- Email: [email protected]
Mapping neuroinflammation in vivo in healthy aging and Alzheimer's disease: A PET study using a novel translocator protein 18kDA (TSPO) radioligand, [18F]-FEPPA
Poster Presentations: P4
P693
optimised VBM approach (FSL-VBM). Subcortical atrophy was evaluated by active shape model implemented in FIRST analysis. Results: SIENAX analysis displayed the total brain atrophy in AD patients. VBM analysis showed atrophy in the bilateral mediotemporal regions, as well as in posterior brain regions. Atrophy of the bilateral thalami and hippocampi was identified and also showed to be regionally specific. Vertex analysis of the segmented thalami and hippocampi indicated shrinking of the bilateral anterior thalami and the left medial hippocampus. Interestingly, the loss of thalamic volume was highly correlated to the hippocampal atrophy on both sides in AD patients, but not in healthy controls. Conclusions: An integrative approach in multilevel cortical and subcortical evaluation of the structural MRI data showed the pattern of both the global and local atrophy in AD patients compared to healthy controls. In addition to previous results, our study raises the issue of potentially independent atrophy of hippocampi and thalami. Obtaining the complex information about the volume and shape of subcortical structures, followed by the analysis of local changes, along with the global assessment of the neocortical atrophy, can help in the detailed interpretation of AD-related neurodegenerative process. MAPPING NEUROINFLAMMATION IN VIVO IN HEALTHYAGING AND ALZHEIMER’S DISEASE: A PET STUDY USING A NOVEL TRANSLOCATOR PROTEIN 18KDA (TSPO) RADIOLIGAND, [18F]FEPPA
P4-164
Ivonne Suridjan, Rusjan Pablo, Bruce Pollock, Aristotle Voineskos, Alan Wilson, Houle Sylvain, Romina Mizrahi, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Background: Increased density of activated microglia is one of the cellular markers of neuroinflammation. Microglia activation is characterized by the overexpression of the 18kDA Translocator Protein (TSPO), which can be quantified in-vivo using a TSPO PET targeting radioligand. The overexpression of TSPO has been reported in many age-related disorders including the Alzheimer’s disease (AD), however studies of neuroinflammation in healthy aging are limited. The aim of the present study is to examine neuroinflammation by quantifying TSPO expression using a novel TSPO PET radioligand, [18 F]-FEPPA in both healthy and AD individuals. We hypothesized that (1) neuroinflammation is related to healthy aging, and (2) neuroinflammation is elevated in AD patients. Methods: So far, 2 AD patients (age¼ 54 + 9 years) and 19 healthy volunteers (mean age 51 + 16 years) were included in the study. To assess the effect of age on neuroinflammation, the healthy volunteers were divided into two groups: young (n ¼ 10, age <55 years) and old (n ¼ 9, age > 55 years). Dynamical [18 F]-FEPPA-PET scan with full arterial sampling was acquired on HRRTPET camera and analyzed using the 2-tissue compartment model as previously described (Rusjan 2011). A repeated measure ANOVA analysis was performed to compare [18 F]-FEPPA total volumes of distribution (V T) in the hippocampus (HC), temporal (TC), prefrontal cortex (PFC) between the (1) young (n ¼ 10) and old group (n ¼ 9), and (2) the AD patients (n ¼ 2) and healthy controls (n ¼ 19). Results: We found no significant difference in regional [18 F]-FEPPA V T between the young and old healthy groups (F (1,17)¼ 0.953; P ¼ 0.343. The AD patients showed a significantly greater
