- Email: [email protected]
Effects of metabolic syndrome, antihypertensive medications, and statins on PiB deposition in cognitively normal subjects
P878
Developing Topics
on MMSE. The average age was 79.8 65.9 year old. The disease duration is 3.3 6 2.0 years. They are divided into two groups according to the specific binding ratio (SBR) of 123I-FP-CIT SPECT. The SBR is derived from a measure of total striatal count (TossiciBolt L et al, Eur J Nucl Med Mol Imaging 2006, 33:1491). The patients with less than 4.0 on the SBR were referred to the low DAT group (L-DAT, N¼ 11) and those with more than 4.0 were designated to the normal DAT group (N-DAT, N ¼ 8). A three-dimensional stereotactic surface projection (3D-SSP) analysis of SPECT was performed using the interface software iSSP5 and iSSP35_2tZ (Nihon Medi-Physics Corporation,Tokyo, Japan).We used Z-score 2 as a cut off value. Results: There was no significant difference of age, disease duration and score of MMSE and UPDRS part III between L-DAT and N-DAT group. The left lateral and bilateral medial parietal lobe demonstrated decreased rCBF in the all patients examined compared with age-matched controls. When we compared rCBF SPECT between L-DAT and N-DAT group, L-DAT group showed lower rCBF in the bilateral medial frontal and medial parietal lobe than N-DAT group. Conclusions: Low rCBF in the medial prefrontal cortex may be helpful to differentiate DLB from AD.
related to more cortical amyloid deposition. Although MetS was not related to amyloid deposition, central obesity was associated with greater cortical amyloid in women irrespective of medication status. Conclusions: ARBs and diuretics were associated with less amyloid deposition. Prospective studies should confirm this benefit of antihypertensive drugs and establish whether such modifications translate into measurable clinical outcomes. Women may be particularly sensitive to detrimental effects of obesity on the aging brain. This must be taken into consideration while planning future interventions.
P4-254
CHARACTERIZATION OF REGIONAL BINDING OF CLINICAL AMYLOID TRACERS IN AUTOSOMAL DOMINANT AND SPORADIC ALZHEIMER’S DISEASE BRAINS AND THEIR INTERACTIONS WITH RESVERATROL
Ruiqing Ni1, Per-G€oran Gillberg1, Matti Viitanen1, Liisa Myllykangas2, angstr€om4, Nenad Bogdanovic1,3, Inger Nennesmo1, Bengt L Agneta Nordberg1,5, 1Karolinska Institutet, Stockholm, Sweden; 2University of Helsinki, Helsinki, Finland; 3Oslo University, Oslo, Norway; 4Uppsala University, Uppsala, Sweden; 5Karolinska University Hospital Huddinge, Stockholm, Sweden. Contact e-mail: [email protected] Background: Amyloid PET enables early detection of fibrillar amy-
P4-253
EFFECTS OF METABOLIC SYNDROME, ANTIHYPERTENSIVE MEDICATIONS, AND STATINS ON PIB DEPOSITION IN COGNITIVELY NORMAL SUBJECTS
Lidia Glodzik1, Henry Rusinek1, Elizabeth Pirraglia1, Wai Tsui2, Lisa Mosconi1, Yi Li1, Pauline McHugh1, John Murray1, Schantel Williams3, Catherine Randall1, Tracy Butler1, Anup Deshpande1, Shankar Vallabhajosula4, Mony DeLeon1, 1NYU School of Medicine, New York, NY, USA; 2New York University, New York, NY, USA; 3NYU School of Medicine, New York, NY, USA; 4Weill Cornell Medical College, New York, NY, USA. Contact e-mail: [email protected] Background: Metabolic syndrome (MetS) is a multiplex risk factor for cardiovascular disease that deserves significant attention. While there is a growing recognition of the link between MetS and cognition, little is known about how MetS relates to cortical amyloid deposition. The detection of vascular risk is commonly followed by an introduction of appropriate treatment aimed at risk modification. The treatment itself may affect accumulation of brain amyloid, but this issue is largely unknown. Our aim was to assess the relationships between MetS, antihypertensive and antilipid medications, and cortical amyloid binging of Pittsburgh compound B (PiB) in cognitively healthy adults and elderly. Methods: A crosssectional study of subjects (n¼155) participating in studies of brain aging who underwent Positron Emission Tomography (PET) imaging with PiB. Sixty-seven percent were women, mean age of the entire group was 60.4610.5 years, mean education 16.662.0 years. General linear models were used to compare groups. Predictors of cortical amyloid accumulation were tested with linear regression models. Tested predictors included MetS, visceral obesity, blood pressure, glucose, HDL and triglycerides levels, treatment with angiotensin receptor blockers (ARBs), beta-blockers, diuretics, angiotensin converting enzymes inhibitor, statins, antidepressants, demographics, and ApoE 4 carrier status. Results: After accounting for age and the treatment with antidepressants, the use of ARBs (b¼-.15, p¼.048) and diuretics (b¼-.28, p¼.001) predicted less amyloid accumulation, while statins (b¼.19, p¼.015) were the
