arteries to quantify calcification volume as a measure of atherosclerosis. Cognitive function was assessed with a neuropschycological test battery comprising the following domains: memory, executive function, information processing speed, global cognition and motor speed. On brain MRI, total brain volume (TBV), grey matter volume (GM), white matter volume (WM) and hippocampal volume were assessed. Associations between arterial calcifications (stratified by gender), cognition and brain tissue volumes were assessed with linear regression, adjusted for relevant confounders. Results: Higher CT-assessed calcification load in all vessel beds was associated with worse cognitive scores in all domains. Adjustment for total brain volume attenuated these associations, except for the associations between extracranial and intracranial carotid artery calcifications and motor speed in men. A higher load of extracranial carotid artery calcifications in men and intracranial carotid artery calcifications in women was significantly associated with smaller total brain volume and smaller white matter volume. In women, aortic calcifications were strongly associated with smaller grey matter volume. Calcifications in any vessel bed were not associated with hippocampal volume. Adjustment for cardiovascular risk factors or carotid plaque did not change these associations. Conclusions: A higher arterial calcification load is associated with worse cognitive function. Furthermore, calcification load in specific vessel beds is associated with smaller total brain volume, white matter volume and grey matter volume. The association between arterial calcification load and cognitive function is partly mediated by its effect on brain tissue volumes. O2-04-02
ARTERIAL STIFFNESS IS ASSOCIATED WITH CEREBRAL SMALL VESSEL DISEASE
Mohammad Ikram, Keren Zaccai, Mari€elle Poels, Germaine Verwoert, Meike Vernooij, Jacqueline Witteman, Aad van der Lugt, Francesco Mattace-Raso, Monique Breteler, Erasmus Medical Center, Rotterdam, The Netherlands. Background: Arterial stiffness, as measured by aortic Pulse Wave Velocity (aPWV), is a novel marker of cardiovascular damage and has been associated with cardiovascular disease. Recent studies have also investigated the association with cerebral small vessel disease. However, because most studies were conducted in small samples or pre-selected populations, the results have been inconsistent. In a large cohort study of community-dwelling elderly we investigated the association between arterial stiffness and cerebral small vessel disease. Methods: From the Rotterdam Study 1460 participants (45 years of age and older) underwent aPWV measurement and a brain MRI scan. We calculated aPWV by measuring time differences and distances between pulse waves in the carotid and femoral arteries. Using automated MRI analysis we obtained volumes of grey matter, white matter and white matter lesions. Brain infarcts (cortical or lacunar) and microbleeds (lobar or deep) were rated visually according to location. We used linear and logistic regression models to investigate the association between aPWV and brain MRI markers. All analyses were adjusted for age, sex, mean arterial pressure and heart-rate and additionally for relevant cardiovascular risk factors. Subsequently, we stratified the analyses by presence or absence of hypertension. Results: In the total population, higher aPWV was associated with a smaller grey matter volume, and larger white matter lesion volume, but not with brain infarcts or microbleeds. In contrast, after stratification by hypertension we found that higher aPWV was significantly associated with larger white matter lesion volume (difference in standardized volume per SD increase in aPWV 0.12 [95%CI0.02;0.22]), and higher prevalence of lacunar infarcts (OR per SD increase in aPWV 1.54 [1.00-2.36] and deep microbleeds (OR 1.83 [1.11;3.02]). Among persons without hypertension we did not find any significant associations with brain infarcts or microbleeds. Conclusions: We found that arterial stiffness is associated with markers of cerebral small vessel disease; the associations were most pronounced in persons with hypertension.