[18 F]-FEPPA V T in the HC, TC, and PFC (F (1,19)¼ 10.761, P ¼ 0.004). Post-hoc analysis revealed the greatest difference in the mean [18 F]-FEPPA V T was found in the TC (F (1,19) ¼ 14.37, P ¼ 0.001), followed by the HC (F(1,19)¼ 8.72, P ¼ 0.008) and PFC (F (1,19)¼ 7.33, P ¼ 0.014). Conclusions: Our pilot data suggests that neuroinflammation is not related to healthy aging, although it might be present in patients with AD. P4-165
MICROBLEEDS IN LOGOPENIC PROGRESSIVE APHASIA
Jennifer Whitwell, Clifford Jack, Joseph Duffy, Edythe Strand, Jeffrey Gunter, Mathew Senjem, Matthew Murphy, Kejal Kantarci, Mary Machulda, Val Lowe, Keith Josephs, Mayo Clinic, Rochester, Minnesota, United States. Background: Microbleeds (MBs) have been associated with Alzheimer’s disease (AD). They occur in 12-33% of patients with typical Alzheimer’s dementia, although it is unknown whether they also occur in subjects with logopenic progressive aphasia (LPA); an atypical presentation of AD. We aimed to determine whether MBs occur in subjects with LPA, and to investigate associations between MBs and cognition, white matter hyperintensities (WMH) and b-amyloid deposition. Methods: We prospectively recruited nine subjects that met recent clinical criteria for LPA. All subjects underwent a speech and language assessment, neurological assessment, a standardized MRI protocol at 3T, including gradient-recalled echo T2weighted and fluid-attenuated inversion recovery (FLAIR) MRI, and Pittsburgh Compound B (PiB)-PET imaging. All MBs were identified on manual review by an experienced neuroradiologist (CRJ) and assigned a regional location using an atlas. Total and regional WMH burden was measured using an automated intensity based algorithm and a white matter parcellation
Table Demographic Age Sex
Female Male Amount injected SD) Specific Activity (SD) Mass Injected (SD) MMSE CDR Medications used Donepezil Aricept
Healthy n¼ 19
AD n¼ 2
51.53 (16.35) 8 11 4.70 (0.35) 4759.23 (4003.26) 0.85 (0.85) 29.37 (0.80) n/a 0 0
54.00 (9.89) 1 1 5.22 (0.06) 683.64 (47.49) 2.9 (0.23) 16.5 (2.12) 2 2 2
Figure1. Gradient-recalled echo (GRE) T2*-weighted MRI showing microbleeds in each of the three LPA subjects with microbleeds
P693
optimised VBM approach (FSL-VBM). Subcortical atrophy was evaluated by active shape model implemented in FIRST analysis. Results: SIENAX analysis displayed the total brain atrophy in AD patients. VBM analysis showed atrophy in the bilateral mediotemporal regions, as well as in posterior brain regions. Atrophy of the bilateral thalami and hippocampi was identified and also showed to be regionally specific. Vertex analysis of the segmented thalami and hippocampi indicated shrinking of the bilateral anterior thalami and the left medial hippocampus. Interestingly, the loss of thalamic volume was highly correlated to the hippocampal atrophy on both sides in AD patients, but not in healthy controls. Conclusions: An integrative approach in multilevel cortical and subcortical evaluation of the structural MRI data showed the pattern of both the global and local atrophy in AD patients compared to healthy controls. In addition to previous results, our study raises the issue of potentially independent atrophy of hippocampi and thalami. Obtaining the complex information about the volume and shape of subcortical structures, followed by the analysis of local changes, along with the global assessment of the neocortical atrophy, can help in the detailed interpretation of AD-related neurodegenerative process. MAPPING NEUROINFLAMMATION IN VIVO IN HEALTHYAGING AND ALZHEIMER’S DISEASE: A PET STUDY USING A NOVEL TRANSLOCATOR PROTEIN 18KDA (TSPO) RADIOLIGAND, [18F]FEPPA
P4-164