loid-beta (Ab) plaque deposition in Alzheimer’s disease (AD) with different regional binding in autosomal dominant AD (ADAD) compared to sporadic AD. To further explore the underlying mechanisms, we compared the binding properties of 3H-AZD2184, 3HPIB, 3H-florbetaben and methyl-3H-BTA-1 in ADAD and sporadic AD postmortem brain tissues, and examined whether the binding of amyloid tracers was influenced by different phenols such as resveratrol. Methods: Brain tissues from cortical regions and striatum of 6 ADAD of different mutation types (APPswe, PS1 M146V and PS1 ED9), 13 sporadic AD and 14 control cases were investigated. Binding properties of 3H-AZD2184, 3H-PIB, 3H-florbetaben and methyl-3H-BTA-1 were assessed by saturation and competitive binding assays in brain homogenates. Bielschowsky silver staining was performed in the frontal cortex and striatum sections from ADAD and sporadic AD cases. Binding assays and autoradiography using aforementioned tracers were performed in the presence of phenols (b-naphthol, p-nitrophenol, and resveratrol). Results: The amyloid tracers 3H-PIB, 3H-florbetaben, 3H-AZD2184 and BTA-1 showed a similar high-affinity binding site (affinity range 0.1-1.0 nM), but a low-affinity binding site with varying affinity (range 7-325 nM) in the frontal cortex of sporadic AD. AZD2184 detected an additional binding site (affinity 33 nM) in the frontal cortex of ADAD compared to sporadic AD. In addition, significantly increased binding of 3H-AZD2184 and 3H-PIB was measured in the striatum of ADAD compared to controls and sporadic AD. Resveratrol reduced in a competitive manner the binding in sporadic AD and ADAD, with the highest affinity for 3 H-AZD2184 (z 5 nM). Conclusions: Clinical amyloid PET tracers show a similar high-affinity binding sites, but vary substantially in affinity for the low-affinity binding sites. AZD2184 binding studies in ADAD brain detected both an additional binding sites in the frontal cortex as well as an increased binding in the striatum as possible sign for differences in Ab plaque composition. Difference observed in the binding properties and interactions with resveratrol between amyloid tracers imply binding to different sites on Ab fibrils or to different Ab structures.
Developing Topics
on MMSE. The average age was 79.8 65.9 year old. The disease duration is 3.3 6 2.0 years. They are divided into two groups according to the specific binding ratio (SBR) of 123I-FP-CIT SPECT. The SBR is derived from a measure of total striatal count (TossiciBolt L et al, Eur J Nucl Med Mol Imaging 2006, 33:1491). The patients with less than 4.0 on the SBR were referred to the low DAT group (L-DAT, N¼ 11) and those with more than 4.0 were designated to the normal DAT group (N-DAT, N ¼ 8). A three-dimensional stereotactic surface projection (3D-SSP) analysis of SPECT was performed using the interface software iSSP5 and iSSP35_2tZ (Nihon Medi-Physics Corporation,Tokyo, Japan).We used Z-score 2 as a cut off value. Results: There was no significant difference of age, disease duration and score of MMSE and UPDRS part III between L-DAT and N-DAT group. The left lateral and bilateral medial parietal lobe demonstrated decreased rCBF in the all patients examined compared with age-matched controls. When we compared rCBF SPECT between L-DAT and N-DAT group, L-DAT group showed lower rCBF in the bilateral medial frontal and medial parietal lobe than N-DAT group. Conclusions: Low rCBF in the medial prefrontal cortex may be helpful to differentiate DLB from AD.
related to more cortical amyloid deposition. Although MetS was not related to amyloid deposition, central obesity was associated with greater cortical amyloid in women irrespective of medication status. Conclusions: ARBs and diuretics were associated with less amyloid deposition. Prospective studies should confirm this benefit of antihypertensive drugs and establish whether such modifications translate into measurable clinical outcomes. Women may be particularly sensitive to detrimental effects of obesity on the aging brain. This must be taken into consideration while planning future interventions.
P4-254
CHARACTERIZATION OF REGIONAL BINDING OF CLINICAL AMYLOID TRACERS IN AUTOSOMAL DOMINANT AND SPORADIC ALZHEIMER’S DISEASE BRAINS AND THEIR INTERACTIONS WITH RESVERATROL
Ruiqing Ni1, Per-G€oran Gillberg1, Matti Viitanen1, Liisa Myllykangas2, angstr€om4, Nenad Bogdanovic1,3, Inger Nennesmo1, Bengt L Agneta Nordberg1,5, 1Karolinska Institutet, Stockholm, Sweden; 2University of Helsinki, Helsinki, Finland; 3Oslo University, Oslo, Norway; 4Uppsala University, Uppsala, Sweden; 5Karolinska University Hospital Huddinge, Stockholm, Sweden. Contact e-mail: [email protected] Background: Amyloid PET enables early detection of fibrillar amy-
P4-253
EFFECTS OF METABOLIC SYNDROME, ANTIHYPERTENSIVE MEDICATIONS, AND STATINS ON PIB DEPOSITION IN COGNITIVELY NORMAL SUBJECTS
Lidia Glodzik1, Henry Rusinek1, Elizabeth Pirraglia1, Wai Tsui2, Lisa Mosconi1, Yi Li1, Pauline McHugh1, John Murray1, Schantel Williams3, Catherine Randall1, Tracy Butler1, Anup Deshpande1, Shankar Vallabhajosula4, Mony DeLeon1, 1NYU School of Medicine, New York, NY, USA; 2New York University, New York, NY, USA; 3NYU School of Medicine, New York, NY, USA; 4Weill Cornell Medical College, New York, NY, USA. Contact e-mail: [email protected] Background: Metabolic syndrome (MetS) is a multiplex risk factor for cardiovascular disease that deserves significant attention. While there is a growing recognition of the link between MetS and cognition, little is known about how MetS relates to cortical amyloid deposition. The detection of vascular risk is commonly followed by an introduction of appropriate treatment aimed at risk modification. The treatment itself may affect accumulation of brain amyloid, but this issue is largely unknown. Our aim was to assess the relationships between MetS, antihypertensive and antilipid medications, and cortical amyloid binging of Pittsburgh compound B (PiB) in cognitively healthy adults and elderly. Methods: A crosssectional study of subjects (n¼155) participating in studies of brain aging who underwent Positron Emission Tomography (PET) imaging with PiB. Sixty-seven percent were women, mean age of the entire group was 60.4610.5 years, mean education 16.662.0 years. General linear models were used to compare groups. Predictors of cortical amyloid accumulation were tested with linear regression models. Tested predictors included MetS, visceral obesity, blood pressure, glucose, HDL and triglycerides levels, treatment with angiotensin receptor blockers (ARBs), beta-blockers, diuretics, angiotensin converting enzymes inhibitor, statins, antidepressants, demographics, and ApoE 4 carrier status. Results: After accounting for age and the treatment with antidepressants, the use of ARBs (b¼-.15, p¼.048) and diuretics (b¼-.28, p¼.001) predicted less amyloid accumulation, while statins (b¼.19, p¼.015) were the
loid-beta (Ab) plaque deposition in Alzheimer’s disease (AD) with different regional binding in autosomal dominant AD (ADAD) compared to sporadic AD. To further explore the underlying mechanisms, we compared the binding properties of 3H-AZD2184, 3HPIB, 3H-florbetaben and methyl-3H-BTA-1 in ADAD and sporadic AD postmortem brain tissues, and examined whether the binding of amyloid tracers was influenced by different phenols such as resveratrol. Methods: Brain tissues from cortical regions and striatum of 6 ADAD of different mutation types (APPswe, PS1 M146V and PS1 ED9), 13 sporadic AD and 14 control cases were investigated. Binding properties of 3H-AZD2184, 3H-PIB, 3H-florbetaben and methyl-3H-BTA-1 were assessed by saturation and competitive binding assays in brain homogenates. Bielschowsky silver staining was performed in the frontal cortex and striatum sections from ADAD and sporadic AD cases. Binding assays and autoradiography using aforementioned tracers were performed in the presence of phenols (b-naphthol, p-nitrophenol, and resveratrol). Results: The amyloid tracers 3H-PIB, 3H-florbetaben, 3H-AZD2184 and BTA-1 showed a similar high-affinity binding site (affinity range 0.1-1.0 nM), but a low-affinity binding site with varying affinity (range 7-325 nM) in the frontal cortex of sporadic AD. AZD2184 detected an additional binding site (affinity 33 nM) in the frontal cortex of ADAD compared to sporadic AD. In addition, significantly increased binding of 3H-AZD2184 and 3H-PIB was measured in the striatum of ADAD compared to controls and sporadic AD. Resveratrol reduced in a competitive manner the binding in sporadic AD and ADAD, with the highest affinity for 3 H-AZD2184 (z 5 nM). Conclusions: Clinical amyloid PET tracers show a similar high-affinity binding sites, but vary substantially in affinity for the low-affinity binding sites. AZD2184 binding studies in ADAD brain detected both an additional binding sites in the frontal cortex as well as an increased binding in the striatum as possible sign for differences in Ab plaque composition. Difference observed in the binding properties and interactions with resveratrol between amyloid tracers imply binding to different sites on Ab fibrils or to different Ab structures.