Ivonne Suridjan, Rusjan Pablo, Bruce Pollock, Aristotle Voineskos, Alan Wilson, Houle Sylvain, Romina Mizrahi, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. Background: Increased density of activated microglia is one of the cellular markers of neuroinflammation. Microglia activation is characterized by the overexpression of the 18kDA Translocator Protein (TSPO), which can be quantified in-vivo using a TSPO PET targeting radioligand. The overexpression of TSPO has been reported in many age-related disorders including the Alzheimer’s disease (AD), however studies of neuroinflammation in healthy aging are limited. The aim of the present study is to examine neuroinflammation by quantifying TSPO expression using a novel TSPO PET radioligand, [18 F]-FEPPA in both healthy and AD individuals. We hypothesized that (1) neuroinflammation is related to healthy aging, and (2) neuroinflammation is elevated in AD patients. Methods: So far, 2 AD patients (age¼ 54 + 9 years) and 19 healthy volunteers (mean age 51 + 16 years) were included in the study. To assess the effect of age on neuroinflammation, the healthy volunteers were divided into two groups: young (n ¼ 10, age <55 years) and old (n ¼ 9, age > 55 years). Dynamical [18 F]-FEPPA-PET scan with full arterial sampling was acquired on HRRTPET camera and analyzed using the 2-tissue compartment model as previously described (Rusjan 2011). A repeated measure ANOVA analysis was performed to compare [18 F]-FEPPA total volumes of distribution (V T) in the hippocampus (HC), temporal (TC), prefrontal cortex (PFC) between the (1) young (n ¼ 10) and old group (n ¼ 9), and (2) the AD patients (n ¼ 2) and healthy controls (n ¼ 19). Results: We found no significant difference in regional [18 F]-FEPPA V T between the young and old healthy groups (F (1,17)¼ 0.953; P ¼ 0.343. The AD patients showed a significantly greater
[18 F]-FEPPA V T in the HC, TC, and PFC (F (1,19)¼ 10.761, P ¼ 0.004). Post-hoc analysis revealed the greatest difference in the mean [18 F]-FEPPA V T was found in the TC (F (1,19) ¼ 14.37, P ¼ 0.001), followed by the HC (F(1,19)¼ 8.72, P ¼ 0.008) and PFC (F (1,19)¼ 7.33, P ¼ 0.014). Conclusions: Our pilot data suggests that neuroinflammation is not related to healthy aging, although it might be present in patients with AD. P4-165
MICROBLEEDS IN LOGOPENIC PROGRESSIVE APHASIA
Jennifer Whitwell, Clifford Jack, Joseph Duffy, Edythe Strand, Jeffrey Gunter, Mathew Senjem, Matthew Murphy, Kejal Kantarci, Mary Machulda, Val Lowe, Keith Josephs, Mayo Clinic, Rochester, Minnesota, United States. Background: Microbleeds (MBs) have been associated with Alzheimer’s disease (AD). They occur in 12-33% of patients with typical Alzheimer’s dementia, although it is unknown whether they also occur in subjects with logopenic progressive aphasia (LPA); an atypical presentation of AD. We aimed to determine whether MBs occur in subjects with LPA, and to investigate associations between MBs and cognition, white matter hyperintensities (WMH) and b-amyloid deposition. Methods: We prospectively recruited nine subjects that met recent clinical criteria for LPA. All subjects underwent a speech and language assessment, neurological assessment, a standardized MRI protocol at 3T, including gradient-recalled echo T2weighted and fluid-attenuated inversion recovery (FLAIR) MRI, and Pittsburgh Compound B (PiB)-PET imaging. All MBs were identified on manual review by an experienced neuroradiologist (CRJ) and assigned a regional location using an atlas. Total and regional WMH burden was measured using an automated intensity based algorithm and a white matter parcellation
Table Demographic Age Sex
Female Male Amount injected SD) Specific Activity (SD) Mass Injected (SD) MMSE CDR Medications used Donepezil Aricept
Healthy n¼ 19
AD n¼ 2
51.53 (16.35) 8 11 4.70 (0.35) 4759.23 (4003.26) 0.85 (0.85) 29.37 (0.80) n/a 0 0
54.00 (9.89) 1 1 5.22 (0.06) 683.64 (47.49) 2.9 (0.23) 16.5 (2.12) 2 2 2
Figure1. Gradient-recalled echo (GRE) T2*-weighted MRI showing microbleeds in each of the three LPA subjects with microbleeds